Complex locus A1BG and ZNF497: Difference between revisions

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|title=A1BG alpha-1-B glycoprotein
|title=A1BG alpha-1-B glycoprotein
|url=https://www.ncbi.nlm.nih.gov/gene/1
|url=https://www.ncbi.nlm.nih.gov/gene/1
|accessdate=May 10, 2013 }}</ref> Additionally, A1BG, in current nucleotide numbering (58,345,183-58,353,492), is located adjacent to the ZSCAN22 gene (58,326,994-58,342,332) on the positive DNA strand, as well as the ZNF837 (58,367,623 - 58,381,030, complement) and ZNF497 (58,354,357 - 58,362,751, complement) genes on the negative strand.<ref name=A1BG/> In the current nucleotide numbering, the A1BG untranslated region (UTR) has been expanded so that with ZSCAN22 ending at 58,342,332, the nucleotides used in this study are 58,342,347 to 58,346,897 on both strands, with the current UTR for A1BG beginning at 58,345,183.
|accessdate=May 10, 2013 }}</ref> Additionally, A1BG, in current nucleotide numbering (58,345,183-58,353,492), is located adjacent to the ZSCAN22 gene (58,326,994-58,342,332) on the positive DNA strand, as well as the ZNF837 (58,367,623 - 58,381,030, complement) and ZNF497 (58,354,357 - 58,362,751, complement) genes on the negative strand.<ref name=A1BG/>
 
In the current nucleotide numbering, the A1BG untranslated region (UTR) has been expanded so that with ZSCAN22 ending at 58,342,332, the nucleotides used in this study are 58,342,333 to 58,346,892 on both strands, with the current UTR for A1BG beginning at 58,345,183. On the other side of A1BG ending at 58,353,492, the nucleotides used are 58,353,493 to 58,357,937. With ZNF497 beginning at 58,354,357, this study goes into ZNF497 to 58,357,937 or 3580 nucleotides from its downstream TSS or 4445 nucleotides from the TSS of A1BG downstream from ZNF497.
 
For example, an abscisic acid responsive element (ABRE) with the consensus sequence of  ACGTG(G/T)C (Watanabe ''et al''. 2017) occurs in the positive strand in the negative direction from ZSCAN22 to A1BG as ACGTGGC ending at 4239 nucleotides from the end of ZSCAN22 or 58,346,571, where the A is at 58,346,565 inside the UTR of A1BG.


==Introduction==
==Introduction==
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===WD-40 repeat family===
===WD-40 repeat family===
{{main|WD-40 repeat family}}
{{main|WD-40 repeat family}}
"Receptor for activated C kinase (RACK1) is a highly conserved, eukaryotic protein of the WD-40 repeat family. [...] During ''Phaseolus vulgaris'' root development, RACK1 (PvRACK1) mRNA expression was induced by auxins, abscissic acid, cytokinin, and gibberellic acid."<ref name=Flores>{{ cite journal
"Receptor for activated C kinase (RACK1) is a highly conserved, eukaryotic protein of the WD-40 repeat family. [...] During ''Phaseolus vulgaris'' root development, RACK1 (PvRACK1) mRNA expression was induced by auxins, abscisic acid, cytokinin, and gibberellic acid."<ref name=Flores>{{ cite journal
|author=Tania Islas-Flores, Gabriel Guillén, Xóchitl Alvarado-Affantranger, Miguel Lara-Flores, Federico Sánchez, and Marco A. Villanueva
|author=Tania Islas-Flores, Gabriel Guillén, Xóchitl Alvarado-Affantranger, Miguel Lara-Flores, Federico Sánchez, and Marco A. Villanueva
|title=PvRACK1 Loss-of-Function Impairs Cell Expansion and Morphogenesis in ''Phaseolus vulgaris'' L. Root Nodules
|title=PvRACK1 Loss-of-Function Impairs Cell Expansion and Morphogenesis in ''Phaseolus vulgaris'' L. Root Nodules
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|accessdate=25 April 2021 }}</ref>
|accessdate=25 April 2021 }}</ref>


====Abscissic acid (ABA) response elements====
====Abscisic acid (ABA) response elements====
{{main|ABA-response element gene transcriptions}}
{{main|ABA-response element gene transcriptions#ABRE samplings}}


====Auxin response factors====
====Auxin response factors====
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=====C boxes (Song hybrids)=====
=====C boxes (Song hybrids)=====
{{main|C box gene transcriptions#Hybrid C, G box samplings}}
{{main|C box gene transcriptions#Hybrid C, G box samplings}}
Hybrids described by Song:<ref name=Song/> C/A-box (TGACGTAT), C/G-box (TGACGTGT), C/T-box (TGACGTTA).
Hybrids: C/A-box (TGACGTAT), C/G-box (TGACGTGT), C/T-box (TGACGTTA).


====CAMPs====
====CAMPs====
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=====TboxZs=====
=====TboxZs=====
{{main|T box gene transcriptions#T box (Zhang) samplings}}
{{main|T box gene transcriptions#T box (Zhang) samplings}}
====Vboxes====
{{main|V box gene transcriptions#V box samplings}}


====Z-boxes====
====Z-boxes====
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====Factor II B recognition elements====
====Factor II B recognition elements====
{{main|Factor II B recognition element gene transcriptions#BREu samplings}}
{{main|Factor II B recognition element gene transcriptions#BREu samplings}}
====Forkhead boxes====
{{main|Forkhead box gene transcriptions#Forkhead box samplings}}


====Homeoboxes====
====Homeoboxes====
Line 385: Line 395:
====MREs====
====MREs====
{{main|MYB recognition element gene transcriptions#MRE samplings}}
{{main|MYB recognition element gene transcriptions#MRE samplings}}
====Tryptophan residues====
{{main|Interferon regulatory factor gene transcriptions#Tryptophan residue samplings}}


===Basic helix-loop-helix (bHLH) transcription factors===
===Basic helix-loop-helix (bHLH) transcription factors===
{{main|Basic helix–loop–helix}}
{{main|Basic helix–loop–helix}}
"The [palindromic E-box motif (CACGTG)] motif is bound by the transcription factor Pho4, [and has the] class of basic helix-loop-helix DNA binding domain and core recognition sequence (Zhou and O'Shea 2011)."<ref name=Rossi/>
"The [palindromic E-box motif (CACGTG)] motif is bound by the transcription factor Pho4, [and has the] class of basic helix-loop-helix DNA binding domain and core recognition sequence (Zhou and O'Shea 2011)."<ref name=Rossi>{{ cite journal
|author=Matthew J. Rossi, William K.M. Lai and B. Franklin Pugh
|title=Genome-wide determinants of sequence-specific DNA binding of general regulatory factors
|journal=Genome Research
|date=21 March 2018
|volume=28
|issue=
|pages=497-508
|url=https://genome.cshlp.org/content/28/4/497.full
|arxiv=
|bibcode=
|doi=10.1101/gr.229518.117
|pmid=29563167
|accessdate=31 August 2020 }}</ref>


"Pho4 bound to virtually all E-boxes ''in vitro'' (96%) [...]. That was not the case ''in vivo'', where only 5% were bound by Pho4, under activating conditions as determined by ChIP-seq [Zhou and O'Shea 2011]."<ref name=Rossi/>
"Pho4 bound to virtually all E-boxes ''in vitro'' (96%) [...]. That was not the case ''in vivo'', where only 5% were bound by Pho4, under activating conditions as determined by ChIP-seq [Zhou and O'Shea 2011]."<ref name=Rossi/>
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===="Class C"====
===="Class C"====
{{main|N box gene transcriptions#"Class C" (Leal) samplings}}
{{main|N box gene transcriptions#"Class C" (Leal) samplings}}
===="Class I"====
=====TCFs=====
{{main|Transcription factor 3 gene transcriptions#TCF3 samplings}}


====DIOXs====
====DIOXs====
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====M-boxes====
====M-boxes====
{{main|M box gene transcriptions}}


Consensus sequences: TCAYRTG or CAYRTGA, TCA(C/T)(A/G)TG or CA(C/T)(A/G)TGA<ref name=Hoek/> ~ (T/N)CA(C/T)(A/G)TG(A/N).
=====M box (Bertolotto)=====
{{main|M box gene transcriptions#M box (Bertolotto) samplings}}


The M box consensus sequence GTCATGTGCT<ref name=Bertolotto>{{ cite journal
=====M-box (Hoek)=====
|author=Corine Bertolotto, Roser Buscà, Patricia Abbe, Karine Bille, Edith Aberdam, Jean-Paul Ortonne, and Robert Ballotti
{{main|M box gene transcriptions#M-box (Hoek) samplings}}
|title=Different ''cis''-Acting Elements Are Involved in the Regulation of TRP1 and TRP2 Promoter Activities by Cyclic AMP: Pivotal Role of M Boxes (GTCATGTGCT) and of Microphthalmia
|journal=Molecular and Cellular Biology
|date=February 1998
|volume=18
|issue=2
|pages=694–702
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC108780/
|arxiv=
|bibcode=
|doi=
|pmid=9447965
|accessdate=8 December 2018 }}</ref> does not occur on either side of A1BG. The random datasets had only one occurrence GTCATGTGCT at 1977 in the distal promoter.


Using a more general M-box consensus of (T/N)CA(C/T)(A/G)TG(A/N) yielded four sequences in the negative direction and twelve in the positive direction. Of these only TCACATGA at 325 in the negative direction and TCACATGT at 3957, CCATGTGA at 3903, and CCACATGA at 3708 in the positive direction conform to TCAYRTG or CAYRTGA<ref name=Hoek/>. The random datasets had 25 occurrences of the general consensus but only fifteen fit TCAYRTG or CAYRTGA<ref name=Hoek/>, nine in the arbitrary negative direction and six in the positive direction. The disparity between real occurrences and random occurrences suggests that the real occurrences are likely active or can be activated.
=====M-box (Ripoll)=====
{{main|M box gene transcriptions#M-box (Ripoll) samplings}}


The M-box with the consensus sequence TCACATGA<ref name=Ripoll>{{ cite journal
====SER elements====
|author=Vera M. Ripoll, Nicholas A. Meadows, Liza-Jane Raggatt, Ming K. Chang, Allison R. Pettit, Alan I. Cassady and David A. Hume
{{main|Serum response element gene transcriptions#SER samplings}}
|title=Microphthalmia transcription factor regulates the expression of the novel osteoclast factor GPNMB
|journal=Gene
|date=30 April 2005
|volume=413
|issue=1-2
|pages=32-41
|url=https://research-repository.griffith.edu.au/bitstream/handle/10072/61380/95248_1.pdf?sequence=1
|arxiv=
|bibcode=
|doi=10.1016/j.gene.2008.01.014
|pmid=
|accessdate=18 March 2021 }}</ref> occurred only once TCACATGA at 325 in the negative direction. There were no occurrences among the random datasets.


M-box consensus sequence is GGTCATGTGCT.<ref name=Zhao>{{ cite journal
===Basic helix-span-helix===
|author=Yuanyuan Zhao, Jinzhu Meng, Guoqing Cao, Pengfei Gao & Changsheng Dong
|title=Screening the optimal activity region of the dopachrome tautomerase gene promoter in sheep skin melanocytes
|journal=Journal of Applied Animal Research
|date=28 August 2018
|volume=46
|issue=1
|pages=1382-1388
|url=https://www.tandfonline.com/doi/pdf/10.1080/09712119.2018.1512497
|arxiv=
|bibcode=
|doi=10.1080/09712119.2018.1512497
|pmid=
|accessdate=6 August 2021 }}</ref> This contains the core consensus sequence GTCATGTGCT.<ref name=Bertolotto/>


====SER elements====
====Activating proteins====
{{main|Activating protein gene transcriptions}}


Consensus sequences: ACAGGATGT.
=====AP2as=====
{{main|Activating protein gene transcriptions#AP-2 alpha consensus sequences}}


===Basic helix-span-helix===
=====APCo1s=====
{{main|Activating protein gene transcriptions#Activating protein samplings (Cohen)}}


====Activating proteins====
=====APCo2s=====
{{main|Activating protein gene transcriptions}}
{{main|Activating protein gene transcriptions#Activating protein (Cohen2) samplings}}
The activating protein GCCTGGCC (Cohen) has eight occurrences on both sides of A1BG in its promoters: five from the negative direction from ZSCAN22 (two in the UTR and three in the distal promoter), and three from the positive direction in the distal promoter. But, sampling the random datasets (ten for GCCTGGCC and the same ten for the inverse complement GGCCAGGC found no occurrences. This indicates these sequences in the promoters of either side of A1BG are likely real and activable.


The second activating protein TCCCCCGCCC (Cohen) had only one occurrence that being in the positive direction toward A1BG from ZNF497 ending at 4440 nts inside A1BG gene downstream from the TSS at 4300 nts. But, sampling the random datasets (ten for TCCCCCGCCC and the same ten for the inverse complement GGGCGGGGGA found no occurrences. This indicates this sequence in the promoter of the ZNF497 side of A1BG is likely real and activable.
=====APM3Ns=====
{{main|Activating protein gene transcriptions#Activating protein samplings (Murata, 3N)}}


The activating protein TCTTCCC (Yao) has three occurrences around A1BG: two in the negative direction: TCTTCCC at 1657, GGGAAGA at 620 in the distal promoter, and one in the positive direction CCCTTCT at 4264 which is only one nts from being inside the core promoter and is likely a core promoter transcription factor.
=====APM4Ns=====
{{main|Activating protein gene transcriptions#Activating protein samplings (Murata, 4N)}}


Testing the random datasets with TCTTCCC<ref name=Yao/> (Yao) and its complement inverse GGGAAGA yielded three sequences in the negative direction: GGGAAGA at 4383, TCTTCCC at 3951, and TCTTCCC at 924, for ten datasets (0.3 per dataset), versus two real sequences. For the positive direction, the random datasets yielded four sequences: TCTTCCC at 1995, TCTTCCC at 1201, GGGAAGA at 1193, and GGGAAGA at 468, (0.4 per dataset) versus one real sequence.
=====Yao1s=====
{{main|Activating protein gene transcriptions#Activating protein samplings (Yao1)}}


In both instances, the sequences found in random datasets were much less common than in the real directions around A1BG.
=====Yao2s=====
{{main|Activating protein gene transcriptions#Activating protein samplings (Yao2)}}


The second activating protein consensus sequence CTCCCA<ref name=Yao>{{ cite journal
=====Yau3s=====
| author = Yao EF, Denison MS
{{main|Activating protein gene transcriptions#Activating protein samplings (Yao3)}}
| title = DNA sequence determinants for binding of transformed Ah receptor to a dioxin-responsive enhancer
"[[Pemphigus foliaceus]] (PF) is an autoimmune disease, endemic in Brazilian rural areas, characterized by acantholysis and accompanied by complement activation, with generalized or localized distribution of painful epidermal blisters. [[CD59]] is an essential complement regulator, inhibiting formation of the membrane attack complex, and mediating signal transduction and activation of T lymphocytes. ''CD59'' has different transcripts by alternative splicing, of which only two are widely expressed, suggesting the presence of regulatory sites in their noncoding regions. To date, there is no association study with polymorphisms in ''CD59'' noncoding regions and susceptibility to autoimmune diseases. In this study, we aimed to evaluate if ''CD59'' polymorphisms have a possible regulatory effect on gene expression and susceptibility to PF. Six noncoding polymorphisms were haplotyped in 157 patients and 215 controls by sequence-specific [[polymerase chain reaction|PCR]], and CD59 mRNA levels were measured in 82 subjects, by qPCR. The ''rs861256-allele-G'' (''rs861256*G'') was associated with increased mRNA expression (''p'' = .0113) and PF susceptibility in women (OR = 4.11, ''p'' = .0001), which were also more prone to develop generalized lesions (OR = 4.3, ''p'' = .009) and to resist disease remission (OR = 3.69, ''p'' = .045). Associations were also observed for ''rs831625*G'' (OR = 3.1, ''p'' = .007) and ''rs704697*A'' (OR = 3.4, ''p'' = .006) in Euro-Brazilian women, and for ''rs704701*C'' (OR = 2.33, ''p'' = .037) in Afro-Brazilians. These alleles constitute the ''GGCCAA'' haplotype, which also increases PF susceptibility (OR = 4.9, ''p'' = .045) and marks higher mRNA expression (''p'' = .0025). [...] higher ''CD59'' transcriptional levels may be related with PF susceptibility (especially in women), probably due to the effect of genetic polymorphism and to the CD59 role in T cell signal transduction."<ref name=Silva>{{ cite journal
| journal = Biochemistry
| volume = 31
| issue = 21
| pages = 5060–7
| date = June 1992
| pmid = 1318077
| doi = 10.1021/bi00136a019 }}</ref> and its inverse complement TGGGAG occur nine times in the UTR of A1BG, whereas four random datasets contain mostly one and once two such sequences. None of either occur in the core promoters. None occur in the proximal promoters in either real direction, but two occur (10 %) in the random datasets. In the distal promoters, nine to ten real sequences occur, whereas one to 1.4 occur per each random dataset. These results indicate that these sequences are likely real and activable.
 
"Pemphigus foliaceus (PF) is an autoimmune disease, endemic in Brazilian rural areas, characterized by acantholysis and accompanied by complement activation, with generalized or localized distribution of painful epidermal blisters. CD59 is an essential complement regulator, inhibiting formation of the membrane attack complex, and mediating signal transduction and activation of T lymphocytes. ''CD59'' has different transcripts by alternative splicing, of which only two are widely expressed, suggesting the presence of regulatory sites in their noncoding regions. To date, there is no association study with polymorphisms in ''CD59'' noncoding regions and susceptibility to autoimmune diseases. In this study, we aimed to evaluate if ''CD59'' polymorphisms have a possible regulatory effect on gene expression and susceptibility to PF. Six noncoding polymorphisms were haplotyped in 157 patients and 215 controls by sequence-specific [polymerase chain reaction (PCR)] PCR, and CD59 mRNA levels were measured in 82 subjects, by qPCR. The ''rs861256-allele-G'' (''rs861256*G'') was associated with increased mRNA expression (''p'' = .0113) and PF susceptibility in women (OR = 4.11, ''p'' = .0001), which were also more prone to develop generalized lesions (OR = 4.3, ''p'' = .009) and to resist disease remission (OR = 3.69, ''p'' = .045). Associations were also observed for ''rs831625*G'' (OR = 3.1, ''p'' = .007) and ''rs704697*A'' (OR = 3.4, ''p'' = .006) in Euro-Brazilian women, and for ''rs704701*C'' (OR = 2.33, ''p'' = .037) in Afro-Brazilians. These alleles constitute the ''GGCCAA'' haplotype, which also increases PF susceptibility (OR = 4.9, ''p'' = .045) and marks higher mRNA expression (''p'' = .0025). [...] higher ''CD59'' transcriptional levels may be related with PF susceptibility (especially in women), probably due to the effect of genetic polymorphism and to the CD59 role in T cell signal transduction."<ref name=Silva>{{ cite journal
|author=Amanda Salviano-Silva, Maria Luiza Petzl-Erler & Angelica Beate Winter Boldt
|author=Amanda Salviano-Silva, Maria Luiza Petzl-Erler & Angelica Beate Winter Boldt
|title=''CD59'' polymorphisms are associated with gene expression and different sexual susceptibility to pemphigus foliaceus
|title=''CD59'' polymorphisms are associated with gene expression and different sexual susceptibility to pemphigus foliaceus
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|pmid=
|pmid=
|accessdate=27 September 2021 }}</ref>
|accessdate=27 September 2021 }}</ref>
The third activating protein consensus sequence GGCCAA can occur within the "optimal TCDD-AhR DNA-binding consensus sequence of GCGTGNNA/TNNNC/G [...]."<ref name=Yao/> or (C/G)NNN(A/T)NNGTGCG which yields two UTRs TTGGCC at 4099, TTGGCC at 3948 and six distal promoters (one in the negative direction) and five in the positive direction. The random datasets yielded usually one to two UTRs with an average of 0.4 per data set, two core promoters for an average of 0.1, two proximal promoters, and twenty-one distal promoters for 0.9 and 1.2 per direction, whereas the real nucleotides have no core promoters and six distal promoters (one in the negative direction and five in the positive direction).
Two activating protein response elements have been investigated: [G/C]CCN(3,4)GG[G/C] and GCCCACGGG.<ref name=Murata/> The second does not occur on either side of A1BG and also did not occur in the random datasets. The first one which is more general occurred in the core promoter (two) and proximal promoter (two) for the positive direction only. Both directions occurred in the distal promoters: negative direction (two) and positive direction (eighteen). In the random datasets: twenty-one consensus sequences occurred in the UTR for an average of 3.6 per dataset, three were core promoters in the arbitrarily chosen positive direction for 0.6 average, two proximal promoters (one negative, one positive direction) and the distal promoters had twenty-two in the negative direction and positive direction for an average of 4.4 in either direction. There was essentially no agreement between real and random consensus sequences. Therefore, the more general activating protein is likely or activable.


===Stem-loops===
===Stem-loops===
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{{clear}}
{{clear}}


====Adenylate–uridylate rich elements (Bakheet)====
====AUREs====
{{main|Adenylate–uridylate rich element gene transcriptions#Adenylate–uridylate rich element (Bakheet) samplings}}


"The 3′UTRs were searched for the 13-bp pattern WWWUAUUUAUWW with mismatch=−1 which was computationally derived as previously described ( 2 ). The pattern was further statistically validated against larger sets of mRNA data (10 872 mRNA with 3′UTR; GenBank 119) showing occurrence of the motif in 6.8% of human mRNA."<ref name=Bakheet>{{ cite journal
====Adenylate–uridylate rich elements (Chen and Shyu, Class I)====
|author=Tala Bakheet, Bryan R. G. Williams, and Khalid S. A. Khabar
{{main|Adenylate–uridylate rich element gene transcriptions#ATTTA (Chen and Shyu, Class I) samplings}}
|title=ARED 2.0: an update of AU-rich element mRNA database
|journal=Nucleic Acids Research
|date=1 January 2003
|volume=31
|issue=1
|pages=421-423
|url=https://academic.oup.com/nar/article/31/1/421/2401201?login=true
|arxiv=
|bibcode=
|doi=10.1093/nar/gkg023
|pmid=
|accessdate=23 March 2021 }}</ref> This consensus sequence when in a promoter would be WWWUAUUUAUWW=(A/T)(A/T)(A/T)TATTTAT(A/T)(A/T).<ref name=Bakheet/> This sequence occurred only twice in the promoters of A1BG both in the negative direction: negative strand, negative direction TTTTATTTATTA at 4076 and a complement inverse on the positive strand, negative direction AAATAAATAATA at 4077. Both are in the UTR of A1BG in the negative direction.


The twenty random datasets yielded a direct sequence AATTATTTATTT at 859 in the arbitrary positive direction and a complement inverse TAATAAATAAAA at 1499 in the arbitrary negative direction, both in the distal promoters. The real sequences are likely active or activable.
====Adenylate–uridylate rich elements (Chen and Shyu, Class II)====
{{main|Adenylate–uridylate rich element gene transcriptions#UUAUUUA(U/A)(U/A) (Chen and Shyu, Class II) samplings}}


====Adenylate–uridylate rich elements (Chen and Shyu, Class I)====
====Adenylate–uridylate rich elements (Chen and Shyu, Class III)====
{{main|Adenylate–uridylate rich element gene transcriptions#ATTT (Chen and Shyu, Class III)}}


"Class I AUUUA-containing AREs had 1-3 copies of scattered AUUUA motifs coupled with a nearby U-rich region or U stretch".<ref name=Siegel/> This consensus sequence when in a promoter would be AUUUA=ATTTA. The real promoters have two sequences in the UTR of A1BG: negative strand, negative direction, ATTTA at 4073 and positive strand, negative direction, ATTTA at 4535; two sequences in the proximal promoters: negative strand, negative direction, ATTTA at 2636 and negative strand, positive direction, ATTTA at 4135; and two sequences in the distal promoters: negative strand, negative direction, ATTTA at 1698, and positive strand, positive direction, ATTTA at 3428.
====MERs====
{{main|Adenylate–uridylate rich element gene transcriptions#Overlapping (Siegel) mers}}


The random datasets had very different results: of the five arbitrarily chosen negative direction datasets, three had eleven sequences in the UTR for a 2.2 average; the ten datasets had only one sequence in a core promoter ATTTA at 4287 for an average of 0.1;, the ten datasets had three sequences in the proximal promoters for an average of 0.3; and the ten datasets had forty-nine for an average of 4.9 per direction.
====Constitutive decay elements====
{{main|Adenylate–uridylate rich element gene transcriptions#Constitutive decay element (Siegel) samplings}}


====Adenylate–uridylate rich elements (Chen and Shyu, Class II)====
==={{chem|Cys|2|His|2}} SP / Kruppel-like factor (KLF) transcription factor family===


Class "II AUUUA-containing AREs had at least two overlapping copies of the nonamer UUAUUUA(U/A)(U/A) in a U-rich region."<ref name=Siegel/> UUAUUUA(U/A)(U/A) in the promoters would be TTATTTA(A/T)(A/T).
The {{chem|Cys|2|His|2}}-like fold group ({{chem|Cys|2|His|2}}) is by far the best-characterized class of zinc fingers, and is common in mammalian transcription factors, where such domains adopt a simple ββα fold and have the amino acid sequence motif:<ref name=Pabo2001>{{cite journal | author = Pabo CO, Peisach E, Grant RA | title = Design and selection of novel Cys2His2 zinc finger proteins | journal = Annual Review of Biochemistry | volume = 70 | pages = 313–40 | date = 2001 | pmid = 11395410 | doi = 10.1146/annurev.biochem.70.1.313 }}</ref>


The real promoters have only one occurrence: in the UTR, negative strand, negative direction: TTATTTATT at 4075.
:X<sub>2</sub>-Cys-X<sub>2,4</sub>-Cys-X<sub>12</sub>-His-X<sub>3,4,5</sub>-His


The twenty random datasets had four sequences all in the distal promoters for an average of 0.2. The one real occurrence is likely active or activable.
====Alcohol dehydrogenase repressor 1====
{{main|Adr1p gene transcriptions#ADR samplings}}


====Adenylate–uridylate rich elements (Chen and Shyu, Class III)====
====SP1M1s====
{{main|Specificity protein gene transcriptions#Sp1-box 1 (Motojima) Samplings}}


"Subsequent studies based on analyses of a set of 4884 AUUUA-containing AREs led to a new classification based primarily on the number of overlapping AUUUA-repeats [8, 9, 10]."<ref name=Siegel/>
====SP1M2s====
{{main|Specificity protein gene transcriptions#Sp1-box 2 (Motojima) Samplings}}


Both the sequence ATTT and its inverse complement AAAT were searched on both sides of A1BG. An overlap would occur e.g. as follows ATTT occurs on the negative strand in the negative direction at 4514, i.e. ATTT ends at 4514, ATT ends at 4513, AT ends at 4512, and the A occurs at 4511. A first overlap would be ATTTATTT beginning at 4510, but the next ATTT ends at 4072. In order to overlap an occurrence near A1BG would need to end at -4 before the specific occurrence. For example, ATTT ends at 3014, but the further away ARE is ATTT at 3009, which is -5 rather than -4 so there is no overlapping repeat. For the negative strand in the negative direction there are no ATTTATTT overlapping repeats. For each of the direct sequences there are no overlapping repeats. However, for the inverse complements, there is an overlapping sequence positive strand, negative direction: AAAT at 4073 and AAAT at 4069, yielding AAATAAAT at 4073.
====SP-1 (Sato)s====
{{main|Specificity protein gene transcriptions#Sp-1 (Sato) samplings}}


For the twenty random datasets, there are (1) AURIIIr5: ATTT at 859 and ATTT at 855 for ATTTATTT at 859, (2) AURIIIr6: ATTT at 1143 and ATTT at 1139 for ATTTATTT at 1143, and (3) AURIIIr7ci: AAAT at 3634 and AAAT at 3630 for AAATAAAT at 3634. This yields a probability of 0.15 for direct and inverse complement whereas the real promoters have one occurrence. The sequence AAATAAAT at 4073 in the UTR of A1BG (negative direction) is likely active or activable. The two that did occur in the random datasets were both in the arbitrary positive direction. Choosing the other datasets would put one in the UTR and the other in the distal promoter.
====SP1 (Yao)s====
{{main|Specificity protein gene transcriptions#Sp1 (Yao) samplings}}


====Adenylate–uridylate rich overlapping (Siegel) elements====
====YY1Ts====
{{main|YY1 gene transcriptions#YY1 CCATCTT samplings}}


"Cluster 1 and 2 motifs total 13 nucleotides, with AU-rich segments flanking one or two AUUUA core motifs, respectively. Clusters 3, 4 and 5 include 3, 4, or 5 exact AUUUA repeats respectively."<ref name=Siegel/> "Naive Effective Length Pentamers: Pentamers classified by the “effective length” according to the formula floor((length(nt) + registration − 2)/4). “Registration” refers to the starting nucleotides of the ARE within the initial AUUUA pentamer: an ARE that starts AUUU*=0, UUUA*=1, UUAU*=2, and UAUU*=3. No mismatches allowed."<ref name=Siegel/>
===AP-2/EREBP-related factors===


To find possible ATTT regions within the promoters an algorithm was written to look for sequences of "(A/T)(A/T)(A/T)(A/T)(A/T)(A/T)(A/T)(A/T)(A/T)" so that an ATTTA can occur at least once for each of the first five nts. Only the negative strand, negative direction need be considered as the positive strand contains the complements. Possible ATTT regions with overlaps appear to exist such as "TTTATTATT at 4224" but continued examination shows that "TTTTATTAT at 4223" it is not. Another "ATTTATTAT at 4077" upon continuation shows "ATTTATTAT at 4077, TATTTATTA at 4076, TTATTTATT at 4075, TTTATTTAT at 4074, TTTTATTTA at 4073, TTTTTATTT at 4072" that an "ATTTA" is present but overlapping is unlikely. No other such "ATTTA" sequence wa found in either direction or side of A1BG.
====AGC boxes====
{{main|AGC box gene transcriptions#AGC box samplings}}


In the random datasets an "ATTTAAAAA at 2395" was found in ''ARESr0'', as was a complement "TAAATAAAA at 1499, ATAAATAAA at 1498, AATAAATAA at 1497, TAATAAATA at 1496, ATAATAAAT at 1495, AATAATAAA at 1494". Others were found "TTTTATTTA at 3611, ATTTTATTT at 3610" and "AATTTAATT at 1007, AAATTTAAT at 1006, AAAATTTAA at 1005" in ''ARESr1'', "TAAATTTTT at 3953, ATAAATTTT at 3952, AATAAATTT at 3951, TAATAAATT at 3950, ATAATAAAT at 3949", "AAATTAATT at 1556, TAAATTAAT at 1555" and "TTAAATTTA at 1771" in ''ARESr2'', "TAAATTTTA at 4196, TTAAATTTT at 4195, TTTAAATTT at 4194, TTTTAAATT at 4193, TTTTTAAAT at 4192" in ''ARESr3'', "TATATTTAA at 3724, TTATATTTA at 3723" and "TTAATAAAT at 2444, TTTAATAAA at 2443" in ''ARESr4'', "ATTATAAAT at 1564, AATTATAAA at 1563" and "AAATTTATT at 492" in ''ARESr5'', "TAAATATAA at 2239, TTAAATATA at 2238, TTTAAATAT at 2237, TTTTAAATA at 2236, ATTTTAAAT at 2235, AATTTTAAA at 2234" and "ATTTATTTA at 1144, TATTTATTT at 1143, ATATTTATT at 1142, TATATTTAT at 1141", "TATTTATTA at 919" and "AATTATTTA at 187" in ''ARESr6'', "TTAAAAATA at 3920, TTTAAAAAT at 3919, ATTTAAAAA at 3918, AATTTAAAA at 3917, TAATTTAAA at 3916" and "AAATAAATT at 3635, TAAATAAAT at 3634, ATAAATAAA at 3633, TATAAATAA at 3632" in ''ARESr7'', "TTTTAAATA at 3609" in ''ARESr8'', and "ATTATTTAA at 810, AATTATTTA at 809" in ''ARESr9''; for an occurrence of nineteen possible overlaps in ten datasets for 1.9 per dataset compared with one for two or 0.5 for the real promoters which suggests that the occurrence is likely active or activable but insufficient when two or more are needed.
===AP-1 transcription factor network (Pathway)===


====Constitutive decay elements====
Sixty-nine genes are included in the AP-1 transcription factor network (Pathway).<ref name=AP-1TFN>{{ cite web
|author=NCBI
|title=AP-1 transcription factor network
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=9 March 2021
|url=https://pubchem.ncbi.nlm.nih.gov/pathway/Pathway%20Interaction%20Database:ap1_pathway
|accessdate=26 October 2021 }}</ref>


Constitutive "decay elements (CDEs) [4, 18][...] are conserved stem loop motifs that bind to the proteins Roquin and Roquin2, resulting in increased mRNA decay [18]. CDEs include an upper stem-loop sequence of the form UUCYRYGAA flanked by lower stem sequences. Lower stem sequences are formed by 2-5 nt pairs of reverse-complementary sequences (e.g. CCUUCYRYGAAGG has a lower stem length of 2)."<ref name=Siegel>{{ cite journal
====AGCEs====
|author=David A. Siegel, Olivier Le Tonqueze, Anne Biton, Noah Zaitlen, and David J. Erle
{{main|AGCE gene transcriptions#AGCE samplings}}
|title=Massively Parallel Analysis of Human 3′ UTRs Reveals that AU-Rich Element Length and Registration Predict mRNA Destabilization
|journal=bioRxiv
|date=12 February 2020
|volume=
|issue=
|pages=
|url=https://www.biorxiv.org/content/biorxiv/early/2020/02/12/2020.02.12.945063.full.pdf
|arxiv=
|bibcode=
|doi=10.1101/2020.02.12.945063
|pmid=
|accessdate=23 March 2021 }}</ref>


For transcription a CDE would occur as TTC(C/T)(A/G)(C/T)GAA for an upper stem-loop sequence. This would be expected to be flanked by lower stem sequences such as CC...GG. The only consensus sequence found on either side of A1BG is TTCCATGAA at 128 in the distal promoter in the positive direction from ZNF497 toward A1BG for an occurrence of 0.125 (1/8). On the two sides of this sequence are GA...CG up to AGAGA...CGGAA which are not the reverse (inverse)-complement of each other. This CDE does not have a CC...GG on the sides so appears to be incomplete or may be a random occurrence rather than a likely active or activable response element.
===Zinc finger DNA-binding domains===


Of the ten random direct datasets, two consensus sequences occurred: CDEr8: TTCCATGAA at 1472 and CDEr9: TTCTATGAA at 2350. Likewise for the reverse-complements: CDEr4ci: TTCGCGGAA at 2553 and CDEr5ci: TTCGTGGAA at 633. The odd random datasets were arbitrarly chosen as the positive direction. Such a choice suggests a probability of 0.2 for a positive direction CDE. All random occurrences were in the distal promoters though two (TTCGCGGAA at 2553 and TTCTATGAA at 2350) were near the halfway points (2280 nts and 2222.5 nts) between the genes. These results suggest that the upper stem-loop CDE TTCCATGAA at 128 may be a random occurrence or likely active or activable possibly for ZNF497.
====AnRE1s====
{{main|Androgen response element gene transcriptions#Androgen response element1 (Kouhpayeh) samplings}}


==={{chem|Cys|2|His|2}}===
====AnDRE2s====
{{main|Androgen response element gene transcriptions#Androgen response element2 (Kouhpayeh) samplings}}


The {{chem|Cys|2|His|2}}-like fold group (C2H2) is by far the best-characterized class of zinc fingers, and is common in mammalian transcription factors, where such domains adopt a simple ββα fold and have the amino acid sequence motif:<ref name=Pabo2001>{{cite journal | author = Pabo CO, Peisach E, Grant RA | title = Design and selection of novel Cys2His2 zinc finger proteins | journal = Annual Review of Biochemistry | volume = 70 | pages = 313–40 | date = 2001 | pmid = 11395410 | doi = 10.1146/annurev.biochem.70.1.313 }}</ref>
====AnREWs====
{{main|Androgen response element gene transcriptions#Androgen response element (Wilson) samplings}}


:X<sub>2</sub>-Cys-X<sub>2,4</sub>-Cys-X<sub>12</sub>-His-X<sub>3,4,5</sub>-His
====B-boxes====
{{main|B box gene transcriptions#B box (Johnson) samplings}}


====Alcohol dehydrogenase repressor 1====
====Box Bs====
{{main|B box gene transcriptions#B1 box (Sanchez) samplings}}
 
===β-Scaffold factors===


"''Saccharomyces cerevisiae'' Alcohol dehydrogenase repressor 1 (Adr1p, YDR216W) is the transcription activator of the ADH2 gene (alcohol dehydrogenase 2) [1,2], which participates in the metabolic switch from glucose to ethanol or glycerol as food sources in yeast. Adr1p is involved in the activation of a number of genes of the respiratory metabolism, including those that regulate peroxisomes and phospholipid biosynthesis [3,4]."<ref name=Buttinelli>{{ cite journal
"Higher animals have [transcription factor] TF genes for the basic domain, the β-scaffold factor, and other new
|author=Memmo Buttinelli, Gianna Panetta, Ambra Bucci, Daniele Frascaria, Veronica Morea and Adriana Erica Miele
structures; however, their total proportion is less than 15% and most are [zinc (Zn)-coordinating factor] ZF and [Helix-Turn-Helix] HTH genes."<ref name=Nagata>{{ cite book
|title=Protein Engineering of Multi-Modular Transcription Factor Alcohol Dehydrogenase Repressor 1 (Adr1p), a Tool for Dissecting In Vitro Transcription Activation
|author=Toshifumi Nagata, Aeni Hosaka-Sasaki and Shoshi Kikuchi
|journal=Biomolecules
|title=The Evolutionary Diversification of Genes that Encode Transcription Factor Proteins in Plants, In: ''Plant Transcription Factors Evolutionary, Structural and Functional Aspects''
|date=17 September 2019
|publisher=Academic Press
|volume=9
|location=
|issue=9
|date=2016
|pages=497
|editor=Daniel H. Gonzalez
|url=https://www.mdpi.com/2218-273X/9/9/497/htm
|pages=73-97
|url=https://www.sciencedirect.com/science/article/pii/B9780128008546000051
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.3390/biom9090497
|doi=10.1016/B978-0-12-800854-6.00005-1
|pmid=
|pmid=
|accessdate=30 October 2020 }}</ref> The upstream activating sequence (UAS) for Adr1p is TTGGGG or TTGG(A/G)G.<ref name=Tang/>
|isbn=978-0-12-800854-6
|accessdate=28 November 2021 }}</ref>


In the real promoters of A1BG, Adr1 occurs in the UTRs six times, Adr1 occurs in the core promoter in the positive direction TTGGGG at 4302. In the proximal promoters, it occurs once in the negative direction. The only other occurrences are in each direction in the distal promoters: negative direction (seventeen times) and positive direction (eleven times).
====ATA boxes====
{{main|ATA box gene transcriptions#ATA box samplings}}


But in the random datasets, Adr1 occurs sixteen times for ten datasets or 1.6 times in the UTR, once for ten datasets in the negative direction for 0.1 and two of three less than or equal to 4445 for ten datasets (0.2) in the arbitrary positive direction in the core promoters, once in the negative direction for ten datasets (0.1) and twice in the positive direction for 0.2 in the proximal promoters, for the distal promoters ten datasets had twenty occurrences for 2.0 per dataset in the negative direction, and thirty-eight occurrences for ten datasets in the arbitrary positive direction for 3.8.
====Γ-interferon activated sequences====
{{main|Γ-interferon activated sequence gene transcriptions#Γ-interferon activated sequence samplings}}


===AP-2/EREBP-related factors===
====HMG boxes====
{{main|HMG box gene transcriptions#HMG box samplings}}


====AGC boxes====
===Zn(II)<sub>2</sub>Cys<sub>6</sub> proteins===


"cDNA clones have been identified representing 4 novel DNA-binding proteins, called ethylene-responsive element binding proteins (EREBPs), that specifically bind the ERE AGC box".<ref name=Metzger>{{ cite journal
"The transcription factors Uga3, Dal81 and Leu3 belong to the class III family (Zn(II)<sub>2</sub>Cys<sub>6</sub> proteins), and they recognize highly related sequences rich in GGC triplets [15]."<ref name=Ruiz>{{ cite journal
|author=Gerhard Leubner-Metzger, Luciana Petruzzelli, Rosa Waldvogel, Regina Vögeli-Lange, and Frederick Meins, Jr.
|author=Marcos Palavecino-Ruiz, Mariana Bermudez-Moretti, Susana Correa-Garcia
|title=Ethylene-responsive element binding protein (EREBP) expression and the transcriptional regulation of class I β-1, 3-glucanase during tobacco seed germination
|title=Unravelling the transcriptional regulation of Saccharomyces cerevisiae UGA genes: the dual role of transcription factor LEU3
|journal=Plant Molecular Biology
|journal=Microbiology
|date=November 1998
|date=1 November 2017
|volume=38
|volume=
|issue=5
|issue=
|pages=785-95
|pages=
|url=http://link.springer.com/article/10.1023/A:1006040425383
|url=https://www.researchgate.net/profile/Mariana_Bermudez3/publication/320571623_Unravelling_the_transcriptional_regulation_of_Saccharomyces_cerevisiae_UGA_genes_the_dual_role_of_transcription_factor_Leu3/links/5c62114c299bf1d14cbf7ade/Unravelling-the-transcriptional-regulation-of-Saccharomyces-cerevisiae-UGA-genes-the-dual-role-of-transcription-factor-Leu3.pdf
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.1023/A:1006040425383
|doi=10.1099/mic.0.000560
|pmid=
|pmid=
|accessdate=2014-05-02 }}</ref>
|accessdate=21 February 2021 }}</ref>


In the real promoters on either side of A1BG only one AGC box occurs on the positive strand, negative direction GGCGGCT at 1754 in the distal promoter. These four strands in two directions yielded only this consensus sequence for a rate of 0.25 per strand.
====Dal81====


In the twenty random datasets there are ten sequences: three in the UTR (arbitrary negative direction), one on the core promoter (arbitrary positive direction), one in the proximal promoter (arbitrary positive direction), and five in the distal promoters, for a response rate of 0.5 per strand. The striking difference between the real promoters and the random promoters suggests that the limited response of the real promoters is likely active or activable. A1BG coding strand is on the positive strand, negative direction which adds some weight to the likelihood this AGC box is used.
====GCC boxes====
{{main|AGC box gene transcriptions#GCC box samplings}}


{|class="wikitable"
====GGC triplets====
|-
{{main|GGC triplet gene transcriptions#GGC samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 0 || 2 || 0 || 0
|-
| Randoms || UTR || arbitrary negative || 3 || 10 || 0.3 || 0.25
|-
| Randoms || UTR || alternate negative || 2 || 10 || 0.2 || 0.25
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || negative || 0 || 10 || 0 || 0.05
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || positive || 1 || 10 || 0.1 || 0.05
|-
| Reals || Proximal || negative || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || negative || 0 || 10 || 0 || 0.05
|-
| Reals || Proximal || positive || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || positive || 1 || 10 || 0.1 || 0.05
|-
| Reals || Distal || negative || 1 || 2 || 0.5 || 0.25
|-
| Randoms || Distal || negative || 2 || 10 || 0.2 || 0.25
|-
| Reals || Distal || positive || 0 || 2 || 0 || 0.25
|-
| Randoms || Distal || positive || 3 || 10 || 0.3 || 0.25
|}


Comparison:
=====GGCGGC triplets=====
{{main|GGC triplet gene transcriptions#GGCGGC triplet samplings}}


The occurrence of a real AGC box is greater than the randoms. This suggests that the real AGC box is likely active or activable.
====Leu3====
{{main|Leu3 gene transcriptions#Leu samplings|GGC triplet gene transcriptions#Leu3 samplings}}


===AP-1 transcription factor network (Pathway)===
====Uga3====
{{main|Leu3 gene transcriptions}}


Sixty-nine genes are included in the AP-1 transcription factor network (Pathway).<ref name=AP-1TFN>{{ cite web
===Hairpin-hinge-hairpin-tail===
|author=NCBI
|title=AP-1 transcription factor network
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=9 March 2021
|url=https://pubchem.ncbi.nlm.nih.gov/pathway/Pathway%20Interaction%20Database:ap1_pathway
|accessdate=26 October 2021 }}</ref>


====AGCEs====
"In addition to this ACA box, they have the consensus H box sequence (5'-ANANNA-3') but have no other primary sequence identity. Despite this lack of primary sequence conservation, the H and ACA boxes are embedded in an evolutionarily conserved hairpin-hinge-hairpin-tail core secondary structure with the H box in the single-stranded hinge region and the ACA box in the single-stranded tail (5, 16)."<ref name=Mitchell>{{ cite journal
{{main|AGCE gene transcriptions#AGCE samplings}}
|author=James R. Mitchell, Jeffrey Cheng, ang Kathleen Collins
|title=A Box H/ACA Small Nucleolar RNA-Like Domain at the Human Telomerase RNA 3' End
|journal=Molecular and Cellular Biology
|date=January 1999
|volume=19
|issue=1
|pages=567–576
|url=http://mcb.asm.org/content/19/1/567.full.pdf
|arxiv=
|bibcode=
|doi=
|pmid=
|accessdate=5 November 2018 }}</ref>


===Zinc finger DNA-binding domains===
====H and ACA boxes====
{{main|H and ACA box gene transcriptions#H and ACA boxes in promoters of A1BG}}


====AnRE1s====
====H-boxes (Grandbastien)====
{{main|Androgen response element gene transcriptions#Androgen response element1 (Kouhpayeh) samplings}}
{{main|H box gene transcriptions#H-box (Grandbastien) samplings}}


====AnDRE2s====
====H-boxes (Lindsay)====
{{main|Androgen response element gene transcriptions#Androgen response element2 (Kouhpayeh) samplings}}
{{main|H box gene transcriptions#H-box (Lindsay) samplings}}


====AnREWs====
====H boxes (Mitchell)====
{{main|Androgen response element gene transcriptions#Androgen response element (Wilson) samplings}}
{{main|H box gene transcriptions#H boxes (Mitchell) samplings}}


====B-boxes====
====H boxes (Rozhdestvensky)====
{{main|B box gene transcriptions#B box (Johnson) samplings}}
{{main|H box gene transcriptions#H boxes (Rozhdestvensky) in promoters of A1BG}}


====Box Bs====
===Unknown response element types===
{{main|B box gene transcriptions#B1 box (Sanchez) samplings}}


===β-Scaffold factors===
====ACEs====
{{main|MYB recognition element gene transcriptions#ACE samplings}}


"Higher animals have [transcription factor] TF genes for the basic domain, the β-scaffold factor, and other new
====BBCABW Inrs====
structures; however, their total proportion is less than 15% and most are [zinc (Zn)-coordinating factor] ZF and [Helix-Turn-Helix] HTH genes."<ref name=Nagata>{{ cite book
{{main|Initiator element gene transcriptions#BBCABW samplings}}
|author=Toshifumi Nagata, Aeni Hosaka-Sasaki and Shoshi Kikuchi
|title=The Evolutionary Diversification of Genes that Encode Transcription Factor Proteins in Plants, In: ''Plant Transcription Factors Evolutionary, Structural and Functional Aspects''
|publisher=Academic Press
|location=
|date=2016
|editor=Daniel H. Gonzalez
|pages=73-97
|url=https://www.sciencedirect.com/science/article/pii/B9780128008546000051
|arxiv=
|bibcode=
|doi=10.1016/B978-0-12-800854-6.00005-1
|pmid=
|isbn=978-0-12-800854-6
|accessdate=28 November 2021 }}</ref>


====ATA boxes====
====Calcineurin-responsive transcription factors====
{{main|Calcineurin-responsive transcription factor gene transcriptions#CRT samplings}}


In the real promoters for A1BG, nine consensus ATA boxes (direct and complement inverse) occur in the UTR between ZSCAN22 and A1BG for an occurrence of 4.5 (two strands in one direction). No consensus sequences occur in either core promoter, only one occurs in the four proximal promoters for two directions, occurrence 0.25. The distal promoters have only two consensus sequences for an occurrence of 0.5.
====Carbs====
{{main|Carbohydrate response element gene transcriptions#ACCGG (Carb) samplings}}


The random sequences (ten direct and ten complement inverses) had four sequences in the UTR for an occurrence of 0.4 (one of two directions). The core promoters had only two for 0.2, the proximal promoters had two for 0.2, and the distal promoters had eighteen and thirteen per direction for 1.8 and 1.3.
====Carb1s====
{{main|Carbohydrate response element gene transcriptions#CCCAT (Carb1) samplings}}


Comparing the two, the real sequences are far more common in the UTR and much less common further away from the transcription start sites suggesting that the real sequences are likely active or activable.
====Cat8s====
Whether the ATA box is bound by transcription factors possessing a β-Scaffold is not yet known or the source not yet found.
{{main|Cat8p gene transcriptions#Cat8p samplings}}


====Γ-interferon activated sequences====
====Cell-cycle box variants====
{{Main|Cell-cycle box gene transcriptions#CCB variant samplings}}


"Computer analysis of the nt −653 to nt −483 region identified two sites that resemble the [γ-interferon activated sequence] GAS consensus sequence, TTNCNNNAA (19). Similar GAS-like sites have been shown to mediate the effects of various cytokines, including [growth hormone] GH, on the transcription of other genes (19, 20). The first site, TTCCTAGAA (ALS-GAS1), is located between nt −633 and nt −625; the second site, TTAGACAAA (ALS-GAS2), is located between nt −553 and nt −545."<ref name=Ooi>{{ cite journal
====CGCG boxes====
|author=Guck T. Ooi, Kelley R. Hurst, Matthew N. Poy, Matthew M. Rechler, Yves R. Boisclair
{{main|CGCG box gene transcriptions#CGCG box samplings}}
|title=Binding of STAT5a and STAT5b to a Single Element Resembling a γ-Interferon-Activated Sequence Mediates the Growth Hormone Induction of the Mouse Acid-Labile Subunit Promoter in Liver Cells
|journal=Molecular Endocrinology
|date=1 May 1998
|volume=12
|issue=5
|pages=675-687
|url=https://academic.oup.com/mend/article/12/5/675/2754376
|arxiv=
|bibcode=
|doi=10.1210/mend.12.5.0115
|pmid=9605930
|accessdate=9 September 2020 }}</ref>


{|class="wikitable"
====Circadian control elements====
|-
{{main|Circadian control element gene transcriptions#CCE samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 7 || 2 || 3.5 || 3.5
|-
| Randoms || UTR || arbitrary negative || 31 || 10 || 2.9 || 2.75
|-
| Randoms || UTR || alternate negative || 24 || 10 || 2.4 || 2.75
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || negative || 0 || 10 || 0 || 0.25
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || positive || 5 || 10 || 0.5 || 0.25
|-
| Reals || Proximal || negative || 0 || 2 || 0 || 0.5
|-
| Randoms || Proximal || negative || 3 || 10 || 0.3 || 0.3
|-
| Reals || Proximal || positive || 2 || 2 || 1.0 || 0.5
|-
| Randoms || Proximal || positive || 3 || 10 || 0.3 || 0.3
|-
| Reals || Distal || negative || 10 || 2 || 5.0 || 3.25
|-
| Randoms || Distal || negative || 41 || 10 || 4.1 || 4.65
|-
| Reals || Distal || positive || 3 || 2 || 1.5 || 3.25
|-
| Randoms || Distal || positive || 52 || 10 || 5.2 || 4.65
|}


Comparison:
====Cold-responsive elements====
{{main|Cold-responsive element gene transcriptions#Cold-responsive element samplings}}


The occurrences of real Γ-interferon activated sequences are systematically outside the range of the randoms. This suggests that the real responsive element consensus sequences are likely active or activable.
====Copper response elements====
{{main|Copper response element gene transcriptions}}


====HMG boxes====
=====CuREQs=====
{{main|Copper response element gene transcriptions#CuRE (Quinn) samplings}}


"Most HMG box proteins contain two or more HMG boxes and appear to bind DNA in a relatively sequence-aspecific manner (5, 13, 15, 16 and references therein). [...] they all appear to bind to the minor groove of the A/T A/T C A A A G-motif (10, 14, 18-20)."<ref name=Laudet>{{ cite journal
=====CuREPs=====
|author=Vincent Laudet, Dominique Stehelin and Hans Clevers
{{main|Copper response element gene transcriptions#CuRE (Park) samplings}}
|title=Ancestry and diversity of the HMG box superfamily
|journal=Nucleic Acids Research
|date=1993
|volume=21
|issue=10
|pages=2493-501
|url=https://academic.oup.com/nar/article-pdf/21/10/2493/4086740/21-10-2493.pdf
|arxiv=
|bibcode=
|doi=
|pmid=
|accessdate=2017-04-05 }}</ref>


{|class="wikitable"
====Cytoplasmic polyadenylation elements====
|-
{{main|Cytoplasmic polyadenylation element gene transcriptions#CPE samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 1 || 2 || 0.5 || 0.5
|-
| Randoms || UTR || arbitrary negative || 9 || 10 || 0.9 || 0.6
|-
| Randoms || UTR || alternate negative || 3 || 10 || 0.3 || 0.6
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || arbitrary negative || 0 || 10 || 0 || 0
|-
| Randoms || Core || alternate negative || 0 || 10 || 0 || 0
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || arbitrary positive || 0 || 10 || 0 || 0
|-
| Randoms || Core || alternate positive || 0 || 10 || 0 || 0
|-
| Reals || Proximal || negative || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || arbitrary negative || 1 || 10 || 0.1 || 0.05
|-
| Randoms || Proximal || alternate negative || 0 || 10 || 0 || 0.05
|-
| Reals || Proximal || positive || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || arbitrary positive || 0 || 10 || 0 || 0.1
|-
| Randoms || Proximal || alternate positive || 2 || 10 || 0.2 || 0.1
|-
| Reals || Distal || negative || 2 || 2 || 1 || 1
|-
| Randoms || Distal || arbitrary negative || 11 || 10 || 1.1 || 0.8
|-
| Randoms || Distal || alternate negative || 5 || 10 || 0.5 || 0.8
|-
| Reals || Distal || positive || 0 || 2 || 0 || 0
|-
| Randoms || Distal || arbitrary positive || 8 || 10 || 0.8 || 1.35
|-
| Randoms || Distal || alternate positive || 19 || 10 || 1.9 || 1.35
|}


Comparison:
====DAF-16 binding elements====
{{main|DAF-16 binding element gene transcriptions#DBE samplings}}


The occurrences of real HMG boxes are within the range of the randoms. This suggests that the real HMG boxes are likely random.
====D box (Samarsky)====
{{main|D box gene transcriptions#Dbox (Samarsky) samplings}}


===Zn(II)<sub>2</sub>Cys<sub>6</sub> proteins===
====D box (Voronina)====
{{main|D box gene transcriptions#D box (Voronina) samplings}}


"The transcription factors Uga3, Dal81 and Leu3 belong to the class III family (Zn(II)<sub>2</sub>Cys<sub>6</sub> proteins), and they recognize highly related sequences rich in GGC triplets [15]."<ref name=Ruiz/>
====D-box (Motojima)====
{{main|D box gene transcriptions#(Motojima) samplings}}


====Dal81====
====dBRE====
{{main|Downstream TFIIB recognition element gene transcriptions#dBRE samplings}}


====GCC boxes====
====Downstream core elements====
{{main|Downstream core element gene transcriptions}}
 
====DCE SI====
{{main|Downstream core element gene transcriptions#Downstream core element SI samplings}}


"Expression of the osmotin gene is similar to that of the OLP gene. The osmotin gene also has several AGCCGCC sequences; a complete AGCCGCC (from -50 to -44), a slightly modified CGCCGCC (from -144 to -138), and an AGCCGCC sequence in reverse orientation (from -162 to -156)."<ref name=Sato/>
====DCE SII====
{{main|Downstream core element gene transcriptions#Downstream core element SII samplings}}


GCC boxes occur in the
====DCE SIII====
# AGC boxes: "The GCC box, also referred to as the '''AGC box''' (10), GCC element (11), or AGCCGCC sequence (13), is an ethylene-responsive element found in the promoters of a large number of [pathogenesis related] PR genes whose expression is up-regulated following pathogen attack."<ref name=Buttner>{{ cite journal
{{main|Downstream core element gene transcriptions#Downstream core element SIII samplings}}
|author=Michael Büttner and Karam B. Singh
 
|title=''Arabidopsis thaliana'' ethylene-responsive element binding protein (AtEBP), an ethylene-inducible, GCC box DNA-binding protein interacts with an ocs element binding protein
====DPE (Juven-Gershon)====
|journal=Proceedings of the National Academy of Sciences of the United States of America
{{main|Downstream promoter element gene transcriptions#DPE (Juven-Gershon) samplings}}
|date=May 27, 1997
|volume=94
|issue=11
|pages=5961-6
|url=http://www.pnas.org/content/94/11/5961.long
|arxiv=
|bibcode=
|doi=
|pmid=
|accessdate=2014-05-02 }}</ref>
# DNA damage response elements (DRE) (Sumrada, core): "A consensus sequence, 5'-TAGCCGCCGRRRR-3' (where R = an unspecified purine nucleoside [A/G],was generated from these data."<ref name=Sumrada/>
# GGC triplets: "The transcription factors Uga3, Dal81 and Leu3 belong to the class III family (Zn(II)<sub>2</sub>Cys<sub>6</sub> proteins), and they recognize highly related sequences rich in GGC triplets [15]."<ref name=Ruiz>{{ cite journal
|author=Marcos Palavecino-Ruiz, Mariana Bermudez-Moretti and Susana Correa-Garcia
|title=Unravelling the transcriptional regulation of ''Saccharomyces cerevisiae UGA'' genes: the dual role of transcription factor Leu3
|journal=Microbiology
|date=12 October 2017
|volume=163
|issue=
|pages=1692-1701
|url=https://www.researchgate.net/profile/Mariana-Bermudez-2/publication/320571623_Unravelling_the_transcriptional_regulation_of_Saccharomyces_cerevisiae_UGA_genes_the_dual_role_of_transcription_factor_Leu3/links/5c62114c299bf1d14cbf7ade/Unravelling-the-transcriptional-regulation-of-Saccharomyces-cerevisiae-UGA-genes-the-dual-role-of-transcription-factor-Leu3.pdf
|arxiv=
|bibcode=
|doi=10.1099/mic.0.000560
|pmid=
|accessdate=20 April 2021 }}</ref>
# Kozak sequences: GCCGCC(A/G)CCATGG.<ref name=Kozak1987>{{ cite journal
|author=Kozak Marilyn
|date=October 1987
|title=An analysis of 5'-noncoding sequences from 699 vertebrate messenger RNAs
|url=http://nar.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=3313277
|journal=Nucleic Acids Research
|volume=15
|issue=20
|pages=8125–8148
|doi=10.1093/nar/15.20.8125
|pmid=3313277 }}</ref>


{|class="wikitable"
====DPE (Kadonaga)====
|-
{{main|Downstream promoter element gene transcriptions#DPE (Kadonaga) samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)  
|-
| Reals || UTR || negative || 0 || 2 || 0 || 0
|-
| Randoms || UTR || arbitrary negative || 7 || 10 || 0.7 || 0.6
|-
| Randoms || UTR || alternate negative || 5 || 10 || 0.5 || 0.6
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || negative || 0 || 10 || 0 || 0.05
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || positive || 1 || 10 || 0.1 || 0.05
|-
| Reals || Proximal || negative || 1 || 2 || 0.5 || 0.25
|-
| Randoms || Proximal || negative || 1 || 10 || 0.1 || 0.1
|-
| Reals || Proximal || positive || 0 || 2 || 0 || 0.25
|-
| Randoms || Proximal || positive || 1 || 10 || 0.1 || 0.1
|-
| Reals || Distal || negative || 1 || 2 || 0.5 || 1.75
|-
| Randoms || Distal || negative || 9 || 10 || 0.9 || 1.05
|-
| Reals || Distal || positive || 6 || 2 || 3.0 || 1.75
|-
| Randoms || Distal || positive || 12 || 10 || 1.2 || 1.05
|}


Comparison:
====DPE (Matsumoto)====
{{main|Downstream promoter element gene transcriptions#DPE (Matsumoto) samplings}}


The occurrences of real GCC boxes are greater than the randoms. This suggests that the real GCC boxes are likely active or activable.
====EIN3 binding sites====
{{main|EIN3 binding site gene transcriptions#EIN3 samplings}}


====GGC triplets====
====Endosperm expressions====
{{main|GGC triplet gene transcriptions}}
{{main|Endosperm expression gene transcriptions#Endosperm expression samplings}}
"The transcription factors Uga3, Dal81 and Leu3 belong to the class III family (Zn(II)<sub>2</sub>Cys<sub>6</sub> proteins), and they recognize highly related sequences rich in GGC triplets [15]."<ref name=Ruiz/>


{|class="wikitable"
====Estrogen response elements====
|-
{{main|Estrogen response element gene transcriptions}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 79 || 2 || 39.3 || 39.3
|-
| Randoms || UTR || arbitrary negative || 283 || 10 || 28.3 || 28.4
|-
| Randoms || UTR || alternate negative || 285 || 10 || 28.5 || 28.4
|-
| Reals || Core || negative || 0 || 2 || 0 || 3.75
|-
| Randoms || Core || negative || 9 || 10 || 0.9 || 1.875
|-
| Reals || Core || positive || 15 || 2 || 7.5 || 3.75
|-
| Randoms || Core || positive || 66 || 10 || 6.6 || 1.875
|-
| Reals || Proximal || negative || 13 || 2 || 6.5 || 6.25
|-
| Randoms || Proximal || negative || 32 || 10 || 3.2 || 2.95
|-
| Reals || Proximal || positive || 12 || 2 || 6.0 || 6.25
|-
| Randoms || Proximal || positive || 27 || 10 || 2.7 || 2.95
|-
| Reals || Distal || negative || 156 || 2 || 78 || 135
|-
| Randoms || Distal || negative || 414 || 10 || 41.4 || 59.6
|-
| Reals || Distal || positive || 384 || 2 || 192 || 135
|-
| Randoms || Distal || positive || 778 || 10 || 77.8 || 59.6
|}


Comparison:
=====ERE1s=====
{{main|Estrogen response element gene transcriptions#ERE1 (Driscoll) samplings}}


The occurrences of real GGC triplets are larger than the randoms. This suggests that the real GGC triplets are likely active or activable.
=====ERE2s=====
{{main|Estrogen response element gene transcriptions#EREs (Driscoll) samplings}}


====Leu3====
====GAAC elements====
{{main|Leu3 gene transcriptions|GGC triplet gene transcriptions}}
{{main|GAAC element gene transcriptions#GAAC element samplings}}
"Known consensus string Type of motifs LEU3 CCGNNNNCGG or GGCNNNNGCC Gapped motif".<ref name=Reddy>{{ cite journal
|author=Uyyala Srinivasulu Reddy, Michael Arock, A.V. Reddy
|title=Discovering of gapped motifs using particle swarm optimisation
|journal=International Journal of Computational Intelligence in Bioinformatics and Systems Biology
|date=20 April 2020
|volume=2
|issue=1
|pages=1-21
|url=https://www.inderscienceonline.com/doi/abs/10.1504/IJCIBSB.2020.106858
|arxiv=
|bibcode=
|doi=10.1504/IJCIBSB.2020.106858
|pmid=
|accessdate=20 April 2021 }}</ref>


{|class="wikitable"
====GC boxes (Briggs)====
|-
{{main|GC box gene transcriptions#GC box (Briggs) samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)  
|-
| Reals || UTR || negative || 1 || 2 || 0.5 || 0.5
|-
| Randoms || UTR || arbitrary negative || 40 || 10 || 4.0 || 4.45
|-
| Randoms || UTR || alternate negative || 49 || 10 || 4.9 || 4.45
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || negative || 1 || 10 || 0.1 || 0.7
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || positive || 13 || 10 || 1.3 || 0.7
|-
| Reals || Proximal || negative || 1 || 2 || 0.5 || 0.25
|-
| Randoms || Proximal || negative || 2 || 10 || 0.2 || 0.2
|-
| Reals || Proximal || positive || 0 || 2 || 0 || 0.25
|-
| Randoms || Proximal || positive || 2 || 10 || 0.2 || 0.2
|-
| Reals || Distal || negative || 7 || 2 || 3.5 || 4.5
|-
| Randoms || Distal || negative || 51 || 10 || 5.1 || 6.9
|-
| Reals || Distal || positive || 11 || 2 || 5.5 || 4.5
|-
| Randoms || Distal || positive || 87 || 10 || 8.7 || 6.9
|}


Comparison:
====GC boxes (Ye)====
{{main|GC box gene transcriptions#GC box (Ye) samplings}}


The occurrences of real UTR, proximals and distals for Leu3 and are systematically lower than the randoms. This suggests that the real Leu3s are likely active or activable.
====GC boxes (Zhang)====
{{main|GC box gene transcriptions#GC box (Zhang) samplings}}


====Uga3====
====GCR1s====
{{main|Leu3 gene transcriptions}}
{{main|Gcr1p gene transcriptions#GCR1 samplings}}


===Hairpin-hinge-hairpin-tail===
====GREs====
{{main|Gibberellin responsive element gene transcriptions#GRE samplings}}


"In addition to this ACA box, they have the consensus H box sequence (5'-ANANNA-3') but have no other primary sequence identity. Despite this lack of primary sequence conservation, the H and ACA boxes are embedded in an evolutionarily conserved hairpin-hinge-hairpin-tail core secondary structure with the H box in the single-stranded hinge region and the ACA box in the single-stranded tail (5, 16)."<ref name=Mitchell/>
====GT boxes (Sato)====
{{main|TC element gene transcriptions#GT box (Sato) samplings}}


====H and ACA boxes====
====Hex sequences====
{{main|H and ACA box gene transcriptions}}
{{main|Hex sequence gene transcriptions#Hex core samplings}}
The combined consensus sequence is ACAGGA.<ref name=Mitchell>{{ cite journal
|author=James R. Mitchell, Jeffrey Cheng, ang Kathleen Collins
|title=A Box H/ACA Small Nucleolar RNA-Like Domain at the Human Telomerase RNA 3' End
|journal=Molecular and Cellular Biology
|date=January 1999
|volume=19
|issue=1
|pages=567–576
|url=http://mcb.asm.org/content/19/1/567.full.pdf
|arxiv=
|bibcode=
|doi=
|pmid=
|accessdate=5 November 2018 }}</ref>


{|class="wikitable"
====HY boxes====
|-
{{main|HY box gene transcriptions#HY box samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 3 || 2 || 1.5 || 1.5
|-
| Randoms || UTR || arbitrary negative || 2 || 10 || 0.2 || 0.2
|-
| Randoms || UTR || alternate negative || 2 || 10 || 0.2 || 0.2
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || negative || 0 || 10 || 0 || 0
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || positive || 0 || 10 || 0 || 0
|-
| Reals || Proximal || negative || 0 || 2 || 0 || 0.25
|-
| Randoms || Proximal || negative || 0 || 10 || 0 || 0.05
|-
| Reals || Proximal || positive || 1 || 2 || 0.5 || 0.25
|-
| Randoms || Proximal || positive || 1 || 10 || 0.1 || 0.05
|-
| Reals || Distal || negative || 2 || 2 || 1.0 || 2.25
|-
| Randoms || Distal || negative || 8 || 10 || 0.8 || 0.65
|-
| Reals || Distal || positive || 7 || 2 || 3.5 || 2.25
|-
| Randoms || Distal || positive || 5 || 10 || 0.5 || 0.65
|}


Comparison:
====IFNs====
{{main|Interferon regulatory factor gene transcriptions#IFN-stimulated response element samplings}}


The occurrences of real H and ACA box consensus sequences are greater than the randoms. This suggests that the real H and ACA box consensus sequences are likely active or activable.
====Inr-like, TCTs====
{{main|Initiator element gene transcriptions#Inr-like, TCTs sampling}}


====H-boxes (Grandbastien)====
====IRF3s====
{{main|Interferon regulatory factor gene transcriptions#IRF-3 samplings}}
 
====IRSs====
{{main|Interferon regulatory factor gene transcriptions#IRS consensus samplings}}


H box in ''Solanaceae'' has the following consensus sequence CC(A/T)ACCNNNNNNN(A/C)T.<ref name=Grandbastien>{{ cite journal
====KAR2s====
|author=M.-A. Grandbastien, C. Audeon, E. Bonnivard, J.M. Casacuberta, B. Chalhoub, A.-P.P. Costa, Q.H. Le, D. Melayah, M. Petit, C. Poncet, S.M. Tam, M.-A. Van Sluys, C. Mhiri
{{main|Hac1p gene transcriptions#KAR2 samplings}}
|title=Stress activation and genomic impact of Tnt1 retrotransposons in Solanaceae
|journal=Cytogenetic and Genomic Research
|date=July 2005
|volume=110
|issue=1-4
|pages=229-41
|url=https://www.researchgate.net/profile/Corinne_Mhiri/publication/7666072_Stress_activation_and_genomic_impact_of_Tnt1_retrotransposons_in_Solanaceae/links/548089040cf20f081e7258e9/Stress-activation-and-genomic-impact-of-Tnt1-retrotransposons-in-Solanaceae.pdf
|arxiv=
|bibcode=
|doi=10.1159/000084957
|pmid=
|accessdate=5 November 2018 }}</ref>


{|class="wikitable"
====MBE1s====
|-
{{main|Musashi binding element gene transcriptions#MBE1 samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 1 || 2 || 0.5 || 0.5
|-
| Randoms || UTR || arbitrary negative || 1 || 10 || 0.1|| 0.1
|-
| Randoms || UTR || alternate negative || 1 || 10 || 0.1 || 0.1
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || arbitrary negative || 0 || 10 || 0 || 0
|-
| Randoms || Core || alternate negative || 0 || 10 || 0 || 0
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || arbitrary positive || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Core || alternate positive || 1 || 10 || 0.1 || 0.1
|-
| Reals || Proximal || negative || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || negative || 0 || 10 || 0 || 0
|-
| Reals || Proximal || positive || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || positive || 0 || 10 || 0 || 0
|-
| Reals || Distal || negative || 0 || 2 || 0 || 0
|-
| Randoms || Distal || arbitrary negative || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Distal || alternate negative || 1 || 10 || 0.1 || 0.1
|-
| Reals || Distal || positive || 0 || 2 || 0 || 0
|-
| Randoms || Distal || arbitrary positive || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Distal || alternate positive || 1 || 10 || 0.1 || 0.1
|}


Comparison:
====MBE2s====
{{main|Musashi binding element gene transcriptions#MBE2 samplings}}


The occurrences of real H-box (Grandbastien) is greater than the randoms. This suggests that the real H-box (Grandbastien) is likely active or activable.
====MBE3s====
{{main|Musashi binding element gene transcriptions#MBE3 samplings}}


====H-boxes (Lindsay)====
====NF𝜿BSs====
{{main|Nuclear factor gene transcriptions#NF𝜿B (Sato) samplings}}


"The KAP-2 protein [...] binds to the H-box (CCTACC) element in the bean CHS15 chalcone synthase promoter".<ref name=Lindsay>{{ cite journal
====PREs====
|author=William P. Lindsay, Fiona M. McAlister, Qun Zhu, Xian-Zhi He, Wolfgang Dröge-Laser, Susie Hedrick, Peter Doerner, Chris Lamb and Richard A. Dixon
{{main|Polycomb response element gene transcriptions#Core samplings}}
|title=KAP-2, a protein that binds to the H-box in a bean chalcone synthase promoter, is a novel plant transcription factor with sequence identity to the large subunit of human Ku autoantigen
|journal=Plant Molecular Biology
|date=July 2002
|volume=49
|issue=5
|pages=503–514
|url=https://link.springer.com/article/10.1023/A:1015505316379
|arxiv=
|bibcode=
|doi=10.1023/A:1015505316379
|pmid=
|accessdate=5 October 2019 }}</ref>


{|class="wikitable"
====Pribs====
|-
{{main|Pribnow box gene transcriptions#Pribnow box samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 1 || 2 || 0.5 || 0.5
|-
| Randoms || UTR || arbitrary negative || 7 || 10 || 0.7 || 0.7
|-
| Randoms || UTR || alternate negative || 7 || 10 || 0.7 || 0.7
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || arbitrary negative || 0 || 10 || 0 || 0
|-
| Randoms || Core || alternate negative || 0 || 10 || 0 || 0
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || arbitrary positive || 3 || 10 || 0.3 || 0.15
|-
| Randoms || Core || alternate positive || 0 || 10 || 0 || 0.15
|-
| Reals || Proximal || negative || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || arbitrary negative || 1 || 10 || 0.1 || 0
|-
| Randoms || Proximal || alternate negative || 0 || 10 || 0 || 0
|-
| Reals || Proximal || positive || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || arbitrary positive || 1 || 10 || 0.1 || 0.1
|-
| Randoms || Proximal || alternate positive || 1 || 10 || 0.1 || 0.1
|-
| Reals || Distal || negative || 2 || 2 || 1 || 1
|-
| Randoms || Distal || arbitrary negative || 10 || 10 || 1 || 0.7
|-
| Randoms || Distal || alternate negative || 4 || 10 || 0.4 || 0.7
|-
| Reals || Distal || positive || 5 || 2 || 2.5 || 2.5
|-
| Randoms || Distal || arbitrary positive || 7 || 10 || 0.7 || 1.15
|-
| Randoms || Distal || alternate positive || 16 || 10 || 1.6 || 1.15
|}


Comparison:
====RAREs====
{{main|Retinoic acid response element gene transcriptions#RARE samplings}}


The occurrences of real H-boxes (Lindsay) are less than the randoms for the UTRs, the distals are greater than the randoms for the positive direction and equal to or greater than the randoms for the negative direction. This suggests that the real responsive element consensus sequences are likely active or activable.
====Rgts====
{{main|Rgt1p gene transcriptions#RGT samplings}}


====H boxes (Mitchell)====
====ROREs====
{{main|ROR-response element gene transcriptions#RORE samplings}}


They "have the consensus H box sequence (5'-ANANNA-3') but have no other primary sequence identity."<ref name=Mitchell/>
====SERVs====
{{main|Servenius sequence gene transcriptions#Servenius samplings}}


{|class="wikitable"
====STAT5s====
|-
{{main|STAT5 gene transcription laboratory#STAT5 samplings}}
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 144 || 2 || 72 || 72
|-
| Randoms || UTR || arbitrary negative || 265 || 10 || 26.5 || 28.55
|-
| Randoms || UTR || alternate negative || 306 || 10 || 30.6 || 28.55
|-
| Reals || Core || negative || 21 || 2 || 10.5 || 10.5
|-
| Randoms || Core || arbitrary negative || 5 || 10 || 0.5 || 0.6
|-
| Randoms || Core || alternate negative || 7 || 10 || 0.7 || 0.6
|-
| Reals || Core || positive || 5 || 2 || 2.5 || 2.5
|-
| Randoms || Core || arbitrary positive || 36 || 10 || 3.6 || 3.45
|-
| Randoms || Core || alternate positive || 33 || 10 || 3.3 || 3.45
|-
| Reals || Proximal || negative || 21 || 2 || 10.5 || 10.5
|-
| Randoms || Proximal || arbitrary negative || 19 || 10 || 1.9 || 2.65
|-
| Randoms || Proximal || alternate negative || 34 || 10 || 3.4 || 2.65
|-
| Reals || Proximal || positive || 17 || 2 || 8.5 || 8.5
|-
| Randoms || Proximal || arbitrary positive || 40 || 10 || 4.0 || 3.8
|-
| Randoms || Proximal || alternate positive || 36 || 10 || 3.6 || 3.8
|-
| Reals || Distal || negative || 288 || 2 || 144.0 || 144.0
|-
| Randoms || Distal || arbitrary negative || 478 || 10 || 47.8 || 44.0
|-
| Randoms || Distal || alternate negative || 402 || 10 || 40.2 || 44.0
|-
| Reals || Distal || positive || 130 || 2 || 65.0 || 65.0
|-
| Randoms || Distal || arbitrary positive || 659 || 10 || 65.9 || 66.45
|-
| Randoms || Distal || alternate positive || 670 || 10 || 67.0 || 66.45
|}


Comparison:
====STREs====
{{main|Msn2,4p gene transcriptions#Stress-response element samplings}}


For the occurrences of real H boxes (Mitchell), the UTRs are systematically greater than the randoms, the real core negatives are systematically greater, the real core positives are systematically less than the randoms, real proximals are systematically greater than the randoms and the real distals are systematically outside the range of the randoms. This suggests that the real H boxes (Mitchell) are likely active or activable.
====Sucroses====
{{main|Sucrose box gene transcriptions#Sucrose box samplings}}


====H boxes (Rozhdestvensky)====
====TACTs====
{{main|TACTAAC box gene transcriptions#TACT samplings}}


An H box has a consensus sequence of 3'-ACACCA-5'.<ref name=Rozhdestvensky>{{ cite journal
====TAGteams====
|author=Timofey S. Rozhdestvensky, Thean Hock Tang, Inna V. Tchirkova, Jürgen Brosius, Jean‐Pierre Bachellerie and Alexander Hüttenhofer
{{main|TAGteam gene transcriptions#TAGteam samplings}}
|title=Binding of L7Ae protein to the K‐turn of archaeal snoRNAs: a shared RNA binding motif for C/D and H/ACA box snoRNAs in Archaea
|journal=Nucleic Acids Research
|month=
|year=2003
|volume=31
|issue=3
|pages=869-77
|url=http://nar.oxfordjournals.org/content/31/3/869.long
|arxiv=
|bibcode=
|doi=10.1093/nar/gkg175
|pmid=
|accessdate=2014-06-08 }}</ref>


===Unknown response element types===
====TAPs====
{{main|Tapetum box gene transcriptions#Tapetum box samplings}}


====ACEs====
====TATAs====
{{main|MYB recognition element gene transcriptions#ACE samplings}}
{{main|TATA box gene transcriptions#TATA box samplings}}
Examining the promoter regions upstream from ZSCAN22 to A1BG and downstream from ZNF497 to A1BG for TATA boxes has shown that TATA boxes in various forms are present and likely active or activable: (1) TATAAAA (Carninci 2006), (2) TATA(A/T)A(A/T) (Watson 2014), (3) TATA(A/T)AA(A/G) (Juven-Gershon 2010), and (4) TATA(A/T)A(A/T)(A/G) (Basehoar 2004).


====BBCABW Inrs====
The TATA boxes have the pattern of appearing in only the negative direction UTRs, proximal and distals. The shorter TATA box: TATAAA does appear as above but also in the positive direction as the complement inverse TTTATA at 2588 in the distal promoter.
{{main|Initiator element gene transcriptions#BBCABW samplings}}


====Calcineurin-responsive transcription factors====
====TATABs====
{{main|Calcineurin-responsive transcription factor gene transcriptions}}
{{main|TATA box gene transcriptions#TATA box (Butler 2002) samplings}}
The calcineurin-responsive transcription factors occur (1.5) in the UTR between ZSCAN22 and A1BG and at 2.5 in the distal promoters.


The random datasets had an occurrence of 0.4 in the UTR, 0.1 in the core promoters, and 0.2 in the negative direction distal promoters and 0.7 in the positive direction.
====TATACs====
{{main|TATA box gene transcriptions#TATA boxes (Carninci 2006) samplings}}


The disparity indicates that the CRTs are likely active or activable.
====TATAJs====
{{main|TATA box gene transcriptions#TATA box (Juven-Gershon 2010) samplings}}


====Carbs====
====TATAWs====
{{main|Carbohydrate response element gene transcriptions#ACCGG (Carb) samplings}}
{{main|TATA box gene transcriptions#TATA box (Watson 2014) samplings}}


====Carb1s====
====TEAs====
{{main|Carbohydrate response element gene transcriptions#CCCAT (Carb1) samplings}}
{{main|TEA consensus sequence gene transcriptions#TEA samplings}}


====Cat8s====
====TECs====
{{main|Cat8p gene transcriptions}}
{{main|Tec1p gene transcriptions#Tec1 samplings}}
The upstream activating sequence (UAS) for Cat8p is 5'-CGGNBNVMHGGA-3', where N = A, C, G, T, B = C, G, T, V = A, C, G, M = A, C, and H = A, C, T; i.e. 5'-CGG(A/C/G/T)(C/G/T)(A/C/G/T)(A/C/G)(A/C)(A/C/T)GGA-3'.<ref name=Tang/>


The real promoters have only two Cat8s: TCCGTGCCACCG at 2528 and TCCGTGCCACCG at 657, both inverse complements and on the negative strand in the negative direction in the distal promoter for an occurrence of 0.5.
====THRs====
{{main|Thyroid hormone response element gene transcriptions#THR samplings}}


The random datasets had response elements in the UTRs (0.1) and proximal promoters (0.1) as well as the distal promoters (0.25), specifically in the negative direction (0.2) and 0.3 in the positive direction.
====TRFs====
{{main|Telomeric repeat DNA-binding factor gene transcriptions#TRF samplings}}


Even though there are only two real Cat8 response elements in the distal promoter, they are likely active or activable.
====UPREs====
{{main|Unfolded protein response element gene transcriptions#UPRE samplings}}


====Cell-cycle box variants====
====UPRE-1s====
{{Main|Cell-cycle box gene transcriptions}}
{{main|Hac1p gene transcriptions#UPRE-1 samplings}}
The real promoters have been examined for the CCB variants: CACGAAA, ACGAAA and C-CGAAA, where C-C indicates CC with the likely A being absent (CCGAAA). The inverse complements are TTTCGTG, TTTCGT and TTTCG-G (TTTCGG). The possibility of finding these CCB variants has been performed using a general consensus sequence of NNCGAAA, the expected variants should occur if present. The real promoters have CCB variants only in the distal promoters. In the negative direction, the variants occur ACGAAA at 494 and ACGAAA at 312. The actual general consensus sequence occurrences are GGCGAAA at 2157, TACGAAA at 494, and GACGAAA at 312. CACGAAA or CCGAAA never occurred. The inverse complements occur in the negative and positive direction: TTTCGT at 2479, TTTCGT at 2473 and TTTCGT at 186, and TTTCGGG at 1752, negative strand, positive strand: TTTCGTG at 3600, TTTCGT at 2006, respectively. The occurrences are 2.5 and 1.5 per direction.


The random datasets had twenty-three UTR general consensus sequences for an occurrence of 2.3. Of these the CCB variants had the following frequencies: CACGAAA (0), ACGAAA (2) and CCGAAA (5). The inverse complements had TTTCGTG (0), TTTCGT (1) and TTTCGG (6). The remaining nine were of the general consensus sequence of NNCGAAA or TTTCGNN.
====URS (Sumrada, core)====
{{main|DNA damage response element gene transcriptions#URS1 (Sumrada, core) samplings}}


The random datasets had three general consensus sequences in arbitrary positive direction core promoter only for an occurrence of 0.3 (two strands, one direction) or 0.15 (four strands, both directions). The proximal general consensus sequences (five) had occurrences of 0.2 and 0.3.
====VDREs====
{{main|Vitamin D response element gene transcriptions#VDRE samplings}}


The distal promoters for the random datasets had twenty-six in the arbitrary negative direction for an occurrence of 2.6 and forty-two in the positive direction for an occurrence of 4.2.
====XCPE1s====
{{main|X core promoter element gene transcriptions#XCPE1 samplings}}


As the choices for direction are arbitrary for the random datasets an average occurrence would be 3.25. Even separately the real occurrences are lower than the random ones albeit not by much for the real negative direction (2.5) vs. the arbitrarily chosen negative direction (2.6) for the randoms. The randoms also had UTR, core and proximal promoter occurrences where the reals have none.
====Yaps====
{{main|Yap1p,2p gene transcriptions#Yap samplings}}


These results suggest that the real variants ACGAAA (2), TTTCGT (5) and TTTCGG (1), are likely active or activable.
====YYRNWYY Inrs====
{{main|Initiator element gene transcriptions#YYRNWYY samplings}}


====CGCG boxes====
==A1BG orthologs==
{{main|CGCG box gene transcriptions}}
All of the real CGCG boxes found are more closely associated with ZSCAN22 or ZNF497 than A1BG.


The real promoters only have three CGCG boxes closer to ZSCAN22 (for an occurrence of 1.5) or thirty-two closer to ZNF497 than A1BG (for an occurrence of 16.0).
===''Geotrypetes seraphini''===
[[Image:Geotrypetes seraphini 81151944.jpg|thumb|right|250px|''Geotrypetes seraphini'', the Gaboon caecilian, is a species of amphibian. Credit: [https://www.inaturalist.org/users/7865 Marius Burger].{{tlx|free media}}]]
''Geotrypetes seraphini'', the Gaboon caecilian, is a species of amphibian in the family ''Dermophiidae''.<ref name=IUCN>{{cite journal |author=IUCN SSC Amphibian Specialist Group |date=2019 |title=''Geotrypetes seraphini'' |volume=2019 |page=e.T59557A16957715 |url=https://en.wikipedia.org/wiki/IUCN_Red_List
|doi=10.2305/IUCN.UK.2019-1.RLTS.T59557A16957715.en |accessdate=16 November 2021}}</ref>


The random datasets had fifteen CGCG boxes in the A1BG UTR on the ZSCAN22 side for an occurrence of 3.0.
Its A1BG ortholog has 368 aa vs 495 aa for ''Homo sapiens''.
{{clear}}
 
==ZSCAN22==
{{main|ZSCAN22}}
# Gene ID: 342945 is ZSCAN22 zinc finger and SCAN domain containing 22 on 19q13.43.<ref name=HGNC342945>{{ cite web
|author=HGNC
|title=ZSCAN22 zinc finger and SCAN domain containing 22 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=13 March 2020
|url=https://www.ncbi.nlm.nih.gov/gene/342945
|accessdate=2019-12-18 }}</ref> ZSCAN22 is transcribed in the negative direction from LOC100887072.<ref name=HGNC342945/>
# Gene ID: 102465484 is MIR6806 microRNA 6806 on 19q13.43: "microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop."<ref name=RefSeq102465484>{{ cite web
|author=RefSeq
|title=MIR6806 microRNA 6806 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=10 September 2009
|url=https://www.ncbi.nlm.nih.gov/gene/102465484
|accessdate=2019-12-18 }}</ref> MIR6806 is transcribed in the negative direction from LOC105372480.<ref name=RefSeq102465484/>


The random datasets had two CGCG boxes in the core promoter (arbitrary positive direction) for an occurrences of 0.2.
Of the some 111 gaps between genes on chromosome locus 19q13.43 as of 4 August 2020, gap number 88 is between ZSCAN22 and A1BG. But, there is no gap between ZNF497 and A1BG.


In the proximal promoters the random datasets had one (positive direction) for an occurrence of 0.1.
==Promoters==


The distal promoters had twenty sequences in the arbitrary negative direction some closer to A1BG some to ZSCAN22 for an occurrence of 4.0. There were thirty sequences in the arbitrary positive direction some closer to A1BG than to ZNF497 for an occurrence of 6.0.
The core promoter begins approximately -35 nts upstream from the transcription start site (TSS). For the numbered nucleotides between ZSCAN22 and A1BG the core promoter extends from 4425 nts up to 4460 nts (TSS). The proximal promoter extends from approximately -250 to the TSS or 4210 nts up to 4460 nts. The distal promoter begins at about 2460 nts and extends to about 4210 nts.


The disparity between the real consensus sequences regarding their occurrences closer to the zinc fingers than A1BG and between the values of occurrences in the distal promoters 1.5 in the negative direction vs 4.0 and 16.0 vs 6.0 in the positive direction suggests that the real consensus sequences are likely active or activable probably for the respective zinc fingers.
From the ZNF497 side the core promoter begins about 4265 nts up to 4300 nts, the proximal promoter from 4050 nts to 4265 nts, and the distal promoter from 2300 nts to 4050 nts.


====Circadian control elements====
==Alpha-1-B glycoprotein==
{{main|Circadian control element gene transcriptions}}
{{main|Alpha-1-B glycoprotein}}
"The circadian control element [CCE] (circadian; Anderson ''et al.'', 1994) was found in 10 FvTCP genes."<ref name=Wei>{{ cite journal
'''Def.''' "a substance that induces an immune response, usually foreign"<ref name=AntigenWikt>{{ cite web
|author=Wei Wei, Yang Hu, Meng-Yuan Cui, Yong-Tao Han, Kuan Gao, and Jia-Yue Feng
|author=[[wikt:User:Jag123|Jag123]]
|title=Identification and Transcript Analysis of the TCP Transcription Factors in the Diploid Woodland Strawberry ''Fragaria vesca''
|title=antigen
|journal=Frontiers in Plant Science
|publisher=Wikimedia Foundation, Inc
|date=22 December 2016
|location=San Francisco, California
|volume=7
|date=7 March 2005
|issue=
|url=https://en.wiktionary.org/wiki/antigen
|pages=1937
|accessdate=7 March 2020 }}</ref> is called an '''antigen'''.
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5177655/#B2
|arxiv=
|bibcode=
|doi=10.3389/fpls.2016.01937
|pmid=28066489
|accessdate=29 November 2020 }}</ref> Circadian control elements (CAANNNNATC).<ref name=Sharma>{{ cite journal
|author=Bhaskar Sharma & Joemar Taganna
|title=Genome-wide analysis of the U-box E3 ubiquitin ligase enzyme gene family in tomato
|journal=Scientific Reports
|date=12 June 2020
|volume=10
|issue=9581
|pages=
|url=https://www.nature.com/articles/s41598-020-66553-1
|arxiv=
|bibcode=
|doi=10.1038/s41598-020-66553-1
|pmid=32533036
|accessdate=27 August 2020 }}</ref>


In the real promoters there is only one CCE, an inverse complement: GATGGGGTTG at 3804 in the ZSCAN22 - A1BG UTR for an occurrence of 0.5 (its complement CTACCCCAAC is on the negative strand in the negative direction).
'''Def.''' any "substance that elicits [an] immune response"<ref name=ImmunogenWikt>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title=immunogen
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=21 April 2008
|url=https://en.wiktionary.org/wiki/immunogen
|accessdate=8 March 2020 }}</ref> is called an '''immunogen'''.


The random datasets had two CCEs in the UTR out of ten strands for 0.2. There are also one core promoter for an occurrence of 0.1, no proximal promoter, and five (arbitrary negative direction) and nine (positive direction) distal promoters for 0.5 and 0.9 occurrences, respectively.
An antigen "or immunogen is a molecule that sometimes stimulates an immune system response."<ref name=AntigenWikidoc>{{ cite web
|author=C. Michael Gibson
|title=Antigen
|publisher=WikiDoc Foundation
|location=Boston, Massachusetts
|date=27 April 2008
|url=https://www.wikidoc.org/index.php/Antigen
|accessdate=8 March 2020 }}</ref> But, "the immune system does not consist of only antibodies",<ref name=AntigenWikidoc/> instead it "encompasses all substances that can be recognized by the [[adaptive immune system]]."<ref name=AntigenWikidoc/>


Comparing the real and random results, the one CCE in the real promoters is likely active or activable.
'''Def.''' "a protein produced by B-lymphocytes that binds to [a specific antigen or]<ref name=AntibodyWikt1>{{ cite web
|author=[[wikt:User:Williamsayers79|Williamsayers79]]
|title=antibody
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=26 February 2007
|url=https://en.wiktionary.org/wiki/antibody
|accessdate=7 March 2020 }}</ref> an antigen"<ref name=AntibodyWikt>{{ cite web
|author=[[wikt:User:Jag123|Jag123]]
|title=antibody
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=7 March 2005
|url=https://en.wiktionary.org/wiki/antibody
|accessdate=7 March 2020 }}</ref> is called an '''[[antibody]]'''.


====Cold-responsive elements====
Five different antibody isotypes are known in mammals, which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter.<ref name=Market>{{ cite journal
{{main|Cold-responsive element gene transcriptions}}
|author=Eleonora Market, F. Nina Papavasiliou
The randoms have fourteen consensus sequences in the ZSCAN22-A1BG UTR with an occurrence of 1.4. The reals have sixteen sequences with an occurrence of 8.0 which is much larger than the randoms.
|date=2003
 
|url=http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0000016
The randoms had core promoters: one in the arbitrary negative direction and two in the positive direction for occurrences of 0.1 and 0.2, respectively. The reals have no sequences in the core promoters.
|title=V(D)J Recombination and the Evolution of the Adaptive Immune System
|journal=PLoS Biology
|volume=1
|issue=1
|pages=e16
|doi=10.1371/journal.pbio.0000016 }}</ref>


The randoms had two in the negative direction for an occurrence of 0.2 and two in the positive direction also for an occurrence of 0.2. The reals have three sequences in the negative direction only for an occurrence of 1.5.
Although the general structure of all antibodies is very similar, a small region, known as the hypervariable region, at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures to exist, where each of these variants can bind to a different target, known as an antigen.<ref name=Janeway5>{{ cite book | author = Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik | title = Immunobiolog. | edition = 5th ed. | publisher = Garland Publishing | date = 2001 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10 | isbn = 0-8153-3642-X }}</ref>


In the distal promoters, the randoms had twenty-five in the negative direction for an occurrence of 2.5. There were forty-two in the positive direction for an occurrence of 4.2.
'''Def.''' "any of the glycoproteins in blood serum that respond to invasion by foreign antigens and that protect the host by removing pathogens;"<ref name=ImmunoglobulinWikt>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title= immunoglobulin
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=25 February 2006
|url=https://en.wiktionary.org/wiki/immunoglobulin
|accessdate=7 March 2020 }}</ref> "an antibody"<ref name=ImmunoglobulinWikt1>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title= immunoglobulin
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=28 April 2008
|url=https://en.wiktionary.org/wiki/immunoglobulin
|accessdate=7 March 2020 }}</ref> is called an '''[[immunoglobulin]]'''.


The reals have twenty-two sequences in the negative direction for an occurrence of 11.0 and thirty-six in the positive direction for an occurrence of 18.0. Both of these are systematically higher than the randoms.
Gene ID: 1 is A1BG [[alpha-1-B glycoprotein]] on 19q13.43, a 54.3 kDa [[protein]] in humans that is encoded by the A1BG [[gene]].<ref name=RefSeq1>{{ cite web
 
|author=RefSeq
With the exceptions of the core promoters, the real UTR, proximal and distal promoters have systematically many more sequences than the randoms. This suggests that these promoters are likely active or activable.
|title=A1BG alpha-1-B glycoprotein [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=10 December 2019
|url=https://www.ncbi.nlm.nih.gov/gene/1
|accessdate=2019-12-18 }}</ref> A1BG is transcribed in the positive direction from ZNF497.<ref name=RefSeq1/> "The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins."<ref name=RefSeq1/>
# NP_570602.2  alpha-1B-glycoprotein precursor, '''cd05751''' Location: 401 → 493 Ig1_LILRB1_like; First immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILR)B1 (also known as LIR-1) and similar proteins, '''smart00410''' Location: 218 → 280 IG_like; Immunoglobulin like, '''pfam13895''' Location: 210 → 301 Ig_2; Immunoglobulin domain and '''cl11960''' Location: 28 → 110 Ig; Immunoglobulin domain.<ref name=RefSeq1/>


====Copper response elements====
Patients who have pancreatic ductal [[adenocarcinoma]] show an [[overexpression]] of A1BG in [[pancreatic juice]].<ref name=Tian>{{ cite journal
{{main|Copper response element gene transcriptions}}
|author=Mei Tian, Ya-Zhou Cui, Guan-Hua Song, Mei-Juan Zong, Xiao-Yan Zhou, Yu Chen, Jin-Xiang Han
"A consensus copper-response element [CuRE] TTTGC(T/G)C(A/G) (12) is a binding site for Mac1p."<ref name=Quinn>{{ cite journal
| title = Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients
|author=Jeanette M. Quinn, Paola Barraco, Mats Eriksson and Sabeeha Merchant
| journal = BMC Cancer
|title=Coordinate Copper- and Oxygen-responsive ''Cyc6'' and ''Cpx1'' Expression in ''Chlamydomonas'' Is Mediated by the Same Element
| volume = 8
|journal=Journal of Biological Chemistry
| issue =
|date=March 2000
| pages = 241
|volume=275
| date = 2008
|issue=9
| pmid = 18706098
|pages=6080-6089
| pmc = 2528014
|url=https://www.sciencedirect.com/science/article/pii/S0021925818304551
| doi = 10.1186/1471-2407-8-241
|arxiv=
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528014/ }}</ref>
|bibcode=
|doi=10.1074/jbc.275.9.6080
|pmid=
|accessdate=1 April 2021 }}</ref>


The only copper response element conforming to the Quinn consensus sequence is an inverse complement CGCGCAAA at 163 in the positive strand, negative direction distal promoter with an occurrence of 0.5.
===Immunoglobulin supergene family===
{{main|Immunoglobulin supergene family}}
"𝛂<sub>1</sub>B-glycoprotein(𝛂<sub>1</sub>B) [...] consists of a single polypeptide chain N-linked to four
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂<sub>1</sub>B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂<sub>1</sub>B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂<sub>1</sub>B [...] exhibits sequence similarity to other members of the [[immunoglobulin supergene family]] such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."<ref name=Ishioka/>


The random datasets had one inverse complement consensus sequence in the UTR CGAGCAAA at 2440 with an occurrence of 0.1. In the distal promoters there were two inverse complement consensus sequences in the arbitrary negative direction for an occurrence of 0.2. The low occurrences among the randoms suggests that the one real occurrence is likely active or activable even though there is only one. It also occurs in the positive strand as does A1BG.
"Some of the domains of 𝛂<sub>1</sub>B show significant homology to variable (V) and constant (C) regions of certain immunoglobulins. Likewise, there is statistically significant homology between 𝛂<sub>1</sub>B and the secretory component (SC) of human IgA (15) and also with the extracellular portion of the rabbit receptor for transepithelial transport of polymeric immunoglobulins (IgA and IgM). Mostov et al. (16) have called the later protein the poly-Ig receptor or poly-IgR and have shown that it is the precursor of SC."<ref name=Ishioka/>


"An additional EMSA result demonstrated that [''Aspergillus fumigatus'' (Af)] AfMac1 directly binds to a copper response element in the promoter regions of the ''ctrA2'' and ''ctrC'' genes with a defined consensus DNA motif (5′-TGTGCTCA-3′) (Park et al., 2017<ref name=Park>{{ cite journal
The immunoglobulin supergene family is "the group of proteins that have immunoglobulin-like domains, including histocompatibility antigens, the T-cell antigen receptor, poly-IgR, and other proteins involved in the vertebrate immune response (17)."<ref name=Ishioka/>
|author=Yong-Sung Park, Tae-Hyoung Kim and Cheol-Won Yun
|title=Functional characterization of the copper transcription factor AfMac1 from ''Aspergillus fumigatus''
|journal=Biochemical Journal
|date=3 July 2017
|volume=474
|issue=14
|pages=2365-2378
|url=https://portlandpress.com/biochemj/article-abstract/474/14/2365/49495/Functional-characterization-of-the-copper?redirectedFrom=fulltext
|arxiv=
|bibcode=
|doi=10.1042/BCJ20170191
|pmid=
|accessdate=2 April 2021 }}</ref>), which is strikingly similar to the Mac1-binding motif in ''S. cerevisiae'' (Jamison McDaniels et al., 1999; Keller et al., 2000), suggesting that the mechanism of Mac1-mediated copper homeostasis may be conserved across fungal species."<ref name=JSong>{{ cite journal
|author=Jinxing Song, Rongpeng Li and Jihong Jiang
|title=Copper Homeostasis in ''Aspergillus fumigatus'': Opportunities for Therapeutic Development
|journal=Frontiers in Microbiology
|date=12 April 2019
|volume=10
|issue=
|pages=774
|url=https://www.frontiersin.org/articles/10.3389/fmicb.2019.00774/full
|arxiv=
|bibcode=
|doi=10.3389/fmicb.2019.00774
|pmid=
|accessdate=2 April 2021 }}</ref>


The consensus sequence for the copper response element (Park 2017): TGTGCTCA, only occurs as an inverse complement TGAGCACA at 3740 on the negative strand in the positive direction in the distal promoter closer to A1BG than ZNF497. This inverse complement has an occurrence of 0.5.
"The internal homology in primary structure [...] and the presence of an intrasegment disulfide bond suggest that 𝛂<sub>1</sub>B is composed of five structural domains that arose by duplication of a primordial gene coding for about 95 amino acid residues."<ref name=Ishioka/>


The randoms also have only one occurrence, an inverse complement TGAGCACA at 2259 in the arbitrary positive direction. This inverse complement had an occurrence of 0.1. The difference in occurrences between real and random suggests that the real TGAGCACA at 3740 is likely active or activable.
"Unlike immunoglobulins (25), ceruloplasmin (6), and hemopexin (7), 𝛂<sub>1</sub>B is not subject to limited interdomain cleavage by proteolytic enzymes. At least, we were not able to produce such fragments by use of a variety of proteases. This stability of 𝛂<sub>1</sub>B is probably associated with the frequency of proline in the sequences linking the domains [...]."<ref name=Ishioka/>


====Cytoplasmic polyadenylation elements====
"A peptide identified in the late and early milk proteomes showed homology to eutherian alpha 1B glycoprotein (A1BG), a plasma protein with unknown function<sup>46</sup>, as well as venom inhibitors characterised in the Southern opossum ''Didelphis marsupialis'' (DM43 and DM46<sup>47,48,49</sup>), all members of the immunoglobulin superfamily. To characterise the relationship between the peptide sequence identified in koala, A1BG, DM43 and DM46, a phylogenetic tree was constructed [...] including all marsupial and monotreme homologs (identified by BLAST), three phylogenetically representative eutherian sequences, with human IGSF1 and TARM1, related members of the immunoglobulin super family, used as outgroups. This phylogeny indicates that A1BG-like proteins in marsupials and the ''Didelphis'' antitoxic proteins are homologs of eutherian A1BG, with excellent bootstrap support (98%). The marsupial A1BG-like sequences and the ''Didelphis'' antitoxic proteins formed a single clade with strong bootstrap support (97%)."<ref name=Morris>{{ cite journal
{{main|Cytoplasmic polyadenylation element gene transcriptions}}
|author=Katrina M. Morris, Denis O’Meally, Thiri Zaw, Xiaomin Song, Amber Gillett, Mark P. Molloy, Adam Polkinghorne, and Katherine Belova
"Cytoplasmic polyadenylation is determined by the cytoplasmic polyadenylation element (CPE; consensus sequence UUUUUAU) that resides in mRNA 3′ untranslated regions (UTRs)."<ref name=Ivshina>{{ cite journal
|title=Characterisation of the immune compounds in koala milk using a combined transcriptomic and proteomic approach
|author=Maria Ivshina, Paul Lasko, and Joel D. Richter
|journal=Scientific Reports
|title=Cytoplasmic polyadenylation element binding proteins in development, health, and disease
|date=7 October 2016
|journal=Annual Review of Cell and Developmental Biology
|volume=6
|date=October 2014
|volume=30
|issue=
|issue=
|pages=393-415
|pages=35011
|url=https://www.annualreviews.org/doi/abs/10.1146/annurev-cellbio-101011-155831
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054531/
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.1146/annurev-cellbio-101011-155831
|doi=10.1038/srep35011
|pmid=
|pmid=27713568
|accessdate=17 April 2021 }}</ref>
|accessdate=14 March 2020 }}</ref>


{|class="wikitable"
"Human TARM1 and IGSF1, related members of the immunoglobulin superfamily are used as outgroups. The tree was constructed using the maximum likelihood approach and the JTT model with bootstrap support values from 500 bootstrap tests. Bootstrap values less than 50% are not displayed. Accession numbers: Tasmanian devil (''Sarcophilus harrisii''; XP_012402143), Wallaby (''Macropus eugenii''; FY619507), Possum (''Trichosurus vulpecula''; DY596639) Virginia opossum (''Didelphis virginiana''; AAA30970, AAN06914), Southern opossum (''Didelphis marsupialis''; AAL82794, P82957, AAN64698), Human (''Homo sapiens''; P04217, B6A8C7, Q8N6C5), Platypus (''Ornithorhychus anatinus''; ENSOANP00000000762), Cow (''Bos taurus''; Q2KJF1), Alpaca (''Vicugna pacos''; XP_015107031)."<ref name=Morris/>
|-
! Reals or randoms !! Promoters !! direction !! Numbers !! Strands !! Occurrences !! Averages (± 0.1)
|-
| Reals || UTR || negative || 3 || 2 || 1.5 || 1.5
|-
| Randoms || UTR || arbitrary negative || 1 || 10 || 0.1 || 0.1
|-
| Randoms || UTR || alternate negative || 1 || 10 || 0.1 || 0.1
|-
| Reals || Core || negative || 0 || 2 || 0 || 0
|-
| Randoms || Core || negative || 0 || 10 || 0 || 0
|-
| Reals || Core || positive || 0 || 2 || 0 || 0
|-
| Randoms || Core || positive || 0 || 10 || 0 || 0
|-
| Reals || Proximal || negative || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || negative || 0 || 10 || 0 || 0
|-
| Reals || Proximal || positive || 0 || 2 || 0 || 0
|-
| Randoms || Proximal || positive || 0 || 10 || 0 || 0
|-
| Reals || Distal || negative || 6 || 2 || 3 || 1.5
|-
| Randoms || Distal || negative || 8 || 10 || 0.8 || 0.45
|-
| Reals || Distal || positive || 0 || 2 || 0 || 1.5
|-
| Randoms || Distal || positive || 1 || 10 || 0.1 || 0.45
|}


Comparison:
"The sequences of 𝛂<sub>1</sub>B-glycoprotein (38) and chicken N-CAM (neural cell-adhesion molecule) (39) have been shown to be related to the immunoglobulin supergene family."<ref name=Paxton>{{ cite journal
 
|author=R. J. Paxton, G. Mooser, H. Pande, T. D. Lee, and J. E. Shively
The occurrences of real cytoplasmic polyadenylation elements are larger than the randoms. This suggests that the real cytoplasmic polyadenylation elements are likely active or activable.
|title=Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family
 
|journal=Proceedings of the National Academy of Sciences USA
====DAF-16 binding elements====
|date=1 February 1987
{{main|DAF-16 binding element gene transcriptions}}
|volume=84
"Most paralogous FOX proteins bind to the canonical DNA response element 5′-RYAAAYA-3′ (R = A or G, Y = C or T)<sup>11–13</sup>."<ref name=Li2017>{{ cite journal
|issue=4
|author=Jun Li, Ana Carolina Dantas Machado, Ming Guo, Jared M. Sagendorf, Zhan Zhou, Longying Jiang, Xiaojuan Chen, Daichao Wu, Lingzhi Qu, Zhuchu Chen, Lin Chen, Remo Rohs, and Yongheng Chen
|pages=920-924
|title=Structure of the forkhead domain of FOXA2 bound to a complete DNA consensus site
|url=https://www.pnas.org/content/pnas/84/4/920.full.pdf
|journal=Biochemistry
|date=25 July 2017
|volume=56
|issue=29
|pages=3745-3753
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5614898/
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.1021/acs.biochem.7b00211
|doi=10.1073/pnas.84.4.920
|pmid=28644006
|pmid=3469650
|accessdate=28 August 2020 }}</ref>
|accessdate=26 March 2020 }}</ref>


For the reals there are five in the UTR between ZSCAN22 and A1BG for an occurrence of 2.5.
A1BG contains the immunoglobulin domain: '''cl11960''' and three immunoglobulin-like domains: '''pfam13895''', '''cd05751''' and '''smart00410'''.


Only one proximal promoter occurs in the positive direction for an occurrence of 0.5.
"Immunoglobulin (Ig) domain ['''cl11960'''] found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond."<ref name=NCBI386229>{{ cite web
 
|author=NCBI
The distal promoters have eight consensus sequences for an occurrence of 4.0.
|title=Conserved Protein Domain Family cl11960: Ig Superfamily
 
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
The randoms had ten UTRs for an occurrence of 1.0, three proximal promoters for an occurrence of 0.15, and eighteen arbitrary distal promoters in the negative direction for an occurrence of 1.8, twenty-three in the arbitrary positive direction for an occurrence of 2.3.
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=2 February 2016
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=386229
|accessdate=22 May 2020 }}</ref>


A comparison shows that the reals are systematically higher in occurrences that the randoms to suggest that the reals are likely active or activable.
"This domain ['''pfam13895'''] contains immunoglobulin-like domains."<ref name=NCBI372793>{{ cite web
|author=NCBI
|title=Conserved Protein Domain Family pfam13895: Ig_2
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=5 August 2015
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=372793
|accessdate=24 May 2020 }}</ref>


====D box (Samarsky)====
"Ig1_LILR_KIR_like: ['''cd05751'''] domain similar to the first immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILRs) and Natural killer inhibitory receptors (KIRs). This group includes LILRB1 (or LIR-1), LILRA5 (or LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (or CD89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3,and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1 (LIR-1), LILRB2 (LIR-2), and LILRB3 (LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LIR-1 (LILRB1), and LIR-2 (LILRB2), show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1 (LIR-1), and LILRB2 (LIR-2), and two in the case of LILRB4 (LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst."<ref name=NCBI319306>{{ cite web
{{main|D box gene transcriptions}}
|author=NCBI
For "box C/D snoRNAs, boxes C and D and an adjoining stem form a vital structure, known as the box C/D motif."<ref name=Samarsky/> Adjoining Domain B and overlapping for two nucleotides is Box D: GUCUGA from Domain B where "GU" are also at the end of Domain B, with the inverse being AGUCUG and replacing U with T yields a likely consensus sequence to search for AGTCTG.<ref name=Samarsky/>
|title=Conserved Protein Domain Family cd05751: Ig1_LILR_KIR_like
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=16 August 2016
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=319306
|accessdate=24 May 2020 }}</ref>


The real consensus sequences are AGTCTG at 2947 in the UTR between A1BG and ZSCAN22 with an occurrence of 0.5, three in the distal promoter also in the negative direction for an occurrence of 1.5, and six in the positive direction for an occurrence of 3.0.
"IG domains ['''smart00410'''] that cannot be classified into one of IGv1, IGc1, IGc2, IG."<ref name=NCBI214653>{{ cite web
 
|author=NCBI
The randoms had one in the UTR: AGTCTG at 4073 in the arbitrary negative direction for an occurrence of 0.1, four in the negative direction in the distal promoter for an occurrence of 0.4 and seven in the positive direction for an occurrence of 0.7.
|title=Conserved Protein Domain Family smart00410: IG_like
 
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
By comparison, the occurrences are systematically higher for the reals than the randoms which suggests that the reals are likely active or activable.
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=16 January 2013
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=214653
|accessdate=24 May 2020 }}</ref>
"𝛂<sub>1</sub>B-glycoprotein(𝛂<sub>1</sub>B) [...] consists of a single polypeptide chain N-linked to four
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂<sub>1</sub>B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂<sub>1</sub>B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂<sub>1</sub>B [...] exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."<ref name=Ishioka>{{ cite journal
|author=Noriaki Ishioka, Nobuhiro Takahashi, and Frank W. Putnam
|title=Amino acid sequence of human plasma 𝛂<sub>1</sub>B-glycoprotein: Homology to the immunoglobulin supergene family
|journal=Proceedings of the National Academy of Sciences USA
|date=April 1986
|volume=83
|issue=8
|pages=2363-7
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC323297/pdf/pnas00312-0089.pdf
|arxiv=
|bibcode=
|doi=10.1073/pnas.83.8.2363
|pmid=3458201
|accessdate=9 March 2020 }}</ref>


====D box (Voronina)====
===A1BG protein species===
{{main|D box gene transcriptions}}
The reals have four consensus sequences in the UTR for an occurrence of 2.0.


There is only one core promoter of eight promoters for an occurrence of 0.125.
'''Def.''' a "group of plants or animals having similar appearance"<ref name=SpeciesWikt>{{ cite web
 
|author=[[wikt:User:24.98.118.180|24.98.118.180]]
Proximal promoters have two occurrences among eight possibilities for an occurrence of 0.25.
|title=species
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=28 February 2007
|url=https://en.wiktionary.org/wiki/species
|accessdate=25 March 2020 }}</ref> or "the largest group of organisms in which [any]<ref name=Species1/> two individuals [of the appropriate sexes or mating types]<ref name=Species1>{{ cite web
|author=[[w:User:Peter coxhead|Peter coxhead]]
|title=Species
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=22 August 2018
|url=https://en.wikipedia.org/wiki/Species
|accessdate=25 March 2020 }}</ref> can produce fertile offspring, typically by sexual reproduction"<ref name=Species>{{ cite web
|author=[[w:User:Chiswick Chap|Chiswick Chap]]
|title=Species
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=1 December 2016
|url=https://en.wikipedia.org/wiki/Species
|accessdate=25 March 2020 }}</ref> is called a '''species'''.


Distal promoters have twenty-eight consensus sequences in the negative direction for an occurrence 3.5.
The gene contains 20 distinct introns.<ref name=AceView>{{ cite web
|title=AceView: A1BG
|url=https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=a1bg&submit=Go
|accessdate=May 11, 2013 }}</ref> Transcription produces 15 different mRNAs, 10 alternatively spliced variants and 5 unspliced forms.<ref name="AceView"/> There are 4 probable alternative promoters, 4 non overlapping alternative last exons and 7 validated alternative polyadenylation sites.<ref name="AceView"/> The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 4 cassette exons, overlapping exons with different boundaries, splicing versus retention of 3 introns.<ref name="AceView"/>


In the positive direction has twenty-three consensus sequences in the positive direction for an occurrence 2.875.
====Variants or isoforms====


The randoms had seventeen UTR consensus sequences for an occurrence of 1.7.
'''Def.''' a "different sequence of a gene (locus)"<ref name=VariantWikt>{{ cite web
|author=[[wikt:User:Pdeitiker|Pdeitiker]]
|title=variant
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=26 July 2008
|url=https://en.wiktionary.org/wiki/variant
|accessdate=25 March 2020 }}</ref> is called a '''variant'''.


The randoms had one core promoter from twenty opportunities for an occurrence of 0.05.
'''Def.''' any "of several different forms of the same protein, arising from either single nucleotide polymorphisms,<ref name=IsoformWikt1>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title=isoform
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=6 January 2007
|url=https://en.wiktionary.org/wiki/isoform
|accessdate=2 December 2018 }}</ref> differential splicing of mRNA, or post-translational modifications (e.g. sulfation, glycosylation, etc.)"<ref name=IsoformWikt2>{{ cite web
|author=[[wikt:User:72.178.245.181|72.178.245.181]]
|title=isoform
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=30 November 2008
|url=https://en.wiktionary.org/wiki/isoform
|accessdate=2 December 2018 }}</ref> is called an '''isoform'''.


In the proximal promoters, the randoms had three in the arbitrary negative direction and four in the positive direction for occurrences of 0.3 and 0.4.
Regarding additional isoforms, mention has been made of "new genetic variants of A1BG."<ref name=Eiberg>{{ cite journal
 
|author=H Eiberg, ML Bisgaard, J Mohr
For the distal promoters, the negative direction had twenty-nine consensus sequences for an occurrence of 2.9.
|title=Linkage between alpha 1B-glycoprotein (A1BG) and Lutheran (LU) red blood group system: assignment to chromosome 19: new genetic variants of A1BG
 
|journal=Clinical genetics
In the positive direction, the randoms had thirty-four consensual sequences for an occurrence of 3.4.
|date=1 December 1989
 
|volume=36
In comparison for the distal promoters, the random sequences had approximately the same occurrences as the reals. For the proximal promoters the randoms had slightly more occurrences than the reals. For the core promoters, the randoms had slightly less occurrences. For the UTR the randoms had slightly less occurrences than the reals (1.7 vs. 2.0). Based on the UTR and core promoters it appears that the reals are likely active or activable.
|issue=6
 
|pages=415-8
====D-box (Motojima)====
|url=http://europepmc.org/abstract/MED/2591067
{{main|D box gene transcriptions}}
D-box (TGAGTGG).<ref name=Motojima>{{ cite journal
|author=Masaru Motojima, Takao Ando and Toshimasa Yoshioka
|title=Sp1-like activity mediates angiotensin-II-induced plasminogen-activator inhibitor type-1 (''PAI-1'') gene expression in mesangial cells
|journal=Biomedical Journal
|date=10 July 2000
|volume=349
|issue=2
|pages=435-441
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1221166/pdf/10880342.pdf
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.1042/0264-6021:3490435
|doi=
|pmid=10880342
|pmid=2591067
|accessdate=13 August 2020 }}</ref>
|accessdate=2017-10-08 }}</ref>


The real promoters have two inverse complements in the UTR positive strand, negative direction: CCACTCA at 4487 nucleotides from the end of gene ZSCAN22 and negative strand, negative direction: CCACTCA at 3827, for an occurrence of 0.5.
"Proteomic analysis revealed that [a circulating] set of plasma proteins was α 1 B-glycoprotein ('''A1BG''') and its
 
post-translationally modified isoforms."<ref name=Stehle>{{ cite journal
In the distal promoters, there is an inverse complement (ic) between ZNF497 and A1BG negative strand, positive direction: TGAGTGG at 3449 for an occurrence of 0.25.
|author=John R. Stehle Jr., Mark E. Weeks, Kai Lin, Mark C. Willingham, Amy M. Hicks, John F. Timms, Zheng Cui
 
|title=Mass spectrometry identification of circulating alpha-1-B glycoprotein, increased in aged female C57BL/6 mice
The random datasets had one UTR TGAGTGG at 4502 for an occurrence of 0.1.
|journal=Biochimica et Biophysica Acta (BBA) - General Subjects
 
|date=January 2007
They had one proximal promoter D-box consensus sequence: TGAGTGG at 4148 in the arbitrary positive direction for an occurrence of 0.05.
|volume=1770
 
|issue=1
The distal promoters had two consensus sequence ics: CCACTCA at 1766 and CCACTCA at 1365 for an occurrence of 0.1.
|pages=79-86
 
|url=http://www.sciencedirect.com/science/article/pii/S0304416506001826
Comparing the two results, the occurrences are higher for the real UTR consensus sequences and the distal promoter consensus sequences than the randoms suggesting that the reals are likely active or activable.
 
====DRE (Sumrada, core)====
{{main|DNA damage response element gene transcriptions}}
"A consensus sequence, 5'-TAGCCGCCGRRRR-3' (where R = an unspecified purine nucleoside [A/G],was generated from these data."<ref name=Sumrada>{{ cite journal
|author=Roberta A. Sumrada and Terrance G. Cooper
|title=Ubiquitous upstream repression sequences control activation of the inducible arginase gene in yeast
|journal=Proceedings of the National Academy of Sciences USA
|date=June 1987
|volume=84
|issue=
|pages=3997-4001
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC305008/pdf/pnas00277-0054.pdf
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.1073/pnas.84.12.3997
|doi=10.1016/j.bbagen.2006.06.020
|pmid=3295874
|pmid=16945486
|accessdate=6 September 2020 }}</ref>
|accessdate=2017-10-08 }}</ref>


"The extent of homology for the entire 13 bp ranged from 56 to 100%. However, for the symmetrical core sequence CCGCC 75 to 100% homology was observed with only conservative substitutions occurring in the nonhomologous positions."<ref name=Sumrada/>
Pharmacogenomic variants have been reported.<ref name=McDonough/>


The real UTR has two consensus sequences for an occurrence of 1.0.
====Genotypes====


The core promoters are only in the positive direction (three) for an occurrence of 0.75.
'''Def.''' the "part (DNA sequence) of the genetic makeup of an organism which determines a specific characteristic (phenotype) of that organism"<ref name=GenotypeWikt1>{{ cite web
 
|author=[[wikt:User:DTLHS|DTLHS]]
The proximal promoters have two in the negative direction and one in the positive direction for occurrences of 1.0 and 0.5, respectively.
|title=genotype
 
|publisher=Wikimedia Foundation, Inc
The distal promoters have ten in the negative direction for an occurrence of 5.0. In the positive direction the reals have eleven for an occurrence of 5.5.
|location=San Francisco, California
 
|date=10 January 2018
The random datasets had twenty-nine UTR consensus sequences for an occurrence of 2.9.
|url=https://en.wiktionary.org/wiki/genotype
 
|accessdate=25 March 2020 }}</ref> or a "group of organisms having the same genetic constitution" <ref name=GenotypeWikt>{{ cite web
Randoms had four core promoters for an occurrence of 0.2.
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
 
|title=genotype
Randoms had four proximal promoters for an occurrence of 0.2.
|publisher=Wikimedia Foundation, Inc
 
|location=San Francisco, California
Randoms had thirty-five arbitrary negative direction distal promoters for an occurrence of 3.5.
|date=22 October 2005
|url=https://en.wiktionary.org/wiki/genotype
|accessdate=25 March 2020 }}</ref>is called a '''genotype'''.


In the arbitrary positive direction the randoms had sixty-six distastes promoters for an occurrence of 6.6.
There are A1BG genotypes.<ref name=McDonough>{{ cite journal
|author=Caitrin W. McDonough, Yan Gong, Sandosh Padmanabhan, Ben Burkley, Taimour Y. Langaee, Olle Melander, Carl J. Pepine, Anna F. Dominiczak, Rhonda M. Cooper-DeHoff, and Julie A. Johnson
|title=Pharmacogenomic Association of Nonsynonymous SNPs in ''SIGLEC12'', ''A1BG'', and the Selectin Region and Cardiovascular Outcomes
|journal=Hypertension
|date=June 2013
|volume=62
|issue=1
|pages=48-54
|url=http://hyper.ahajournals.org/content/hypertensionaha/early/2013/05/20/HYPERTENSIONAHA.111.00823.full.pdf
|arxiv=
|bibcode=
|doi=10.1161/HYPERTENSIONAHA.111.00823
|pmid=23690342
|accessdate=2017-10-08 }}</ref>


By comparison, the randoms outnumber the reals for UTRs (2.9 vs. 1.0, respectively), but the reals outnumber the randoms regarding core promoters (0.75 vs. 0.2), proximal promoters (1.5 vs. 0.2), and just for the distal promoters (total of 10.5 vs. 10.1, respectively). The disparity rather than overlap suggests that the reals are likely active or activable.
A1BG has a genetic risk score of rs893184.<ref name=McDonough/>


====dBRE====
"A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39×10<sup>−5</sup>)."<ref name=McDonough/>
{{main:Downstream TFIIB recognition element gene transcriptions}}
There are two sets of BREs: one (BREu) found immediately upstream of the TATA box, with the consensus SSRCGCC [(C/G)(C/G)(A/G)CGCC]; the other (BREd) found around 7 nucleotides downstream, with the consensus RTDKKKK [(A/G)T(A/G/T)(G/T)(G/T)(G/T)(G/T)].<ref name=WilsonD>{{cite web |last1=Wilson |first1=David B. |title=Drosophila Core Promoter Motifs |url=http://gander.wustl.edu/~wilson/core_promoter_motifs.html |accessdate=2 April 2019}}</ref><ref name=Gershon>{{cite journal |last1=Juven-Gershon |first1=T |last2=Kadonaga |first2=JT |title=Regulation of gene expression via the core promoter and the basal transcriptional machinery. |journal=Developmental Biology |date=15 March 2010 |volume=339 |issue=2 |pages=225–9 |doi=10.1016/j.ydbio.2009.08.009 |pmid=19682982 |pmc=2830304}}</ref>


The reals have twenty-eight UTRs on the negative strand in the negative direction and thirty on the positive strand in the negative direction for a total of fifty-eight with an occurrence of 29.0.
====Polymorphs====


The randoms had one hundred and nineteen for an occurrence of 11.9. There's more than twice as many reals as randoms.
'''Def.''' the "regular existence of two or more different genotypes within a given species or population; also, variability of amino acid sequences within a gene's protein"<ref name=PolymorphismWikt>{{ cite web
|author=[[wikt:User:Widsith|Widsith]]
|title=polymorphism
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=28 March 2012
|url=https://en.wiktionary.org/wiki/polymorphism
|accessdate=25 March 2020 }}</ref> is called '''polymorphism'''.


The real core promoters are one on the positive strand in the negative direction for an occurrence of 0.5. There are two on the negative strand in the positive direction and three on the positive strand in the positive direction for an occurrence of 2.5.
'''Def.''' "one of a number of alternative forms of the same gene occupying a given position, [or locus],<ref name=AlleleWikt1>{{ cite web
|author=[[wikt:User:217.105.66.98|217.105.66.98]]
|title=allele
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=8 September 2016
|url=https://en.wiktionary.org/wiki/allele
|accessdate=25 March 2020 }}</ref> on a chromosome"<ref name=AlleleWikt>{{ cite web
|author=[[wikt:User:138.130.33.215|138.130.33.215]]
|title=allele
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=7 April 2004
|url=https://en.wiktionary.org/wiki/allele
|accessdate=25 March 2020 }}</ref> is called an '''allele'''.


The randoms had two in the arbitrary negative direction for an occurrence of 0.2. There were twenty-three in the arbitrary positive direction for an occurrence of 2.3, but eight of the twenty-three are out of range for the random data set so the actual occurrence is 1.5. The reals slightly outnumber the randoms.
"rs893184 causes a histidine (His) to arginine (Arg) [nonsynonymous single nucleotide polymorphism (nsSNP), A (minor) for G (major)] substitution at amino acid position 52 in A1BG."<ref name=McDonough/>


For the proximal promoters, the reals have eight consensus sequences in the negative direction for an occurrence of 4.0, and seven in the positive direction for 3.5. The randoms had twenty in the arbitrary negative direction for an occurrence of 2.0, and twenty-two in the positive direction for an occurrence of 2.2. The reals outnumber the randoms.
"Genetic polymorphism of human plasma (serum) alpha 1B-glycoprotein (alpha 1B) was observed using one-dimensional horizontal polyacrylamide gel electrophoresis (PAGE) pH 9.0 of plasma samples followed by Western blotting with specific antiserum to alpha 1B."<ref name=Gahne>{{ cite journal
 
|author=B. Gahne, R. K. Juneja, and A. Stratil
With the distal promoters: there are a total of one hundred and thirty-one real distal promoters, forty-three on the negative strand in the negative direction, forty on the positive strand in the negative direction (total 83, occurrence is 41.5), eighteen on the negative strand in the positive direction, and thirty on the positive strand in the positive direction (total 48, occurrence is 24.0). The total occurrences are 32.75.
|title=Genetic polymorphism of human plasma alpha 1B-glycoprotein: phenotyping by immunoblotting or by a simple method of 2-D electrophoresis
 
|journal=Human Genetics
The randoms had the following results: twenty-three (dBREr0), twenty (dBREr2), eighteen (dBREr4), seventeen (dBREr6), seventeen (dBREr8), eighteen (dBREr0ci), eighteen (dBREr2ci), twenty-three (dBREr4ci), twenty-two (dBREr6ci), twenty (dBREr8ci) for a total of 196 in the arbitrary negative direction yielding an occurrence 19.6.
|date=June 1987
 
|volume=76
For the arbitrary positive direction: twenty-seven (dBREr1), twenty-eight (dBREr3), twenty-eight (dBREr5), twenty-two (dBREr7), twenty-six (dBREr9), twenty-five (dBREr1ci), twenty-four (dBREr3ci), thirty (dBREr5ci), thirty (dBREr7ci), thirty-five (dBREr9ci) for a total of 275 in the arbitrary positive direction yielding an occurrence 27.5. The total number of consensus sequences (471) yields an occurrence of 23.55 with an error of ± 4.
|issue=2
 
|pages=111-5
Comparing the distal promoters, the negative direction is higher than the randoms, whereas the positive direction is comparable to the randoms. This suggests that as least in the negative direction the reals are likely active or activable, but in the positive direction the core and proximal promoter are likely active or activable, but the distal promoter sequences may be random.
|url=https://link.springer.com/article/10.1007%2FBF00284904
 
====Downstream core elements====
{{main|Downstream core element gene transcriptions}}
The consensus sequence for the DCE is CTTC...CTGT...AGC.<ref name=Lee/> These three consensus elements are referred to as subelements: "S<sub>I</sub> is CTTC, S<sub>II</sub> is CTGT, and S<sub>III</sub> is AGC."<ref name=Lee/>
 
A core promoter that contains all three subelements of the downstream core element may be much less common than one containing only one or two.<ref name=Lee/> "S<sub>I</sub> resides approximately from +6 to +11, S<sub>II</sub> from +16 to +21, and S<sub>III</sub> from +30 to +34."<ref name=Lee>{{ cite journal
|author=Dong-Hoon Lee, Naum Gershenzon, Malavika Gupta, Ilya P. Ioshikhes, Danny Reinberg and Brian A. Lewis
|title=Functional Characterization of Core Promoter Elements: the Downstream Core Element Is Recognized by TAF1
|journal=Molecular and Cellular Biology
|date=November 2005
|volume=25
|issue=21
|pages=9674-86
|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1265815/
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.1128/MCB.25.21.9674-9686.2005
|doi=10.1007/bf00284904
|pmid=16227614
|pmid=3610142
|accessdate=2010-10-23 }}</ref>
|accessdate=25 March 2020 }}</ref>


The number of nucleotides between each subelement can apparently vary down to none.
''A1B*5'' is a "new allele [...] of human plasma 𝜶<sub>1</sub>B-glycoprotein [...]."<ref name=Juneja1989>{{ cite journal
 
|author=R.K. Juneja, G. Beckman, M. Lukka, B. Gahne, and C. Ehnholm
====DCE SI====
|title=Plasma α<sub>1</sub>B-Glycoprotein Allele Frequencies in Finns and Swedish Lapps: Evidence for a New α<sub>1</sub>B Allele
{{main|Downstream core element gene transcriptions}}
|journal=Human Heredity
The consensus sequence for the DCE is CTTC...CTGT...AGC.<ref name=Lee/> These three consensus elements are referred to as subelements: "S<sub>I</sub> is CTTC, S<sub>II</sub> is CTGT, and S<sub>III</sub> is AGC."<ref name=Lee>{{ cite journal
|date=1989
|author=Dong-Hoon Lee, Naum Gershenzon, Malavika Gupta, Ilya P. Ioshikhes, Danny Reinberg and Brian A. Lewis
|volume=39
|title=Functional Characterization of Core Promoter Elements: the Downstream Core Element Is Recognized by TAF1
|issue=1
|journal=Molecular and Cellular Biology
|pages=32-36
|date=November 2005
|url=https://www.karger.com/Article/Abstract/153828
|volume=25
|issue=21
|pages=9674-86
|url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1265815/
|arxiv=
|arxiv=
|bibcode=
|bibcode=
|doi=10.1128/MCB.25.21.9674-9686.2005
|doi=10.1159/000153828
|pmid=16227614
|pmid=2759622
|accessdate=2010-10-23 }}</ref>
|accessdate=25 March 2020 }}</ref>


The real downstream core elements in the UTR between ZSCAN22 and A1BG have seven sequences for an occurrence of 3.5. The random data sets had thirty-six sequences for an occurrence of 7.0.
"Genetic polymorphism of human plasma 𝜶<sub>1</sub>B-glycoprotein (𝜶<sub>1</sub>B) was reported first, in brief, by Altland ''et al.'' [1983; also given in Altkand and Hacklar, 1984]. A detailed description of human 𝜶<sub>1</sub>B polymorphism was reported in subsequent studies [Gahne ''et al.'', 1987; Juneja ''et al.'', 1988, 1989]. Five different 𝜶<sub>1</sub>B alleles (''A1B*1, A1B*2, A1B*3, A1B*4'' and ''A1B*5'') were reported. In Caucasian whites, the frequencies of ''A1B*1'' and ''''A1B*2'' were about 0.95 and 0.05, respectively. ''A1B*4'' was observed in 2 related Czech individuals. In American blacks, ''A1B*1'' and ''A1B*2'' occurred with a frequency of 0.73 and 0.21, respectively, while a new allele, viz, ''A1B*3'' had a frequency of 0.06. ''A1B*5'' was observed only in Swedish Lapps and in Finns with a frequency of 0.04 and 0.007, respectively."<ref name=Juneja>{{ cite journal
|author=R.K. Juneja, N. Saha, B. Gahne and J.S.H. Tay
|title=Distribution of Plasma Alpha-1-B-Glycoprotein Phenotypes in Several Mongoloid Populations of East Asia
|journal=Human Heredity
|date=1989
|volume=39
|issue=
|pages=218-222
|url=https://www.karger.com/Article/PDF/153863
|arxiv=
|bibcode=
|doi=10.1159/000153863
|pmid=2583734
|accessdate=25 March 2020 }}</ref>


The real DCE in the core promoters (two) have an occurrence of 0.5. The random data sets had one for an occurrence of 0.2.
"The frequency of ''A1B*1'' varied from 0.89 to 0.91 and that of ''A1B*2'' from 0.08 to 0.10. The ''A1B*3'' allele, reported previously only in American blacks, was observed with a frequency range of 0.003-0.01 in 3 of the Chinese populations, in Koreans and in Malays. A new 𝜶<sub>1</sub>B allele (''A1B*6'') was observed in 2 Chinese individuals."<ref name=Juneja/>


The real DCE in the proximal promoters (seven) have an occurrence of 1.75. The randoms had seven for an occurrence of 0.7.
====Phenotypes====


The real DCE in the distal promoters (sixty) have an occurrence of 15. The randoms had one hundred and fifty-one for an occurrence of 5.1.
'''Def.''' the "appearance of an organism based on a single trait [multifactorial combination of genetic traits and environmental factors]<ref name=PhenotypeWikt2>{{ cite web
|author=[[wikt:User:24.235.196.118|24.235.196.118]]
|title=phenotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=23 September 2007
|url=https://en.wiktionary.org/wiki/phenotype
|accessdate=2016-10-04 }}</ref>, especially used in pedigrees"<ref name=PhenotypeWikt1>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title=phenotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=14 February 2005
|url=https://en.wiktionary.org/wiki/phenotype
|accessdate=2016-10-04 }}</ref> or any "observable characteristic of an organism, such as its morphological, developmental, biochemical or physiological properties, or its behavior"<ref name=PhenotypeWikt>{{ cite web
|author=[[wikt:User:N2e|N2e]]
|title=phenotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=3 July 2008
|url=https://en.wiktionary.org/wiki/phenotype
|accessdate=2016-10-04 }}</ref> is called a '''phenotype'''.


The disparity between the reals and randoms was often as much as a factor of 2 which suggests that the real DCE SI is likely active or activable.
"The three different phenotypes of α1B observed (designated 1-1, 1-2, and 2-2) were apparently identical to those reported by Altland et al. (1983), who used double one-dimensional electrophoresis. Family data supported the hypothesis that the three α1B phenotypes are determined by two codominant alleles at an autosomal locus, designated A1B. Allele frequencies in a Swedish population were: A1B *1, 0.937; A1B *2, 0.063; PIC, 0.111."<ref name=Gahne/>


====DCE SII====
====Protein species====
{{main|Downstream core element gene transcriptions}}
The reals have seventeen on the negative strand, in the negative direction in the UTR and twenty-one on the positive strand, in the negative direction, for an average occurrence of 19.0.


The randoms had fifty-two in the UTR for an occurrence of 5.2.
"Both protein species of [alpha 1-beta glycoprotein] A1B (A1Ba, p = 0.008; f.c.= +1.62, A1Bb, p = 0.003; f.c. = +1.82) [...] were apparently overexpressed in patients with PTCa [...]."<ref name=Abdullah>{{ cite journal
|author=Mardiaty Iryani Abdullah, Ching Chin Lee, Sarni Mat Junit, Khoon Leong Ng, and Onn Haji Hashim
|title=Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins
|journal=Peer J
|date=13 September 2016
|volume=4
|issue=
|pages=e2450
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028788/
|arxiv=
|bibcode=
|doi=10.7717/peerj.2450
|pmid=27672505
|accessdate=15 March 2020 }}</ref>


The reals have three in the positive direction only for an average occurrence of 1.5. But, reals could have been present in the negative direction core promoter, so the total average occurrence is 0.75.
A1BG is mainly produced in the liver, and is secreted to plasma to levels of approximately 0.22 mg/mL.<ref name=Ishioka/>


The randoms had two in the arbitrary negative direction in the core promoter for an occurrence of 0.2 and seven in the arbitrary positive direction for an average occurrence of 0.7.
===CRISPs===


For the proximal promoters, the reals have three in the negative direction for an average occurrence of 1.5 and two in the positive direction for an average occurrence of 1.0.
The human cysteine-rich secretory protein (CRISP3) "is present in exocrine secretions and in secretory granules of neutrophilic granulocytes and is believed to play a role in innate immunity."<ref name=Udby>{{ cite journal
 
|author=Udby L, Sørensen OE, Pass J, Johnsen AH, Behrendt N, Borregaard N, Kjeldsen L.
The randoms had one in the arbitrary negative direction for an occurrence of 0.1 and ten in the positive direction for an average occurrence of 1.0, for an average occurrence of 0.55.
|title=Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma
 
|journal=Biochemistry
For the distal promoters, the reals have fifteen on the negative strand, in the negative direction, and thirty-two on the positive strand, in the negative direction for an average occurrence of 23.5. The randoms have seventy-five in the arbitrary negative direction for an average occurrence of 7.5.
|date=12 October 2004
 
|volume=43
The reals have fifty-two on the negative strand, in the positive direction and twenty-nine on the positive strand, positive direction, for an average occurrence of 40.5. The randoms had one hundred and nine for an average occurrence of 10.9.
|issue=40
 
|pages=12877-86
Comparatively, the reals in the UTR between ZSCAN22 and A1BG are likely active or activable. For the core promoters, the randoms are close in occurrences but lower than the reals to suggest that the reals are likely active or activable.
|url=https://pubs.acs.org/doi/10.1021/bi048823e
 
|arxiv=
For the proximal promoters, again the occurrences for the randoms are at or on average below that of the reals suggesting that the reals are likely active or activable.
|bibcode=
|doi=10.1021/bi048823e
|pmid=15461460
|accessdate=2011-11-28 }}</ref> CRISP3 has a relatively high content in human plasma.<ref name=Udby/>


The distal promoters in the real promoters have systematically much higher occurrences than the randoms suggesting that the reals are likely active or activable.
"The A1BG-CRISP-3 complex is noncovalent with a 1:1 stoichiometry and is held together by strong electrostatic forces."<ref name=Udby/> "Similar [complex formation] between toxins from snake venom and A1BG-like plasma proteins ... inhibits the toxic effect of snake venom metalloproteinases or myotoxins and protects the animal from envenomation."<ref name=Udby/>


====DCE SIII====
Opossums have a remarkably robust immune system, and show partial or total immunity to the venom of rattlesnakes, ''Agkistrodon piscivorus'', cottonmouths, and other ''Crotalinae'', pit vipers.<ref>{{ cite web
{{main|Downstream core element gene transcriptions}}
|url=http://www.wildliferescueleague.org/report/opossum.html
The reals have nine consensus sequences DCE SIII directs or complement inverses on the negative strand in the negative direction. There are seventy consensus sequences DCE SIII directs or complement inverses on the positive strand in the negative direction. The overall occurrence is 39.5. The randoms have two hundred and twenty-seven consensus sequences DCE SIII for an occurrence of 22.7 which is much less than the reals suggesting the UTRs are likely active or activable.
|title=The Opossum: Our Marvelous Marsupial, The Social Loner
|publisher=Wildlife Rescue League }}</ref><ref>[http://www.scielo.br/scielo.php?pid=S0104-79301999000100005&script=sci_arttext Journal Of Venomous Animals And Toxins – Anti-Lethal Factor From Opossum Serum Is A Potent Antidote For Animal, Plant And Bacterial Toxins]. Retrieved 2009-12-29.</ref>


There are nine real core promoters, all in the positive direction (4.5 vs. 0.0 in the negative direction), for an overall occurrence of 2.25. The core promoter randoms, nine in the negative direction (0.9 occurrence), thirty-nine in the positive direction but fifteen are not allowed for twenty-four (2.4 occurrence), had thirty-three consensus sequences for an average occurrence of 1.65. Taken separately by direction, the occurrences for the reals are much higher than that for the randoms suggesting that they are likely active or activable.
"Crisp3 [is] mainly [expressed] in the salivary glands, pancreas, and prostate."<ref name=Haendler>{{ cite journal
 
|author=B Haendler, J Krätzschmar, F Theuring and W D Schleuning
The proximal promoters (real) have ten sequences in the negative direction (5.0 occurrence) and one in the positive direction (0.5 occurrence) for an overall occurrence of 2.75. The proximal promoter randoms, twenty-one in the negative direction (2.1 occurrence), thirty-eight in the positive direction (3.8 occurrence), had fifty-nine consensus sequences (twenty-one in the arbitrary negative direction, thirty-eight in the positive direction) for an overall occurrence of 2.95. The apparent proximal promoters are roughly within 2.95 ± 0.2 of the randoms suggesting that the proximal promoters are likely random. Taken by direction, the reals are outside the range of the randoms suggesting that they are likely active or activable.
|title=Transcripts for cysteine-rich secretory protein-1 (CRISP-1; DE/AEG) and the novel related CRISP-3 are expressed under androgen control in the mouse salivary gland.
 
|journal=Endocrinology
The distal promoters for the real promoters, one hundred and fifteen in the negative direction (57.5 occurrence), two hundred and fifty-three in the positive direction (126.5 occurrence), are three hundred and sixty-eight for an overall occurrence of 92.0. The randoms, three hundred and seventeen in the negative direction (31.7 occurrence), five hundred and twenty-three in the positive direction (52.0 occurrence), had eight hundred and forty sequences for an overall occurrence of 42.0, which is systematically lower than the reals suggesting that the reals are likely active or activable.
|date=July 1993
 
|volume=133
Taking directions into account, the reals generally appear to be likely active or activable.
|issue=1
 
|pages=192-8
====DPE (Juven-Gershon)====
|url=http://endo.endojournals.org/content/133/1/192.full.pdf+html
{{main|Downstream promoter element gene transcriptions}}
|arxiv=
|bibcode=
|doi=10.1210/en.133.1.192
|pmid= 8319566
|accessdate=2012-02-20 }}</ref> "CRISP3 is highly expressed in the human cauda epididymidis and ampulla of vas deferens (Udby et al. 2005)."<ref name=Haendler/>


====DPE (Kadonaga)====
==A1BG-AS1==
{{main|Downstream promoter element gene transcriptions}}


====DPE (Matsumoto)====
Gene ID: 503538 is [[A1BG-AS1]] A1BG antisense RNA 1.<ref name=HGNC503538>{{ cite web
{{main|Downstream promoter element gene transcriptions}}
|author=HGNC
|title=A1BG-AS1 A1BG antisense RNA 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=10 December 2019
|url=https://www.ncbi.nlm.nih.gov/gene/503538
|accessdate=2019-12-18 }}</ref> A1BG-AS1 is transcribed in the negative direction from ZSCAN22.<ref name=HGNC503538/>


====EIN3 binding sites====
Gene ID 503538 extends from 58,351,390 to 58,355,183. It is a long, non-coding (lnc) RNA.<ref name=Bai>{{ cite journal
{{main|EIN3 binding site gene transcriptions}}
|author=Jigang Bai, Bowen Yao, Liang Wang, Liankang Sun, Tianxiang Chen, Runkun Liu, Guozhi Yin, Qiuran Xu, Wei Yang
 
|title=lncRNA A1BG-AS1 suppresses proliferation and invasion of hepatocellular carcinoma cells by targeting miR-216a-5p
====Endosperm expressions====
|journal=
{{main|Endosperm expression gene transcriptions}}
|date=June 2019
 
|volume=120
====GAAC elements====
|issue=6
{{main|GAAC element gene transcriptions}}
|pages=10310-10322
 
|url=https://pubmed.ncbi.nlm.nih.gov/30556161/
====GC boxes (Briggs)====
|arxiv=
{{main|GC box gene transcriptions}}
 
====GC boxes (Ye)====
{{main|GC box gene transcriptions}}
 
====GCR1s====
{{main|Gcr1p gene transcriptions}}
 
====GT boxes (Sato)====
{{main|TC element gene transcriptions}}
 
====Hex sequences====
{{main|Hex sequence gene transcriptions}}
 
====HY boxes====
{{main|HY box gene transcriptions}}
 
====IFNs====
{{main|Interferon regulatory factor gene transcriptions#IFN-stimulated response element samplings}}
 
====Inr-like, TCTs====
{{main|Initiator element gene transcriptions#Inr-like, TCTs sampling}}
 
====IRF3s====
{{main|Interferon regulatory factor gene transcriptions#IRF-3 samplings}}
 
====IRSs====
{{main|Interferon regulatory factor gene transcriptions#IRS consensus samplings}}
 
====KAR2s====
{{main|Hac1p gene transcriptions#KAR2 samplings}}
 
====MBE1s====
{{main|Musashi binding element gene transcriptions}}
 
====MBE2s====
{{main|Musashi binding element gene transcriptions}}
 
====MBE3s====
{{main|Musashi binding element gene transcriptions}}
 
====UPREs====
{{main|Unfolded protein response element gene transcriptions}}
 
====UPRE-1s====
{{main|Hac1p gene transcriptions}}
 
====Tryptophan residues====
{{main|Interferon regulatory factor gene transcriptions#Tryptophan residue samplings}}
 
====YYRNWYY Inrs====
{{main|Initiator element gene transcriptions#YYRNWYY samplings}}
 
==A1BG orthologs==
 
===''Geotrypetes seraphini''===
[[Image:Geotrypetes seraphini 81151944.jpg|thumb|right|250px|''Geotrypetes seraphini'', the Gaboon caecilian, is a species of amphibian. Credit: [https://www.inaturalist.org/users/7865 Marius Burger].{{tlx|free media}}]]
''Geotrypetes seraphini'', the Gaboon caecilian, is a species of amphibian in the family ''Dermophiidae''.<ref name=IUCN>{{cite journal |author=IUCN SSC Amphibian Specialist Group |date=2019 |title=''Geotrypetes seraphini'' |volume=2019 |page=e.T59557A16957715 |url=https://en.wikipedia.org/wiki/IUCN_Red_List
|doi=10.2305/IUCN.UK.2019-1.RLTS.T59557A16957715.en |accessdate=16 November 2021}}</ref>
 
Its A1BG ortholog has 368 aa vs 495 aa for ''Homo sapiens''.
{{clear}}
 
==ZSCAN22==
{{main|ZSCAN22}}
# Gene ID: 342945 is ZSCAN22 zinc finger and SCAN domain containing 22 on 19q13.43.<ref name=HGNC342945>{{ cite web
|author=HGNC
|title=ZSCAN22 zinc finger and SCAN domain containing 22 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=13 March 2020
|url=https://www.ncbi.nlm.nih.gov/gene/342945
|accessdate=2019-12-18 }}</ref> ZSCAN22 is transcribed in the negative direction from LOC100887072.<ref name=HGNC342945/>
# Gene ID: 102465484 is MIR6806 microRNA 6806 on 19q13.43: "microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop."<ref name=RefSeq102465484>{{ cite web
|author=RefSeq
|title=MIR6806 microRNA 6806 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=10 September 2009
|url=https://www.ncbi.nlm.nih.gov/gene/102465484
|accessdate=2019-12-18 }}</ref> MIR6806 is transcribed in the negative direction from LOC105372480.<ref name=RefSeq102465484/>
 
Of the some 111 gaps between genes on chromosome locus 19q13.43 as of 4 August 2020, gap number 88 is between ZSCAN22 and A1BG. But, there is no gap between ZNF497 and A1BG.
 
==Promoters==
 
The core promoter begins approximately -35 nts upstream from the transcription start site (TSS). For the numbered nucleotides between ZSCAN22 and A1BG the core promoter extends from 4425 nts up to 4460 nts (TSS). The proximal promoter extends from approximately -250 to the TSS or 4210 nts up to 4460 nts. The distal promoter begins at about 2460 nts and extends to about 4210 nts.
 
From the ZNF497 side the core promoter begins about 4265 nts up to 4300 nts, the proximal promoter from 4050 nts to 4265 nts, and the distal promoter from 2300 nts to 4050 nts.
 
==Alpha-1-B glycoprotein==
{{main|Alpha-1-B glycoprotein}}
'''Def.''' "a substance that induces an immune response, usually foreign"<ref name=AntigenWikt>{{ cite web
|author=[[wikt:User:Jag123|Jag123]]
|title=antigen
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=7 March 2005
|url=https://en.wiktionary.org/wiki/antigen
|accessdate=7 March 2020 }}</ref> is called an '''antigen'''.
 
'''Def.''' any "substance that elicits [an] immune response"<ref name=ImmunogenWikt>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title=immunogen
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=21 April 2008
|url=https://en.wiktionary.org/wiki/immunogen
|accessdate=8 March 2020 }}</ref> is called an '''immunogen'''.
 
An antigen "or immunogen is a molecule that sometimes stimulates an immune system response."<ref name=AntigenWikidoc>{{ cite web
|author=C. Michael Gibson
|title=Antigen
|publisher=WikiDoc Foundation
|location=Boston, Massachusetts
|date=27 April 2008
|url=https://www.wikidoc.org/index.php/Antigen
|accessdate=8 March 2020 }}</ref> But, "the immune system does not consist of only antibodies",<ref name=AntigenWikidoc/> instead it "encompasses all substances that can be recognized by the [[adaptive immune system]]."<ref name=AntigenWikidoc/>
 
'''Def.''' "a protein produced by B-lymphocytes that binds to [a specific antigen or]<ref name=AntibodyWikt1>{{ cite web
|author=[[wikt:User:Williamsayers79|Williamsayers79]]
|title=antibody
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=26 February 2007
|url=https://en.wiktionary.org/wiki/antibody
|accessdate=7 March 2020 }}</ref> an antigen"<ref name=AntibodyWikt>{{ cite web
|author=[[wikt:User:Jag123|Jag123]]
|title=antibody
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=7 March 2005
|url=https://en.wiktionary.org/wiki/antibody
|accessdate=7 March 2020 }}</ref> is called an '''[[antibody]]'''.
 
Five different antibody isotypes are known in mammals, which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter.<ref name=Market>{{ cite journal
|author=Eleonora Market, F. Nina Papavasiliou
|date=2003
|url=http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0000016
|title=V(D)J Recombination and the Evolution of the Adaptive Immune System
|journal=PLoS Biology
|volume=1
|issue=1
|pages=e16
|doi=10.1371/journal.pbio.0000016 }}</ref>
 
Although the general structure of all antibodies is very similar, a small region, known as the hypervariable region, at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures to exist, where each of these variants can bind to a different target, known as an antigen.<ref name=Janeway5>{{ cite book | author = Charles A Janeway, Jr, Paul Travers, Mark Walport, and Mark J Shlomchik | title = Immunobiolog. | edition = 5th ed. | publisher = Garland Publishing | date = 2001 | url = http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowTOC&rid=imm.TOC&depth=10 | isbn = 0-8153-3642-X }}</ref>
 
'''Def.''' "any of the glycoproteins in blood serum that respond to invasion by foreign antigens and that protect the host by removing pathogens;"<ref name=ImmunoglobulinWikt>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title= immunoglobulin
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=25 February 2006
|url=https://en.wiktionary.org/wiki/immunoglobulin
|accessdate=7 March 2020 }}</ref> "an antibody"<ref name=ImmunoglobulinWikt1>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title= immunoglobulin
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=28 April 2008
|url=https://en.wiktionary.org/wiki/immunoglobulin
|accessdate=7 March 2020 }}</ref> is called an '''[[immunoglobulin]]'''.
 
Gene ID: 1 is A1BG [[alpha-1-B glycoprotein]] on 19q13.43, a 54.3 kDa [[protein]] in humans that is encoded by the A1BG [[gene]].<ref name=RefSeq1>{{ cite web
|author=RefSeq
|title=A1BG alpha-1-B glycoprotein [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=10 December 2019
|url=https://www.ncbi.nlm.nih.gov/gene/1
|accessdate=2019-12-18 }}</ref> A1BG is transcribed in the positive direction from ZNF497.<ref name=RefSeq1/> "The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins."<ref name=RefSeq1/>
# NP_570602.2  alpha-1B-glycoprotein precursor, '''cd05751''' Location: 401 → 493 Ig1_LILRB1_like; First immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILR)B1 (also known as LIR-1) and similar proteins, '''smart00410''' Location: 218 → 280 IG_like; Immunoglobulin like, '''pfam13895''' Location: 210 → 301 Ig_2; Immunoglobulin domain and '''cl11960''' Location: 28 → 110 Ig; Immunoglobulin domain.<ref name=RefSeq1/>
 
Patients who have pancreatic ductal [[adenocarcinoma]] show an [[overexpression]] of A1BG in [[pancreatic juice]].<ref name=Tian>{{ cite journal
|author=Mei Tian, Ya-Zhou Cui, Guan-Hua Song, Mei-Juan Zong, Xiao-Yan Zhou, Yu Chen, Jin-Xiang Han
| title = Proteomic analysis identifies MMP-9, DJ-1 and A1BG as overexpressed proteins in pancreatic juice from pancreatic ductal adenocarcinoma patients
| journal = BMC Cancer
| volume = 8
| issue =
| pages = 241
| date = 2008
| pmid = 18706098
| pmc = 2528014
| doi = 10.1186/1471-2407-8-241
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2528014/ }}</ref>
 
===Immunoglobulin supergene family===
{{main|Immunoglobulin supergene family}}
"𝛂<sub>1</sub>B-glycoprotein(𝛂<sub>1</sub>B) [...] consists of a single polypeptide chain N-linked to four
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂<sub>1</sub>B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂<sub>1</sub>B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂<sub>1</sub>B [...] exhibits sequence similarity to other members of the [[immunoglobulin supergene family]] such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."<ref name=Ishioka/>
 
"Some of the domains of 𝛂<sub>1</sub>B show significant homology to variable (V) and constant (C) regions of certain immunoglobulins. Likewise, there is statistically significant homology between 𝛂<sub>1</sub>B and the secretory component (SC) of human IgA (15) and also with the extracellular portion of the rabbit receptor for transepithelial transport of polymeric immunoglobulins (IgA and IgM). Mostov et al. (16) have called the later protein the poly-Ig receptor or poly-IgR and have shown that it is the precursor of SC."<ref name=Ishioka/>
 
The immunoglobulin supergene family is "the group of proteins that have immunoglobulin-like domains, including histocompatibility antigens, the T-cell antigen receptor, poly-IgR, and other proteins involved in the vertebrate immune response (17)."<ref name=Ishioka/>
 
"The internal homology in primary structure [...] and the presence of an intrasegment disulfide bond suggest that 𝛂<sub>1</sub>B is composed of five structural domains that arose by duplication of a primordial gene coding for about 95 amino acid residues."<ref name=Ishioka/>
 
"Unlike immunoglobulins (25), ceruloplasmin (6), and hemopexin (7), 𝛂<sub>1</sub>B is not subject to limited interdomain cleavage by proteolytic enzymes. At least, we were not able to produce such fragments by use of a variety of proteases. This stability of 𝛂<sub>1</sub>B is probably associated with the frequency of proline in the sequences linking the domains [...]."<ref name=Ishioka/>
 
"A peptide identified in the late and early milk proteomes showed homology to eutherian alpha 1B glycoprotein (A1BG), a plasma protein with unknown function<sup>46</sup>, as well as venom inhibitors characterised in the Southern opossum ''Didelphis marsupialis'' (DM43 and DM46<sup>47,48,49</sup>), all members of the immunoglobulin superfamily. To characterise the relationship between the peptide sequence identified in koala, A1BG, DM43 and DM46, a phylogenetic tree was constructed [...] including all marsupial and monotreme homologs (identified by BLAST), three phylogenetically representative eutherian sequences, with human IGSF1 and TARM1, related members of the immunoglobulin super family, used as outgroups. This phylogeny indicates that A1BG-like proteins in marsupials and the ''Didelphis'' antitoxic proteins are homologs of eutherian A1BG, with excellent bootstrap support (98%). The marsupial A1BG-like sequences and the ''Didelphis'' antitoxic proteins formed a single clade with strong bootstrap support (97%)."<ref name=Morris>{{ cite journal
|author=Katrina M. Morris, Denis O’Meally, Thiri Zaw, Xiaomin Song, Amber Gillett, Mark P. Molloy, Adam Polkinghorne, and Katherine Belova
|title=Characterisation of the immune compounds in koala milk using a combined transcriptomic and proteomic approach
|journal=Scientific Reports
|date=7 October 2016
|volume=6
|issue=
|pages=35011
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5054531/
|arxiv=
|bibcode=
|doi=10.1038/srep35011
|pmid=27713568
|accessdate=14 March 2020 }}</ref>
 
"Human TARM1 and IGSF1, related members of the immunoglobulin superfamily are used as outgroups. The tree was constructed using the maximum likelihood approach and the JTT model with bootstrap support values from 500 bootstrap tests. Bootstrap values less than 50% are not displayed. Accession numbers: Tasmanian devil (''Sarcophilus harrisii''; XP_012402143), Wallaby (''Macropus eugenii''; FY619507), Possum (''Trichosurus vulpecula''; DY596639) Virginia opossum (''Didelphis virginiana''; AAA30970, AAN06914), Southern opossum (''Didelphis marsupialis''; AAL82794, P82957, AAN64698), Human (''Homo sapiens''; P04217, B6A8C7, Q8N6C5), Platypus (''Ornithorhychus anatinus''; ENSOANP00000000762), Cow (''Bos taurus''; Q2KJF1), Alpaca (''Vicugna pacos''; XP_015107031)."<ref name=Morris/>
 
"The sequences of 𝛂<sub>1</sub>B-glycoprotein (38) and chicken N-CAM (neural cell-adhesion molecule) (39) have been shown to be related to the immunoglobulin supergene family."<ref name=Paxton>{{ cite journal
|author=R. J. Paxton, G. Mooser, H. Pande, T. D. Lee, and J. E. Shively
|title=Sequence analysis of carcinoembryonic antigen: identification of glycosylation sites and homology with the immunoglobulin supergene family
|journal=Proceedings of the National Academy of Sciences USA
|date=1 February 1987
|volume=84
|issue=4
|pages=920-924
|url=https://www.pnas.org/content/pnas/84/4/920.full.pdf
|arxiv=
|bibcode=
|doi=10.1073/pnas.84.4.920
|pmid=3469650
|accessdate=26 March 2020 }}</ref>
 
A1BG contains the immunoglobulin domain: '''cl11960''' and three immunoglobulin-like domains: '''pfam13895''', '''cd05751''' and '''smart00410'''.
 
"Immunoglobulin (Ig) domain ['''cl11960'''] found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond."<ref name=NCBI386229>{{ cite web
|author=NCBI
|title=Conserved Protein Domain Family cl11960: Ig Superfamily
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=2 February 2016
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=386229
|accessdate=22 May 2020 }}</ref>
 
"This domain ['''pfam13895'''] contains immunoglobulin-like domains."<ref name=NCBI372793>{{ cite web
|author=NCBI
|title=Conserved Protein Domain Family pfam13895: Ig_2
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=5 August 2015
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=372793
|accessdate=24 May 2020 }}</ref>
 
"Ig1_LILR_KIR_like: ['''cd05751'''] domain similar to the first immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILRs) and Natural killer inhibitory receptors (KIRs). This group includes LILRB1 (or LIR-1), LILRA5 (or LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (or CD89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3,and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1 (LIR-1), LILRB2 (LIR-2), and LILRB3 (LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LIR-1 (LILRB1), and LIR-2 (LILRB2), show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1 (LIR-1), and LILRB2 (LIR-2), and two in the case of LILRB4 (LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst."<ref name=NCBI319306>{{ cite web
|author=NCBI
|title=Conserved Protein Domain Family cd05751: Ig1_LILR_KIR_like
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=16 August 2016
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=319306
|accessdate=24 May 2020 }}</ref>
 
"IG domains ['''smart00410'''] that cannot be classified into one of IGv1, IGc1, IGc2, IG."<ref name=NCBI214653>{{ cite web
|author=NCBI
|title=Conserved Protein Domain Family smart00410: IG_like
|publisher=National Center for Biotechnology Information, U.S. National Library of Medicine
|location=8600 Rockville Pike, Bethesda MD, 20894 USA
|date=16 January 2013
|url=https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=214653
|accessdate=24 May 2020 }}</ref>
"𝛂<sub>1</sub>B-glycoprotein(𝛂<sub>1</sub>B) [...] consists of a single polypeptide chain N-linked to four
glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂<sub>1</sub>B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂<sub>1</sub>B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂<sub>1</sub>B [...] exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."<ref name=Ishioka>{{ cite journal
|author=Noriaki Ishioka, Nobuhiro Takahashi, and Frank W. Putnam
|title=Amino acid sequence of human plasma 𝛂<sub>1</sub>B-glycoprotein: Homology to the immunoglobulin supergene family
|journal=Proceedings of the National Academy of Sciences USA
|date=April 1986
|volume=83
|issue=8
|pages=2363-7
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC323297/pdf/pnas00312-0089.pdf
|arxiv=
|bibcode=
|doi=10.1073/pnas.83.8.2363
|pmid=3458201
|accessdate=9 March 2020 }}</ref>
 
===A1BG protein species===
 
'''Def.''' a "group of plants or animals having similar appearance"<ref name=SpeciesWikt>{{ cite web
|author=[[wikt:User:24.98.118.180|24.98.118.180]]
|title=species
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=28 February 2007
|url=https://en.wiktionary.org/wiki/species
|accessdate=25 March 2020 }}</ref> or "the largest group of organisms in which [any]<ref name=Species1/> two individuals [of the appropriate sexes or mating types]<ref name=Species1>{{ cite web
|author=[[w:User:Peter coxhead|Peter coxhead]]
|title=Species
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=22 August 2018
|url=https://en.wikipedia.org/wiki/Species
|accessdate=25 March 2020 }}</ref> can produce fertile offspring, typically by sexual reproduction"<ref name=Species>{{ cite web
|author=[[w:User:Chiswick Chap|Chiswick Chap]]
|title=Species
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=1 December 2016
|url=https://en.wikipedia.org/wiki/Species
|accessdate=25 March 2020 }}</ref> is called a '''species'''.
 
The gene contains 20 distinct introns.<ref name=AceView>{{ cite web
|title=AceView: A1BG
|url=https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=a1bg&submit=Go
|accessdate=May 11, 2013 }}</ref> Transcription produces 15 different mRNAs, 10 alternatively spliced variants and 5 unspliced forms.<ref name="AceView"/> There are 4 probable alternative promoters, 4 non overlapping alternative last exons and 7 validated alternative polyadenylation sites.<ref name="AceView"/> The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 4 cassette exons, overlapping exons with different boundaries, splicing versus retention of 3 introns.<ref name="AceView"/>
 
====Variants or isoforms====
 
'''Def.''' a "different sequence of a gene (locus)"<ref name=VariantWikt>{{ cite web
|author=[[wikt:User:Pdeitiker|Pdeitiker]]
|title=variant
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=26 July 2008
|url=https://en.wiktionary.org/wiki/variant
|accessdate=25 March 2020 }}</ref> is called a '''variant'''.
 
'''Def.''' any "of several different forms of the same protein, arising from either single nucleotide polymorphisms,<ref name=IsoformWikt1>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title=isoform
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=6 January 2007
|url=https://en.wiktionary.org/wiki/isoform
|accessdate=2 December 2018 }}</ref> differential splicing of mRNA, or post-translational modifications (e.g. sulfation, glycosylation, etc.)"<ref name=IsoformWikt2>{{ cite web
|author=[[wikt:User:72.178.245.181|72.178.245.181]]
|title=isoform
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=30 November 2008
|url=https://en.wiktionary.org/wiki/isoform
|accessdate=2 December 2018 }}</ref> is called an '''isoform'''.
 
Regarding additional isoforms, mention has been made of "new genetic variants of A1BG."<ref name=Eiberg>{{ cite journal
|author=H Eiberg, ML Bisgaard, J Mohr
|title=Linkage between alpha 1B-glycoprotein (A1BG) and Lutheran (LU) red blood group system: assignment to chromosome 19: new genetic variants of A1BG
|journal=Clinical genetics
|date=1 December 1989
|volume=36
|issue=6
|pages=415-8
|url=http://europepmc.org/abstract/MED/2591067
|arxiv=
|bibcode=
|doi=
|pmid=2591067
|accessdate=2017-10-08 }}</ref>
 
"Proteomic analysis revealed that [a circulating] set of plasma proteins was α 1 B-glycoprotein ('''A1BG''') and its
post-translationally modified isoforms."<ref name=Stehle>{{ cite journal
|author=John R. Stehle Jr., Mark E. Weeks, Kai Lin, Mark C. Willingham, Amy M. Hicks, John F. Timms, Zheng Cui
|title=Mass spectrometry identification of circulating alpha-1-B glycoprotein, increased in aged female C57BL/6 mice
|journal=Biochimica et Biophysica Acta (BBA) - General Subjects
|date=January 2007
|volume=1770
|issue=1
|pages=79-86
|url=http://www.sciencedirect.com/science/article/pii/S0304416506001826
|arxiv=
|bibcode=
|doi=10.1016/j.bbagen.2006.06.020
|pmid=16945486
|accessdate=2017-10-08 }}</ref>
 
Pharmacogenomic variants have been reported.<ref name=McDonough/>
 
====Genotypes====
 
'''Def.''' the "part (DNA sequence) of the genetic makeup of an organism which determines a specific characteristic (phenotype) of that organism"<ref name=GenotypeWikt1>{{ cite web
|author=[[wikt:User:DTLHS|DTLHS]]
|title=genotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=10 January 2018
|url=https://en.wiktionary.org/wiki/genotype
|accessdate=25 March 2020 }}</ref> or a "group of organisms having the same genetic constitution" <ref name=GenotypeWikt>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title=genotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=22 October 2005
|url=https://en.wiktionary.org/wiki/genotype
|accessdate=25 March 2020 }}</ref>is called a '''genotype'''.
 
There are A1BG genotypes.<ref name=McDonough>{{ cite journal
|author=Caitrin W. McDonough, Yan Gong, Sandosh Padmanabhan, Ben Burkley, Taimour Y. Langaee, Olle Melander, Carl J. Pepine, Anna F. Dominiczak, Rhonda M. Cooper-DeHoff, and Julie A. Johnson
|title=Pharmacogenomic Association of Nonsynonymous SNPs in ''SIGLEC12'', ''A1BG'', and the Selectin Region and Cardiovascular Outcomes
|journal=Hypertension
|date=June 2013
|volume=62
|issue=1
|pages=48-54
|url=http://hyper.ahajournals.org/content/hypertensionaha/early/2013/05/20/HYPERTENSIONAHA.111.00823.full.pdf
|arxiv=
|bibcode=
|doi=10.1161/HYPERTENSIONAHA.111.00823
|pmid=23690342
|accessdate=2017-10-08 }}</ref>
 
A1BG has a genetic risk score of rs893184.<ref name=McDonough/>
 
"A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39×10<sup>−5</sup>)."<ref name=McDonough/>
 
====Polymorphs====
 
'''Def.''' the "regular existence of two or more different genotypes within a given species or population; also, variability of amino acid sequences within a gene's protein"<ref name=PolymorphismWikt>{{ cite web
|author=[[wikt:User:Widsith|Widsith]]
|title=polymorphism
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=28 March 2012
|url=https://en.wiktionary.org/wiki/polymorphism
|accessdate=25 March 2020 }}</ref> is called '''polymorphism'''.
 
'''Def.''' "one of a number of alternative forms of the same gene occupying a given position, [or locus],<ref name=AlleleWikt1>{{ cite web
|author=[[wikt:User:217.105.66.98|217.105.66.98]]
|title=allele
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=8 September 2016
|url=https://en.wiktionary.org/wiki/allele
|accessdate=25 March 2020 }}</ref> on a chromosome"<ref name=AlleleWikt>{{ cite web
|author=[[wikt:User:138.130.33.215|138.130.33.215]]
|title=allele
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=7 April 2004
|url=https://en.wiktionary.org/wiki/allele
|accessdate=25 March 2020 }}</ref> is called an '''allele'''.
 
"rs893184 causes a histidine (His) to arginine (Arg) [nonsynonymous single nucleotide polymorphism (nsSNP), A (minor) for G (major)] substitution at amino acid position 52 in A1BG."<ref name=McDonough/>
 
"Genetic polymorphism of human plasma (serum) alpha 1B-glycoprotein (alpha 1B) was observed using one-dimensional horizontal polyacrylamide gel electrophoresis (PAGE) pH 9.0 of plasma samples followed by Western blotting with specific antiserum to alpha 1B."<ref name=Gahne>{{ cite journal
|author=B. Gahne, R. K. Juneja, and A. Stratil
|title=Genetic polymorphism of human plasma alpha 1B-glycoprotein: phenotyping by immunoblotting or by a simple method of 2-D electrophoresis
|journal=Human Genetics
|date=June 1987
|volume=76
|issue=2
|pages=111-5
|url=https://link.springer.com/article/10.1007%2FBF00284904
|arxiv=
|bibcode=
|doi=10.1007/bf00284904
|pmid=3610142
|accessdate=25 March 2020 }}</ref>
 
''A1B*5'' is a "new allele [...] of human plasma 𝜶<sub>1</sub>B-glycoprotein [...]."<ref name=Juneja1989>{{ cite journal
|author=R.K. Juneja, G. Beckman, M. Lukka, B. Gahne, and C. Ehnholm
|title=Plasma α<sub>1</sub>B-Glycoprotein Allele Frequencies in Finns and Swedish Lapps: Evidence for a New α<sub>1</sub>B Allele
|journal=Human Heredity
|date=1989
|volume=39
|issue=1
|pages=32-36
|url=https://www.karger.com/Article/Abstract/153828
|arxiv=
|bibcode=
|doi=10.1159/000153828
|pmid=2759622
|accessdate=25 March 2020 }}</ref>
 
"Genetic polymorphism of human plasma 𝜶<sub>1</sub>B-glycoprotein (𝜶<sub>1</sub>B) was reported first, in brief, by Altland ''et al.'' [1983; also given in Altkand and Hacklar, 1984]. A detailed description of human 𝜶<sub>1</sub>B polymorphism was reported in subsequent studies [Gahne ''et al.'', 1987; Juneja ''et al.'', 1988, 1989]. Five different 𝜶<sub>1</sub>B alleles (''A1B*1, A1B*2, A1B*3, A1B*4'' and ''A1B*5'') were reported. In Caucasian whites, the frequencies of ''A1B*1'' and ''''A1B*2'' were about 0.95 and 0.05, respectively. ''A1B*4'' was observed in 2 related Czech individuals. In American blacks, ''A1B*1'' and ''A1B*2'' occurred with a frequency of 0.73 and 0.21, respectively, while a new allele, viz, ''A1B*3'' had a frequency of 0.06. ''A1B*5'' was observed only in Swedish Lapps and in Finns with a frequency of 0.04 and 0.007, respectively."<ref name=Juneja>{{ cite journal
|author=R.K. Juneja, N. Saha, B. Gahne and J.S.H. Tay
|title=Distribution of Plasma Alpha-1-B-Glycoprotein Phenotypes in Several Mongoloid Populations of East Asia
|journal=Human Heredity
|date=1989
|volume=39
|issue=
|pages=218-222
|url=https://www.karger.com/Article/PDF/153863
|arxiv=
|bibcode=
|doi=10.1159/000153863
|pmid=2583734
|accessdate=25 March 2020 }}</ref>
 
"The frequency of ''A1B*1'' varied from 0.89 to 0.91 and that of ''A1B*2'' from 0.08 to 0.10. The ''A1B*3'' allele, reported previously only in American blacks, was observed with a frequency range of 0.003-0.01 in 3 of the Chinese populations, in Koreans and in Malays. A new 𝜶<sub>1</sub>B allele (''A1B*6'') was observed in 2 Chinese individuals."<ref name=Juneja/>
 
====Phenotypes====
 
'''Def.''' the "appearance of an organism based on a single trait [multifactorial combination of genetic traits and environmental factors]<ref name=PhenotypeWikt2>{{ cite web
|author=[[wikt:User:24.235.196.118|24.235.196.118]]
|title=phenotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=23 September 2007
|url=https://en.wiktionary.org/wiki/phenotype
|accessdate=2016-10-04 }}</ref>, especially used in pedigrees"<ref name=PhenotypeWikt1>{{ cite web
|author=[[wikt:User:SemperBlotto|SemperBlotto]]
|title=phenotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=14 February 2005
|url=https://en.wiktionary.org/wiki/phenotype
|accessdate=2016-10-04 }}</ref> or any "observable characteristic of an organism, such as its morphological, developmental, biochemical or physiological properties, or its behavior"<ref name=PhenotypeWikt>{{ cite web
|author=[[wikt:User:N2e|N2e]]
|title=phenotype
|publisher=Wikimedia Foundation, Inc
|location=San Francisco, California
|date=3 July 2008
|url=https://en.wiktionary.org/wiki/phenotype
|accessdate=2016-10-04 }}</ref> is called a '''phenotype'''.
 
"The three different phenotypes of α1B observed (designated 1-1, 1-2, and 2-2) were apparently identical to those reported by Altland et al. (1983), who used double one-dimensional electrophoresis. Family data supported the hypothesis that the three α1B phenotypes are determined by two codominant alleles at an autosomal locus, designated A1B. Allele frequencies in a Swedish population were: A1B *1, 0.937; A1B *2, 0.063; PIC, 0.111."<ref name=Gahne/>
 
====Protein species====
 
"Both protein species of [alpha 1-beta glycoprotein] A1B (A1Ba, p = 0.008; f.c.= +1.62, A1Bb, p = 0.003; f.c. = +1.82) [...] were apparently overexpressed in patients with PTCa [...]."<ref name=Abdullah>{{ cite journal
|author=Mardiaty Iryani Abdullah, Ching Chin Lee, Sarni Mat Junit, Khoon Leong Ng, and Onn Haji Hashim
|title=Tissue and serum samples of patients with papillary thyroid cancer with and without benign background demonstrate different altered expression of proteins
|journal=Peer J
|date=13 September 2016
|volume=4
|issue=
|pages=e2450
|url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5028788/
|arxiv=
|bibcode=
|doi=10.7717/peerj.2450
|pmid=27672505
|accessdate=15 March 2020 }}</ref>
 
A1BG is mainly produced in the liver, and is secreted to plasma to levels of approximately 0.22 mg/mL.<ref name=Ishioka/>
 
===CRISPs===
 
The human cysteine-rich secretory protein (CRISP3) "is present in exocrine secretions and in secretory granules of neutrophilic granulocytes and is believed to play a role in innate immunity."<ref name=Udby>{{ cite journal
|author=Udby L, Sørensen OE, Pass J, Johnsen AH, Behrendt N, Borregaard N, Kjeldsen L.
|title=Cysteine-rich secretory protein 3 is a ligand of alpha1B-glycoprotein in human plasma
|journal=Biochemistry
|date=12 October 2004
|volume=43
|issue=40
|pages=12877-86
|url=https://pubs.acs.org/doi/10.1021/bi048823e
|arxiv=
|bibcode=
|bibcode=
|doi=10.1021/bi048823e
|doi=10.1002/jcb.28315
|pmid=15461460
|pmid=30556161
|accessdate=2011-11-28 }}</ref> CRISP3 has a relatively high content in human plasma.<ref name=Udby/>
|accessdate=16 May 2023 }}</ref> Extensive evidence indicates that long noncoding RNAs (lncRNAs) regulate the tumorigenesis and progression of hepatocellular carcinoma (HCC).<ref name=Bai/>
 
"The A1BG-CRISP-3 complex is noncovalent with a 1:1 stoichiometry and is held together by strong electrostatic forces."<ref name=Udby/> "Similar [complex formation] between toxins from snake venom and A1BG-like plasma proteins ... inhibits the toxic effect of snake venom metalloproteinases or myotoxins and protects the animal from envenomation."<ref name=Udby/>
 
Opossums have a remarkably robust immune system, and show partial or total immunity to the venom of rattlesnakes, ''Agkistrodon piscivorus'', cottonmouths, and other ''Crotalinae'', pit vipers.<ref>{{ cite web
|url=http://www.wildliferescueleague.org/report/opossum.html
|title=The Opossum: Our Marvelous Marsupial, The Social Loner
|publisher=Wildlife Rescue League }}</ref><ref>[http://www.scielo.br/scielo.php?pid=S0104-79301999000100005&script=sci_arttext Journal Of Venomous Animals And Toxins – Anti-Lethal Factor From Opossum Serum Is A Potent Antidote For Animal, Plant And Bacterial Toxins]. Retrieved 2009-12-29.</ref>


"Crisp3 [is] mainly [expressed] in the salivary glands, pancreas, and prostate."<ref name=Haendler>{{ cite journal
The underexpression of A1BG-AS1 was found in HCC via analysis of The Cancer Genome Atlas database.<ref name=Bai/> A1BG-AS1 expression in HCC was markedly lower than that in noncancerous tissues.<ref name=Bai/>
|author=B Haendler, J Krätzschmar, F Theuring and W D Schleuning
|title=Transcripts for cysteine-rich secretory protein-1 (CRISP-1; DE/AEG) and the novel related CRISP-3 are expressed under androgen control in the mouse salivary gland.
|journal=Endocrinology
|date=July 1993
|volume=133
|issue=1
|pages=192-8
|url=http://endo.endojournals.org/content/133/1/192.full.pdf+html
|arxiv=
|bibcode=
|doi=10.1210/en.133.1.192
|pmid= 8319566
|accessdate=2012-02-20 }}</ref> "CRISP3 is highly expressed in the human cauda epididymidis and ampulla of vas deferens (Udby et al. 2005)."<ref name=Haendler/>


==ZNF497==
==ZNF497==
{{main|ZNF497}}
{{main|ZNF497}}
Gene ID: 503538 is [[A1BG-AS1]] A1BG antisense RNA 1.<ref name=HGNC503538>{{ cite web
|author=HGNC
|title=A1BG-AS1 A1BG antisense RNA 1 [ Homo sapiens (human) ]
|publisher=National Center for Biotechnology Information
|location=U.S. National Library of Medicine, 8600 Rockville Pike, Bethesda MD, 20894 USA
|date=10 December 2019
|url=https://www.ncbi.nlm.nih.gov/gene/503538
|accessdate=2019-12-18 }}</ref> A1BG-AS1 is transcribed in the negative direction from ZSCAN22.<ref name=HGNC503538/>


Gene ID: 162968 is [[ZNF497]] zinc finger protein 497.<ref name=HGNC162968>{{ cite web
Gene ID: 162968 is [[ZNF497]] zinc finger protein 497.<ref name=HGNC162968>{{ cite web

Latest revision as of 21:09, 16 May 2023

Associate Editor(s)-in-Chief: Henry A. Hoff

Alpha-1-B glycoprotein is a 54.3 kDa protein in humans that is encoded by the A1BG gene.[1] The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins.

A1BG was located on the DNA strand of chromosome 19.[2] Additionally, A1BG, in current nucleotide numbering (58,345,183-58,353,492), is located adjacent to the ZSCAN22 gene (58,326,994-58,342,332) on the positive DNA strand, as well as the ZNF837 (58,367,623 - 58,381,030, complement) and ZNF497 (58,354,357 - 58,362,751, complement) genes on the negative strand.[2]

In the current nucleotide numbering, the A1BG untranslated region (UTR) has been expanded so that with ZSCAN22 ending at 58,342,332, the nucleotides used in this study are 58,342,333 to 58,346,892 on both strands, with the current UTR for A1BG beginning at 58,345,183. On the other side of A1BG ending at 58,353,492, the nucleotides used are 58,353,493 to 58,357,937. With ZNF497 beginning at 58,354,357, this study goes into ZNF497 to 58,357,937 or 3580 nucleotides from its downstream TSS or 4445 nucleotides from the TSS of A1BG downstream from ZNF497.

For example, an abscisic acid responsive element (ABRE) with the consensus sequence of ACGTG(G/T)C (Watanabe et al. 2017) occurs in the positive strand in the negative direction from ZSCAN22 to A1BG as ACGTGGC ending at 4239 nucleotides from the end of ZSCAN22 or 58,346,571, where the A is at 58,346,565 inside the UTR of A1BG.

Introduction

"Many important disease-related pathways utilize transcription factors that specifically bind DNA (e.g., c-Myc, HIF-1, TCF1, p53) as key nodes or endpoints in complex signaling networks. In such cases the transcription factor itself is often the most attractive target. However, drugging transcription factors is challenging owing to an absence of small ligand binding sites in their DNA-binding domain and the presence of a highly charged DNA-binding surface [1]."[3]

If a specific gene appears to be involved in a disease-related or deleterious pathway being able to alter its expression so as to improve the person's health may be needed. To alter its expression constructively may require knowing what regulatory elements exist in the gene's nearby promoters.

Response elements

Identifying a bona fide response element is more difficult than a simple inspection. In order to attribute the response element to a candidate sequence, some observations have to be conducted using molecular, biological and biophysical methods and functional approaches. Findings may indicate that response element in the promoter is a functional element.[4]

A likely response element found by simple inspection may also be inactive due to methylation.

Response Elements: "Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions."[5]

"Under conditions of stress, a transcription activator protein binds to the response element and stimulates transcription. If the same response element sequence is located in the control regions of different genes, then these genes will be activated by the same stimuli, thus producing a coordinated response."[6]

WD-40 repeat family

"Receptor for activated C kinase (RACK1) is a highly conserved, eukaryotic protein of the WD-40 repeat family. [...] During Phaseolus vulgaris root development, RACK1 (PvRACK1) mRNA expression was induced by auxins, abscisic acid, cytokinin, and gibberellic acid."[7]

Abscisic acid (ABA) response elements

Auxin response factors

ARFUs
ARFBs
ARF2s
ARF5s

CAACTC regulatory elements

CAREs (Fan)
CAREs (Garaeva)

Cytokinins

ARR1s
ARR10s
ARR12s
ARRFs
ARRR1s
ARRR2s

Coupling elements

CE3Ws
CE3Ds

EREs

Gibberellic acid response elements

GAREs
GAREL1s

Hypoxia response elements

HIFs
HREs
CACAs

Pyrimidine boxes

TAT boxes

TATFs
TATYs

General Regulatory Factors

The following general regulatory factors occur in the promoters between ZSCAN22, A1BG and ZNF497 on human chromosome 19.

Abfms

Rap1s

Reb1s

Tbf1s

Basic leucine zipper (bZIP) class response elements

A-boxes

ACGTs

"A majority of the plant bZIP proteins isolated to date recognize elements with an ACGT core (Foster et al., 1994)."[8]

"Most recombinant bZIP proteins can interact with ACGT elements derived from different plant genes, albeit with different affinity. Systematic protein/DNA binding studies have shown that sequences flanking the ACGT core affect bZIP protein binding specificity. These studies have provided the basis for a concise ACGT nomenclature and defined high-affinity A-box, C-box, and G-box elements."[9]

"HY5 binds to the promoter of light-responsive genes featuring "ACGT-containing elements" such as the G-box (CACGTG), C-box (GACGTC), Z-box (ATACGGT), and A-box (TACGTA) (4, 6)."[10]

Activating transcription factors

ATFBs
ATFKs

Affinity Capture-Western; Two-hybrid transcription factors

AFTs

Box As

C-boxes

C-boxes come in several varieties:

C-boxes (Johnson)
C boxes (Samarsky)
C boxes (Voronina)
C boxes (Song)
C boxes (Song hybrids)

Hybrids: C/A-box (TGACGTAT), C/G-box (TGACGTGT), C/T-box (TGACGTTA).

CAMPs

ESRE

The endoplasmic reticulum stress response element (ESRE) has two parts: (1) CCAAT and (2) CCACG which are tested separately then compared to see if any parts have any nine nucleotides between them.

CCAAT
CCACG

According to So (2018) the endoplasmic reticulum stress response element should be CCAAT-N9-CCACG. Samplings demonstrate that the ideal CCAAT-N9-CCACG or its complement inverse do not occur on either side of A1BG or close to ZSCAN22 or ZNF497.

Hap motif

G-boxes

G-box (CACGTG)

GCN4 motif

GCREs (Gcn4)

Migs

Nuclear factors

NFATs
HNF6s

T boxes

TboxCs
TboxZs

Vboxes

Z-boxes

ZboxGs
ZboxSps

Helix-turn-helix (HTH) transcription factors

Gene ID: 4602 is MYB [myeloblastosis] MYB proto-oncogene, transcription factor on 6q23.3: "This gene encodes a protein with three HTH DNA-binding domains that functions as a transcription regulator. This protein plays an essential role in the regulation of hematopoiesis. This gene may be aberrently expressed or rearranged or undergo translocation in leukemias and lymphomas, and is considered to be an oncogene. Alternative splicing results in multiple transcript variants."[11]

CadC binding domains

Factor II B recognition elements

Forkhead boxes

Homeoboxes

Homeodomains

HSE3 (Eastmond)

HSE4 (Eastmond)

HSE8 GAP1 (Eastmond)

HSE9 GAP2 (Eastmond)

Hsf (Tang)

MREs

Tryptophan residues

Basic helix-loop-helix (bHLH) transcription factors

"The [palindromic E-box motif (CACGTG)] motif is bound by the transcription factor Pho4, [and has the] class of basic helix-loop-helix DNA binding domain and core recognition sequence (Zhou and O'Shea 2011)."[12]

"Pho4 bound to virtually all E-boxes in vitro (96%) [...]. That was not the case in vivo, where only 5% were bound by Pho4, under activating conditions as determined by ChIP-seq [Zhou and O'Shea 2011]."[12]

"Pho4 possesses the intrinsic ability to bind every E-box, but in vivo is prevented from binding by chromatin unless assisted by chromatin remodelers (Svaren et al. 1994) that are targeted at promoter regions."[12]

"On one end of that spectrum, typical transcription factors like Pho4 do not appear to compete with nucleosomes and instead predominantly sample motifs that already exist in the [nucleosome-free promoter regions] NFRs generated by other factors. In vitro (PB-exo), Pho4 bound nearly every instance of an E-box motif across the yeast genome. However, in vivo, Pho4 is a low-abundance protein that is recruited to the nucleus upon phosphate starvation by other factors, to act at a few dozen genes (Komeili and O'Shea 1999; Zhou and O'Shea 2011). Since Pho4 appears unable to compete with nucleosomes, competent sites that are occluded by nucleosomes are invisible to Pho4."[12]

The Pho4 homodimer binds to DNA sequences containing the bHLH binding site CACGTG.[13]

The upstream activating sequence (UAS) for Pho4p is CAC(A/G)T(T/G) in the promoters of HIS4 and PHO5 regarding phosphate limitation with respect to regulation of the purine and histidine biosynthesis pathways [66].[14]

bHLH proteins typically bind to a consensus sequence called an E-box, CANNTG.[15]

"A computer search for transcription promoter elements [...] showed the presence of a prominent TATA box 22 nucleotides upstream of the transcription start site and an Sp1 site at position -42 to -33. The 5'-flanking sequence also contains three E boxes with CANNTG consensus sequences at positions -464 to -459, -90 to -85, and -52 to -47 that have been marked as E box, E1 box, and E2 box, respectively [...]. In addition, the 5'-flanking region contains one or more GRE, XRE, GATA-1, GCN-4, PEA-3, AP1, and AP2 consensus motifs and also three imperfect CArG sites [...]."[16]

AhRYs

AHRE-IIs

AEREs

CAT boxes

CAT-box-like elements

"Class C"

"Class I"

TCFs

DIOXs

Enhancer boxes

ChoRE motifs
CarbE1s
CarbE2s
CarbE3s
Phors

Palindromic E-box motif (CACGTG).

E2 boxes

GATAs

Gln3s

Glucocorticoid response elements

ICRE (Lopes)

ICRE (Schwank)

Pho4

QRDREs

Carbon source-responsive elements

CATTCAs
TCCGs

XREs

Basic helix-loop-helix leucine zipper transcription factors

Basic helix-loop-helix leucine zipper transcription factors are, as their name indicates, transcription factors containing both Basic helix-loop-helix and leucine zipper motifs.

Examples include Microphthalmia-associated transcription factor and Sterol regulatory element-binding protein (SREBP).

MITF recognizes E-box (CAYRTG) and M-box (TCAYRTG or CAYRTGA) sequences in the promoter regions of target genes.[17]

Serum response element gene transcriptions: The SRE wild type (SREwt) contains the nucleotide sequence ACAGGATGTCCATATTAGGACATCTGC, of which CCATATTAGG is the CArG box, TTAGGACAT is the C/EBP box, and CATCTG is the E box.[18]

"Serum response factor (SRF) is an important transcription factor that regulates cardiac and skeletal muscle genes during development, maturation and adult aging [17,18]. SRF regulates its target genes by binding to serum response elements (SREs), which contain a consensus CC(A/T)6GG (CArG) motif."[19]

CArG boxes

MITF E-boxes

RREs

Consensus sequence: CATCTG.

M-boxes

M box (Bertolotto)
M-box (Hoek)
M-box (Ripoll)

SER elements

Basic helix-span-helix

Activating proteins

AP2as
APCo1s
APCo2s
APM3Ns
APM4Ns
Yao1s
Yao2s
Yau3s

"Pemphigus foliaceus (PF) is an autoimmune disease, endemic in Brazilian rural areas, characterized by acantholysis and accompanied by complement activation, with generalized or localized distribution of painful epidermal blisters. CD59 is an essential complement regulator, inhibiting formation of the membrane attack complex, and mediating signal transduction and activation of T lymphocytes. CD59 has different transcripts by alternative splicing, of which only two are widely expressed, suggesting the presence of regulatory sites in their noncoding regions. To date, there is no association study with polymorphisms in CD59 noncoding regions and susceptibility to autoimmune diseases. In this study, we aimed to evaluate if CD59 polymorphisms have a possible regulatory effect on gene expression and susceptibility to PF. Six noncoding polymorphisms were haplotyped in 157 patients and 215 controls by sequence-specific PCR, and CD59 mRNA levels were measured in 82 subjects, by qPCR. The rs861256-allele-G (rs861256*G) was associated with increased mRNA expression (p = .0113) and PF susceptibility in women (OR = 4.11, p = .0001), which were also more prone to develop generalized lesions (OR = 4.3, p = .009) and to resist disease remission (OR = 3.69, p = .045). Associations were also observed for rs831625*G (OR = 3.1, p = .007) and rs704697*A (OR = 3.4, p = .006) in Euro-Brazilian women, and for rs704701*C (OR = 2.33, p = .037) in Afro-Brazilians. These alleles constitute the GGCCAA haplotype, which also increases PF susceptibility (OR = 4.9, p = .045) and marks higher mRNA expression (p = .0025). [...] higher CD59 transcriptional levels may be related with PF susceptibility (especially in women), probably due to the effect of genetic polymorphism and to the CD59 role in T cell signal transduction."[20]

Stem-loops

File:Stem-loop.svg
An example of an RNA stem-loop is shown. Credit: Sakurambo.{{free media}}

As an important secondary structure of RNA, a stem-loop can direct RNA folding, protect structural stability for messenger RNA (mRNA), provide recognition sites for RNA binding proteins, and serve as a substrate for enzymatic reactions.[21]

Hairpin loops are often elements found within the 5'UTR of prokaryotes. These structures are often bound by proteins or cause the attenuation of a transcript in order to regulate translation.[22]

The mRNA stem-loop structure forming at the ribosome binding site may control an initiation of translation.[23][24]

AUREs

Adenylate–uridylate rich elements (Chen and Shyu, Class I)

Adenylate–uridylate rich elements (Chen and Shyu, Class II)

Adenylate–uridylate rich elements (Chen and Shyu, Class III)

MERs

Constitutive decay elements

Cys
2
His
2
SP / Kruppel-like factor (KLF) transcription factor family

The Cys
2
His
2
-like fold group (Cys
2
His
2
) is by far the best-characterized class of zinc fingers, and is common in mammalian transcription factors, where such domains adopt a simple ββα fold and have the amino acid sequence motif:[25]

X2-Cys-X2,4-Cys-X12-His-X3,4,5-His

Alcohol dehydrogenase repressor 1

SP1M1s

SP1M2s

SP-1 (Sato)s

SP1 (Yao)s

YY1Ts

AP-2/EREBP-related factors

AGC boxes

AP-1 transcription factor network (Pathway)

Sixty-nine genes are included in the AP-1 transcription factor network (Pathway).[26]

AGCEs

Zinc finger DNA-binding domains

AnRE1s

AnDRE2s

AnREWs

B-boxes

Box Bs

β-Scaffold factors

"Higher animals have [transcription factor] TF genes for the basic domain, the β-scaffold factor, and other new structures; however, their total proportion is less than 15% and most are [zinc (Zn)-coordinating factor] ZF and [Helix-Turn-Helix] HTH genes."[27]

ATA boxes

Γ-interferon activated sequences

HMG boxes

Zn(II)2Cys6 proteins

"The transcription factors Uga3, Dal81 and Leu3 belong to the class III family (Zn(II)2Cys6 proteins), and they recognize highly related sequences rich in GGC triplets [15]."[28]

Dal81

GCC boxes

GGC triplets

GGCGGC triplets

Leu3

Uga3

Hairpin-hinge-hairpin-tail

"In addition to this ACA box, they have the consensus H box sequence (5'-ANANNA-3') but have no other primary sequence identity. Despite this lack of primary sequence conservation, the H and ACA boxes are embedded in an evolutionarily conserved hairpin-hinge-hairpin-tail core secondary structure with the H box in the single-stranded hinge region and the ACA box in the single-stranded tail (5, 16)."[29]

H and ACA boxes

H-boxes (Grandbastien)

H-boxes (Lindsay)

H boxes (Mitchell)

H boxes (Rozhdestvensky)

Unknown response element types

ACEs

BBCABW Inrs

Calcineurin-responsive transcription factors

Carbs

Carb1s

Cat8s

Cell-cycle box variants

CGCG boxes

Circadian control elements

Cold-responsive elements

Copper response elements

CuREQs
CuREPs

Cytoplasmic polyadenylation elements

DAF-16 binding elements

D box (Samarsky)

D box (Voronina)

D-box (Motojima)

dBRE

Downstream core elements

DCE SI

DCE SII

DCE SIII

DPE (Juven-Gershon)

DPE (Kadonaga)

DPE (Matsumoto)

EIN3 binding sites

Endosperm expressions

Estrogen response elements

ERE1s
ERE2s

GAAC elements

GC boxes (Briggs)

GC boxes (Ye)

GC boxes (Zhang)

GCR1s

GREs

GT boxes (Sato)

Hex sequences

HY boxes

IFNs

Inr-like, TCTs

IRF3s

IRSs

KAR2s

MBE1s

MBE2s

MBE3s

NF𝜿BSs

PREs

Pribs

RAREs

Rgts

ROREs

SERVs

STAT5s

STREs

Sucroses

TACTs

TAGteams

TAPs

TATAs

Examining the promoter regions upstream from ZSCAN22 to A1BG and downstream from ZNF497 to A1BG for TATA boxes has shown that TATA boxes in various forms are present and likely active or activable: (1) TATAAAA (Carninci 2006), (2) TATA(A/T)A(A/T) (Watson 2014), (3) TATA(A/T)AA(A/G) (Juven-Gershon 2010), and (4) TATA(A/T)A(A/T)(A/G) (Basehoar 2004).

The TATA boxes have the pattern of appearing in only the negative direction UTRs, proximal and distals. The shorter TATA box: TATAAA does appear as above but also in the positive direction as the complement inverse TTTATA at 2588 in the distal promoter.

TATABs

TATACs

TATAJs

TATAWs

TEAs

TECs

THRs

TRFs

UPREs

UPRE-1s

URS (Sumrada, core)

VDREs

XCPE1s

Yaps

YYRNWYY Inrs

A1BG orthologs

Geotrypetes seraphini

File:Geotrypetes seraphini 81151944.jpg
Geotrypetes seraphini, the Gaboon caecilian, is a species of amphibian. Credit: Marius Burger.{{free media}}

Geotrypetes seraphini, the Gaboon caecilian, is a species of amphibian in the family Dermophiidae.[30]

Its A1BG ortholog has 368 aa vs 495 aa for Homo sapiens.

ZSCAN22

  1. Gene ID: 342945 is ZSCAN22 zinc finger and SCAN domain containing 22 on 19q13.43.[31] ZSCAN22 is transcribed in the negative direction from LOC100887072.[31]
  2. Gene ID: 102465484 is MIR6806 microRNA 6806 on 19q13.43: "microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop."[32] MIR6806 is transcribed in the negative direction from LOC105372480.[32]

Of the some 111 gaps between genes on chromosome locus 19q13.43 as of 4 August 2020, gap number 88 is between ZSCAN22 and A1BG. But, there is no gap between ZNF497 and A1BG.

Promoters

The core promoter begins approximately -35 nts upstream from the transcription start site (TSS). For the numbered nucleotides between ZSCAN22 and A1BG the core promoter extends from 4425 nts up to 4460 nts (TSS). The proximal promoter extends from approximately -250 to the TSS or 4210 nts up to 4460 nts. The distal promoter begins at about 2460 nts and extends to about 4210 nts.

From the ZNF497 side the core promoter begins about 4265 nts up to 4300 nts, the proximal promoter from 4050 nts to 4265 nts, and the distal promoter from 2300 nts to 4050 nts.

Alpha-1-B glycoprotein

Def. "a substance that induces an immune response, usually foreign"[33] is called an antigen.

Def. any "substance that elicits [an] immune response"[34] is called an immunogen.

An antigen "or immunogen is a molecule that sometimes stimulates an immune system response."[35] But, "the immune system does not consist of only antibodies",[35] instead it "encompasses all substances that can be recognized by the adaptive immune system."[35]

Def. "a protein produced by B-lymphocytes that binds to [a specific antigen or][36] an antigen"[37] is called an antibody.

Five different antibody isotypes are known in mammals, which perform different roles, and help direct the appropriate immune response for each different type of foreign object they encounter.[38]

Although the general structure of all antibodies is very similar, a small region, known as the hypervariable region, at the tip of the protein is extremely variable, allowing millions of antibodies with slightly different tip structures to exist, where each of these variants can bind to a different target, known as an antigen.[39]

Def. "any of the glycoproteins in blood serum that respond to invasion by foreign antigens and that protect the host by removing pathogens;"[40] "an antibody"[41] is called an immunoglobulin.

Gene ID: 1 is A1BG alpha-1-B glycoprotein on 19q13.43, a 54.3 kDa protein in humans that is encoded by the A1BG gene.[42] A1BG is transcribed in the positive direction from ZNF497.[42] "The protein encoded by this gene is a plasma glycoprotein of unknown function. The protein shows sequence similarity to the variable regions of some immunoglobulin supergene family member proteins."[42]

  1. NP_570602.2 alpha-1B-glycoprotein precursor, cd05751 Location: 401 → 493 Ig1_LILRB1_like; First immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILR)B1 (also known as LIR-1) and similar proteins, smart00410 Location: 218 → 280 IG_like; Immunoglobulin like, pfam13895 Location: 210 → 301 Ig_2; Immunoglobulin domain and cl11960 Location: 28 → 110 Ig; Immunoglobulin domain.[42]

Patients who have pancreatic ductal adenocarcinoma show an overexpression of A1BG in pancreatic juice.[43]

Immunoglobulin supergene family

"𝛂1B-glycoprotein(𝛂1B) [...] consists of a single polypeptide chain N-linked to four glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂1B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂1B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂1B [...] exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."[44]

"Some of the domains of 𝛂1B show significant homology to variable (V) and constant (C) regions of certain immunoglobulins. Likewise, there is statistically significant homology between 𝛂1B and the secretory component (SC) of human IgA (15) and also with the extracellular portion of the rabbit receptor for transepithelial transport of polymeric immunoglobulins (IgA and IgM). Mostov et al. (16) have called the later protein the poly-Ig receptor or poly-IgR and have shown that it is the precursor of SC."[44]

The immunoglobulin supergene family is "the group of proteins that have immunoglobulin-like domains, including histocompatibility antigens, the T-cell antigen receptor, poly-IgR, and other proteins involved in the vertebrate immune response (17)."[44]

"The internal homology in primary structure [...] and the presence of an intrasegment disulfide bond suggest that 𝛂1B is composed of five structural domains that arose by duplication of a primordial gene coding for about 95 amino acid residues."[44]

"Unlike immunoglobulins (25), ceruloplasmin (6), and hemopexin (7), 𝛂1B is not subject to limited interdomain cleavage by proteolytic enzymes. At least, we were not able to produce such fragments by use of a variety of proteases. This stability of 𝛂1B is probably associated with the frequency of proline in the sequences linking the domains [...]."[44]

"A peptide identified in the late and early milk proteomes showed homology to eutherian alpha 1B glycoprotein (A1BG), a plasma protein with unknown function46, as well as venom inhibitors characterised in the Southern opossum Didelphis marsupialis (DM43 and DM4647,48,49), all members of the immunoglobulin superfamily. To characterise the relationship between the peptide sequence identified in koala, A1BG, DM43 and DM46, a phylogenetic tree was constructed [...] including all marsupial and monotreme homologs (identified by BLAST), three phylogenetically representative eutherian sequences, with human IGSF1 and TARM1, related members of the immunoglobulin super family, used as outgroups. This phylogeny indicates that A1BG-like proteins in marsupials and the Didelphis antitoxic proteins are homologs of eutherian A1BG, with excellent bootstrap support (98%). The marsupial A1BG-like sequences and the Didelphis antitoxic proteins formed a single clade with strong bootstrap support (97%)."[45]

"Human TARM1 and IGSF1, related members of the immunoglobulin superfamily are used as outgroups. The tree was constructed using the maximum likelihood approach and the JTT model with bootstrap support values from 500 bootstrap tests. Bootstrap values less than 50% are not displayed. Accession numbers: Tasmanian devil (Sarcophilus harrisii; XP_012402143), Wallaby (Macropus eugenii; FY619507), Possum (Trichosurus vulpecula; DY596639) Virginia opossum (Didelphis virginiana; AAA30970, AAN06914), Southern opossum (Didelphis marsupialis; AAL82794, P82957, AAN64698), Human (Homo sapiens; P04217, B6A8C7, Q8N6C5), Platypus (Ornithorhychus anatinus; ENSOANP00000000762), Cow (Bos taurus; Q2KJF1), Alpaca (Vicugna pacos; XP_015107031)."[45]

"The sequences of 𝛂1B-glycoprotein (38) and chicken N-CAM (neural cell-adhesion molecule) (39) have been shown to be related to the immunoglobulin supergene family."[46]

A1BG contains the immunoglobulin domain: cl11960 and three immunoglobulin-like domains: pfam13895, cd05751 and smart00410.

"Immunoglobulin (Ig) domain [cl11960] found in the Ig superfamily. The Ig superfamily is a heterogenous group of proteins, built on a common fold comprised of a sandwich of two beta sheets. Members of this group are components of immunoglobulin, neuroglia, cell surface glycoproteins, such as, T-cell receptors, CD2, CD4, CD8, and membrane glycoproteins, such as, butyrophilin and chondroitin sulfate proteoglycan core protein. A predominant feature of most Ig domains is a disulfide bridge connecting the two beta-sheets with a tryptophan residue packed against the disulfide bond."[47]

"This domain [pfam13895] contains immunoglobulin-like domains."[48]

"Ig1_LILR_KIR_like: [cd05751] domain similar to the first immunoglobulin (Ig)-like domain found in Leukocyte Ig-like receptors (LILRs) and Natural killer inhibitory receptors (KIRs). This group includes LILRB1 (or LIR-1), LILRA5 (or LIR9), an activating natural cytotoxicity receptor NKp46, the immune-type receptor glycoprotein VI (GPVI), and the IgA-specific receptor Fc-alphaRI (or CD89). LILRs are a family of immunoreceptors expressed on expressed on T and B cells, on monocytes, dendritic cells, and subgroups of natural killer (NK) cells. The human LILR family contains nine proteins (LILRA1-3,and 5, and LILRB1-5). From functional assays, and as the cytoplasmic domains of various LILRs, for example LILRB1 (LIR-1), LILRB2 (LIR-2), and LILRB3 (LIR-3) contain immunoreceptor tyrosine-based inhibitory motifs (ITIMs) it is thought that LIR proteins are inhibitory receptors. Of the eight LIR family proteins, only LIR-1 (LILRB1), and LIR-2 (LILRB2), show detectable binding to class I MHC molecules; ligands for the other members have yet to be determined. The extracellular portions of the different LIR proteins contain different numbers of Ig-like domains for example, four in the case of LILRB1 (LIR-1), and LILRB2 (LIR-2), and two in the case of LILRB4 (LIR-5). The activating natural cytotoxicity receptor NKp46 is expressed in natural killer cells, and is organized as an extracellular portion having two Ig-like extracellular domains, a transmembrane domain, and a small cytoplasmic portion. GPVI, which also contains two Ig-like domains, participates in the processes of collagen-mediated platelet activation and arterial thrombus formation. Fc-alphaRI is expressed on monocytes, eosinophils, neutrophils and macrophages; it mediates IgA-induced immune effector responses such as phagocytosis, antibody-dependent cell-mediated cytotoxicity and respiratory burst."[49]

"IG domains [smart00410] that cannot be classified into one of IGv1, IGc1, IGc2, IG."[50] "𝛂1B-glycoprotein(𝛂1B) [...] consists of a single polypeptide chain N-linked to four glucosamine oligosaccharides. The polypeptide has five intrachain disulfide bonds and contains 474 amino acid residues. [...] 𝛂1B exhibits internal duplication and consists of five repeating structural domains, each containing about 95 amino acids and one disulfide bond. [...] several domains of 𝛂1B, especially the third, show statistically significant homology to variable regions of certain immunoglobulin light and heavy chains. 𝛂1B [...] exhibits sequence similarity to other members of the immunoglobulin supergene family such as the receptor for transepithelial transport of IgA and IgM and the secretory component of human IgA."[44]

A1BG protein species

Def. a "group of plants or animals having similar appearance"[51] or "the largest group of organisms in which [any][52] two individuals [of the appropriate sexes or mating types][52] can produce fertile offspring, typically by sexual reproduction"[53] is called a species.

The gene contains 20 distinct introns.[54] Transcription produces 15 different mRNAs, 10 alternatively spliced variants and 5 unspliced forms.[54] There are 4 probable alternative promoters, 4 non overlapping alternative last exons and 7 validated alternative polyadenylation sites.[54] The mRNAs appear to differ by truncation of the 5' end, truncation of the 3' end, presence or absence of 4 cassette exons, overlapping exons with different boundaries, splicing versus retention of 3 introns.[54]

Variants or isoforms

Def. a "different sequence of a gene (locus)"[55] is called a variant.

Def. any "of several different forms of the same protein, arising from either single nucleotide polymorphisms,[56] differential splicing of mRNA, or post-translational modifications (e.g. sulfation, glycosylation, etc.)"[57] is called an isoform.

Regarding additional isoforms, mention has been made of "new genetic variants of A1BG."[58]

"Proteomic analysis revealed that [a circulating] set of plasma proteins was α 1 B-glycoprotein (A1BG) and its post-translationally modified isoforms."[59]

Pharmacogenomic variants have been reported.[60]

Genotypes

Def. the "part (DNA sequence) of the genetic makeup of an organism which determines a specific characteristic (phenotype) of that organism"[61] or a "group of organisms having the same genetic constitution" [62]is called a genotype.

There are A1BG genotypes.[60]

A1BG has a genetic risk score of rs893184.[60]

"A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39×10−5)."[60]

Polymorphs

Def. the "regular existence of two or more different genotypes within a given species or population; also, variability of amino acid sequences within a gene's protein"[63] is called polymorphism.

Def. "one of a number of alternative forms of the same gene occupying a given position, [or locus],[64] on a chromosome"[65] is called an allele.

"rs893184 causes a histidine (His) to arginine (Arg) [nonsynonymous single nucleotide polymorphism (nsSNP), A (minor) for G (major)] substitution at amino acid position 52 in A1BG."[60]

"Genetic polymorphism of human plasma (serum) alpha 1B-glycoprotein (alpha 1B) was observed using one-dimensional horizontal polyacrylamide gel electrophoresis (PAGE) pH 9.0 of plasma samples followed by Western blotting with specific antiserum to alpha 1B."[66]

A1B*5 is a "new allele [...] of human plasma 𝜶1B-glycoprotein [...]."[67]

"Genetic polymorphism of human plasma 𝜶1B-glycoprotein (𝜶1B) was reported first, in brief, by Altland et al. [1983; also given in Altkand and Hacklar, 1984]. A detailed description of human 𝜶1B polymorphism was reported in subsequent studies [Gahne et al., 1987; Juneja et al., 1988, 1989]. Five different 𝜶1B alleles (A1B*1, A1B*2, A1B*3, A1B*4 and A1B*5) were reported. In Caucasian whites, the frequencies of A1B*1 and ''A1B*2 were about 0.95 and 0.05, respectively. A1B*4 was observed in 2 related Czech individuals. In American blacks, A1B*1 and A1B*2 occurred with a frequency of 0.73 and 0.21, respectively, while a new allele, viz, A1B*3 had a frequency of 0.06. A1B*5 was observed only in Swedish Lapps and in Finns with a frequency of 0.04 and 0.007, respectively."[68]

"The frequency of A1B*1 varied from 0.89 to 0.91 and that of A1B*2 from 0.08 to 0.10. The A1B*3 allele, reported previously only in American blacks, was observed with a frequency range of 0.003-0.01 in 3 of the Chinese populations, in Koreans and in Malays. A new 𝜶1B allele (A1B*6) was observed in 2 Chinese individuals."[68]

Phenotypes

Def. the "appearance of an organism based on a single trait [multifactorial combination of genetic traits and environmental factors][69], especially used in pedigrees"[70] or any "observable characteristic of an organism, such as its morphological, developmental, biochemical or physiological properties, or its behavior"[71] is called a phenotype.

"The three different phenotypes of α1B observed (designated 1-1, 1-2, and 2-2) were apparently identical to those reported by Altland et al. (1983), who used double one-dimensional electrophoresis. Family data supported the hypothesis that the three α1B phenotypes are determined by two codominant alleles at an autosomal locus, designated A1B. Allele frequencies in a Swedish population were: A1B *1, 0.937; A1B *2, 0.063; PIC, 0.111."[66]

Protein species

"Both protein species of [alpha 1-beta glycoprotein] A1B (A1Ba, p = 0.008; f.c.= +1.62, A1Bb, p = 0.003; f.c. = +1.82) [...] were apparently overexpressed in patients with PTCa [...]."[72]

A1BG is mainly produced in the liver, and is secreted to plasma to levels of approximately 0.22 mg/mL.[44]

CRISPs

The human cysteine-rich secretory protein (CRISP3) "is present in exocrine secretions and in secretory granules of neutrophilic granulocytes and is believed to play a role in innate immunity."[73] CRISP3 has a relatively high content in human plasma.[73]

"The A1BG-CRISP-3 complex is noncovalent with a 1:1 stoichiometry and is held together by strong electrostatic forces."[73] "Similar [complex formation] between toxins from snake venom and A1BG-like plasma proteins ... inhibits the toxic effect of snake venom metalloproteinases or myotoxins and protects the animal from envenomation."[73]

Opossums have a remarkably robust immune system, and show partial or total immunity to the venom of rattlesnakes, Agkistrodon piscivorus, cottonmouths, and other Crotalinae, pit vipers.[74][75]

"Crisp3 [is] mainly [expressed] in the salivary glands, pancreas, and prostate."[76] "CRISP3 is highly expressed in the human cauda epididymidis and ampulla of vas deferens (Udby et al. 2005)."[76]

A1BG-AS1

Gene ID: 503538 is A1BG-AS1 A1BG antisense RNA 1.[77] A1BG-AS1 is transcribed in the negative direction from ZSCAN22.[77]

Gene ID 503538 extends from 58,351,390 to 58,355,183. It is a long, non-coding (lnc) RNA.[78] Extensive evidence indicates that long noncoding RNAs (lncRNAs) regulate the tumorigenesis and progression of hepatocellular carcinoma (HCC).[78]

The underexpression of A1BG-AS1 was found in HCC via analysis of The Cancer Genome Atlas database.[78] A1BG-AS1 expression in HCC was markedly lower than that in noncancerous tissues.[78]

ZNF497

Gene ID: 162968 is ZNF497 zinc finger protein 497.[79] ZNF497 is transcribed in the positive direction from RNA5SP473.[79]

  1. NP_001193938.1 zinc finger protein 497: "Transcript Variant: This variant (2) lacks an alternate exon in the 5' UTR, compared to variant 1. Variants 1 and 2 encode the same protein."[79]
  2. NP_940860.2 zinc finger protein 497: "Transcript Variant: This variant (1) is the longer transcript. Variants 1 and 2 encode the same protein."[79]

Gene ID: 100419840 is LOC100419840 zinc finger protein 446 pseudogene.[80] LOC100419840 may be transcribed in the positive direction from LOC105372483.[80]

Gene ID: 105372483 is LOC105372483 uncharacterized LOC105372483 ncRNA.[81] LOC105372483 is transcribed in the negative direction from LOC100419840.[81]

Gene ID: 106479017 is RNA5SP473 RNA, 5S ribosomal pseudogene 473.[82] RNA5SP473 may be transcribed in the negative direction from ZNF497.[82]

GC contents

Approximately "76% of human core promoters lack TATA-like elements, have a high GC content, and are enriched in Sp1 binding sites."[83]

CpG islands typically occur at or near the transcription start site of genes, particularly housekeeping genes, in vertebrates.[84]

The number of CG or GC pairs near the TSS for A1BG appears to be low: between ZSCAN22 and A1BG are 8.2 % CG/GC and between ZNF497 and A1BG are 15 % CG/GC.

19q13.43

Regulatory elements and regions

Functions of A1BG

"Receptors of the leukocyte receptor cluster (LRC) play a range of important functions in the human immune system."[85]

"The leukocyte receptor cluster (LRC) is a family of structurally related genes for immunoregulatory receptors. Originally, the term LRC was introduced to emphasize the linkage of the genes encoding killer immunoglobulin-like receptors (KIRs), leukocyte Ig-like receptors (LILRs), and FcαR on human chromosome 19q13.4 (Wagtmann et al. 1997; Wende et al. 1999). Subsequently, it has been found that the region contains some other structurally related genes, such as NCR1, GPVI, LAIR1, LAIR2, and OSCAR (Meyaard et al. 1997; Sivori et al. 1997; Clemetson et al. 1999; Kim et al. 2002). Most recently, the LRC has been further extended by adding two more genes named VSTM1/SIRL1 and TARM1 (Steevels et al. 2010; Radjabova et al. 2015)."[85]

"Except for LAIR2, which is a secreted protein, all human LRC products are type I cell surface receptors with extracellular regions composed of 1–4 C2-type Ig-like domains."[85]

The "eutherian LRC family, in addition to commonly recognized members, includes two new, IGSF1 and alpha-1-B glycoprotein (A1BG)."[85]

"Nucleotide sequences were retrieved and analyzed using utilities at the NCBI (https://www.ncbi.nlm.nih.gov/, last accessed May 20, 2019) and Ensemble (http://www.ensembl.org, last accessed May 20, 2019) websites."[85]

"In our previous studies, it was observed that the Ig-like domains of the frog and chicken LRC proteins reproducibly showed homology not only to known LRC members but also to the products of four mammalian genes that to our knowledge have never been considered in the phylogenetic analyses of LRC. These genes are VSTM1, TARM1, A1BG, and IGSF1. VSTM1 and TARM1 are the most recently identified members of the human LRC (Steevels et al. 2010; Radjabova et al. 2015). A1BG encodes alpha-1 B glycoprotein, a soluble component of mammalian blood plasma that is known for half a century (Schultze et al. 1963). The protein is composed of five Ig-like domains and has been shown to bind to CRISP-3, a small polypeptide that is present in exocrine secretions of neutrophilic granulocytes and that is believed to play a role in innate immunity (Udby et al. 2004). In the human genome, A1BG maps to 19q13.4 some 3.3 Mb away from GPVI [...]."[85]

"The attribution of IGSF1 and A1BG domains to the LRC was supported by their 3D structures predicted using homology modeling [...]."[85]

"Noteworthy is that the D1 and D6 domains of IgSF1 fall into one clade with the N-terminal (d1) domains of A1BG and OSCAR (cluster B1). Closer relationship of A1BG and OSCAR was supported by clustering of the d2–d5 domains of A1BG with membrane-proximal (d2) domain of OSCAR (cluster B2)."[85]

"Altogether, these results support the attribution of IGSF1 and A1BG to the LRC and suggest their relatedness to OSCAR, TARM1, and VSTM1."[85]

"Clustering of the N-terminal domains of OSCAR, IGSF1, and A1BG with each other and with IGSF1 d6 was also reproduced. Finally, the d2 domains of OSCAR cluster with the d2–d5 domains of A1BG (fig. 5). These results further justify grouping IGSF1, A1BG, OSCAR, TARM1, and VSTM1 into a distinct group B."[85]

Hypotheses

  1. Downstream core promoters may work as transcription factors even as their complements or inverses.
  2. In addition to the DNA binding sequences listed above, the transcription factors that can open up and attach through the local epigenome need to be known and specified.
  3. Each DNA binding domain serving as a transcription factor for the promoter of any immunoglobulin supergene family member, also serves or is present in the promoters for A1BG.
  4. The function of A1BG is the same as other immunoglobulin genes possessing the immunoglobulin domain cl11960 and/or any of three immunoglobulin-like domains: pfam13895, cd05751 and smart00410 in the order and nucleotide sequence: cd05751 Location: 401 → 493, smart00410 Location: 218 → 280, pfam13895 Location: 210 → 301 and cl11960 Location: 28 → 110.

See also

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External links

{{Phosphate biochemistry}}