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{{ | {{Use British English|date=February 2018}}{{Infobox_gene}} | ||
{{Infobox_gene}} | '''Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2''' is a [[protein]] that in [[humans]] is encoded by the ''SERPINA2'' [[gene]]. Serine peptidase inhibitor, clade A member 2 belongs to the member of [[serine]] family of proteins which have a functional activity of inhibiting [[Serine protease|serine proteases]].<ref name="entrez">{{cite web | title = Entrez Gene: Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2| url = https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=390502| accessdate = 2017-09-21 <!-- T20:25:01.030-08:00 --> }}</ref> | ||
'''Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2''' is a [[protein]] that in humans is encoded by the SERPINA2 [[gene]]. Serine peptidase inhibitor, clade A member 2 belongs to the member of serine family of proteins which have a functional activity of inhibiting serine proteases.<ref name="entrez">{{cite web | title = Entrez Gene: Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2| url = | |||
== Discovery == | == Discovery == | ||
SERPINA2 was known as pseudogenes as it had a very similar structure and function to SERPINA1. During the cloning characterisation of alpha 1- antitrypsin like gene it was discovered that SERPINA2 did not have any promoter but did contain substantial homology to SERPINA1 gene sequence.<ref name="pmid=2901833">{{cite journal | vauthors = Hofker MH, Nelen M, Klasen EC, Nukiwa T, Curiel D, Crystal RG, Frants RR | title = Cloning and characterization of an alpha 1-antitrypsin like gene 12 KB downstream of the genuine alpha 1-antitrypsin gene | journal = Biochemical and Biophysical Research Communications | volume = 155 | issue = 2 | pages = 634–42 | date = September 1988 | pmid = 2901833 | doi = 10.1016/S0006-291X(88)80542-4 }}</ref> | SERPINA2 was known as [[pseudogenes]] as it had a very similar structure and function to [[SERPINA1]]. During the cloning characterisation of alpha 1- [[antitrypsin]] like gene, it was discovered that ''SERPINA2'' did not have any [[Promoter (genetics)|promoter]] but did contain substantial [[Homology (biology)|homology]] to ''SERPINA1'' [[gene sequence]].<ref name="pmid=2901833">{{cite journal | vauthors = Hofker MH, Nelen M, Klasen EC, Nukiwa T, Curiel D, Crystal RG, Frants RR | title = Cloning and characterization of an alpha 1-antitrypsin like gene 12 KB downstream of the genuine alpha 1-antitrypsin gene | journal = Biochemical and Biophysical Research Communications | volume = 155 | issue = 2 | pages = 634–42 | date = September 1988 | pmid = 2901833 | doi = 10.1016/S0006-291X(88)80542-4 }}</ref> | ||
== Gene location == | == Gene location == | ||
SERPINA2 | ''SERPINA2'' is located at 14q32.13.<ref name="pmid=24172014">{{cite journal | vauthors = Heit C, Jackson BC, McAndrews M, Wright MW, Thompson DC, Silverman GA, Nebert DW, Vasiliou V | title = Update of the human and mouse SERPIN gene superfamily | journal = Human Genomics | volume = 7 | issue = 1 | pages = 22 | date = October 2013 | pmid = 24172014 | pmc = 3880077 | doi = 10.1186/1479-7364-7-22 }}</ref> | ||
== Gene expression and localisation == | == Gene expression and localisation == | ||
Extracellular predictions of SERPINs and common domain clades show that ER localisation of SERPINA2 are most likely be more, these common ER motifs indicates their localisation are most likely to be in the ER.<ref name="pmid= 23826168">{{cite journal | vauthors = Marques PI, Ferreira Z, Martins M, Figueiredo J, Silva DI, Castro P, Morales-Hojas R, Simões-Correia J, Seixas S | title = SERPINA2 is a novel gene with a divergent function from SERPINA1 | journal = | Extracellular predictions of SERPINs and common domain clades show that ER localisation of SERPINA2 are most likely be more, these common ER motifs indicates their localisation are most likely to be in the ER.<ref name="pmid= 23826168">{{cite journal | vauthors = Marques PI, Ferreira Z, Martins M, Figueiredo J, Silva DI, Castro P, Morales-Hojas R, Simões-Correia J, Seixas S | title = SERPINA2 is a novel gene with a divergent function from SERPINA1 | journal = PLOS ONE | volume = 8 | issue = 6 | pages = e66889 | date = June 2013 | pmid = 23826168 | doi = 10.1371/journal.pone.0066889 | pmc=3691238}}</ref> | ||
== Structure == | == Structure == | ||
Population studies indicate that this gene is polymorphic. Deletions, frameshift mutations and a critical start codon mutation (ATG | Population studies indicate that this gene is [[Gene polymorphism|polymorphic]]. [[Deletion (genetics)|Deletions]], [[frameshift mutations]], and a critical [[start codon]] mutation (ATG to ATA) have been found in some populations, as well as an [[allele]] that can encode a functional protein. This gene may be an evolving pseudogene.<ref name="pmid=17135331" /> The reference genome contains the start codon mutation and has a [[coding region]] deletion. A three-dimensional model of SERPINA2 was created using the non-deleted form of crystal structure, which is homologous with the SERPINA1 protein. The model was created using swissmodel in [[ExPASy|EXPASY]], and has shown that SERPINA2 preserves a [[Serpin|SERPIN]] reactive centre loop which is most compatible with protease inhibitory activity. The consensus sequence surrounding the reactive centre loop have diverged considerably so that now it contains [[tryptophan]] sarin motifs instead of the [[methionine]] serine motif.<ref name="pmid=23826168"/> | ||
== Function == | == Function == | ||
SERPINA2 was previously identified as pseudogene however, recently there have been new evidence which specifies that SERPINA2 produces an active transcript that is responsible for encoding protein located in the endoplasmic reticulum. A detailed study of the SERPINA2 gene across multiple ethnic groups have relieved that with the addition of SERPINA2 gene therein a haplotype characterisation by partial deletion which has patterns suggesting positive selection of loss of function of SERPINA2 protein.<ref name="pmid=24172014" /> | ''SERPINA2'' was previously identified as pseudogene; however, recently there have been new evidence which specifies that ''SERPINA2'' produces an active transcript that is responsible for encoding protein located in the [[endoplasmic reticulum]]. A detailed study of the ''SERPINA2'' gene across multiple ethnic groups have relieved that with the addition of ''SERPINA2'' gene therein a [[haplotype]] characterisation by partial deletion which has patterns suggesting positive selection of loss of function of SERPINA2 protein.<ref name="pmid=24172014" /> | ||
SERPINA2 studies have shown different results regarding the extent of sequence degeneration it can undergo.<ref name="pmid=17135331">{{cite journal | vauthors = Seixas S, Suriano G, Carvalho F, Seruca R, Rocha J, Di Rienzo A | title = Sequence diversity at the proximal 14q32.1 SERPIN subcluster: evidence for natural selection favoring the pseudogenization of SERPINA2 | journal = Molecular Biology and Evolution | volume = 24 | issue = 2 | pages = 587–98 | date = February 2007 | pmid = 17135331 | doi = 10.1093/molbev/msl187 }}</ref> Bao et al. (1988) describes in his studies that sequence with RNA splice sites are preserved in SERPINA2 and when expressed it encodes a new secretory protein (SERPIN) with different substrate specificity. These studies with SERPINA2 in humans have concluded that recent positive selection is favoured by the loss of SERPINA2 function and pseudogenization.<ref name="pmid=2842251">{{cite journal | vauthors = Bao JJ, Reed-Fourquet L, Sifers RN, Kidd VJ, Woo SL | title = Molecular structure and sequence homology of a gene related to alpha 1-antitrypsin in the human genome | journal = Genomics | volume = 2 | issue = 2 | pages = 165–73 | date = February 1988 | pmid = 2842251 | doi = 10.1016/0888-7543(88)90099-7 }}</ref> | SERPINA2 studies have shown different results regarding the extent of sequence degeneration it can undergo.<ref name="pmid=17135331">{{cite journal | vauthors = Seixas S, Suriano G, Carvalho F, Seruca R, Rocha J, Di Rienzo A | title = Sequence diversity at the proximal 14q32.1 SERPIN subcluster: evidence for natural selection favoring the pseudogenization of SERPINA2 | journal = Molecular Biology and Evolution | volume = 24 | issue = 2 | pages = 587–98 | date = February 2007 | pmid = 17135331 | doi = 10.1093/molbev/msl187 }}</ref> Bao et al. (1988) describes in his studies that sequence with [[Rna splice sites|RNA splice sites]] are preserved in SERPINA2, and when expressed, it encodes a new secretory protein (SERPIN) with different substrate specificity. These studies with SERPINA2 in humans have concluded that recent positive selection is favoured by the loss of SERPINA2 function and pseudogenization.<ref name="pmid=2842251">{{cite journal | vauthors = Bao JJ, Reed-Fourquet L, Sifers RN, Kidd VJ, Woo SL | title = Molecular structure and sequence homology of a gene related to alpha 1-antitrypsin in the human genome | journal = Genomics | volume = 2 | issue = 2 | pages = 165–73 | date = February 1988 | pmid = 2842251 | doi = 10.1016/0888-7543(88)90099-7 }}</ref> ''SERPINA2'' genes are mostly expressed in [[leukocytes]] and [[testes]] which gives a [[residual expression]] in [[liver]]. SERPINA2 have been linked with on going adaptive process linked with advantages in the role of fertility and host [[Pathogenic bacteria|pathogen]] interactions.<ref name="pmid=23826168">{{cite journal | vauthors = Marques PI, Ferreira Z, Martins M, Figueiredo J, Silva DI, Castro P, Morales-Hojas R, Simões-Correia J, Seixas S | title = SERPINA2 is a novel gene with a divergent function from SERPINA1 | journal = PLOS ONE | volume = 8 | issue = 6 | pages = e66889 | date = June 2013 | pmid = 23826168 | doi = 10.1371/journal.pone.0066889 | pmc=3691238}}</ref> | ||
SERPINA2 | |||
== Mutations == | == Mutations == | ||
A critical mutation present in the start codon and an 2kb deletion over exon IV and part of exon V. This deletion in the start codon occurs at a frequency of 30%.<ref name="pmid=2901833"/> | A critical mutation present in the start codon and an 2kb deletion over [[exon]] IV and part of exon V. This deletion in the start codon occurs at a frequency of 30%.<ref name="pmid=2901833"/> Studies with ''SERPINA2'' ''in vitro'' and ''in vivo'' have shown that it expresses stable proteins with n-linked [[glycosylation]] with a molecular weight of 52kDa and compatible with regular SERPINs <ref name="pmid=23826168"/> | ||
Studies with SERPINA2 in vitro and in vivo have shown that it expresses stable proteins with n-linked glycosylation with a molecular weight of 52kDa and compatible with regular SERPINs <ref name="pmid=23826168"/> | |||
== Disease associated == | == Disease associated == | ||
SERPINA2 is a member of SERPIN family which are known as protein coding genes | SERPINA2 is a member of SERPIN family, which are known as protein coding genes. A disease associated with this gene is [[emphysema]], due to aat protein deficiency. SERPINA2 has similar function to SERPINA1 and is related to the function of serine type peptidase inhibitor activity.<ref name="SERPINA2 Gene - GeneCards | A1ATR Protein | A1ATR Antibody">{{cite web | url = https://www.genecards.org/cgi-bin/carddisp.pl?gene=SERPINA2 | title = SERPINA2 | work = GeneCards }}</ref> | ||
== References == | == References == | ||
| Line 33: | Line 30: | ||
== Further reading == | == Further reading == | ||
{{refbegin|33em}} | {{refbegin|33em}} | ||
* {{cite journal | | *{{cite journal|last1=Merkel|first1=PA|last2=Xie|first2=G|last3=Monach|first3=PA|last4=Ji|first4=X|last5=Ciavatta|first5=DJ|title=Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis|journal=Arthritis & Rheumatology|date=May 2017|volume=69|issue=5|page=1054-66|doi=10.1002/art.40034|pmid=28029757|pmc=5434905}} | ||
* {{cite journal | vauthors = Namciu SJ, Friedman RD, Marsden MD, Sarausad LM, Jasoni CL, Fournier RE | title = Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1 | journal = Mammalian Genome | volume = 15 | issue = 3 | pages = 162–78 | date = March 2004 | pmid = 15014966 | doi = 10.1007/s00335-003-2311-y }} | * {{cite journal|last=|first=|vauthors=Namciu SJ, Friedman RD, Marsden MD, Sarausad LM, Jasoni CL, Fournier RE|title=Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1|url=|journal=Mammalian Genome|volume=15|issue=3|pages=162–78|date=March 2004|pmid=15014966|via=|doi=10.1007/s00335-003-2311-y}} | ||
* {{cite journal | | * {{cite journal|last=|first=|vauthors=Rollini P, Fournier RE|title=Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1|url=|journal=Mammalian Genome|volume=8|issue=12|pages=913–6|date=December 1997|pmid=9383284|via=|doi=10.1007/s003359900610}} | ||
* {{cite journal|last=|first=|vauthors=Gettins PG, Olson ST|title=Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance|journal=Biochemical Journal|volume=473|issue=15|pages=2273–2293|date=August 2016|pmid=27470592|via=|doi=10.1042/bcj20160014|pmc=5266585}} | |||
* {{cite journal |vauthors=Gettins PG, Olson ST |title=Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance |journal=Biochemical Journal |volume=473 |issue=15 |pages=2273–2293 |date=August 2016 |pmid=27470592}} | |||
{{refend}} | {{refend}} | ||
{{Serpins}} | {{Serpins}} | ||
Revision as of 08:29, 23 March 2018
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| External IDs | GeneCards: [1] | ||||||
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| UniProt |
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| Location (UCSC) | n/a | n/a | |||||
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Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2 is a protein that in humans is encoded by the SERPINA2 gene. Serine peptidase inhibitor, clade A member 2 belongs to the member of serine family of proteins which have a functional activity of inhibiting serine proteases.[1]
Discovery
SERPINA2 was known as pseudogenes as it had a very similar structure and function to SERPINA1. During the cloning characterisation of alpha 1- antitrypsin like gene, it was discovered that SERPINA2 did not have any promoter but did contain substantial homology to SERPINA1 gene sequence.[2]
Gene location
SERPINA2 is located at 14q32.13.[3]
Gene expression and localisation
Extracellular predictions of SERPINs and common domain clades show that ER localisation of SERPINA2 are most likely be more, these common ER motifs indicates their localisation are most likely to be in the ER.[4]
Structure
Population studies indicate that this gene is polymorphic. Deletions, frameshift mutations, and a critical start codon mutation (ATG to ATA) have been found in some populations, as well as an allele that can encode a functional protein. This gene may be an evolving pseudogene.[5] The reference genome contains the start codon mutation and has a coding region deletion. A three-dimensional model of SERPINA2 was created using the non-deleted form of crystal structure, which is homologous with the SERPINA1 protein. The model was created using swissmodel in EXPASY, and has shown that SERPINA2 preserves a SERPIN reactive centre loop which is most compatible with protease inhibitory activity. The consensus sequence surrounding the reactive centre loop have diverged considerably so that now it contains tryptophan sarin motifs instead of the methionine serine motif.[6]
Function
SERPINA2 was previously identified as pseudogene; however, recently there have been new evidence which specifies that SERPINA2 produces an active transcript that is responsible for encoding protein located in the endoplasmic reticulum. A detailed study of the SERPINA2 gene across multiple ethnic groups have relieved that with the addition of SERPINA2 gene therein a haplotype characterisation by partial deletion which has patterns suggesting positive selection of loss of function of SERPINA2 protein.[3]
SERPINA2 studies have shown different results regarding the extent of sequence degeneration it can undergo.[5] Bao et al. (1988) describes in his studies that sequence with RNA splice sites are preserved in SERPINA2, and when expressed, it encodes a new secretory protein (SERPIN) with different substrate specificity. These studies with SERPINA2 in humans have concluded that recent positive selection is favoured by the loss of SERPINA2 function and pseudogenization.[7] SERPINA2 genes are mostly expressed in leukocytes and testes which gives a residual expression in liver. SERPINA2 have been linked with on going adaptive process linked with advantages in the role of fertility and host pathogen interactions.[6]
Mutations
A critical mutation present in the start codon and an 2kb deletion over exon IV and part of exon V. This deletion in the start codon occurs at a frequency of 30%.[2] Studies with SERPINA2 in vitro and in vivo have shown that it expresses stable proteins with n-linked glycosylation with a molecular weight of 52kDa and compatible with regular SERPINs [6]
Disease associated
SERPINA2 is a member of SERPIN family, which are known as protein coding genes. A disease associated with this gene is emphysema, due to aat protein deficiency. SERPINA2 has similar function to SERPINA1 and is related to the function of serine type peptidase inhibitor activity.[8]
References
- ↑ "Entrez Gene: Serpin peptidase inhibitor, clade A (alpha-1 antiproteinase, antitrypsin), member 2". Retrieved 2017-09-21.
- ↑ 2.0 2.1 Hofker MH, Nelen M, Klasen EC, Nukiwa T, Curiel D, Crystal RG, Frants RR (September 1988). "Cloning and characterization of an alpha 1-antitrypsin like gene 12 KB downstream of the genuine alpha 1-antitrypsin gene". Biochemical and Biophysical Research Communications. 155 (2): 634–42. doi:10.1016/S0006-291X(88)80542-4. PMID 2901833.
- ↑ 3.0 3.1 Heit C, Jackson BC, McAndrews M, Wright MW, Thompson DC, Silverman GA, Nebert DW, Vasiliou V (October 2013). "Update of the human and mouse SERPIN gene superfamily". Human Genomics. 7 (1): 22. doi:10.1186/1479-7364-7-22. PMC 3880077. PMID 24172014.
- ↑ Marques PI, Ferreira Z, Martins M, Figueiredo J, Silva DI, Castro P, Morales-Hojas R, Simões-Correia J, Seixas S (June 2013). "SERPINA2 is a novel gene with a divergent function from SERPINA1". PLOS ONE. 8 (6): e66889. doi:10.1371/journal.pone.0066889. PMC 3691238. PMID 23826168.
- ↑ 5.0 5.1 Seixas S, Suriano G, Carvalho F, Seruca R, Rocha J, Di Rienzo A (February 2007). "Sequence diversity at the proximal 14q32.1 SERPIN subcluster: evidence for natural selection favoring the pseudogenization of SERPINA2". Molecular Biology and Evolution. 24 (2): 587–98. doi:10.1093/molbev/msl187. PMID 17135331.
- ↑ 6.0 6.1 6.2 Marques PI, Ferreira Z, Martins M, Figueiredo J, Silva DI, Castro P, Morales-Hojas R, Simões-Correia J, Seixas S (June 2013). "SERPINA2 is a novel gene with a divergent function from SERPINA1". PLOS ONE. 8 (6): e66889. doi:10.1371/journal.pone.0066889. PMC 3691238. PMID 23826168.
- ↑ Bao JJ, Reed-Fourquet L, Sifers RN, Kidd VJ, Woo SL (February 1988). "Molecular structure and sequence homology of a gene related to alpha 1-antitrypsin in the human genome". Genomics. 2 (2): 165–73. doi:10.1016/0888-7543(88)90099-7. PMID 2842251.
- ↑ "SERPINA2". GeneCards.
Further reading
- Merkel, PA; Xie, G; Monach, PA; Ji, X; Ciavatta, DJ (May 2017). "Identification of Functional and Expression Polymorphisms Associated With Risk for Antineutrophil Cytoplasmic Autoantibody-Associated Vasculitis". Arthritis & Rheumatology. 69 (5): 1054-66. doi:10.1002/art.40034. PMC 5434905. PMID 28029757.
- Namciu SJ, Friedman RD, Marsden MD, Sarausad LM, Jasoni CL, Fournier RE (March 2004). "Sequence organization and matrix attachment regions of the human serine protease inhibitor gene cluster at 14q32.1". Mammalian Genome. 15 (3): 162–78. doi:10.1007/s00335-003-2311-y. PMID 15014966.
- Rollini P, Fournier RE (December 1997). "Molecular linkage of the human alpha 1-antitrypsin and corticosteroid-binding globulin genes on chromosome 14q32.1". Mammalian Genome. 8 (12): 913–6. doi:10.1007/s003359900610. PMID 9383284.
- Gettins PG, Olson ST (August 2016). "Inhibitory serpins. New insights into their folding, polymerization, regulation and clearance". Biochemical Journal. 473 (15): 2273–2293. doi:10.1042/bcj20160014. PMC 5266585. PMID 27470592.