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{{Infobox_gene}}
{{PBB_Controls
'''Transmembrane and Tetratricopeptide repeat containing 4''' is a [[protein]] that in humans is encoded by the ''TMTC4'' [[gene]].<ref name="entrez">{{cite web | work = Entrez Gene | title = TMTC4 transmembrane and tetratricopeptide repeat containing 4 | url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84899 }}</ref> This protein crosses the [[plasma membrane]] 10 times, and resides in the [[Endoplasmic reticulum|ER]] lumen and [[cytosol]]. The predicted structure of the TMTC4 protein is a series of [[alpha helix|alpha-helices]].
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| update_protein_box = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Gene ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Transmembrane and tetratricopeptide repeat containing 4
| HGNCid = 25904
| Symbol = TMTC4
| AltSymbols =; FLJ14624; FLJ22153
| OMIM = 
| ECnumber = 
| Homologene = 32796
| MGIid = 1921050
| Function = {{GNF_GO|id=GO:0005488 |text = binding}}
| Component =
| Process =
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 84899
    | Hs_Ensembl = ENSG00000125247
    | Hs_RefseqProtein = NP_001073137
    | Hs_RefseqmRNA = NM_001079669
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 13
    | Hs_GenLoc_start = 100054189
    | Hs_GenLoc_end = 100125171
    | Hs_Uniprot = 
    | Mm_EntrezGene = 70551
    | Mm_Ensembl = ENSMUSG00000041594
    | Mm_RefseqmRNA = NM_028651
    | Mm_RefseqProtein = NP_082927
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 14
    | Mm_GenLoc_start = 122054155
    | Mm_GenLoc_end = 122118441
    | Mm_Uniprot = 
  }}
}}
'''Transmembrane and tetratricopeptide repeat containing 4''', also known as '''TMTC4''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: TMTC4 transmembrane and tetratricopeptide repeat containing 4| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=84899| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot. See Template:PBB_Controls to Stop updates. -->
TMTC4 is located on [[Chromosome 13 (human)|chromosome 13]] at 13q32.3. The gene is flanked by ADP ribosylation factor 4 pseudogene 3 (ARF4P3) on the left, and ribosomal protein S26 pseudogene 47 (RPS26P47) on the right. TMTC4 spans 4043 bp and has a total of 23 exons.<ref name="entrez" />
{{PBB_Summary
| section_title =
| summary_text =
}}


==References==
== mRNA ==
{{reflist|2}}
 
==Further reading==
TMTC4 has seven [[Protein isoform|isoform]] variants, the most common being isoform 1 at 4043 bp.<ref name="entrez" />
{{refbegin | 2}}
{| class="wikitable"
{{PBB_Further_reading
|'''Isoform'''
| citations =
|'''Length (bp)'''
*{{cite journal  | author=Hartley JL, Temple GF, Brasch MA |title=DNA cloning using in vitro site-specific recombination. |journal=Genome Res. |volume=10 |issue= 11 |pages= 1788-95 |year= 2001 |pmid= 11076863 |doi=  }}
|-
*{{cite journal  | author=Wiemann S, Weil B, Wellenreuther R, ''et al.'' |title=Toward a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs. |journal=Genome Res. |volume=11 |issue= 3 |pages= 422-35 |year= 2001 |pmid= 11230166 |doi= 10.1101/gr.154701 }}
|1
*{{cite journal  | author=Christian SL, McDonough J, Liu Cy CY, ''et al.'' |title=An evaluation of the assembly of an approximately 15-Mb region on human chromosome 13q32-q33 linked to bipolar disorder and schizophrenia. |journal=Genomics |volume=79 |issue= 5 |pages= 635-56 |year= 2002 |pmid= 11991713 |doi= 10.1006/geno.2002.6765 }}
|4043
*{{cite journal  | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
|-
*{{cite journal  | author=Ota T, Suzuki Y, Nishikawa T, ''et al.'' |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40-5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 }}
|2
*{{cite journal  | author=Dunham A, Matthews LH, Burton J, ''et al.'' |title=The DNA sequence and analysis of human chromosome 13. |journal=Nature |volume=428 |issue= 6982 |pages= 522-8 |year= 2004 |pmid= 15057823 |doi= 10.1038/nature02379 }}
|3833
*{{cite journal  | author=Gerhard DS, Wagner L, Feingold EA, ''et al.'' |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121-7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 }}
|-
*{{cite journal | author=Rual JF, Hirozane-Kishikawa T, Hao T, ''et al.'' |title=Human ORFeome version 1.1: a platform for reverse proteomics. |journal=Genome Res. |volume=14 |issue= 10B |pages= 2128-35 |year= 2004 |pmid= 15489335 |doi= 10.1101/gr.2973604 }}
|3
*{{cite journal | author=Wiemann S, Arlt D, Huber W, ''et al.'' |title=From ORFeome to biology: a functional genomics pipeline. |journal=Genome Res. |volume=14 |issue= 10B |pages= 2136-44 |year= 2004 |pmid= 15489336 |doi= 10.1101/gr.2576704 }}
|3500
*{{cite journal  | author=Tao WA, Wollscheid B, O'Brien R, ''et al.'' |title=Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry. |journal=Nat. Methods |volume=2 |issue= 8 |pages= 591-8 |year= 2005 |pmid= 16094384 |doi= 10.1038/nmeth776 }}
|-
*{{cite journal  | author=Kimura K, Wakamatsu A, Suzuki Y, ''et al.'' |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes. |journal=Genome Res. |volume=16 |issue= 1 |pages= 55-65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 }}
|4
*{{cite journal  | author=Mehrle A, Rosenfelder H, Schupp I, ''et al.'' |title=The LIFEdb database in 2006. |journal=Nucleic Acids Res. |volume=34 |issue= Database issue |pages= D415-8 |year= 2006 |pmid= 16381901 |doi= 10.1093/nar/gkj139 }}
|4217
}}
|-
|5
|4120
|-
|6
|4037
|-
|7
|3827
|}
The [[Five prime untranslated region|5’ UTR]] for TMTC4 is short and in many of the shorter isoforms, portions of this untranslated region are cut. In comparison, the 3’ UTR is long and is often complete across the seven isoforms.
 
== Protein ==
 
=== Physical properties ===
 
The [[molecular weight]] for TMTC4 is 85.0 kdal, and there are no positive, negative, or neutral clusters of amino acids or charge runs exceeding the normal lengths. When looking at a distant [[Homology (biology)|ortholog]] (purple sea urchin) the molecular weight of TMTC4 is 85.5 kdal and there, again, are no charge runs, positive, negative or neutral clusters, or unusual spacings.  There are strong similarities in protein composition across species. The [[isoelectric point]] for the [[domain of unknown function]] (DUF 1736) is lower than that of the protein overall.
[[File:Schematic Illustration.png|thumb|Schematic illustration of known and predicted domains and motifs for TMTC4]]
{| class="wikitable"
|'''Domain'''
|'''Amino Acids'''
|'''Molecular Weight (kdal)'''
|'''Isoelectric Point'''
|-
|''Human TMTC4''
|760
|85.0
|9.135
|-
|''DUF 1736''
|75
|8.6
|4.123
|-
|''TPR repeats''
|234
|26.7
|9.509
|}
 
=== Domains ===
 
[[File:Secondary Structure for TMTC4.png|thumb|Predicted secondary structure of TMTC4. Starting at blue and going to red, the diagram illustrates the n-terminus through the c-terminus.]]TMTC4 has ten [[Transmembrane protein|transmembrane]] regions, all of them spaced within the first half of the protein.<ref name="motif_scan">{{cite web | url = http://myhits.isb-sib.ch/cgi-bin/motif_scan | title = Motif Scan | publisher = Swiss Institute of Bioinformatics | access-date=2017-05-04 }}</ref>
 
TMTC4 is layered with [[tetratricopeptide]] (TPR) repeat sequences that are a part of the TPR superfamily of proteins. DUF1736 is present upstream of the TPR region. A seven residue repeat (SRR) is located toward the end of the protein, and it is thought to encode a [[Coiled coil|coiled-coil]] structure.<ref name="pmid18555680">{{cite journal | vauthors = Grigoryan G, Keating AE | title = Structural specificity in coiled-coil interactions | journal = Current Opinion in Structural Biology | volume = 18 | issue = 4 | pages = 477–83 | year = 2008 | pmid = 18555680 | pmc = 2567808 | doi = 10.1016/j.sbi.2008.04.008 }}</ref> Another member of the TPR family, PFTA (protein prenyltransferases alpha subunit repeat), is located within the protein’s TPR region and is believed to be involved in [[signal transduction]] and [[Vesicle trafficking|vesicular traffic]] regulation.<ref>{{cite journal | vauthors = Zhang H, Grishin NV | title = The alpha-subunit of protein prenyltransferases is a member of the tetratricopeptide repeat family | journal = Protein Science | volume = 8 | issue = 8 | pages = 1658–67 | date = August 1999 | pmid = 10452610 | pmc = 2144414 | doi = 10.1110/ps.8.8.1658 }}</ref> LSPR coagulation factor V, also a repeat motif, is located within the TPR region, and is thought to be a central regulator of [[hemostasis]].<ref>{{cite web | url = http://www.ebi.ac.uk/interpro/entry/IPR009271 | title = Coagulation factor V, LSPD (IPR009271) | publisher = EMBL-EBI | work = InterPro | access-date = 2017-04-27 }}</ref>
 
=== Secondary structure ===
 
TMTC4 takes on a series of [[alpha-helix]] structures, especially within the TPR region, though there are a minimal amount of beta-strand structures spaced throughout the beginning half of the protein.<ref>{{cite web | url = http://zhanglab.ccmb.med.umich.edu/I-TASSER/output/S325695/j2663g/ | title = I-TASSER results | work = I-TASSER | publisher = University of Michigan | access-date = 2017-04-27 }}</ref>
 
=== Post-translational modifications ===
 
[[File:TMTC4 image.png|thumb|Predicted post-translational modifications of TMTC4 protein]]
There are four predicted [[nuclear localization signals]], each tagging the protein for [[nuclear import]].<ref name="motif_scan" /> At the very end of the protein, however, there is a predicted [[ER retention]] signal which would prevent the protein from leaving the ER. The protein has three predicted [[N-glycosylation]] sites, potentially altering its structure and function and there are ten predicted [[protein phosphorylation|phosphorylation sites]], each a possible activation site for a regulatory mechanism.<ref name="motif_scan" />
 
== Expression ==
 
TMTC4 is expressed in all human tissues. The gene, however, is most highly expressed in the [[brain]] and in the [[spinal cord]].<ref>{{cite web | url = https://www.ncbi.nlm.nih.gov/geoprofiles/2906582 | title = 2906582 | work = GEO Profiles | publisher = NCBI | access-date = 2017-04-27 }}</ref>
 
Protein abundance seems to be lower than normal for TMTC4.
 
=== Regulation ===
 
There is one possible [[Promoter (genetics)|promoter]] for the TMTC4 gene, located in the 5’ UTR but before the start of the [[coding sequence]].
 
== Function ==
 
Currently the function of TMTC4 has not been characterized.
 
== Interacting proteins ==
 
Possible interacting proteins are NRG1, PEX19, HERC3, TXNDC15, and COL1A1 . All of these were detected through affinity chromatography.<ref>{{cite journal | vauthors = Huttlin EL, Ting L, Bruckner RJ, Gebreab F, Gygi MP, Szpyt J, Tam S, Zarraga G, Colby G, Baltier K, Dong R, Guarani V, Vaites LP, Ordureau A, Rad R, Erickson BK, Wühr M, Chick J, Zhai B, Kolippakkam D, Mintseris J, Obar RA, Harris T, Artavanis-Tsakonas S, Sowa ME, De Camilli P, Paulo JA, Harper JW, Gygi SP | display-authors = 6 | title = The BioPlex Network: A Systematic Exploration of the Human Interactome | journal = Cell | volume = 162 | issue = 2 | pages = 425–40 | date = July 2015 | pmid = 26186194 | pmc = 4617211 | doi = 10.1016/j.cell.2015.06.043 | url = http://europepmc.org/articles/PMC4617211#SD7 }}</ref>
{| class="wikitable"
|'''Protein Name'''
|'''Known function'''
|'''Location'''
|-
|''Neuregulin 1 [NRG1]''
|mediates cell to cell signaling<ref name="GeneCards_NRG1">{{cite web | url = http://www.genecards.org/cgi-bin/carddisp.pl?gene=nrg1 | title=NRG1 Gene | work = GeneCards | access-date = 2017-04-27 }}</ref>
|membrane glycoprotein<ref name="GeneCards_NRG1" />
|-
|''Peroxisomal Biogenesis Factor 19 [PEX19]''
|cytosolic chaperone<ref name="GeneCards_PEX19">{{cite web | url = http://www.genecards.org/cgi-bin/carddisp.pl?gene=pex19 | title = PEX19 Gene | work = GeneCards | access-date = 2017-04-27 }}</ref>
|membrane receptor protein<ref name="GeneCards_PEX19" />
|-
|''ECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 3 [HERC3]''
|member of the ubiquitin ligase family<ref name="GeneCards_HERC3">{{cite web | url = http://www.genecards.org/cgi-bin/carddisp.pl?gene=herc3 | title = HERC3 Gene | work = GeneCards | access-date = 2017-04-27 }}</ref>
|cytosol<ref name="GeneCards_HERC3" />
|-
|''Thioredoxin Domain Containing 15 [TXNDC15]''
|Not known
|Not known
|-
|''Collagen Type I Alpha 1 Chain [COL1A1]''
|triple helix collagen protein<ref name="GeneCards_COL1A1">{{cite web | url = http://www.genecards.org/cgi-bin/carddisp.pl?gene=col1a1 | title = COL1A1 Gene |work = GeneCards | access-date = 2017-04-27 }}</ref>
|extracellular<ref name="GeneCards_COL1A1" />
|}
 
== Homology ==
 
=== Orthologs ===
 
[[Ortholog]] space for TMTC4 spans a large portion of [[Timeline of the evolutionary history of life|evolutionary time]]. TMTC4 is present in [[mammal]]s, [[reptile]]s, [[amphibian]]s, [[bird]]s, [[fish]], and [[invertebrate]]s. It is not present in [[plant]]s, [[bacteria]], [[archaea]], or [[fungi]].<ref>{{cite web | url = https://blast.ncbi.nlm.nih.gov/Blast.cgi | title = BLAST: Basic Local Alignment Search Tool | publisher = NCBI | access-date = 2017-04-27 }}</ref> 
{| class="wikitable"
|'''Sequence Number'''
|'''Genus and Species'''
|'''Common Name'''
|'''Accession # (protein)'''
|'''Identity'''
|'''Date of Divergence (MYA)'''
|-
|'''1'''
|''Heterocephalus glaber''
|[[Naked mole rat]]
|EHB03258.1
|88%
|94
|-
|'''2'''
|''Rattus norvegicus''
|[[Brown rat]]
|NP_001127886.1
|90%
|94
|-
|'''3'''
|''Myotis brandtii''
|[[Brandt's bat]]
|EPQ01527.1
|90%
|94
|-
|'''4'''
|''Pteropus alecto''
|[[Black flying fox]]
|XP_006909447.1
|93%
|88
|-
|'''5'''
|''Erinaceus europaeus''
|[[European hedgehog]]
|XP_016040457.1
|85%
|94
|-
|'''6'''
|''Sorex araneus''
|[[Common shrew]]
|XP_004614101.1
|86%
|94
|-
|'''7'''
|''Sus scrofa''
|[[Wild boar]]
|NP_001239134.1
|91%
|94
|-
|'''8'''
|''Lipotes vexillifer''
|[[Baiji]]
|XP_007461591.1
|90%
|88
|-
|'''9'''
|''Ailuropoda melanoleuca''
|[[Giant panda]]
|XP_019650336.1
|90%
|94
|-
|'''10'''
|''Acinonyx jubatus''
|[[Cheetah]]
|XP_014931490.1
|93%
|94
|-
|'''11'''
|''Tyto alba''
|[[Barn owl]]
|KFV56414.1
|85%
|320
|-
|'''12'''
|''Charadrius vociferus''
|[[Killdeer]]
|KGL87053.1
|84%
|320
|-
|'''13'''
|''Python bivittatus''
|[[Burmese python]]
|XP_007425712.1
|81%
|320
|-
|'''14'''
|''Anolis carolinensis''
|[[Carolina anole]]
|XP_008105174.1
|82%
|320
|-
|'''15'''
|''Xenopus tropicalis''
|[[Western clawed frog]]
|NP_001121486.1
|38%
|353
|-
|'''16'''
|''Nanorana parkeri''
|[[Nanorana parkeri]]
|XP_018432106.1
|73%
|353
|-
|'''17'''
|''Callorhinchus milii''
|[[Australian ghostshark]]
|XP_007885231.1
|68%
|465
|-
|'''18'''
|''Crassostrea gigas''
|[[Pacific oyster]]
|XP_011422949.1
|50%
|758
|-
|'''19'''
|''Strongylocentrotus purpuratus''
|[[Strongylocentrotus purpuratus|Purple sea urchin]]
|XP_011670776.1
|49%
|627
|}
 
=== Paralogs ===
 
[[Homology (biology)|Paralog]] space for TMTC4 spans the gene family TMTC. There are four genes in this gene family: TMTC1, [[TMTC2]], TMTC3, and TMTC4. TMTC1 and TMTC3 split from TMTC4 about 1200 million years ago, while [[TMTC2]] split from TMTC4 1400 million years ago. Both of these events happened somewhere between invertebrates and plants.
{{clear}}
 
== References ==
{{reflist|33em}}
 
== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Hartley JL, Temple GF, Brasch MA | title = DNA cloning using in vitro site-specific recombination | journal = Genome Research | volume = 10 | issue = 11 | pages = 1788–95 | date = November 2000 | pmid = 11076863 | pmc = 310948 | doi = 10.1101/gr.143000 }}
* {{cite journal | vauthors = Christian SL, McDonough J, Liu Cy CY, Shaikh S, Vlamakis V, Badner JA, Chakravarti A, Gershon ES | title = An evaluation of the assembly of an approximately 15-Mb region on human chromosome 13q32-q33 linked to bipolar disorder and schizophrenia | journal = Genomics | volume = 79 | issue = 5 | pages = 635–56 | date = May 2002 | pmid = 11991713 | doi = 10.1006/geno.2002.6765 }}
* {{cite journal | vauthors = Rual JF, Hirozane-Kishikawa T, Hao T, Bertin N, Li S, Dricot A, Li N, Rosenberg J, Lamesch P, Vidalain PO, Clingingsmith TR, Hartley JL, Esposito D, Cheo D, Moore T, Simmons B, Sequerra R, Bosak S, Doucette-Stamm L, Le Peuch C, Vandenhaute J, Cusick ME, Albala JS, Hill DE, Vidal M | title = Human ORFeome version 1.1: a platform for reverse proteomics | journal = Genome Research | volume = 14 | issue = 10B | pages = 2128–35 | date = October 2004 | pmid = 15489335 | pmc = 528929 | doi = 10.1101/gr.2973604 }}
* {{cite journal | vauthors = Wiemann S, Arlt D, Huber W, Wellenreuther R, Schleeger S, Mehrle A, Bechtel S, Sauermann M, Korf U, Pepperkok R, Sültmann H, Poustka A | title = From ORFeome to biology: a functional genomics pipeline | journal = Genome Research | volume = 14 | issue = 10B | pages = 2136–44 | date = October 2004 | pmid = 15489336 | pmc = 528930 | doi = 10.1101/gr.2576704 }}
* {{cite journal | vauthors = Tao WA, Wollscheid B, O'Brien R, Eng JK, Li XJ, Bodenmiller B, Watts JD, Hood L, Aebersold R | title = Quantitative phosphoproteome analysis using a dendrimer conjugation chemistry and tandem mass spectrometry | journal = Nature Methods | volume = 2 | issue = 8 | pages = 591–8 | date = August 2005 | pmid = 16094384 | doi = 10.1038/nmeth776 }}
* {{cite journal | vauthors = Mehrle A, Rosenfelder H, Schupp I, del Val C, Arlt D, Hahne F, Bechtel S, Simpson J, Hofmann O, Hide W, Glatting KH, Huber W, Pepperkok R, Poustka A, Wiemann S | title = The LIFEdb database in 2006 | journal = Nucleic Acids Research | volume = 34 | issue = Database issue | pages = D415-8 | date = January 2006 | pmid = 16381901 | pmc = 1347501 | doi = 10.1093/nar/gkj139 }}
{{refend}}
{{refend}}


{{protein-stub}}
[[Category:Biology of bipolar disorder]]
{{WikiDoc Sources}}

Revision as of 12:03, 15 September 2017

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Transmembrane and Tetratricopeptide repeat containing 4 is a protein that in humans is encoded by the TMTC4 gene.[1] This protein crosses the plasma membrane 10 times, and resides in the ER lumen and cytosol. The predicted structure of the TMTC4 protein is a series of alpha-helices.

Gene

TMTC4 is located on chromosome 13 at 13q32.3. The gene is flanked by ADP ribosylation factor 4 pseudogene 3 (ARF4P3) on the left, and ribosomal protein S26 pseudogene 47 (RPS26P47) on the right. TMTC4 spans 4043 bp and has a total of 23 exons.[1]

mRNA

TMTC4 has seven isoform variants, the most common being isoform 1 at 4043 bp.[1]

Isoform Length (bp)
1 4043
2 3833
3 3500
4 4217
5 4120
6 4037
7 3827

The 5’ UTR for TMTC4 is short and in many of the shorter isoforms, portions of this untranslated region are cut. In comparison, the 3’ UTR is long and is often complete across the seven isoforms.

Protein

Physical properties

The molecular weight for TMTC4 is 85.0 kdal, and there are no positive, negative, or neutral clusters of amino acids or charge runs exceeding the normal lengths. When looking at a distant ortholog (purple sea urchin) the molecular weight of TMTC4 is 85.5 kdal and there, again, are no charge runs, positive, negative or neutral clusters, or unusual spacings. There are strong similarities in protein composition across species. The isoelectric point for the domain of unknown function (DUF 1736) is lower than that of the protein overall.

File:Schematic Illustration.png
Schematic illustration of known and predicted domains and motifs for TMTC4
Domain Amino Acids Molecular Weight (kdal) Isoelectric Point
Human TMTC4 760 85.0 9.135
DUF 1736 75 8.6 4.123
TPR repeats 234 26.7 9.509

Domains

File:Secondary Structure for TMTC4.png
Predicted secondary structure of TMTC4. Starting at blue and going to red, the diagram illustrates the n-terminus through the c-terminus.

TMTC4 has ten transmembrane regions, all of them spaced within the first half of the protein.[2]

TMTC4 is layered with tetratricopeptide (TPR) repeat sequences that are a part of the TPR superfamily of proteins. DUF1736 is present upstream of the TPR region. A seven residue repeat (SRR) is located toward the end of the protein, and it is thought to encode a coiled-coil structure.[3] Another member of the TPR family, PFTA (protein prenyltransferases alpha subunit repeat), is located within the protein’s TPR region and is believed to be involved in signal transduction and vesicular traffic regulation.[4] LSPR coagulation factor V, also a repeat motif, is located within the TPR region, and is thought to be a central regulator of hemostasis.[5]

Secondary structure

TMTC4 takes on a series of alpha-helix structures, especially within the TPR region, though there are a minimal amount of beta-strand structures spaced throughout the beginning half of the protein.[6]

Post-translational modifications

File:TMTC4 image.png
Predicted post-translational modifications of TMTC4 protein

There are four predicted nuclear localization signals, each tagging the protein for nuclear import.[2] At the very end of the protein, however, there is a predicted ER retention signal which would prevent the protein from leaving the ER. The protein has three predicted N-glycosylation sites, potentially altering its structure and function and there are ten predicted phosphorylation sites, each a possible activation site for a regulatory mechanism.[2]

Expression

TMTC4 is expressed in all human tissues. The gene, however, is most highly expressed in the brain and in the spinal cord.[7]

Protein abundance seems to be lower than normal for TMTC4.

Regulation

There is one possible promoter for the TMTC4 gene, located in the 5’ UTR but before the start of the coding sequence.

Function

Currently the function of TMTC4 has not been characterized.

Interacting proteins

Possible interacting proteins are NRG1, PEX19, HERC3, TXNDC15, and COL1A1 . All of these were detected through affinity chromatography.[8]

Protein Name Known function Location
Neuregulin 1 [NRG1] mediates cell to cell signaling[9] membrane glycoprotein[9]
Peroxisomal Biogenesis Factor 19 [PEX19] cytosolic chaperone[10] membrane receptor protein[10]
ECT And RLD Domain Containing E3 Ubiquitin Protein Ligase 3 [HERC3] member of the ubiquitin ligase family[11] cytosol[11]
Thioredoxin Domain Containing 15 [TXNDC15] Not known Not known
Collagen Type I Alpha 1 Chain [COL1A1] triple helix collagen protein[12] extracellular[12]

Homology

Orthologs

Ortholog space for TMTC4 spans a large portion of evolutionary time. TMTC4 is present in mammals, reptiles, amphibians, birds, fish, and invertebrates. It is not present in plants, bacteria, archaea, or fungi.[13]

Sequence Number Genus and Species Common Name Accession # (protein) Identity Date of Divergence (MYA)
1 Heterocephalus glaber Naked mole rat EHB03258.1 88% 94
2 Rattus norvegicus Brown rat NP_001127886.1 90% 94
3 Myotis brandtii Brandt's bat EPQ01527.1 90% 94
4 Pteropus alecto Black flying fox XP_006909447.1 93% 88
5 Erinaceus europaeus European hedgehog XP_016040457.1 85% 94
6 Sorex araneus Common shrew XP_004614101.1 86% 94
7 Sus scrofa Wild boar NP_001239134.1 91% 94
8 Lipotes vexillifer Baiji XP_007461591.1 90% 88
9 Ailuropoda melanoleuca Giant panda XP_019650336.1 90% 94
10 Acinonyx jubatus Cheetah XP_014931490.1 93% 94
11 Tyto alba Barn owl KFV56414.1 85% 320
12 Charadrius vociferus Killdeer KGL87053.1 84% 320
13 Python bivittatus Burmese python XP_007425712.1 81% 320
14 Anolis carolinensis Carolina anole XP_008105174.1 82% 320
15 Xenopus tropicalis Western clawed frog NP_001121486.1 38% 353
16 Nanorana parkeri Nanorana parkeri XP_018432106.1 73% 353
17 Callorhinchus milii Australian ghostshark XP_007885231.1 68% 465
18 Crassostrea gigas Pacific oyster XP_011422949.1 50% 758
19 Strongylocentrotus purpuratus Purple sea urchin XP_011670776.1 49% 627

Paralogs

Paralog space for TMTC4 spans the gene family TMTC. There are four genes in this gene family: TMTC1, TMTC2, TMTC3, and TMTC4. TMTC1 and TMTC3 split from TMTC4 about 1200 million years ago, while TMTC2 split from TMTC4 1400 million years ago. Both of these events happened somewhere between invertebrates and plants.

References

  1. ↑ 1.0 1.1 1.2 "TMTC4 transmembrane and tetratricopeptide repeat containing 4". Entrez Gene.
  2. ↑ 2.0 2.1 2.2 "Motif Scan". Swiss Institute of Bioinformatics. Retrieved 2017-05-04.
  3. ↑ Grigoryan G, Keating AE (2008). "Structural specificity in coiled-coil interactions". Current Opinion in Structural Biology. 18 (4): 477–83. doi:10.1016/j.sbi.2008.04.008. PMC 2567808. PMID 18555680.
  4. ↑ Zhang H, Grishin NV (August 1999). "The alpha-subunit of protein prenyltransferases is a member of the tetratricopeptide repeat family". Protein Science. 8 (8): 1658–67. doi:10.1110/ps.8.8.1658. PMC 2144414. PMID 10452610.
  5. ↑ "Coagulation factor V, LSPD (IPR009271)". InterPro. EMBL-EBI. Retrieved 2017-04-27.
  6. ↑ "I-TASSER results". I-TASSER. University of Michigan. Retrieved 2017-04-27.
  7. ↑ "2906582". GEO Profiles. NCBI. Retrieved 2017-04-27.
  8. ↑ Huttlin EL, Ting L, Bruckner RJ, Gebreab F, Gygi MP, Szpyt J, et al. (July 2015). "The BioPlex Network: A Systematic Exploration of the Human Interactome". Cell. 162 (2): 425–40. doi:10.1016/j.cell.2015.06.043. PMC 4617211. PMID 26186194.
  9. ↑ 9.0 9.1 "NRG1 Gene". GeneCards. Retrieved 2017-04-27.
  10. ↑ 10.0 10.1 "PEX19 Gene". GeneCards. Retrieved 2017-04-27.
  11. ↑ 11.0 11.1 "HERC3 Gene". GeneCards. Retrieved 2017-04-27.
  12. ↑ 12.0 12.1 "COL1A1 Gene". GeneCards. Retrieved 2017-04-27.
  13. ↑ "BLAST: Basic Local Alignment Search Tool". NCBI. Retrieved 2017-04-27.

Further reading

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