TMEM8A

Last updated
PGAP6
Identifiers
Aliases PGAP6 , M83, TMEM6, TMEM8, transmembrane protein 8A, GPI-PLA2, TMEM8A, post-glycosylphosphatidylinositol attachment to proteins 6, post-GPI attachment to proteins 6
External IDs MGI: 1926283 HomoloGene: 10944 GeneCards: PGAP6
Orthologs
SpeciesHumanMouse
Entrez

58986

60455

Ensembl

n/a

ENSMUSG00000024180

UniProt

Q9HCN3

Q9ESN3

RefSeq (mRNA)

NM_021259

NM_021793

RefSeq (protein)

NP_067082

NP_068565

Location (UCSC)n/a Chr 17: 26.33 – 26.34 Mb
PubMed search [2] [3]
Wikidata
View/Edit Human View/Edit Mouse

Transmembrane protein 8A is a protein that in humans is encoded by the TMEM8A gene (16p13.3.). Evolutionarily, TMEM8A orthologs are found in primates and mammals and in a few more distantly related species. TMEM8A contains five transmembrane domains and one EGF-like domain which are all highly conserved in the ortholog space. Although there is no confirmed function of TMEM8A, through analyzing expression and experimental data, it is predicted that TMEM8A is an adhesion protein that plays a role in keeping T-cells in their resting state.

Contents

Gene

Locus

The human gene TMEM8A is found on chromosome 16 at the band 16p13.3. [4]

TMEM8A-gene.png [5]

The span of this gene on chromosome 16 spans from base pair 420,773 to 437,113 making this gene 16,340 base pairs in length. This gene is found on the minus strand of the chromosome. [6] There are no known isoforms.

Aliases

TMEM8A is also known as Transmembrane protein 8A, Transmembrane Protein 6, Five-Span Transmembrane Protein M83, TMEM6, TMEM8, Transmembrane protein 8 and M83. [7]

Homology

Paralogs

There are two paralogs for TMEM8A found in humans, C9orf127 and TMEM8C. Both of these paralogs are found on Chromosome 9. [8]

Orthologs

The ortholog space of TMEM8A is fairly narrow, with the majority of orthologs found in mammals and in particular primates with only a few exceptions.
Genus and species [8] Common nameClassAccessionPercent identity
Pan troglodytesChimpanzeeMammaliaXP_51070999%
Pongo abeliiOrangutanMammaliaXP_00282596097%
Macaca mulattaRhesus monkeyMammaliaXP_00111846193%
Callithrix jacchusMarmosetMammaliaABZ8034493%
Rattus norvegicusRatMammaliaXP_00107017643%
Bos taurusCowMammaliaNP_00109237769%
Ailuropoda melanoleucaPandaMammaliaEFB1713478%
Canis familiarisDogMammaliaXP_00363916374%
Equus caballusHorseMammaliaXP_00191545278%
Felis catusCatMammaliaXP_00399912175%
Monodelphis domesticaOpossumMammaliaXP_00137811044%
Ornithorhynchus anatinusPlatypusMammaliaXP_00151239850%
Gallus gallusChickenAvesXP_00364324356%
Anolis carolinensisLizardReptiliaXP_00323022953%
Xenopus tropicalisFrogAmphibiaXP_00294347343%
Takifugo rubripesPufferfishActinopterygiiXP_00397588344%
Danio rerioZebrafishAcrinoptergiiXP_0013904044%
Strongylacentrotus putputatusSea urchinEchinoideaXP_79545229%
Drosophila melanogasterFruit flyInsectaNP_65135036%

Protein

Primary sequence

The gene encodes a protein also called TMEM8A. This protein in 771 amino acids in length but has been shown to have a signal peptide from amino acid 1 to 34; the mature form of the protein is only 737 amino acids in length. The precursor form with signal peptide intact has a molecular weight of 84.780 kilodaltons and the mature form with the signal peptide cleaved has a molecular weight of 81.624 kilodaltons [9] TMEM8A has an isoelectric point of the mature form of pI=7.3. [10]

Domains and motifs

TMEM8A is a transmembrane protein with five transmembrane domains, making it one of only three proteins found in the human body with five domains; the other two are CD47 and AC133. The protein also contains an EGF-like domain, which is a sequence of about thirty to forty amino-acid residues, found in the sequence of epidermal growth factor (EGF), that has been shown to be present in a more or less conserved form in a large number of other, mostly animal, proteins. The functional significance of EGF domains in what appear to be unrelated proteins is not yet clear. However, a common feature is that these repeats are found in the extracellular domain of membrane-bound proteins or in proteins known to be secreted. The EGF domain includes six cysteine residues which have been shown (in EGF) to be involved in disulphide bonds. The main structure is a two-stranded beta-sheet followed by a loop to a short C-terminal two-stranded sheet. Subdomains between the conserved cysteines vary in length. [11]

Post-translational modifications

The protein has been shown to undergo glycosylation post-translationally at amino acids 144, 407, and 431. [12] There are also three disulfide bonds between amino acid 498 and 508, 502 and 521, and 523 and 532. These disulfide bonds are all characteristic of proteins with an EGF-like domain.

Secondary Structure

Expression

Expression

Expression TMEM8A.PNG

TMEM8A is found to be expressed ubiquitously throughout the human body; however, it has been shown to be downregulated during CD4+ and CD8+ T-cell activation. [13]

Transcript variants

There are three natural transcript variants of TMEM8A. One is located at amino acid 136 where a threonine is swapped for an alanine. Another is present at amino acid 310 where an isoleucine is swapped for a valine and one at amino acid 567 where an arginine is swapped for a tryptophan. None of these variants result in a change of expression nor any loss/gain of function mutations. [14]

Interacting proteins

Transcription factors

There are many predicted transcription factor binding sites in the TMEM8A promoter. Below is a table of the best possibilities, which have high confidence values, evolutionary conservation, and/or multiple possible binding sites in the promoter.

Transcription FactorStartEndStrandSequence
Insulimoma associated factors113+tggagGGGGtccg
Plemorphic adenoma gene 1325+gaGGGGgtccgggtggcagtgcg
Hypermethylated in cancer 11123-cacTGCCacccgg
Zinc finger with KRAB and SCAN domains 31537-gccatCCCCacccgcactgccac
Glial cells missing homolog 11832+ccccaCCCGcactgc
Basic krueppel-like factor (KLF3)1935+cagtgcGGGTggggatg
Zinc finger protein Spalt-2, sal-like 2, p150(sal2)2333+gcgggtGGGGatg
MYC-associated zinc finger protein related transcription factor2335+gcgggtGGGGatg
Myeloid zinc finger protein MZF12737+gtGGGGatggc
Hypermethylated in cancer 12941-gacTGCCatcccc
Yin and Yang 1 activator sites3860-gacactgCCATcgccactctgact
Y box binding protein 1, has a preference for binding ssDNA4153+cagagTGGCgatg
Glial cells missing homolog 15468-cgccaCCCGcactgc
Wilms Tumor Suppressor7184+ggcagtgTGGGtggcga
Runt-related transcription factor 2 / CBFA1 (core-binding factor, runt domain, alpha subunit 1)7387+cagtGTGGgtggcga
GLI-Kruppel family member GLI37488-atcgCCACccacact
Zinc finger with KRAB and SCAN domains 387103-gccatCCCCacccgcactgccat

Interactions

Protein Interaction Network for TMEM8A Protein Interaction Network for TMEM8A.png
Protein Interaction Network for TMEM8A

TMEM8A has been shown to interact with the following proteins

Related Research Articles

<span class="mw-page-title-main">CYYR1</span> Protein-coding gene in the species Homo sapiens

Cysteine and tyrosine-rich protein 1 is a protein that in humans is encoded by the CYYR1 gene and is located on chromosome 21, location 21q21.2. This protein has a function that is not presently understood.

<span class="mw-page-title-main">TMEM98</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 98 is a single-pass membrane protein that in humans is encoded by the TMEM98 gene. The function of this protein is currently unknown. TMEM98 is also known as UNQ536/PRO1079.

<span class="mw-page-title-main">TMEM8B</span> Protein-coding gene in humans

Transmembrane protein 8B is a protein that in humans is encoded by the TMEM8B gene. It encodes for a transmembrane protein that is 338 amino acids long, and is located on human chromosome 9. Aliases associated with this gene include C9orf127, NAG-5, and NGX61.

<span class="mw-page-title-main">TMEM63A</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 63A is a protein that in humans is encoded by the TMEM63A gene. The mature human protein is approximately 92.1 kilodaltons (kDa), with a relatively high conservation of mass in orthologs. The protein contains eleven transmembrane domains and is inserted into the membrane of the lysosome. BioGPS analysis for TMEM63A in humans shows that the gene is ubiquitously expressed, with the highest levels of expression found in T-cells and dendritic cells.

<span class="mw-page-title-main">Transmembrane protein 53</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 53, or TMEM53, is a protein that is encoded on chromosome 1 in humans. It has no paralogs but is predicted to have many orthologs across eukaryotes.

<span class="mw-page-title-main">TMEM106A</span> Protein-coding gene in the species Homo sapiens

TMEM106A is a gene that encodes the transmembrane protein 106A (TMEM106A) in Homo sapiens. It is located at 17q21.31 on the plus strand next to cancer-related genes NBR1 and BRCA1. The TMEM106A gene contains a domain of unknown function, DUF1356.

<span class="mw-page-title-main">TMEM69</span> Protein-coding gene in the species Homo sapiens

TMEM69, also known as Transmembrane protein 69, is a protein that in humans is encoded by the TMEM69 gene. A notable feature of the protein encoded by TMEM69 is the presence of five transmembrane segments.

<span class="mw-page-title-main">KIAA0922</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 131-like, alternatively named uncharacterized protein KIAA0922, is an integral transmembrane protein encoded by the human gene KIAA0922 that is significantly conserved in eukaryotes, at least through protists. Although the function of this gene is not yet fully elucidated, initial microarray evidence suggests that it may be involved in immune responses. Furthermore, its paralog, prolyl endopeptidase (PREP) whose function is known, provides clues as to the function of TMEM131L.

Transmembrane protein 33 is a protein that in humans, is encoded by the TMEM33 gene, also known as SHINC3. Another name for the TMEM33 protein is DB83.

<span class="mw-page-title-main">Multiple Epidermal Growth Factor-like Domains 8</span> Protein-coding gene in the species Homo sapiens

Megf8 also known as Multiple Epidermal Growth Factor-like Domains 8, is a protein coding gene that encodes a single pass membrane protein, known to participate in developmental regulation and cellular communication. It is located on chromosome 19 at the 49th open reading frame in humans (19q13.2). There are two isoform constructs known for MEGF8, which differ by a 67 amino acid indel. The isoform 2 splice version is 2785 amino acids long, and predicted to be 296.6 kdal in mass. Isoform 1 is composed of 2845 amino acids and predicted to weigh 303.1 kdal. Using BLAST searches, orthologs were found primarily in mammals, but MEGF8 is also conserved in invertebrates and fishes, and rarely in birds, reptiles, and amphibians. A notably important paralog to multiple epidermal growth factor-like domains 8 is ATRNL1, which is also a single pass transmembrane protein, with several of the same key features and motifs as MEGF8, as indicated by Simple Modular Architecture Research Tool (SMART) which is hosted by the European Molecular Biology Laboratory located in Heidelberg, Germany. MEGF8 has been predicted to be a key player in several developmental processes, such as left-right patterning and limb formation. Currently, researchers have found MEGF8 SNP mutations to be the cause of Carpenter syndrome subtype 2.

<span class="mw-page-title-main">TMEM106C</span> Protein-coding gene in the species Homo sapiens

TMEM106C is a gene that encodes the transmembrane protein 106C (TMEM106C) in Homo sapiens It has been found to be overexpressed in cancer cells and also is related to distal arthrogryposis, a condition of stiff joints and irregular muscle development. The TMEM106C gene contains a domain of unknown function, DUF1356, that spans most of the protein. Transmembrane protein 106C also goes by the aliases MGC5576 or MGC111210, LOC79022.

<span class="mw-page-title-main">Transmembrane protein 134</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 134 is a protein encoded by the TMEM134 gene. TMEM134 does not have any other known aliases. There are two transmembrane domains and a domain of unknown function (DUF872). Evolutionary, the majority of the organisms that have this gene are primates and mammals, although there are some organisms dating back to Drosophila and C. elegans. Through current research, there has not been any confirmed function of TMEM134.

TMEM143 is a protein that in humans is encoded by TMEM143 gene. TMEM143, a dual-pass protein, is predicted to reside in the mitochondria and high expression has been found in both human skeletal muscle and the heart. Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.

<span class="mw-page-title-main">TMEM249</span> Protein-coding gene in the species Homo sapiens

TMEM249 is a protein that in humans is encoded by the C8orfk29 gene.

<span class="mw-page-title-main">Transmembrane protein 268</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 268 is a protein that in humans is encoded by TMEM268 gene. The protein is a transmembrane protein of 342 amino acids long with eight alternative splice variants. The protein has been identified in organisms from the common fruit fly to primates. To date, there has been no protein expression found in organisms simpler than insects.

<span class="mw-page-title-main">TMEM176B</span> Protein-coding gene in the species Homo sapiens

Transmembrane Protein 176B, or TMEM176B is a transmembrane protein that in humans is encoded by the TMEM176B gene. It is thought to play a role in the process of maturation of dendritic cells.

Transmembrane Protein 217 is a protein encoded by the gene TMEM217. TMEM217 has been found to have expression correlated with the lymphatic system and endothelial tissues and has been predicted to have a function linked to the cytoskeleton.

<span class="mw-page-title-main">TMEM247</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 247 is a multi-pass transmembrane protein of unknown function found in Homo sapiens encoded by the TMEM247 gene. Notable in the protein are two transmembrane regions near the c-terminus of the translated polypeptide. Transmembrane protein 247 has been found to be expressed almost entirely in the testes.

<span class="mw-page-title-main">TMEM212</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 212 is a protein that in humans is encoded by the TMEM212 gene. The protein consists of 5 transmembrane domains and localizes in the plasma membrane and endoplasmic reticulum. TMEM212 has orthologs in vertebrates but not invertebrates. TMEM212 has been associated with sporadic Parkinson's disease, facial processing, and adiposity in African Americans.

<span class="mw-page-title-main">TEDDM1</span> Protein-coding gene in the species Homo sapiens

Transmembrane epididymal protein 1 is a transmembrane protein encoded by the TEDDM1 gene. TEDDM1 is also commonly known as TMEM45C and encodes 273 amino acids that contains six alpha-helix transmembrane regions. The protein contains a 118 amino acid length family of unknown function. While the exact function of TEDDM1 is not understood, it is predicted to be an integral component of the plasma membrane.

References

  1. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000024180 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ Martin J, Han C, Gordon LA, Terry A, Prabhakar S, She X, Xie G, Hellsten U, Chan YM, Altherr M, Couronne O, Aerts A, Bajorek E, Black S, Blumer H, Branscomb E, Brown NC, Bruno WJ, Buckingham JM, Callen DF, et al. (December 2004). "The sequence and analysis of duplication-rich human chromosome 16" (PDF). Nature. 432 (7020): 988–94. Bibcode:2004Natur.432..988M. doi: 10.1038/nature03187 . PMID   15616553. S2CID   4362044.
  5. ↑ Dib C, Fauré S, Fizames C, Samson D, Drouot N, Vignal A, Millasseau P, Marc S, Hazan J, Seboun E, Lathrop M, Gyapay G, Morissette J, Weissenbach J (1996). "A comprehensive genetic map of the human genome based on 5,264 microsatellites". Nature. 380 (6570): 152–4. Bibcode:1996Natur.380..152D. doi:10.1038/380152a0. PMID   8600387. S2CID   28950185.
  6. ↑ Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR (February 2001). "Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16". Hum. Mol. Genet. 10 (4): 339–52. doi: 10.1093/hmg/10.4.339 . PMID   11157797.
  7. ↑ "PGAP6 Gene - GeneCards | PGAP6 Protein | PGAP6 Antibody".
  8. 1 2 Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (October 1990). "Basic local alignment search tool". J. Mol. Biol. 215 (3): 403–10. doi:10.1016/S0022-2836(05)80360-2. PMID   2231712. S2CID   14441902.
  9. ↑ "Tmem8 transmembrane protein 8 [Mus musculus (house mouse)] - Gene - NCBI".
  10. ↑ Brendel V, Bucher P, Nourbakhsh IR, Blaisdell BE, Karlin S (March 1992). "Methods and algorithms for statistical analysis of protein sequences". Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2002–6. Bibcode:1992PNAS...89.2002B. doi: 10.1073/pnas.89.6.2002 . PMC   48584 . PMID   1549558.
  11. ↑ Kansas GS, Saunders KB, Ley K, Zakrzewicz A, Gibson RM, Furie BC, Furie B, Tedder TF (February 1994). "A role for the epidermal growth factor-like domain of P-selectin in ligand recognition and cell adhesion". J. Cell Biol. 124 (4): 609–18. doi:10.1083/jcb.124.4.609. PMC   2119911 . PMID   7508943.
  12. ↑ Prediction of N-glycosylation sites in human proteins. R. Gupta, E. Jung and S. Brunak. In preparation, 2004.
  13. ↑ Motohashi T, Miyoshi S, Osawa M, Eyre HJ, Sutherland GR, Matsuda Y, Nakamura Y, Shibuya A, Iwama A, Nakauchi H (September 2000). "Molecular cloning and chromosomal mapping of a novel five-span transmembrane protein gene, M83". Biochem. Biophys. Res. Commun. 276 (1): 244–50. doi:10.1006/bbrc.2000.3409. hdl: 2241/1570 . PMID   11006113.
  14. ↑ Ota T, Suzuki Y, Nishikawa T, et al. (January 2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi: 10.1038/ng1285 . PMID   14702039.
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