TMEM63A

Last updated
TMEM63A
Identifiers
Aliases TMEM63A , KIAA0792, transmembrane protein 63A, HLD19
External IDs MGI: 2384789; HomoloGene: 101673; GeneCards: TMEM63A; OMA:TMEM63A - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9725

208795

Ensembl

ENSG00000196187

ENSMUSG00000026519

UniProt

O94886

Q91YT8

RefSeq (mRNA)

NM_014698

NM_144794

RefSeq (protein)

NP_055513

NP_659043

Location (UCSC) Chr 1: 225.85 – 225.88 Mb Chr 1: 180.77 – 180.8 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Transmembrane protein 63A is a protein that in humans is encoded by the TMEM63A gene. [5] [6] [7] The mature human protein is approximately 92.1 kilodaltons (kDa), with a relatively high conservation of mass in orthologs. [8] The protein contains eleven transmembrane domains and is inserted into the membrane of the lysosome. [9] [10] 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. [11]

Contents

Gene

Overview

TMEM63A is located on the negative DNA strand of chromosome 1 at location 1q42.12, spanning base pairs 226,033,237 to 226,070,069. [7] Aliases include KIAA0489 and KIAA0792. The human gene product is a 4,469 base pair mRNA with 25 predicted exons. [12] There are 9 predicted splice isoforms of the gene, three of which are protein coding. Promoter analysis was carried out using El Dorado [13] through the Genomatix software page. The predicted promoter region spans 971 base pairs, from 226,070,920 to 226,069,950 on the negative strand of chromosome 1.

Gene neighborhood

TMEM63A is located adjacent to the EPHX1 gene on the positive sense strand of DNA on chromosome 1, as well as the LEFTY1 gene on the negative sense strand. [7] Other genes in the same area on chromosome 1 include SRP9 and LEFTY3 on the positive strand, and MIR6741 and PYCR2 on the negative strand.

Expression

TMEM63 is ubiquitously expressed throughout the human body at varying levels, occurring with the highest relative prevalence in CD 8+ T cells and CD 4+ T cells. [11] [14] Moderate relative levels of expression are also observed throughout the brain, particularly in the occipital lobe, parietal lobe, and pancreas. [14] Analysis of TMEM63A expression in the mouse using BioGPS revealed more variable expression patterns, with the highest expression being seen in the stomach and large intestine. [11] Using the El Dorado program from Genomatix, transcription factor regulation was predicted, which found that ‘’TMEM63A’’ is highly regulated by E2F cell cycle regulators and EGR1, a factor believed to be a tumor suppressor gene with expression in the brain. [13] The 3’ UTR is predicted to be bound by the regulatory element miR-9/9ab. [15]

Protein

Properties and characteristics

The mature form of the human TMEM63A protein has 807 amino acid residues with an isoelectric point of 6.925. [8] This is fairly conserved across orthologs. A BLAST alignment revealed that the protein contains three domains: RSN1_TM and two domains of unknown function (DUF4463 and DUF221). [16] RSN1_TM is predicted to be involved in Golgi vesicle transport and exocytosis. DUF4463 is cytosolic and distantly homologous to RNA-binding proteins. This domain can be used to determine the orientation of the protein in the membrane, with the N-terminus of the protein being within the lysosome and the C-terminus located in the cytosol.

Post-translational modification has been determined both experimentally and using bioinformatic analysis. There are two likely sites of glycosylation on the protein: N38 and N450. [17] These were predicted using the NetNGlyc program from ExPASy and the TMEM63A amino acid sequence, as well as the inferred orientation of the protein in the membrane. [18] There are three likely sites of phosphorylation on the protein: S85, S98, and S735, which were predicted using the NetPhos program. [19]

The protein has three isoforms. The mature protein is designated isoform CRA. The other two isoforms are X1 and X2, which are 630 amino acid residues and 468 amino acid residues long, respectively. Isoform X1 is missing the N-terminus of the mature protein, while isoform 2 is missing the C-terminus. [8]

Interactions

Using text-based information, TMEM63A is thought to potentially interact with six other proteins: EEF1D, [20] FAM163B, CPNE9, TMEM90A, STAC2, HEATR3, and WDR67. [21]

Function

The function of TMEM63A is not known, although one study found it was in a region likely regulated by mir-200a, linked to epithelial homeostasis. [22] Another found it to be in a quantitative trait locus linked to haloperidol-induced catalepsy. [23]

Evolutionary history

Paralogs

TMEM63A has two paralogs: TMEM63B, which is located at 6p21.1, and TMEM63C, which is located at C14orf171. [24] Alignment between them shows that TMEM63C is more closely related to TMEM63B than TMEM63A. [8] A BLAST alignment showed homology of TMEM63A and TMEM63B to proteins as distantly related as plants, while TMEM63C was homologous only as distantly as in drosophila. [16] This indicates that TMEM63C likely diverged from the two early in invertebrates.

Ortholog space

TMEM63A has a large ortholog space, with homologs present in organisms as distantly related as plants.

Genus and speciesCommon nameClassAccessionPercent identity
Otolemur garnettii Bush baby MammaliaXP_003791028.1 91%
Vicugna pacos Alpaca MammaliaXP_006198896.192%
Mus musculus Mouse MammaliaNP_659043.190%
Trichechus manatus latirostris West Indian manatee MammaliaXP_004375949.189%
Canis lupus familiaris Dog MammaliaNP_001274088.189%
Myotis davidii Mouse-eared bat MammaliaXP_006761379.180%
Pelodiscus sinensis Chinese softshell turtle SauropsidaXP_006118107.171%
Alligator sinensis Chinese alligator ReptiliaXP_006016630.170%
Ficedula albicollis Collared flycatcher AvesXP_005043078.169%
Gallus gallus Red junglefowl AvesXP_419384.368%
Xenopus tropicalis Western clawed frog AmphibiaNP_001072343.165%
Ictalurus punctatus Channel catfish ActinopterygiiAHH42519.154%
Culex quinquefasciatus Southern house mosquito InsectaXP_001861445.134%
Clonorchis sinensis Chinese liver fluke TrematodaGAA53916.123%
Oryza sativa Asian rice LiliopsidaNP_001065504.120%

Related Research Articles

<span class="mw-page-title-main">TRAPPC14</span> Human protein-coding gene on chromosome 7

TRAPPC14 also known as MAP11 is a protein that in human is encoded by the gene TRAPPC14. It was previously referred to by the generic name C7orf43. C7orf43 has no other human alias, but in mice can be found as BC037034.

<span class="mw-page-title-main">RNF128</span> Protein-coding gene in the species Homo sapiens

E3 ubiquitin-protein ligase RNF128 is an enzyme that in humans is encoded by the RNF128 gene.

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

HIKESHI is a protein important in lung and multicellular organismal development that, in humans, is encoded by the HIKESHI gene. HIKESHI is found on chromosome 11 in humans and chromosome 7 in mice. Similar sequences (orthologs) are found in most animal and fungal species. The mouse homolog, lethal gene on chromosome 7 Rinchik 6 protein is encoded by the l7Rn6 gene.

<span class="mw-page-title-main">FAM214A</span> Protein-coding gene in the species Homo sapiens

Protein FAM214A, also known as protein family with sequence similarity 214, A (FAM214A) is a protein that, in humans, is encoded by the FAM214A gene. FAM214A is a gene with unknown function found at the q21.2-q21.3 locus on Chromosome 15 (human). The protein product of this gene has two conserved domains, one of unknown function (DUF4210) and another one called Chromosome_Seg. Although the function of the FAM214A protein is uncharacterized, both DUF4210 and Chromosome_Seg have been predicted to play a role in chromosome segregation during meiosis.

<span class="mw-page-title-main">PRR29</span> Protein-coding gene in the species Homo sapiens

PRR29 is a protein encoded by the PRR29 gene located in humans on chromosome 17 at 17q23.

<span class="mw-page-title-main">TMEM44</span> Protein-coding gene in the species Homo sapiens

TMEM44 is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.

<span class="mw-page-title-main">Chromosome 9 open reading frame 43</span> Protein-coding gene in the species Homo sapiens

Chromosome 9 open reading frame 43 is a protein that in humans is encoded by the C9orf43 gene. The gene is also known as MGC17358 and LOC257169. C9orf43 contains DUF 4647 and a polyglutamine repeat region although protein function is not well understood.

<span class="mw-page-title-main">C9orf50</span> Protein-coding gene in the species Homo sapiens

Chromosome 9 open reading frame 50 is a protein that in humans is encoded by the C9orf50 gene. C9orf50 has one other known alias, FLJ35803. In humans the gene coding sequence is 10,051 base pairs long, transcribing an mRNA of 1,624 bases that encodes a 431 amino acid protein.

LOC101928193 is a protein which in humans is encoded by the LOC101928193 gene. There are no known aliases for this gene or protein. Similar copies of this gene, called orthologs, are known to exist in several different species across mammals, amphibians, fish, mollusks, cnidarians, fungi, and bacteria. The human LOC101928193 gene is located on the long (q) arm of chromosome 9 with a cytogenic location at 9q34.2. The molecular location of the gene is from base pair 133,189,767 to base pair 133,192,979 on chromosome 9 for an mRNA length of 3213 nucleotides. The gene and protein are not yet well understood by the scientific community, but there is data on its genetic makeup and expression. The LOC101928193 protein is targeted for the cytoplasm and has the highest level of expression in the thyroid, ovary, skin, and testes in humans.

<span class="mw-page-title-main">LSMEM2</span> Protein-coding gene in the species Homo sapiens

Leucine rich single-pass membrane protein 2 is a single-pass membrane protein rich in leucine, that in humans is encoded by the LSMEM2 gene. The LSMEM2 protein is conserved in mammals, birds, and reptiles. In humans, LSMEM2 is found to be highly expressed in the heart, skeletal muscle and tongue.

<span class="mw-page-title-main">FAM155B</span> Protein-coding gene in humans

Family with Sequence Similarity 155 Member B is a protein in humans that is encoded by the FAM155B gene. It belongs to a family of proteins whose function is not yet well understood by the scientific community. It is a transmembrane protein that is highly expressed in the heart, thyroid, and brain.

TMEM275 is a protein that in humans is encoded by the TMEM275 gene. TMEM275 has two, highly-conserved, helical trans-membrane regions. It is predicted to reside within the plasma membrane or the endoplasmic reticulum's membrane.

<span class="mw-page-title-main">TMEM169</span> Gene

Transmembrane protein 169 (TMEM169) in humans is encoded by TMEM169 gene. The aliases of TMEM169 include FLJ34263, DKFZp781L2456, and LOC92691. TMEM169 has the highest expression in the brain, particularly the fetal brain. TMEM169 has homologs mammals, reptiles, amphibians, birds, fish, chordates and invertebrates. The most distantly related homolog of TMEM169 is Anopheles albimanus.

<span class="mw-page-title-main">C9orf85</span> Protein-coding gene in the species Homo sapiens

Chromosome 9 open reading frame 85, commonly known as C9orf85, is a protein in Homo sapiens encoded by the C9orf85 gene. The gene is located at 9q21.13. When spliced, four different isoforms are formed. C9orf85 has a predicted molecular weight of 20.17 kdal. Isoelectric point was found to be 9.54. The function of the gene has not yet been confirmed, however it has been found to show high levels of expression in cells of high differentiation.

<span class="mw-page-title-main">TMEM101</span> Protein and gene in humans

Transmembrane protein 101 (TMEM101) is a protein that in humans is encoded by the TMEM101 gene. The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have been linked to breast cancer.

<span class="mw-page-title-main">CCDC190</span> Protein found in humans

Coiled-Coil Domain Containing 190, also known as C1orf110, the Chromosome 1 Open Reading Frame 110, MGC48998 and CCDC190, is found to be a protein coding gene widely expressed in vertebrates. RNA-seq gene expression profile shows that this gene selectively expressed in different organs of human body like lung brain and heart. The expression product of c1orf110 is often called Coiled-coil domain-containing protein 190 with a size of 302 aa. It may get the name because a coiled-coil domain is found from position 14 to 72. At least 6 spliced variants of its mRNA and 3 isoforms of this protein can be identified, which is caused by alternative splicing in human.

<span class="mw-page-title-main">PANO1</span> Mammalian protein found in Homo sapiens

PANO1 is a protein which in humans is encoded by the PANO1 gene. PANO1 is an apoptosis inducing protein that is able to regulate the function of tumor suppressor. More specifically, P14ARF is a protein in which in humans is modulated by the PANO1 gene. P14ARF is known to function as a tumor suppressor. When PANO1 is highly expressed in the cells, it is able to modulate p14ARF by stabilizing it and protecting it from degradation. With a confidence level of 5 out of 5, PANO1 has been theorized to be expressed in the nucleolus of the cell. PANO1 is an intron-less gene. Intron-less genes only make up about 3% of the human genome. A functional analysis of these types of genes revealed that they often have tissue-specific expression in tissues such as the nervous system and testis. This kind of expression is commonly associated with neuropathies, disease, and cancer. The tissue types that PANO1 has the highest expression in, are the cerebellum regions of the brain as well as pituitary and testis tissues.

<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 five 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">TMEM269</span> TMEM269 Protein

Transmembrane Protein 269 (TMEM269) is a protein which in humans is encoded by the TMEM269 gene.

<span class="mw-page-title-main">C10orf53</span> Human gene

C10orf53 is a protein that in humans is encoded by the C10orf53 gene. The gene is located on the positive strand of the DNA and is 30,611 nucleotides in length. The protein is 157 amino acids and the gene has 3 exons. C10orf53 orthologs are found in mammals, birds, reptiles, amphibians, fish, and invertebrates. It is primarily expressed in the testes and at very low levels in the cerebellum, liver, placenta, and trachea.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000196187 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000026519 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Apr 1999). "Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro". DNA Res. 5 (5): 277–86. doi: 10.1093/dnares/5.5.277 . PMID   9872452.
  6. ↑ Seki N, Ohira M, Nagase T, Ishikawa K, Miyajima N, Nakajima D, Nomura N, Ohara O (Feb 1998). "Characterization of cDNA clones in size-fractionated cDNA libraries from human brain". DNA Res. 4 (5): 345–9. doi: 10.1093/dnares/4.5.345 . PMID   9455484.
  7. 1 2 3 "Entrez Gene: TMEM63A transmembrane protein 63A".
  8. 1 2 3 4 "TMEM63A Analysis". Biology Workbench. San Diego Supercomputing Center- University of California San Diego. Retrieved 8 May 2014.[ permanent dead link ]
  9. ↑ Schroder BA, Wrocklage C, Hasilik A, Saftig P (19 October 2010). "The Proteome of Lysosomes". Proteomics. 10 (22): 4053–4076. doi:10.1002/pmic.201000196. PMID   20957757. S2CID   25869334.
  10. ↑ Schroder BA, Wrocklage C, Pan C, Jager R, Kosters B, Schafer H, Elsasser HP, Mann M, Hasilik A (28 August 2007). "Integral and Associated Lysosomal Membrane Proteins". Traffic. 8 (12): 1676–1686. doi: 10.1111/j.1600-0854.2007.00643.x . PMID   17897319.
  11. 1 2 3 "BioGPS: TMEM63A" . Retrieved 12 May 2014.
  12. ↑ "Ensembl: TMEM63A" . Retrieved 8 May 2014.
  13. 1 2 "El Dorado". Genomatix. Retrieved 17 April 2014.[ permanent dead link ]
  14. 1 2 "GDS596/214833_at/TMEM63A". NCBI.
  15. ↑ "TargetScanHuman 6.2". Whitehead Institute for Biomedical Research. Retrieved 23 April 2014.
  16. 1 2 Marchler-Bauer A, et al. (2011). "CDD: A Conserved Domain Database for the functional annotation of proteins". Nucleic Acids Res. 39 (D): 225–229. doi:10.1093/nar/gkq1189. PMC   3013737 . PMID   21109532.
  17. ↑ "O94886 (TM63A_HUMAN)". UniProtKB. Retrieved 5 May 2014.
  18. ↑ Gupta R, Jung E, Brunak S (2004). "Prediction of N-glycosylation sites in human proteins".{{cite journal}}: Cite journal requires |journal= (help)
  19. ↑ Blorn N, Gammeltoft S, Brunak S (1999). "Sequence- and structure-based prediction of eukaryotic protein phosphorylation sites". Journal of Molecular Biology. 294 (5): 1351–1362. doi:10.1006/jmbi.1999.3310. PMID   10600390.
  20. ↑ "GeneCards". Weizmann Institute of Science. Retrieved 16 May 2014.
  21. ↑ "String Database" . Retrieved 16 May 2014.
  22. ↑ Bonnet E, Tatari M, Joshi A, et al. (2010). "Module network inference from a cancer gene expression data set identifies microRNA regulated modules". PLOS ONE. 5 (4): e10162. Bibcode:2010PLoSO...510162B. doi: 10.1371/journal.pone.0010162 . PMC   2854686 . PMID   20418949.
  23. ↑ Hofstetter JR, Hitzemann RJ, Belknap JK, Walter NA, McWeeney SK, Mayeda AR (2008). "Characterization of the quantitative trait locus for haloperidol-induced catalepsy on distal mouse chromosome 1". Genes, Brain and Behavior. 7 (2): 214–223. doi: 10.1111/j.1601-183x.2007.00340.x . PMID   17696997.
  24. ↑ 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.

Further reading

This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.