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词条 TMEM63A
释义

  1. Gene

     Overview  Gene neighborhood  Expression 

  2. Protein

     Properties and characteristics  Interactions   Function  

  3. Evolutionary history

     Paralogs  Ortholog space 

  4. References

  5. Further reading

{{Infobox_gene}}Transmembrane protein 63A is a protein that in humans is encoded by the TMEM63A gene.[1][2][3] The mature human protein is approximately 92.1 kilodaltons (kDa), with a relatively high conservation of mass in orthologs.[4] The protein contains eleven transmembrane domains and is inserted into the membrane of the lysosome.[5][6] 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.[7]

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.[3] Aliases include KIAA0489 and KIAA0792. The human gene product is a 4,469 base pair mRNA with 25 predicted exons.[8] There are 9 predicted splice isoforms of the gene, three of which are protein coding. Promoter analysis was carried out using El Dorado[9] 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.[3] 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.[7][10] Moderate relative levels of expression are also observed throughout the brain, particularly in the occipital lobe, parietal lobe, and pancreas.[10] 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.[7] 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.[9] The 3’ UTR is predicted to be bound by the regulatory element miR-9/9ab.[11]

Protein

Properties and characteristics

The mature form of the human TMEM63A protein has 807 amino acid residues with an isoelectric point of 6.925.[4] 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).[12] 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.[13] 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.[14] There are three likely sites of phosphorylation on the protein: S85, S98, and S735, which were predicted using the NetPhos program.[15]

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.[4]

Interactions

Using text-based information, TMEM63A is thought to potentially interact with six other proteins: EEF1D,[16] FAM163B, CPNE9, TMEM90A, STAC2, HEATR3, and WDR67.[17]

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.[18] Another found it to be in a quantitative trait locus linked to haloperidol-induced catalepsy.[19]

Evolutionary history

Paralogs

TMEM63A has two paralogs: TMEM63B, which is located at 6p21.1, and TMEM63C, which is located at C14orf171.[20] Alignment between them shows that TMEM63C is more closely related to TMEM63B than TMEM63A.[4] 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.[12] 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 species Common name Class Accession Percent identity
Otolemur garnettii Bush baby Mammalia XP_003791028.191%
Vicugna pacos Alpaca Mammalia XP_006198896.1 92%
Mus musculus Mouse Mammalia NP_659043.1 90%
Trichechus manatus latirostris West Indian manatee Mammalia XP_004375949.1 89%
Canis lupis familiaris Dog Mammalia NP_001274088.1 89%
Myotis davidii Mouse-eared bat Mammalia XP_006761379.1 80%
Pelodiscus sinensis Chinese softshell turtle Sauropsida XP_006118107.1 71%
Alligator sinensis Chinese alligator Reptilia XP_006016630.1 70%
Ficedula albicollis Collared flycatcher Aves XP_005043078.1 69%
Gallus gallus Red junglefowl Aves XP_419384.3 68%
Xenopus tropicalis Western clawed frog Amphibia NP_001072343.1 65%
Ictalurus punctatus Channel catfish Actinopterygii AHH42519.1 54%
Culex quinquefasciatus Southern house mosquito Insecta XP_001861445.1 34%
Clonorchis sinensis Chinese liver fluke Trematoda GAA53916.1 23%
Oryza sativa Asian rice Liliopsida NP_001065504.1 20%
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References

1. ^{{cite journal | vauthors = Nagase T, Ishikawa K, Suyama M, Kikuno R, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O | title = 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 | journal = DNA Res | volume = 5 | issue = 5 | pages = 277–86 |date=Apr 1999 | pmid = 9872452 | pmc = | doi =10.1093/dnares/5.5.277 }}
2. ^{{cite journal | vauthors = Seki N, Ohira M, Nagase T, Ishikawa K, Miyajima N, Nakajima D, Nomura N, Ohara O | title = Characterization of cDNA clones in size-fractionated cDNA libraries from human brain | journal = DNA Res | volume = 4 | issue = 5 | pages = 345–9 |date=Feb 1998 | pmid = 9455484 | pmc = | doi =10.1093/dnares/4.5.345 }}
3. ^1 2 {{cite web | title = Entrez Gene: TMEM63A transmembrane protein 63A| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9725| accessdate = }}
4. ^1 2 3 {{cite web|title=TMEM63A Analysis|url=http://seqtool.sdsc.edu/CGI/BW.cgi|work=Biology Workbench|publisher=San Diego Supercomputing Center- University of California San Diego|accessdate=8 May 2014}}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}
5. ^{{cite journal| vauthors= Schroder BA, Wrocklage C, Hasilik A, Saftig P |title=The Proteome of Lysosomes|journal=Proteomics|date=19 October 2010|volume=10|issue=22|pages=4053–4076|doi=10.1002/pmic.201000196|pmid=20957757}}
6. ^{{cite journal| vauthors= Schroder BA, Wrocklage C, Pan C, Jager R, Kosters B, Schafer H, Elsasser HP, Mann M, Hasilik A |title=Integral and Associated Lysosomal Membrane Proteins|journal=Traffic|date=28 August 2007|volume=8|issue=12|pages=1676–1686|doi=10.1111/j.1600-0854.2007.00643.x|pmid=17897319}}
7. ^1 2 {{cite web| title= BioGPS: TMEM63A|url=http://biogps.org/#goto=genereport&id=9725|accessdate= 12 May 2014}}
8. ^{{cite web|title=Ensembl: TMEM63A|url= http://useast.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000196187;r=1:226033237-226070069|accessdate=8 May 2014}}
9. ^1 {{cite web|title=El Dorado|url=http://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=ea25554559dc59a06b1d8f7bfe784e26;RESULT=TMEM63A|publisher=Genomatix|accessdate=17 April 2014}}
10. ^1 {{cite web|title=GDS596/214833_at/TMEM63A|url=https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS596:214833_at|publisher=NCBI}}
11. ^{{cite web|title=TargetScanHuman 6.2|url=http://www.targetscan.org/|publisher= Whitehead Institute for Biomedical Research|accessdate=23 April 2014}}
12. ^1 {{cite journal |vauthors=Marchler-Bauer A, etal | title = CDD: A Conserved Domain Database for the functional annotation of proteins. | journal = Nucleic Acids Res | volume = 39 | issue = D | pages = 225–229 |date=2011| url=https://www.ncbi.nlm.nih.gov/Structure/cdd/wrpsb.cgi?SEQUENCE=NP_055513.2&FULL |doi=10.1093/nar/gkq1189 | pmid=21109532 | pmc=3013737}}
13. ^{{cite web|title=O94886 (TM63A_HUMAN)|url=https://www.uniprot.org/uniprot/O94886|publisher=UniProtKB|accessdate=5 May 2014}}
14. ^{{cite journal|vauthors=Gupta R, Jung E, Brunak S|title=Prediction of N-glycosylation sites in human proteins|date=2004|url=http://www.cbs.dtu.dk/services/NetNGlyc/}}
15. ^{{cite journal|vauthors=Blorn N, Gammeltoft S, Brunak S|title=Sequence- and structure-based prediction of eukaryotic protein phosphorylation sites|date=1999|journal=Journal of Molecular Biology|volume=294|issue=5|pages=1351–1362|doi=10.1006/jmbi.1999.3310|pmid=10600390}}
16. ^{{cite web|title=GeneCards|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM63A&search=TMEM63A|publisher=Weizmann Institute of Science|accessdate=16 May 2014}}
17. ^{{cite web|title=String Database|url=http://string-db.org/newstring_cgi/show_network_section.pl|accessdate=16 May 2014}}
18. ^{{cite journal |vauthors=Bonnet E, Tatari M, Joshi A, etal | title=Module network inference from a cancer gene expression data set identifies microRNA regulated modules. | journal=PLoS ONE | date=2010 | volume=5| issue =4| pages=e10162 |doi=10.1371/journal.pone.0010162 | pmid=20418949 | pmc=2854686 }}
19. ^{{cite journal| vauthors=Hofstetter JR, Hitzemann RJ, Belknap JK, Walter NA, McWeeney SK, Mayeda AR| title= Characterization of the quantitative trait locus for haloperidol-induced catalepsy on distal mouse chromosome 1| journal=Genes, Brain and Behavior|date= 2008|volume=7| issue= 2|pages=214–223| doi=10.1111/j.1601-183x.2007.00340.x| pmid= 17696997}}
20. ^{{cite journal | vauthors = Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ | title = Basic local alignment search tool | journal = J. Mol. Biol. | volume = 215 | issue = 3 | pages = 403–10 |date=October 1990 | pmid = 2231712 | doi = 10.1016/S0022-2836(05)80360-2}}

Further reading

{{refbegin | 2}}
  • {{cite journal |vauthors=Gregory SG, Barlow KF, McLay KE, etal |title=The DNA sequence and biological annotation of human chromosome 1. |journal=Nature |volume=441 |issue= 7091 |pages= 315–21 |year= 2006 |pmid= 16710414 |doi= 10.1038/nature04727 }}
  • {{cite journal |vauthors=Gerhard DS, Wagner L, Feingold EA, etal |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 | pmc=528928 }}
  • {{cite journal |vauthors=Ota T, Suzuki Y, Nishikawa T, etal |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 }}
  • {{cite journal |vauthors=Strausberg RL, Feingold EA, Grouse LH, etal |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 | pmc=139241 }}
  • {{cite journal |vauthors=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1–2 |pages= 149–56 |year= 1997 |pmid= 9373149 |doi=10.1016/S0378-1119(97)00411-3 }}
  • {{cite journal | vauthors=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1–2 |pages= 171–4 |year= 1994 |pmid= 8125298 |doi=10.1016/0378-1119(94)90802-8 }}
{{refend}}
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