View source for TMEM131

{{Short description|Protein-coding gene in the species Homo sapiens}}
{{Infobox_gene}}
'''Transmembrane protein 131''' (TMEM131) is a [[protein]] that is encoded by the ''TMEM131'' [[gene]] in humans.<ref name="NCBI TMEM131 Prot">{{cite web | title = NCBI Protein: TMEM131| url = https://www.ncbi.nlm.nih.gov/protein/150456424| accessdate = 15 April 2012}}</ref>  The TMEM131 protein contains three domains of unknown function 3651 (DUF3651)<ref name="DUF 3651">{{cite web|title=DUF 3651|url=http://pfam.sanger.ac.uk/family/PF12371|accessdate=28 April 2012}}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref>  and two [[transmembrane domain]]s.<ref name="NCBI TMEM131 Prot"/>  This protein has been implicated as having a role in [[T cell]] function and development.<ref name="TMEM131 Methylation">{{cite journal|last=Kerkel|first=Kristi|title=Altered DNA Methylation in Leukocytes with Trisomy 21|journal=PLOS Genet|date=November 2010|volume=6|issue=11|doi=10.1371/journal.pgen.1001212|pmc=2987931|pmid=21124956|pages=e1001212 |doi-access=free }}</ref><ref name="TMEM131 T Cell Development">{{cite journal|last=Tydell|first=Chace|title=Molecular Dissection of Prethymic Progenitor Entry into the T Lymphocyte Developmental Pathway|journal=The Journal of Immunology|date=1 July 2007|volume=179|issue=1|pages=421–438|url=http://www.jimmunol.org/content/179/1/421.long|accessdate=28 April 2012|doi=10.4049/jimmunol.179.1.421|pmid=17579063|doi-access=free}}</ref> ''TMEM131'' also resides in a locus (2q11.1) that is associated with [[Nievergelt's Syndrome]] when deleted.<ref name="2q11.1 Deletion">{{cite journal|last=Steucgen-Gersdorf|first=E|journal=Clinical Genetics|date=December 2008|volume=74|issue=6|pmid=18616733|doi=10.1111/j.1399-0004.2008.01050.x|title=Triangular tibia with fibular aplasia associated with a microdeletion on 2q11.2 encompassing LAF4|pages=560–5|s2cid=32617869}}</ref>
==Role In T Cell Function==
''TMEM131'' has been shown to exhibit [[methylation|hypermethylation]] in patients with [[Down Syndrome]].<ref name="TMEM131 Methylation"/> The authors of this study proposed that, given TMEM131s supposed function in T cell development and function, this hypermethylation may play a role in the suppressed immune function in patients with Down Syndrome.
TMEM131 has also been shown to be up-regulated during the development and differentiation of T cells,<ref name="TMEM131 T Cell Development"/> and has been shown to have relatively high levels of expression in T cells relative to other tissue types.<ref name=GDS596/>
== Gene  ==
===Overview===
[[File:TMEM131 Promoter Schematic Representation.jpg|thumb|200px|right|Predicted promoter sequence layout as well as potential transcriptional start sites (TSS) as predicted by the Genomatix ''El Dorado'' tool.<ref name="El Dorado"/>]]
''TMEM131'' is located on the negative DNA strand (see [[Sense (molecular biology)|Sense]]) of [[chromosome 2]] from 98,372,799 - 98,612,354.<ref name="Gene Locus: TMEM131"/> The gene product is a 6,657 [[base pair]] [[mRNA]] with 41 predicted [[exons]] in the human gene.<ref name="NCBI TMEM131 Prot"/> Ensembl predicts ten alternative splice forms, four of which are protein coding.<ref name="Ensembl: TMEM131">{{cite web|title=Ensembl: TMEM131|url=http://useast.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000075568;gene=ENSG00000075568;r=2:98372799-98612388|accessdate=28 April 2012}}</ref>
Promoter prediction and analysis was carried out using ''El Dorado''<ref name="El Dorado">{{cite web|title=El Dorado|url=http://www.genomatix.de/cgi-bin/eldorado/eldorado.pl?s=ea25554559dc59a06b1d8f7bfe784e26;RESULT=TMEM131_3|publisher=Genomatix|accessdate=5 May 2012}}</ref> through the Genomatix software page.<ref name=Genomatix>{{cite web|title=Genomatix|url=http://www.genomatix.de/|publisher=Genomatix|accessdate=5 May 2012|archive-date=2 December 2021|archive-url=https://web.archive.org/web/20211202010908/https://www.genomatix.de/|url-status=dead}}</ref> The predicted promoter region spans 1002 base pairs from 98,611,892 through 98,612,893 on the minus strand of chromosome 2. The program predicted two potential transcriptional start locations. The first spans 216 base pairs from 98,612,501 through 98,612,716. The second spans 182 base pairs from 98,612,262 through 98,612,443.
=== Gene Neighborhood ===
''TMEM131'' is located directly adjacent to the ''[[ZAP70]]'' gene (98,330,331 - 98,356,323) on the positive DNA strand, as well as numerous [[pseudogene]]s at the 2q11.2 [[locus (genetics)|locus]]. A [[Von Willebrand factor]] containing gene (VWA3B) is located upstream from ''TMEM131'' on the positive strand (98,703,595 - 98,929,410).<ref name="Gene Locus: TMEM131">{{cite web|title=TMEM131: 23505|url=https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=retrieve&list_uids=23505|accessdate=28 April 2012}}</ref>
=== Gene Expression ===
[[File:Insitu131952.jpg|thumb|200px|right|Example of ''in situ'' hybridization data available from BDGP (stage 11 shown).<ref name="in situ Fly Expression"/>]]
''TMEM131'' is expressed in low to moderate levels throughout most of the body, with slightly increased levels occurring in the [[lymph node]]s, [[uterus]] and T cells.<ref name=GDS596>{{cite web|title=GDS596 / TMEM131 / Homo Sapiens - Gene expression profile from 79 physiologically normal tissues|url=https://www.ncbi.nlm.nih.gov/geo/gds/profileGraph.cgi?&dataset=epLLZXTPZ18VJRg_8JWbMK1Qk8T28XK2C1YiY14cPy2627CFYNLKPOGKHHGKHGIICFLUHSMVHAIIEH--88IAgS__6_-Z19W3AG4X6UHGFGHKLIFIHGKRVQTJzDFFOOUTJSPLVUTbLNX0TU1U9TBFGMDCGHYOQI&dataset=mp438af-ccia6eiaeVdj30hcb7fkjb3fOaalhlaaSa-apoX5gefeqpjmeacfljmk3dckhnaj3L8b-foprs2Orkjjffljfj-cN-84kaggpolmlkhllkipmjfalLffn7qo5fjfljenjljlnpmjnj5ehmdallrp96$&gmin=53.000000&gmax=819.800000&absc=&uid=4691892&gds=596&idref=212507_at&annot=TMEM131|publisher=NCBI}}</ref> Expression data in developing fruit fly embryos is available from the BDGP ''in situ'' homepage.<ref name="in situ Fly Expression">{{cite web|title=BDGP in situ|url=http://insitu.fruitfly.org/cgi-bin/ex/report.pl?ftype=1&ftext=CG8370|accessdate=4 May 2012}}</ref>
[[File:TMEM131 GDS596 Expression Profile.png|thumb|250px|center|Expression profile from 79 physiologically normal tissues obtained from various sources for TMEM131.<ref name=GDS596/>]]
== Protein ==
===Properties/Characteristics===
[[File:Protein Schematic TMEM131.jpg|thumb|250px|right|Schematic representation of the TMEM131 protein.]]
The primary function of the TMEM131 protein is not well understood. The human form has 1883 [[amino acid]] residues, with an [[isoelectric point]] of 8.74 and a [[molecular mass]] of 205,100 [[Dalton (unit)|dalton]]s.<ref name="SDSC Align Tool"/> It has been shown to contain two transmembrane domains at residues 1,091-1,111 and 1,118-1,138.  Three DUF3651 regions are located on the N-terminal side of the two adjacent transmembrane domains. These are located at residues 173-245, 502-582, and 639-708. The intercellular location of the protein has not been experimentally determined, but it is thought to reside in either the [[plasma membrane]] or [[endoplasmic reticulum]], with each domain on both the N-terminal and C-terminal sides of the transmembrane regions being cytosolic.<ref name="Expasy: Psort">{{cite web|title=Expasy: Psort|url=http://psort.hgc.jp/cgi-bin/runpsort.pl|accessdate=29 April 2012}}{{Dead link|date=June 2018 |bot=InternetArchiveBot |fix-attempted=no }}</ref>  It contains numerous phosphorylation sites which have been shown both experimentally and with bioinformatic tools.<ref name="NCBI TMEM131 Prot"/><ref name="SDSC Align Tool"/> Bioinformatic analysis of the protein using the ''NetPhos'' tool<ref name="NetPhos Article">{{cite journal|last=Blom|first=N.|author2=Gammeltoft, S.|author3=Brunak, S.|title=Sequence- and structure-based prediction of eukaryotic protein phosphorylation sites.|journal=Journal of Molecular Biology|year=1999|volume=294|issue=5|pages=1351–1362|doi=10.1006/jmbi.1999.3310|url=http://www.cbs.dtu.dk/services/NetPhos/abstract.php|accessdate=5 May 2012|pmid=10600390|archive-date=10 August 2021|archive-url=https://web.archive.org/web/20210810122543/http://www.cbs.dtu.dk/services/NetPhos/abstract.php|url-status=dead}}</ref>  predicted 145 potential phosphorylation sites throughout the entire length of the protein.<ref name="NetPhos TMEM131">{{cite web|last=Blom|first=N.|title=NetPhos TMEM131|url=http://www.cbs.dtu.dk/cgi-bin/nph-webface?jobid=netphos,4FA571EC006BD433&opt=none|publisher=NetPhos|accessdate=5 May 2012}}{{Dead link|date=May 2019 |bot=InternetArchiveBot |fix-attempted=yes }}</ref>
=== Protein Interactions ===
Protein interaction analysis for TMEM131 has been carried out using computational tools. No interactions were identified through the MINT database.<ref name="MINT TMEM131">{{cite web|title=MINT TMEM131|url=http://mint.bio.uniroma2.it/mint/search/search.do}}</ref> A STRING search revealed ten possible protein interactions through [[text mining]], although none of these should be considered actual protein-protein interactions.<ref name="STRING TMEM131">{{cite web|title=STRING TMEM131|url=http://string-db.org/newstring_cgi/show_network_section.pl|accessdate=5 May 2012}}</ref>  Closer analysis of the results shows very little potential for these predictions to be real. The IntAct tool was also used, and this revealed a potential interaction had been found with '''Superoxide dismutase 2''' ([[SOD2]]), which had been identified in a [[yeast]] [[Two-hybrid screening]] study.<ref name="IntAct TMEM131">{{cite web|title=IntAct TMEM131|url=http://www.ebi.ac.uk/intact/|accessdate=5 May 2012}}</ref>
== Conservation ==
===Orthologs===
TMEM131 is conserved throughout all of its [[orthologs]]. The entire protein is highly conserved in [[primate]] orthologs, while conservation is high within the DUF3651 and transmembrane regions in the more distant [[homology (biology)|homologs]].<ref name="pmid12824352">{{cite journal |vauthors=Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG, Thompson JD | title = Multiple sequence alignment with the Clustal series of programs | journal = Nucleic Acids Res. | volume = 31 | issue = 13 | pages = 3497–500 |date=July 2003 | pmid = 12824352 | pmc = 168907 | doi =  10.1093/nar/gkg500}}</ref>
Orthologs were found in species as distantly related to [[Humans]] as the [[Choanoflagellate]] ''Monosiga brevicollis'' using [[BLAST (biotechnology)|BLAST]]<ref name="BLAST">{{cite web | title = NCBI BLAST| url =http://blast.ncbi.nlm.nih.gov/Blast.cgi| accessdate = }}</ref> and the ALIGN tool through the San Diego Super Computer Biology Workbench.<ref name="SDSC Align Tool">{{cite web| title = SDSC Biology Workbench| url = http://seqtool.sdsc.edu/| archive-url = https://web.archive.org/web/20030811031200/http://seqtool.sdsc.edu/| url-status = dead| archive-date = 11 August 2003| accessdate = 15 April 2012}}</ref> The following table gives information on the homologs of TMEM131.
{| class="wikitable sortable"
|-
! [[Genus]] [[Species]] !! Organism Common Name !! Divergence from Humans (MYA) <ref name="Time Tree">{{cite web | title = Time Tree| url =http://www.timetree.org/| accessdate = }}</ref> !! NCBI Protein Accession Number !! Sequence Identity <ref name="SDSC Align Tool"/> !! Protein Length !! Common Gene Name
|-
| [[Homo sapiens]]<ref name="NCBI TMEM131 Prot"/> || Humans || -- || NP_056163.1 || 100% || 1883 || TMEM131
|-
| [[Pan troglodytes]]<ref name="Nucleotide: Ptr">{{cite web | title = NCBI Nucleotide: XP_515638.2| url =https://www.ncbi.nlm.nih.gov/protein/114579058| accessdate = 17 April 2012}}</ref> || Common Chimp || 6.2 || XP_515638.2 || 99.6% || 1883 || TMEM131
|-
| [[Bos taurus]]<ref name="Nucleotide: Bta">{{cite web | title = NCBI Nucleotide: XP_613474| url =https://www.ncbi.nlm.nih.gov/protein/XP_613474.6| accessdate = 17 April 2012}}</ref> || Cattle || 96.6 || XP_613474 || 92.1% || 1876 || TMEM131
|-
| [[Mus musculus]]<ref name="Nucleotide: Mmu">{{cite web | title = NCBI Nucleotide: NP_061360.2| url =https://www.ncbi.nlm.nih.gov/protein/NP_061360.2| accessdate = 17 April 2012}}</ref> || Mouse || 94.5 || NP_061360.2 || 89.7% || 1877 || TMEM131
|-
| [[Monodelphis domestica]]<ref name="Nucleotide: Mdo">{{cite web | title = NCBI Nucleotide: XM_001367646.2| url =https://www.ncbi.nlm.nih.gov/protein/334346991| accessdate =28 April 2012 }}</ref> || {{Not a typo|Opossum}} || 170.0 || XM_001367646.2 || 81.3% || 1840 || TMEM131
|-
| [[Gallus gallus]]<ref name="Nucleotide: Ggu">{{cite web | title = NCBI Nucleotide:XM_001233588.2 | url =https://www.ncbi.nlm.nih.gov/protein/363729065| accessdate = }}</ref>|| Chicken || 323.0 || XM_001233588.2 || 76.3% || 1821 || TMEM131
|-
| [[Xenopus tropicalis]]<ref name="Nucleotide: Xtr">{{cite web | title = NCBI Nucleotide: NP_001135552| url =https://www.ncbi.nlm.nih.gov/protein/213982761| accessdate = 28 April 2012}}</ref>|| Frog || 359.0 || NP_001135552 || 70.3% || 1877 || TMEM131
|-
| [[Danio rerio]]<ref name="Nucleotide: Dre">{{cite web | title = NCBI Nucleotide: XP_001923340.1| url =https://www.ncbi.nlm.nih.gov/protein/189520260| accessdate = }}</ref> || Zebra Fish || 436.8 || XP_001923340.1 || 59.6% || 1799 || Predicted: TMEM131
|-
| [[Caenorhabditis elegans]]<ref name="Nucleotide: Cel">{{cite web | title = NCBI Nucleotide: NP_498059.2| url =https://www.ncbi.nlm.nih.gov/protein/np_498059| accessdate =28 April 2012 }}</ref> || Nematode || 274.8 || NP_498059.2 || 24.1% || 1831 || Hypothetical Protein C27F2.8
|-
| [[Drosophila melanogaster]]<ref name="Nucleotide: Dme">{{cite web | title = NCBI Nucleotide: NP_611073.2| url =https://www.ncbi.nlm.nih.gov/protein/np_611073.2| accessdate =28 April 2012 }}</ref> || Fruit Fly || 725.5 || NP_611073.2 || 24.0% || 1567 || CG8370
|-
| [[Monosiga brevicollis]]<ref name="Nucleotide: Mbr">{{cite web | title = NCBI Nucleotide: XP_001744482.1 | url =https://www.ncbi.nlm.nih.gov/protein/xp_001744482.1| accessdate =28 April 2012 }}</ref> || Choanoflagellate || 856.0 || XP_001744482.1  || 21.2% || 1781 || Hypothetical Protein
|-
|}
===Paralog===
TMEM131 has a single paralog, ''TMEM131L'' or ''[[KIAA0922]]''.<ref name="GeneCards: TMEM131L">{{cite web | title = GeneCards: TMEM131L| url =https://www.genecards.org/cgi-bin/carddisp.pl?gene=KIAA0922| accessdate = 17 April 2012 }}</ref> This gene is very similar to TMEM131, but it does not include the second two of the three DUF3651 regions.
== References ==
{{Reflist|2}}