View source for TMEM143

{{Short description|Protein-coding gene in the species Homo sapiens}}
'''TMEM143''' ([[Transmembrane protein]] 143) is a protein that in humans is encoded by TMEM143 gene.<ref name="TMEM143H">{{cite web|title=TMEM143 transmembrane protein 143 [Homo sapiens (human)]|url=https://www.ncbi.nlm.nih.gov/gene/55260|website=NCBI}}</ref> TMEM143, a dual-pass protein (two transmembrane domains), is predicted to reside in the [[mitochondria]]<ref name="phosphosite">{{cite web|title=Tmem143 (human)|url=http://www.phosphosite.org/proteinAction.do?id=4857838&showAllSites=true|website=NCBI}}</ref><ref name="genecards">{{cite web|title=TMEM143 Gene|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM143|website=GeneCards}}</ref> and high expression has been found in both human [[skeletal muscle]] and the [[heart]].<ref name ="geoprofiles">{{cite web|title=TMEM143 - Normal human tissue expression profiling|url=https://www.ncbi.nlm.nih.gov/geoprofiles/?term=tmem143+GDS424|website=NCBI GeoProfiles}}</ref><ref name="aceview" >{{cite web|title=Homo sapiens gene TMEM143, encoding transmembrane protein 143|url=https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=tmem143&submit=Go|website=NCBI-AceView}}</ref> Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.<ref name="cancer interactions" />
==Gene==
Located on the [[negative strand]] of human DNA, TMEM143 spans 31,882 base pairs on human [[chromosome 19]] (19q13.33), neighbored by genes [[Coiled-coil]] domain containing 114 (CCDC114) and ER lumen protein-retaining receptor 1 (KDELR1).<ref name="TMEM143H" />
==Transcript==
In humans, there are five [[transcript variant]]s encoded by TMEM143 gene (1-5). Variant 1 is the longest [[mRNA]] transcript, with a coding region of 2577 [[nucleotides]] (nt) and a total of 8 [[exon]]s,<ref name="TMEM143H" /><ref name="isoforma" >{{cite web|title=transmembrane protein 143 isoform a [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/NP_060743.2|website=NCBI}}</ref> and possibly most indicative of function. Compared to variant 1, variant 2 (2472 nt, 424 amino acid protein) and variant 3 (2382nt, 394 amino acid protein) lack an in-frame exon in the [[5']] coding region while variant 4 (2277 nt, 359 amino acid protein) lacks two in-frame exons in the 5’ coding region, all leading to an N-terminally [[truncation|truncated]] protein.<ref name="TMEM143H" /> Transcript variant 5 is a non-coding RNA, approximately 2231 nt long, resulting in a transcript candidate for nonsense-mediated mRNA.
==Protein==
There are four [[protein isoform]]s,<ref name="TMEM143H" /> corresponding to a matching variant. Variant 1 codes for isoform a (the longest protein), and variants 2, 3, 4 code for isoforms b, c, and d, respectively. TMEM143 isoform a is 459 amino acids in length, has a molecular weight of 51.6 kDa and an [[isoelectric point]] of 9.7 in humans.<ref name="phosphosite" /> A domain of unknown function (DUF3754) is present within which two transmembrane domains reside, 24 and 16 amino acids in length, both helical in nature.<ref name="isoforma" />
[[File:TMEM143 cartoon.png|thumbnail|right|Scheme of TMEM143 protein: gray markers correspond to phosphorylation sites, red markers correspond to kinase-specific phosphorylation sites, and green sections signify transmembrane domains; DUF3754 is also illustrated]]
The transmembrane domains encompass the uncharged region present at amino acids 278 to 302. A predicted mitochondrial [[target peptide]] resides at the N-terminus spanning 52 amino acids before the cleavage site between amino acids M-51 and G-52.<ref>{{cite journal|last1=Claros|first1=Manuel G.|last2=Vincens|first2=Pierre|title=Computational method to predict mitochondrially imported proteins and their targeting sequences|journal=European Journal of Biochemistry|date=November 1996|volume=241|issue=3|pages=240, 770–786|doi=10.1111/j.1432-1033.1996.00779.x|pmid=8944766|doi-access=free}}</ref> In addition, [[phosphorylation]] sites, both general and [[kinase]]-specific, were predicted to be found throughout the protein, indicating the location of the protein inside the cell.<ref>{{cite journal|last1=Blom|first1=Nikolaj|last2=Gammeltoft|first2=Steen|last3=Brunak|first3=Søren|title=Sequence and structure-based prediction of eukaryotic protein phosphorylation sites|journal=Journal of Molecular Biology|date=December 1999|volume=294|issue=5|pages=1351–1362|doi=10.1006/jmbi.1999.3310|pmid=10600390}}</ref><ref>{{cite journal|last1=Blom|first1=Nikolaj|last2=Sicheritz-Pontén|first2=Thomas|last3=Gupta|first3=Ramneek|last4=Gammeltoft|first4=Steen|last5=Brunak|first5=Søren|title=Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence|journal=Proteomics|date=June 2004|volume=4|issue=6|pages=1633–1649|doi=10.1002/pmic.200300771|pmid=15174133|s2cid=18810164 }}</ref>
==Homology==
===Orthologs===
[[Homology (biology)|Orthologs]] have been identified in more than 85 vertebrate species.<ref name="TMEM143H" /> No TMEM143 orthologs have yet to be identified in birds.
There are currently 85 ortholog species, however all exist as vertebrates only (with the exception of birds), the most distant being [[Latimeria chalumnae]] (coelacanth).<ref name="TMEM143H" /> DUF3754 appears in a majority of the orthologs, a generally conserved region, with slight amino acid alterations to the sequence. This domain has been found in organisms as diverse as [[bacteria]] and [[archaea]], however there are no known orthologs in either organismal domain.<ref name="isoforma" />
===Paralogs===
There are no known [[Homology (biology)|paralogs]] for the human TMEM143 sequence.
==Expression and function==
===Tissue presence===
[[File:TMEM143 AceView.png|thumbnail|TMEM143 expression in Humans and other primates; In humans, the heart and skeletal muscle exhibit high expression (18.8 and 16.4, respectively)]]
Possible human expression of TMEM143 protein occurs in [[Jurkat cells]] (T lymphocyte).<ref name="TMEM143H" /> Organelle association puts TMEM143 in the mitochondria as an [[integral protein]] in the membrane,<ref name="phosphosite" /> as well as the predicted of presence in the [[plasma membrane]], [[endoplasmic reticulum]], [[extracellular matrix]] and the [[Golgi apparatus]].<ref name="genecards" />
High expression has been found in the heart and skeletal muscle, as indicated through human expression profiling.<ref name="aceview" /> [[Microarray]] expression of normal human tissues <ref name ="geoprofiles" /> also predict expression in the heart and skeletal muscle, a 95-97 percentile rank (amongst other tissues tested for normal human expression of TMEM143).
===Interactions===
Through [[text mining]], TMEM143 is shown to have interactions with seven different proteins in humans: Zinc finger protein 541 (ZNF541), DNA-damage inducible 1 homolog 2 (DD12), Paraneoplastic Ma antigen family-like 2 (PNMAL2), Kelch-like 31(JLHL31), Chromosome 14 [[open reading frame]] 28 (C14orf28), Chromosome 14 open reading frame 28 (TRIN71), and Cytoplasmic polyadenylation element binding protein 2 (CPEB).<ref>{{cite journal|last1=Szklarczyk|first1=D.|last2=Franceschini|first2=A.|last3=Wyder|first3=S.|last4=Forslund|first4=K.|last5=Heller|first5=D.|last6=Huerta-Cepas|first6=J.|last7=Simonovic|first7=M.|last8=Roth|first8=A.|last9=Santos|first9=A.|last10=Tsafou|first10=K. P.|last11=Kuhn|first11=M.|last12=Bork|first12=P.|last13=Jensen|first13=L. J.|last14=von Mering|first14=C.|title=STRING v10: protein-protein interaction networks, integrated over the tree of life|journal=Nucleic Acids Research|date=28 October 2014|volume=43|issue=D1|pages=D447–D452|doi=10.1093/nar/gku1003|pmid=25352553|pmc=4383874}}</ref><ref>{{cite web|title=Transmembrane Protein 143|url=http://string-db.org/newstring_cgi/show_network_section.pl|website=STRING10-Known and Predicted Protein-Protein Interactions|accessdate=9 May 2015}}</ref>
ZNF541 and PNMAL2, in relation to TMEM143, have been documented as having a role in the allelic loss of q13.3 of chromosome 19. This loss results in documented cases of malignant [[gliomas]], [[neuroblastoma]]s, and [[ovarian carcinoma]]s, all suggesting a [[tumor suppressor gene|tumor suppression gene]] or genes in this region.<ref name="cancer interactions">{{cite journal|last1=Hartmann|first1=C|last2=Johnk|first2=L|last3=Kitange|first3=G|last4=Wu|first4=Y|last5=Ashworth|first5=LK|last6=Jenkins|first6=RB|last7=Louis|first7=DN|title=Transcript map of the 3.7-Mb D19S112-D19S246 candidate tumor suppressor region on the long arm of chromosome 19.|journal=Cancer Research|date=15 July 2002|volume=62|issue=14|pages=4100–8|pmid=12124348}}</ref> While TMEM143 is not directly referred to in research in this area, it is present in this region on the chromosome, indicating a potential functional role in humans.
Interactions between TMEM143 and DD12, JLHL31, C14orf28, TRIN71, and CPEB (in humans) have been documented through microarray data.<ref>{{cite journal|last1=Lhakhang|first1=Tenzin W.|last2=Chaudhry|first2=M. Ahmad|title=Interactome of Radiation-Induced microRNA-Predicted Target Genes|journal=Comparative and Functional Genomics|date=2012|volume=2012|pages=569731|doi=10.1155/2012/569731|pmid=22924026|pmc=3424689 |doi-access=free }}</ref> Illustrating predicted gene regulation with different [[microRNA]] (miRNA) under [[ionizing radiation]] conditions, TMEM143 and DD12, JLHL31, C14orf28, TRIN71, and CPEB all share predicted regulatory miRNAs. TMEM143 has also been found to be associated with [[adipocyte]] [[Cellular differentiation|differentiation]]. Along with other genes, TMEM143 has been documented as a PPARγ (peroxisome proliferator-activated receptor gamma) target. This indicates the possibility of TMEM143 participation in [[lipid]] [[metabolic pathways]] and lipid cell differentiation<ref>{{cite journal|last1=Nakachi|first1=Yutaka|last2=Yagi|first2=Ken|last3=Nikaido|first3=Itoshi|last4=Bono|first4=Hidemasa|last5=Tonouchi|first5=Mio|last6=Schönbach|first6=Christian|last7=Okazaki|first7=Yasushi|title=Identification of novel PPARγ target genes by integrated analysis of ChIP-on-chip and microarray expression data during adipocyte differentiation|journal=Biochemical and Biophysical Research Communications|date=July 2008|volume=372|issue=2|pages=362–366|doi=10.1016/j.bbrc.2008.05.037|pmid=18489901}}</ref>
== References ==
{{reflist|30em}}
[[Category:Human proteins]]