TMEM106A

The TMEM106A protein has a molecular weight of 28.9 kDa. It has 262 amino acids, 240 of which are in the domain of function. The protein has a transmembrane region.{{cite journal |vauthors=Nakai K, Horton P | title = PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization | journal = Trends Biochem. Sci. | volume = 24 | issue = 1 | pages = 34–6 |date=January 1999 | pmid = 10087920 | doi = 10.1016/S0968-0004(98)01336-X| url = http://psort.hgc.jp }} There is evidence for a secondary transmembrane region in humans but this region is not conserved in related orthologs.{{cite journal |vauthors=Persson B, Argos P | title = Prediction of transmembrane segments in proteins utilising multiple sequence alignments | journal = J. Mol. Biol. | volume = 237 | issue = 2 | pages = 182–92 |date=March 1994 | pmid = 8126732 | doi = 10.1006/jmbi.1994.1220 }} The protein does not contain a signal peptide.{{cite journal |vauthors=Nielsen H, Engelbrecht J, Brunak S, von Heijne G | title = Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites | journal = Protein Eng. | volume = 10 | issue = 1 | pages = 1–6 |date=January 1997 | pmid = 9051728 | doi =10.1093/protein/10.1.1 | doi-access = free }} The protein structure contains a similar proportion of alpha-helix and beta-strand secondary structures (this does not include transmembrane structures).{{cite journal |vauthors=Garnier J, Osguthorpe DJ, Robson B | title = Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins | journal = J. Mol. Biol. | volume = 120 | issue = 1 | pages = 97–120 |date=March 1978 | pmid = 642007 | doi =10.1016/0022-2836(78)90297-8 }}{{cite book | vauthors = Chou PY, Fasman GD | chapter = Prediction of the Secondary Structure of Proteins from their Amino Acid Sequence | title = Advances in Enzymology and Related Areas of Molecular Biology | journal = Adv. Enzymol. Relat. Areas Mol. Biol. | volume = 47 | pages = [https://archive.org/details/advancesinenzymo0047unse/page/45 45–148] | pmid = 364941 | doi = 10.1002/9780470122921.ch2 | series = Advances in Enzymology - and Related Areas of Molecular Biology | date = 1979 | isbn = 9780470122921 | chapter-url = https://archive.org/details/advancesinenzymo0047unse/page/45 }}

File:TMEM106A Secondary Protein Structures.png{{clear}}

There are several areas for post-translational modification for TMEM106A including:

:* Phosphorylation,{{cite journal |vauthors=Blom N, Gammeltoft S, Brunak S | title = Sequence and structure-based prediction of eukaryotic protein phosphorylation sites | journal = J. Mol. Biol. | volume = 294 | issue = 5 | pages = 1351–62 |date=December 1999 | pmid = 10600390 | doi = 10.1006/jmbi.1999.3310 }}

:* N-glycosylation{{cite journal | vauthors = Gupta R, Jung E, Brunak S | title = Prediction of N-glycosylation sites in human proteins | year = 2004 | url = http://www.cbs.dtu.dk/services/NetNGlyc/abstract.php | access-date = 2012-05-08 | archive-date = 2021-06-11 | archive-url = https://web.archive.org/web/20210611151816/http://www.cbs.dtu.dk/services/NetNGlyc/abstract.php | url-status = dead }}

:* Lysine glycosylation{{cite journal |vauthors=Johansen MB, Kiemer L, Brunak S | title = Analysis and prediction of mammalian protein glycation | journal = Glycobiology | volume = 16 | issue = 9 | pages = 844–53 |date=September 2006 | pmid = 16762979 | doi = 10.1093/glycob/cwl009 | citeseerx = 10.1.1.128.831 }}

The TMEM106A gene has two paralogs: TMEM106B and TMEM106C. These paralogs belong to the gene family pfam07092, which belongs to the DUF1356 superfamily. This family consists of several mammalian proteins that are around 250 amino acids in length.{{cite web | title = NCBI Conserved Domains: DUF1356| url =https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=pfam07092}} TMEM106B and TMEM106C are conserved in invertebrates to mammals.

File:TMEM106A tissue expression.png

The TMEM106A gene has been found in only the Chordate phylum.{{cite web | title = NCBI Homologene: TMEM106A| url =https://www.ncbi.nlm.nih.gov/sites/homologene/1699}} Of the three subphyla, TMEM106A is most commonly found in Vertebrata and has also been found in select members of Tunicata, which are invertebrate marine filter feeders. This phylum split occurred 722.5 million years ago.{{cite journal |vauthors=Hedges SB, Dudley J, Kumar S | title = TimeTree: a public knowledge-base of divergence times among organisms | journal = Bioinformatics | volume = 22 | issue = 23 | pages = 2971–2 |date=December 2006 | pmid = 17021158 | doi = 10.1093/bioinformatics/btl505 | url = http://biogps.org/#goto=genereport&id=113277 | doi-access = free }} TMEM106A has not been seen in bacteria, plants, or fungi.

TMEM106A is expressed in several human tissues. The tissues with highest expression are uterus, kidneys, small intestine, and stomach.{{cite web | title = GEO Profiles: TMEM106A transmembrane protein 106A| url =http://biogps.org/#goto=genereport&id=113277 }} EST profiles for orthologs show expression is conserved with greatest expression in kidneys and lesser expression in several other areas.{{cite web | title = EST profiles| url= https://www.ncbi.nlm.nih.gov/est/}}. Some tissues never show expression including: muscle, adipose tissue, and bone.

In Homo sapiens, TMEM106A is located next to NBR1, a gene identified as an ovarian tumor antigen monitored in ovarian cancer.{{cite journal |vauthors=Whitehouse C, Chambers J, Howe K, Cobourne M, Sharpe P, Solomon E | title = NBR1 interacts with fasciculation and elongation protein zeta-1 (FEZ1) and calcium and integrin binding protein (CIB) and shows developmentally restricted expression in the neural tube | journal = Eur. J. Biochem. | volume = 269 | issue = 2 | pages = 538–45 |date=January 2002 | pmid = 11856312 | doi =10.1046/j.0014-2956.2001.02681.x | doi-access = free }} It is also located near BRCA1, a breast cancer tumor suppressor gene.{{cite journal |vauthors=Garcia-Casado Z, Romero I, Fernandez-Serra A, Rubio L, Llopis F, Garcia A, Llombart P, Lopez-Guerrero JA | title = A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer | journal = BMC Med. Genet. | volume = 12| pages = 134 | year = 2011 | pmid = 21989022 | pmc = 3207938 | doi = 10.1186/1471-2350-12-134 | doi-access = free }} The first 140 amino acids of the TMEM106A protein, including portions of DUF1356 and a transmembrane region, are deleted along with BRCA1 during early-onset breast cancer.{{cite journal |vauthors=del Valle J, Feliubadaló L, Nadal M, Teulé A, Miró R, Cuesta R, Tornero E, Menéndez M, Darder E, Brunet J, Capellà G, Blanco I, Lázaro C | title = Identification and comprehensive characterization of large genomic rearrangements in the BRCA1 and BRCA2 genes | journal = Breast Cancer Res. Treat. | volume = 122 | issue = 3 | pages = 733–43 |date=August 2010 | pmid = 19894111 | doi = 10.1007/s10549-009-0613-9 | s2cid = 22991723 | url = https://hal.archives-ouvertes.fr/hal-00535410/file/PEER_stage2_10.1007%252Fs10549-009-0613-9.pdf }}

File:TMEM106A Gene Neighborhood.png

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• {{cite journal |vauthors=Feric M, Zhao B, Hoffert JD, Pisitkun T, Knepper MA | title = Large-scale phosphoproteomic analysis of membrane proteins in renal proximal and distal tubule | journal = Am. J. Physiol., Cell Physiol. | volume = 300 | issue = 4 | pages = C755–70 |date=April 2011 | pmid = 21209370 | pmc = 3074622 | doi = 10.1152/ajpcell.00360.2010 }}

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