The TMEM106A protein has a molecular weight of 28.9 kdal. It has 262 amino acids, 240 of which are in the domain of function.[1] The protein has a transmembrane region.[3] There is evidence for a secondary transmembrane region in humans but this region is not conserved in related orthologs.[4] The protein does not contain a peptide signal protein.[5] The protein structure contains a similar proportion of alpha-helix and beta-strand secondary structures (this does not include transmembrane structures).[6][7]
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.[11] TMEM106B and TMEM106C are conserved in invertebrates to mammals.
The TMEM106A gene has been found in only the Chordate phylum.[16] 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.[17]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.[12][18] EST profiles for orthologs show expression is conserved with greatest expression in kidneys and lesser expression in several other areas.[19] Some tissues never show expression including: muscle, adipose tissue, and bone.
Gene neighborhood
In Homo sapiens, TMEM106A is located next to NBR1, a gene identified as an ovarian tumor antigen monitored in ovarian cancer.[20] It is also located near BRCA1, a breast cancertumor suppressor gene.[21] 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.[22]
↑Persson B, Argos P (March 1994). "Prediction of transmembrane segments in proteins utilising multiple sequence alignments". J. Mol. Biol. 237 (2): 182–92. doi:10.1006/jmbi.1994.1220. PMID8126732.
↑Nielsen H, Engelbrecht J, Brunak S, von Heijne G (January 1997). "Identification of prokaryotic and eukaryotic signal peptides and prediction of their cleavage sites". Protein Eng. 10 (1): 1–6. doi:10.1093/protein/10.1.1. PMID9051728.
↑Garnier J, Osguthorpe DJ, Robson B (March 1978). "Analysis of the accuracy and implications of simple methods for predicting the secondary structure of globular proteins". J. Mol. Biol. 120 (1): 97–120. doi:10.1016/0022-2836(78)90297-8. PMID642007.
↑Chou PY, Fasman GD (1978). "Prediction of the secondary structure of proteins from their amino acid sequence". Adv. Enzymol. Relat. Areas Mol. Biol. 47: 45–148. doi:10.1002/9780470122921.ch2. PMID364941.
↑Blom N, Gammeltoft S, Brunak S (December 1999). "Sequence and structure-based prediction of eukaryotic protein phosphorylation sites". J. Mol. Biol. 294 (5): 1351–62. doi:10.1006/jmbi.1999.3310. PMID10600390.
↑Whitehouse C, Chambers J, Howe K, Cobourne M, Sharpe P, Solomon E (January 2002). "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". Eur. J. Biochem. 269 (2): 538–45. doi:10.1046/j.0014-2956.2001.02681.x. PMID11856312.
↑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 (August 2010). "Identification and comprehensive characterization of large genomic rearrangements in the BRCA1 and BRCA2 genes". Breast Cancer Res. Treat. 122 (3): 733–43. doi:10.1007/s10549-009-0613-9. PMID19894111.
