TMEM106A is a gene that encodes the transmembrane protein 106A (TMEM106A) in Homo sapiens . [5] It is located at 17q21.31 on the plus strand next to cancer-related genes NBR1 and BRCA1 . [5] [6] The TMEM106A gene contains a domain of unknown function, DUF1356. [5]
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. [5] The protein has a transmembrane region. [7] There is evidence for a secondary transmembrane region in humans but this region is not conserved in related orthologs. [8] The protein does not contain a signal peptide. [9] The protein structure contains a similar proportion of alpha-helix and beta-strand secondary structures (this does not include transmembrane structures). [10] [11]
There are several areas for post-translational modification for TMEM106A including:
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. [15] TMEM106B and TMEM106C are conserved in invertebrates to mammals.
| Protein | Accession Number | Amino Acids | Identity Percent | Highest Expression |
|---|---|---|---|---|
| TMEM106A | AAI46977 | 262 | 100 | Kidney [16] |
| TMEM106B | NP_001127704 | 274 | 43 | Ubiquitous [17] |
| TMEM106C | AAI07793 | 231 | 36 | Ubiquitous [18] |
The TMEM106A gene has been found in only the Chordate phylum. [20] 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. [21] TMEM106A has not been seen in bacteria, plants, or fungi.
| Organism | Common Name | Accession Number | Amino Acids | Identity Percent | Notes |
|---|---|---|---|---|---|
| Homo sapiens | Human | AAI46977.1 | 262 | 100 | Mammal |
| Pan troglodytes | Chimpanzee | XP_001154896.2 | 262 | 99.2 | Mammal |
| Pongo abelii | Orangutan | XP_002827523.1 | 262 | 96.2 | Mammal |
| Callithrix jacchus | Marmoset | XP_002748067.1 | 262 | 90.5 | Mammal |
| Canis lupus familiaris | Dog | XP_548074.2 | 262 | 84.8 | Mammal |
| Mus musculus | Mouse | AAH22145.1 | 261 | 66.4 | Mammal |
| Xenopus borealis | Marsabit Clawed Frog | ACC55056.1 | 262 | 59.5 | Reptile |
| Danio rerio | Zebrafish | AAH50177.1 | 282 | 34.5 | Fish |
| Oikopleura dioica | Sea-squirt | CBY08060.1 | 249 | 27.8 | Invertebrate |
TMEM106A is expressed in several human tissues. The tissues with highest expression are uterus, kidneys, small intestine, and stomach. [16] [22] EST profiles for orthologs show expression is conserved with greatest expression in kidneys and lesser expression in several other areas. [23] 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. [24] It is also located near BRCA1 , a breast cancer tumor suppressor gene. [25] 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. [26]
Transmembrane protein 63A is a protein that in humans is encoded by the TMEM63A gene. The mature human protein is approximately 92.1 kilodaltons (kDa), with a relatively high conservation of mass in orthologs. The protein contains eleven transmembrane domains and is inserted into the membrane of the lysosome. 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.
UPF0172 protein FAM158A, also known as c14orf122 or CGI112, is a protein that in humans is encoded by the FAM158A gene located on chromosome 14q11.2.
Transmembrane protein 131-like, alternatively named uncharacterized protein KIAA0922, is an integral transmembrane protein encoded by the human gene KIAA0922 that is significantly conserved in eukaryotes, at least through protists. Although the function of this gene is not yet fully elucidated, initial microarray evidence suggests that it may be involved in immune responses. Furthermore, its paralog, prolyl endopeptidase (PREP) whose function is known, provides clues as to the function of TMEM131L.
Protein FAM46B also known as family with sequence similarity 46 member B is a protein that in humans is encoded by the FAM46B gene. FAM46B contains one protein domain of unknown function, DUF1693. Yeast two-hybrid screening has identified three proteins that physically interact with FAM46B. These are ATX1, PEPP2 and DAZAP2.
Coiled-coil domain containing 130 is a protein that in humans is encoded by the CCDC130 gene. It is part of the U4/U5/U6 tri-snRNP in the U5 portion. This tri-snRNP comes together with other proteins to form complex B of the mature spliceosome. The mature protein is approximately 45 kilodaltons (kDa) and is extremely hydrophilic due to the abnormally high number of charged and polar amino acids. CCDC130 is a highly conserved protein, it has orthologous genes in some yeasts and plants that were found using nucleotide and protein versions of the basic local alignment search tool (BLAST) from the National Center for Biotechnology Information. GEO profiles for CCDC130 have shown that this protein is ubiquitously expressed, but the highest levels of expression are found in T-lymphocytes.
Transmembrane protein 8A is a protein that in humans is encoded by the TMEM8A gene (16p13.3.). Evolutionarily, TMEM8A orthologs are found in primates and mammals and in a few more distantly related species. TMEM8A contains five transmembrane domains and one EGF-like domain which are all highly conserved in the ortholog space. Although there is no confirmed function of TMEM8A, through analyzing expression and experimental data, it is predicted that TMEM8A is an adhesion protein that plays a role in keeping T-cells in their resting state.
Solute carrier family 46 member 3 (SLC46A3) is a protein that in humans is encoded by the SLC46A3 gene. Also referred to as FKSG16, the protein belongs to the major facilitator superfamily (MFS) and SLC46A family. Most commonly found in the plasma membrane and endoplasmic reticulum (ER), SLC46A3 is a multi-pass membrane protein with 11 α-helical transmembrane domains. It is mainly involved in the transport of small molecules across the membrane through the substrate translocation pores featured in the MFS domain. The protein is associated with breast and prostate cancer, hepatocellular carcinoma (HCC), papilloma, glioma, obesity, and SARS-CoV. Based on the differential expression of SLC46A3 in antibody-drug conjugate (ADC)-resistant cells and certain cancer cells, current research is focused on the potential of SLC46A3 as a prognostic biomarker and therapeutic target for cancer. While protein abundance is relatively low in humans, high expression has been detected particularly in the liver, small intestine, and kidney.
CXorf66 also known as Chromosome X Open Reading Frame 66, is a 361aa protein in humans that is encoded by the CXorf66 gene. The protein encoded is predicted to be a type 1 transmembrane protein; however, its exact function is currently unknown.
TMEM106C is a gene that encodes the transmembrane protein 106C (TMEM106C) in Homo sapiens It has been found to be overexpressed in cancer cells and also is related to distal arthrogryposis, a condition of stiff joints and irregular muscle development. The TMEM106C gene contains a domain of unknown function, DUF1356, that spans most of the protein. Transmembrane protein 106C also goes by the aliases MGC5576 or MGC111210, LOC79022.
DEP Domain Containing Protein 1B also known as XTP1, XTP8, HBV XAg-Transactivated Protein 8, [formerly referred to as BRCC3] is a human protein encoded by a gene of similar name located on chromosome 5.
TMEM143 is a protein that in humans is encoded by TMEM143 gene. TMEM143, a dual-pass protein, is predicted to reside in the mitochondria and high expression has been found in both human skeletal muscle and the heart. Interaction with other proteins indicate that TMEM143 could potentially play a role in tumor suppression/expression and cancer regulation.
C8orf48 is a protein that in humans is encoded by the C8orf48 gene. C8orf48 is a nuclear protein specifically predicted to be located in the nuclear lamina. C8orf48 has been found to interact with proteins that are involved in the regulation of various cellular responses like gene expression, protein secretion, cell proliferation, and inflammatory responses. This protein has been linked to breast cancer and papillary thyroid carcinoma.
Vexin is a protein encoded by VXN gene. VXN is found to be highly expressed in regions of the brain and spinal cord.
Transmembrane protein 255A is a protein that is encoded by the TMEM255A gene. TMEM255A is often referred to as family with sequence similarity 70, member A (FAM70A). The TMEM255A protein is transmembrane and is predicted to be located the nuclear envelope of eukaryote organisms.
Transmembrane Protein 217 is a protein encoded by the gene TMEM217. TMEM217 has been found to have expression correlated with the lymphatic system and endothelial tissues and has been predicted to have a function linked to the cytoskeleton.
Proline-rich protein 30 is a protein in humans that is encoded for by the PRR30 gene. PRR30 is a member in the family of Proline-rich proteins characterized by their intrinsic lack of structure. Copy number variations in the PRR30 gene have been associated with an increased risk for neurofibromatosis.
Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene.
C2orf16 is a protein that in humans is encoded by the C2orf16 gene. Isoform 2 of this protein is 1,984 amino acids long. The gene contains 1 exon and is located at 2p23.3. Aliases for C2orf16 include Open Reading Frame 16 on Chromosome 2 and P-S-E-R-S-H-H-S Repeats Containing Sequence.
Transmembrane protein 179 is a protein that in humans is encoded by the TMEM179 gene. The function of transmembrane protein 179 is not yet well understood, but it is believed to have a function in the nervous system.
Family with Sequence Similarity 155 Member B is a protein in humans that is encoded by the FAM155B gene. It belongs to a family of proteins whose function is not yet well understood by the scientific community. It is a transmembrane protein that is highly expressed in the heart, thyroid, and brain.
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