Transmembrane protein 82 (TMEM82) is a protein encoded by the TMEM82 gene in humans.
Gene The TMEM82 gene is found on chromosome 1 (1p36.21) from 15,742,499 to 15,747,982, spanning 5,484 base pairs. It is found on the plus strand and has 6 exons and 5 introns. The SLC25A34 gene is found on TMEM82's antisense strand and ecodes for a mitochondrial carrier protein.
There are a few known genetic variants which alter the molecular phenotype. One is an intergenic mutation that results in a protein product that is associated with Troponin-T. A SNP (T/C, missense) with an allele frequency of about 4% results in a protein product that is associated with Insulin-Like Growth Factor Binding Protein 3, although with a very small effect size.
mRNA
There human mRNA transcript for TMEM82, of which there are no isoforms, has 1,443 nucleotides which encodes a 343 amino acid long precursor protein of about 37kDa including 8 predicted transmembrane domains and 1 disordered region.
Expression In humans, the RNA transcript is expressed highly in the kidney, liver, small intestine, and duodenum and is also expressed in the colon and stomach. Single cell RNA-seq data indicate several tissue specific cell types with enhanced TMEM82 expression in the stomach, colon, kidney, and liver: these cell types include parietal cells, chief cells, gastric mucous cells, mitotic cells, and gastric enteroendochrine cells in the stomach, colon enterocytes in the colon, proximal tubular cells in the kidney, and hepatocytes in the liver. During fetal development it is also expressed in adrenal and heart tissues and becomes highly expressed in the small intestine by 15 weeks of gestation. Its expression cluster is similar to those for genes involved in lipid metabolism. There are several similar mouse polyclonal antibodies, some rabbit polyclonal antibodies, and a couple monoclonal options for available for the TMEM82 protein but with limited evidence for efficacy.
Protein
TMEM82 is listed as pfam15816 for conserved protein domains and is the only member of the superfamily cl24398. TMEM82 is predicted to be an endoplasmic reticulum transmembrane protein. The theoretical isoelectric point of human TMEM82 is 8.57 and it is compositionally 23% leucine.
Post-translational modifications Predicted PTMs of human TMEM82 include phosphorylation, a glycosaminoglcan attachment site, and N-myristoylation.
Function Predicted interaction partners include APOA2 and CYP4F2. TMEM82 has been found to coexpress with proteins involved in lipids, hormones, and xenobiotic and alcohol metabolic pathways; as such, it is hypothesized to function in metabolism.
Homologs
Orthologs of the TMEM82 gene have been identified in 442 organisms including in the chimpanzee, Rhesus monkey, dog, cow, mouse, chicken, zebrafish, and frog and is highly conserved in mammals. TMEM82 is not found in plants or fungi. There are no paralogs of TMEM82 in humans. The end of TMEM82 encompassing its disordered region is the least evolutionarilty constrained relative to the rest of the protein. The following table lists some orthologs and their attributes of TMEM82. +Table of TMEM82 Orthologs and Similarity to human TMEM82Genus/SpeciesCommon NameTaxonomic OrderMedian Date of Divergence (Mya)Accession NumberSequence LengthSequence IdentitySequence SimilarityMammalHomo SapienshumanPrimate0NP_001013663.1 343100%100%MammalCarlito syrichtaPhilippine tarsiePrimate69XP_008056317.136373.979.8MammalMus MusculusHouse mouseRodentia87NP_666099.235676.884.6MammalEquus quaggaPlains zebraPerissodactyla94XP_046518653.134786.590.2BirdMolossus molossusvelvety free-tailed batChiroptera94XP_036113249.134484.690.1BirdAquila chrysaetos chrysaetosvolden eagleAccipitriformes319XP_029872457.132864.174.3BirdSerinus canariaAtlantic canaryPasseriformes319XP_030087344.132963.374.6BirdStrigops habroptilaKākāpōPsittaciformes319XP_030363772.134457.268.6ReptileMauremys reevesiiChinese pond turtleTestudines319XP_039365209.135162.173.6ReptileVaranus komodoensiskomodo dragonUnidentata319XP_044277161.134659.972.9ReptileSphaerodactylus townsenditownsend's least geckoGekkota319XP_048374902 34359.871.6AmphibianThamnophis eleganswestern terrestrial garter snakeUnidentata319XP_032088188.133755.670.1AmphibianGeotrypetes seraphinigaboon caecilianGymnophiona353XP_033777097.134158.170.5AmphibianRana temporariacommon frogAnura353XP_040182718.133854.569.6FishBufo gargarizansChusan Island toadAnura353XP_044138414.133552.370.6FishProtopterus annectensWest African lungfishDipnoi 408XP_043916388.130643.355.9FishLatimeria chalumnaeWest Indian Ocean coelacanthCoelacanthiformes414XP_006004339.131250.363.4FishSalarias fasciatusjewelled BlennyBlenniiformes431XP_029975350.133844.858.6FishThalassophryne amazonicaprehistoric monster fishBatrachoidiformes431XP_034027462.134041.754.5FishDanio reriozebra fishCypriniformes431NP_001186669.133841.356Stegostoma fasciatumzebra sharkChondrichthyes464XP_048417111 34246.163.5
Clinical significance Expression of TMEM82 is dysregulated in hepatocellular carcinoma. TMEM82 is present in the interaction profile of kidney renal cell carcinoma and is a favorable prognostic marker in renal cancer. TMEM82 has enhanced RNA expression in liver and renal cancer but was not correlated with the overall survival of patients with colorectal cancer. A 65.7 kbp long microduplication has been found in patients with congenital lower urinary tract obstruction at the genomic location of TMEM82 gene; the microduplication affects TMEM82 and the other genes located there: FBLIM1, PLEKHM2, SLC25A34, SLC25A34-AS1. TMEM82 is significantly upregulated in glomeruli and predicted to have estrogen response elements.
References