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TMEM82

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TMEM82
Identifiers
AliasesTMEM82, transmembrane protein 82
External IDsMGI: 2384869; HomoloGene: 27088; GeneCards: TMEM82; OMA:TMEM82 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

388595

213989

Ensembl

ENSG00000162460

ENSMUSG00000043085

UniProt

A0PJX8

Q8R115

RefSeq (mRNA)

NM_001013641

NM_145987

RefSeq (protein)

NP_001013663

NP_666099

Location (UCSC)Chr 1: 15.74 – 15.75 MbChr 4: 141.34 – 141.35 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Transmembrane protein 82 (TMEM82) is a protein encoded by the TMEM82 gene in humans.

TMEM82 Gene Neighborhood

Gene

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The TMEM82 gene is found on chromosome 1 (1p36.21) from 15,742,499 to 15,747,982, spanning 5,484 base pairs.[5][6] It is found on the plus strand and has 6 exons and 5 introns.[5][6] The SLC25A34 gene is found on TMEM82's antisense strand and ecodes for a mitochondrial carrier protein.[7]

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.[8][9] 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.[8][10]

mRNA

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Conceptual translation of human TMEM82 mRNA into precursor protein

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.[11]

Expression

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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.[5] 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.[12] 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.[5] Its expression cluster is similar to those for genes involved in lipid metabolism.[13] 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.[14]

Protein

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Predicted Human TMEM82 Tertiary Structure

TMEM82 is listed as pfam15816 for conserved protein domains and is the only member of the superfamily cl24398.[15] TMEM82 is predicted to be an endoplasmic reticulum transmembrane protein.[16] The theoretical isoelectric point of human TMEM82 is 8.57 and it is compositionally 23% leucine.[17][18]

Post-translational modifications

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Predicted PTMs of human TMEM82 include phosphorylation, a glycosaminoglcan attachment site, and N-myristoylation.[19][20]

Human TMEM82 Schematic Diagram with some predicted PTMs

Function

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Predicted interaction partners include APOA2 and CYP4F2.[21] 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.[22]

Homologs

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Multiple Sequence Alignment of TMEM82 Orthologs in Mammals

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.[5] 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.[23] The following table lists some orthologs and their attributes of TMEM82.

Table of TMEM82 Orthologs and Similarity to human TMEM82
Genus/Species Common Name Taxonomic Order Median Date of Divergence (Mya) Accession Number Sequence Length Sequence Identity Sequence Similarity
Mammal Homo Sapiens human Primate 0 NP_001013663.1 343 100% 100%
Mammal Carlito syrichta Philippine tarsie Primate 69 XP_008056317.1 363 73.9 79.8
Mammal Mus Musculus House mouse Rodentia 87 NP_666099.2 356 76.8 84.6
Mammal Equus quagga Plains zebra Perissodactyla 94 XP_046518653.1 347 86.5 90.2
Bird Molossus molossus velvety free-tailed bat Chiroptera 94 XP_036113249.1 344 84.6 90.1
Bird Aquila chrysaetos chrysaetos volden eagle Accipitriformes 319 XP_029872457.1 328 64.1 74.3
Bird Serinus canaria Atlantic canary Passeriformes 319 XP_030087344.1 329 63.3 74.6
Reptile Strigops habroptila kakapo Psittaciformes 319 XP_030363772.1 344 57.2 68.6
Reptile Mauremys reevesii Chinese pond turtle Testudines 319 XP_039365209.1 351 62.1 73.6
Reptile Varanus komodoensis komodo dragon Unidentata 319 XP_044277161.1 346 59.9 72.9
Reptile Sphaerodactylus townsendi townsend's least gecko Gekkota 319 XP_048374902     343 59.8 71.6
Amphibian Thamnophis elegans western terrestrial garter snake Unidentata 319 XP_032088188.1 337 55.6 70.1
Amphibian Geotrypetes seraphini gaboon caecilian Gymnophiona 353 XP_033777097.1 341 58.1 70.5
Amphibian Rana temporaria common frog Anura 353 XP_040182718.1 338 54.5 69.6
Fish Bufo gargarizans Chusan Island toad Anura 353 XP_044138414.1 335 52.3 70.6
Fish Protopterus annectens West African lungfish Dipnoi 408 XP_043916388.1 306 43.3 55.9
Fish Latimeria chalumnae West Indian Ocean coelacanth Coelacanthiformes 414 XP_006004339.1 312 50.3 63.4
Fish Salarias fasciatus jewelled Blenny Blenniiformes 431 XP_029975350.1 338 44.8 58.6
Fish Thalassophryne amazonica prehistoric monster fish Batrachoidiformes 431 XP_034027462.1 340 41.7 54.5
Fish Danio rerio zebra fish Cypriniformes 431 NP_001186669.1 338 41.3 56
Stegostoma fasciatum zebra shark Chondrichthyes 464 XP_048417111   342 46.1 63.5

Clinical significance

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Expression of TMEM82 is dysregulated in hepatocellular carcinoma.[24][25] TMEM82 is present in the interaction profile of kidney renal cell carcinoma and is a favorable prognostic marker in renal cancer.[26] TMEM82 has enhanced RNA expression in liver and renal cancer but was not correlated with the overall survival of patients with colorectal cancer.[13][27] 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.[28] TMEM82 is significantly upregulated in glomeruli and predicted to have estrogen response elements.[29]

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000162460 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000043085 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d e "TMEM82 transmembrane protein 82 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-10-12.
  6. ^ a b "Homo sapiens transmembrane protein 82 (TMEM82), mRNA". 2021-06-26.
  7. ^ "SLC25A34 solute carrier family 25 member 34 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-12-11.
  8. ^ a b "PheGenI: Phenotype-Genotype Integrator - National Center for Biotechnology Information". www.ncbi.nlm.nih.gov. Retrieved 2022-12-11.
  9. ^ Yu B, Barbalic M, Brautbar A, Nambi V, Hoogeveen RC, Tang W, et al. (February 2013). "Association of genome-wide variation with highly sensitive cardiac troponin-T levels in European Americans and Blacks: a meta-analysis from atherosclerosis risk in communities and cardiovascular health studies". Circulation: Cardiovascular Genetics. 6 (1): 82–88. doi:10.1161/CIRCGENETICS.112.963058. PMC 3693561. PMID 23247143.
  10. ^ Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K, Gibbs RA, Butte NF (2012-12-14). "Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population". PLOS ONE. 7 (12): e51954. Bibcode:2012PLoSO...751954C. doi:10.1371/journal.pone.0051954. PMC 3522587. PMID 23251661.
  11. ^ "transmembrane protein 82 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2022-12-11.
  12. ^ "Cell line - TMEM82". www.proteinatlas.org. Retrieved 2022-12-11.
  13. ^ a b "TMEM82 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2022-12-11.
  14. ^ "- TMEM82 antibodies | Antibodypedia". www.antibodypedia.com. Retrieved 2022-12-11.
  15. ^ "CDD Conserved Protein Domain Family: TMEM82". www.ncbi.nlm.nih.gov. Retrieved 2022-12-11.
  16. ^ "Services". healthtech.dtu.dk. Retrieved 2022-12-16.
  17. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2022-12-11.
  18. ^ "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2022-12-11.
  19. ^ "ELM - Search the ELM resource". elm.eu.org. Retrieved 2022-12-16.
  20. ^ "Motif Scan". myhits.sib.swiss. Retrieved 2022-12-16.
  21. ^ "PSICQUIC View". www.ebi.ac.uk. Retrieved 2022-12-16.
  22. ^ Duek P, Gateau A, Bairoch A, Lane L (December 2018). "Exploring the Uncharacterized Human Proteome Using neXtProt". Journal of Proteome Research. 17 (12): 4211–4226. doi:10.1021/acs.jproteome.8b00537. PMID 30191714. S2CID 52171873.
  23. ^ "Aminode". www.aminode.org. Retrieved 2022-12-11.
  24. ^ Lin KT, Shann YJ, Chau GY, Hsu CN, Huang CY (September 2014). "Identification of latent biomarkers in hepatocellular carcinoma by ultra-deep whole-transcriptome sequencing". Oncogene. 33 (39): 4786–4794. doi:10.1038/onc.2013.424. PMID 24141781. S2CID 13653156.
  25. ^ Ho DW, Lo RC, Chan LK, Ng IO (October 2016). "Molecular Pathogenesis of Hepatocellular Carcinoma". Liver Cancer. 5 (4): 290–302. doi:10.1159/000449340. PMC 5075835. PMID 27781201.
  26. ^ "Cancer Cell Metabolism Database ~~ Bioinformatics and Systems Medicine Laboratory ~~". bioinfo.uth.edu. Retrieved 2022-12-11.
  27. ^ Guo S, Sun Y (2022-04-07). "OTOP2, Inversely Modulated by miR-3148, Inhibits CRC Cell Migration, Proliferation and Epithelial-Mesenchymal Transition: Evidence from Bioinformatics Data Mining and Experimental Verification". Cancer Management and Research. 14: 1371–1384. doi:10.2147/CMAR.S345299. PMC 9000554. PMID 35418782.
  28. ^ Schierbaum LM, Schneider S, Herms S, Sivalingam S, Fabian J, Reutter H, et al. (September 2021). "Genome-Wide Survey for Microdeletions or -Duplications in 155 Patients with Lower Urinary Tract Obstructions (LUTO)". Genes. 12 (9): 1449. doi:10.3390/genes12091449. PMC 8468665. PMID 34573432.
  29. ^ Long DA, Kolatsi-Joannou M, Price KL, Dessapt-Baradez C, Huang JL, Papakrivopoulou E, et al. (June 2013). "Albuminuria is associated with too few glomeruli and too much testosterone". Kidney International. 83 (6): 1118–1129. doi:10.1038/ki.2013.45. PMC 3674403. PMID 23447063.
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