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TMEM51

From EverybodyWiki Bios & Wiki



Transmembrane protein 51 (TMEM51) is a protein in humans that is encoded by the TMEM51 gene.[1] It is alternatively known as Chromosome 1 open reading frame 72 (C1orf72) or FLJ10199.

Gene

TMEM51 is located on the first chromosome (1p36.21) on the positive strand, contains 6 exons, and spans 66.7kb.[2] TMEM51 is predicted to be a transmembrane protein due to the two transmembrane domains within its coding sequence.[3]

mRNA

TMEM51 has 6 transcript variant isoforms, transcript variant X1 is 1982 nucleotides long and has.[4] TMEM51 has a 5'UTR spanning 485 nucleotides, and a 3'UTR spanning 735 nucleotides in length[1]. The 3'UTR is well conserved across mammal homologs, indicating that regulation of TMEM51 in the 3'UTR is similar in mammal species.

Protein

File:TMEM51 Compositional Analysis.png
TMEM51 amino acid compositional analysis relative to the human proteome[5].

TMEM51 protein is 252 amino acids in length, weighs 27.8kDa, and has an isoelectric point at pH 5.4.[6] TMEM51 is negatively charged at neutral pH.[5] TMEM51 has two transmembrane domains, featuring a long intracellular region with two disordered regions located within it. TMEM51 is predicted to anchor in the plasma membrane[7], but is experimentally found cytosolically and within the nucleus.[8] TMEM51 has a pat7 nuclear localization motif located on the long, intracellular, disordered side of the protein.[9]

Furin Cleavage Site

File:TMEM51 Protter Diagram.png
Transmembrane diagram of TMEM51[10] with all predicted phosphorylation sites[11], disordered regions, charge domains[12], and the furin cleavage site[13].

TMEM51 contains a furin cleavage site.[13] It is located downstream of the transmembrane domains on the larger, more-disordered, intracellularly facing side of the protein at K89 through Q90.

File:TMEM51 partial tertiary structure.svg
TMEM51 long intracellular segment downstream of both transmembrane domains. The structure is primarily disordered with some alpha helical structure, containing negative and positive charge clusters[12], and a furin protease cleavage site[13] near the n-terminus of this segment.

Expression

TMEM51 is nearly ubiquitously expressed in human tissues.[14] TMEM51 is expressed in the 75th quartile or greater in cerebellum, pancreas, kidney, lung, and spleen tissues.[15][16] TMEM51 expression increases in mouse muscle cells during muscle cell regeneration after damage.[17] TMEM51 expression decreases in mouse liver tissue while fasting.[18]

Protein Interactions

TMEM51 interacts with furin, which cleaves it at TMEM51's designated site. TMEM51 physically interacts with ITCH[19][20], which likely downregulates TMEM51 as ITCH is a ubiquitin E-3 ligase. TMEM51 interacts with other E-3 ubiquitin ligases HECW2 and WWP1, but do not have proven physical associations.[20] TMEM51 physically associates with SARS CoV-2 spike and membrane glycoproteins.[21]

Antisense RNAs

There are two antisense RNAs that are associated with TMEM51; TMEM51 antisense RNA-1[22] and TMEM51 antisense RNA-2.[23]

Clinical Significance

Due to TMEM51's association with ITCH, it's likely to be involved in developmental or immune signaling pathways.[24] TMEM51 is associated with Reynaud's syndrome as it exhibits higher expression in patients with Reynaud's, but does not interact with important Reynaud's genes.[25] TMEM51 expression increases 1.837 fold when NK-lysin protein is present in liver cancer cells.[26] TMEM51 exhibits increased expression in symptomatic type-2 diabetes patients.[27] TMEM51 also plays a role in the contractile function of cardiomyocytes, which plays an important role in blood flow and blood pressure regulation.[28] Due to TMEM51's physical association with SARS CoV-2 glycoproteins, it's likely that TMEM51 is involved in SARS CoV-2's viral life cycle.[29][30]

TMEM51 Homologs

TMEM51 arose approximately 563 million years ago with the rise of vertebrates.[31] TMEM51 has orthologs in mammals, reptiles, birds, amphibians, bony fish, cartilaginous fish, and jawless fish.[2] TMEM51 is found in all vertebrates but no invertebrates.[31] TMEM51 has no paralogs across all taxonomic groups.

TMEM51 Genus Species Common Name Taxonomic Group Date of Divergence Accession Number Sequence Length (aa) Sequence Identitiy Sequence Similarity
Mammals Homo sapiens Human Primates 0 mya NP_001129688.1 253 100.00% 100.00%
Pongo abelii Sumatran Orangutan* Primates 15.2 mya PNJ17216.1 252 99.00% 99.00%
Carlito syrichta Phillippine Tarsier Primates 69 mya XP_008051738.1 252 92.00% 94.00%
Mus musculus House Mouse Rodentia 87 mya NP_001406297.1 249 85.00% 89.00%
Desmodus rotundus Common Vampire Bat Chiroptera 94 mya XP_024410020.1 249 85.00% 92.00%
Manis javanica Malayan Pangolin Pholidota 94 mya KAI5946971.1 349 85.00% 91.00%
Loxodonta africana African Savanna Elephant Proboscidea 99 mya XP_003413504.1 249 86.00% 90.00%
Dasypus novemcinctus Nine-banded Armadillo Cingulata 99 mya XP_004472235.2 248 84.00% 90.00%
Sarcophilus harrisii Tasmanian Devil Dasyuromorphia 160 mya XP_031818680.1 247 76.00% 84.00%
Reptiles and Birds Emydura macquarii macquarii Murray River Turtle Testudines 319 mya XP_067423583.1 252 66.00% 80.00%
Numenius arquata Eurasion curlew Charadriiformes 319 mya XP_074017838.1 251 65.00% 77.00%
Excalfactoria chinensis Blue Breasted Quail Galliformes 319 mya XP_072210478.1 250 64.00% 77.00%
Phaethon lepturus White-Tailed Tropicbird Phaethontidae 319 mya KFQ74947.1 207 57.00% 66.00%
Amphibians Ambystoma mexicanum Axolotl Caudata 353 mya XP_069466990.1 247 55.00% 71.00%
Xenopus tropicalis Tropical Clawed Frog Anura 352 mya XP_031761016.1 236 53.00% 66.00%
Pleurodeles waltl Iberian Ribbed Newt Urodela 352 mya XP_069096873.1 252 53.00% 71.00%
Pelobates fuscus Common Spadefoot Toad Anura 352 mya XP_063292659.1 246 51.00% 68.00%
Bony Fish Danio rerio Zebrafish Cypriniformes 429 mya NP_001071198.2 253 36.00% 58.00%
Cartilaginous Fish Carcharodon carcharias Great White Shark Lamniformes 462 mya XP_041063258.1 238 39.00% 57.00%
Amblyraja radiata Thorny Skate Rajiformes 462 mya XP_032904309.1 248 38.00% 53.00%
Jawless Fish Petromyzon marinus Sea Lamprey Petromyzontiformes 563 mya XP_032818293.1 254 29.00% 42.00%

TMEM51 Homolog table sorted by phylogenetic group and by data of divergence.

*Sequence extended using UCSC Genome Browser.[31]

Works Cited

  1. ↑ 1.0 1.1 "Entrez Gene: Transmembrane protein 51". Retrieved 2012-10-29.
  2. ↑ 2.0 2.1 "AceView: Gene:TMEM51, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2025-09-29.
  3. ↑ "Homo sapiens transmembrane protein 51 (TMEM51), transcript variant 1, mRNA". NCBI. 2025-04-27.
  4. ↑ "PREDICTED: Homo sapiens transmembrane protein 51 (TMEM51), transcript variant X1, mRNA". www.ncbi.nlm.nih.gov. 2025-08-05.
  5. ↑ 5.0 5.1 EMBL-EBI; Institute, European Bioinformatics. "Job Dispatcher homepage | EMBL-EBI". www.ebi.ac.uk. Retrieved 2025-12-12.
  6. ↑ "Expasy - Compute pI/Mw tool". web.expasy.org. Retrieved 2025-12-04.
  7. ↑ "PSORT II Prediction". psort.hgc.jp. Retrieved 2025-12-12.
  8. ↑ "Anti-TMEM51 Human Protein Atlas Antibody". www.atlasantibodies.com. Retrieved 2025-12-12.
  9. ↑ "PSORT II Prediction". psort.hgc.jp. Retrieved 2025-12-12.
  10. ↑ "Protter - interactive protein feature visualization". wlab.ethz.ch. Archived from the original on 2025-06-18. Retrieved 2025-12-12.
  11. ↑ "NetPhos 3.1 - DTU Health Tech - Bioinformatic Services". services.healthtech.dtu.dk. Retrieved 2025-12-12.
  12. ↑ 12.0 12.1 EMBL-EBI; Institute, European Bioinformatics. "Job Dispatcher homepage | EMBL-EBI". www.ebi.ac.uk. Retrieved 2025-12-12.
  13. ↑ 13.0 13.1 13.2 "ProP 1.0 - DTU Health Tech - Bioinformatic Services". services.healthtech.dtu.dk. Retrieved 2025-12-12.
  14. ↑ "TMEM51 transmembrane protein 51 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-04.
  15. ↑ "GDS596 / 218815_s_at". www.ncbi.nlm.nih.gov. Retrieved 2025-12-04.
  16. ↑ www.ncbi.nlm.nih.gov https://www.ncbi.nlm.nih.gov/geo/tools/profileGraph.cgi?ID=GDS424:65653_a. Retrieved 2025-12-04. Missing or empty |title= (help)
  17. ↑ "113970389 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-04.
  18. ↑ "113745837 - GEO Profiles - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-04.
  19. ↑ "IntAct Portal". www.ebi.ac.uk. Retrieved 2025-12-12.
  20. ↑ 20.0 20.1 "26 nodes (human) - STRING interaction network". string-db.org. Retrieved 2025-12-12.
  21. ↑ "BioGRID | Database of Protein, Chemical, and Genetic Interactions". thebiogrid.org. Retrieved 2025-12-12.
  22. ↑ "TMEM51-AS1 TMEM51 antisense RNA 1 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-12.
  23. ↑ "TMEM51-AS2 TMEM51 antisense RNA 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-12.
  24. ↑ "AceView: Gene:ITCH, a comprehensive annotation of human, mouse and worm genes with mRNAs or ESTsAceView". www.ncbi.nlm.nih.gov. Retrieved 2025-12-12.
  25. ↑ Tervi, Anniina; Ramste, Markus; Abner, Erik; Cheng, Paul; Lane, Jacqueline M.; Maher, Matthew; Valliere, Jesse; Lammi, Vilma; Strausz, Satu; Riikonen, Juha; Nguyen, Trieu; Martyn, Gabriella E.; Sheth, Maya U.; Xia, Fan; Docampo, Mauro Lago (2024-09). "Genetic and functional analysis of Raynaud's syndrome implicates loci in vasculature and immunity". Cell Genomics. 4 (9): 100630. doi:10.1016/j.xgen.2024.100630. PMC 11480858 Check |pmc= value (help). PMID 39142284 Check |pmid= value (help). Check date values in: |date= (help)
  26. ↑ Fan, Kuohai; Li, Hongquan; Wang, Zhirui; Du, Wenjuan; Yin, Wei; Sun, Yaogui; Jiang, Junbing (2016-01-02). "Expression and purification of the recombinant porcine NK-lysin in Pichia pastoris and observation of anticancer activity in vitro". Preparative Biochemistry & Biotechnology. 46 (1): 65–70. doi:10.1080/10826068.2014.979206. ISSN 1082-6068. PMID 25357101.
  27. ↑ García-Calzón, Sonia; Maguolo, Alice; Eichelmann, Fabian; Edsfeldt, Andreas; Perfilyev, Alexander; Maziarz, Marlena; Lindström, Axel; Sun, Jiangming; Briviba, Monta; Schulze, Matthias B.; Klovins, Janis; Ahlqvist, Emma; Gonçalves, Isabel; Ling, Charlotte (2025-08). "Epigenetic biomarkers predict macrovascular events in individuals with type 2 diabetes". Cell Reports Medicine. 6 (8): 102290. doi:10.1016/j.xcrm.2025.102290. Check date values in: |date= (help)
  28. ↑ Sung, Yun Ju; de las Fuentes, Lisa; Winkler, Thomas W; Chasman, Daniel I; Bentley, Amy R; Kraja, Aldi T; Ntalla, Ioanna; Warren, Helen R; Guo, Xiuqing; Schwander, Karen; Manning, Alisa K; Brown, Michael R; Aschard, Hugues; Feitosa, Mary F; Franceschini, Nora (2019-08-01). "A multi-ancestry genome-wide study incorporating gene–smoking interactions identifies multiple new loci for pulse pressure and mean arterial pressure". Human Molecular Genetics. 28 (15): 2615–2633. doi:10.1093/hmg/ddz070. ISSN 0964-6906. PMC 6644157 Check |pmc= value (help). PMID 31127295.
  29. ↑ "M membrane glycoprotein [Severe acute respiratory syndrome coronavirus 2] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-12.
  30. ↑ "S surface glycoprotein [Severe acute respiratory syndrome coronavirus 2] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2025-12-12.
  31. ↑ 31.0 31.1 31.2 "UCSC Genome Browser Home". genome.ucsc.edu. Retrieved 2025-12-12.


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