TMEM81

Last updated
TMEM81
Identifiers
Aliases TMEM81 , HC3107, KVLA2788, UNQ2788, transmembrane protein 81
External IDs MGI: 1921876 HomoloGene: 12579 GeneCards: TMEM81
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_203376

NM_029025

RefSeq (protein)

NP_976310

NP_083301

Location (UCSC) Chr 1: 205.08 – 205.08 Mb Chr 1: 132.43 – 132.44 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Predicted tertiary structure of TMEM81 (extracellular region only) from I-TASSER. The structure was visualized using PyMol. Predicted tertiary structure of TMEM81 (extracellular region) from I-TASSER.png
Predicted tertiary structure of TMEM81 (extracellular region only) from I-TASSER. The structure was visualized using PyMol.

Transmembrane Protein 81 or TMEM81 is a protein that in humans is encoded by the TMEM81 gene. TMEM81 is a poorly-characterized transmembrane protein which contains an extracellular immunoglobulin domain. [6]

Contents

Gene

TMEM81 is also known as HC3107, UNQ2788, KVLA2788, [6] or MGC75217. [7] In humans, TMEM81 is located on chromosomal band 1q32.1 between the genes CNTN2 and RBBP5 on the reverse strand. [8] The TMEM81 gene is 1332 base pairs long and encodes one transcript containing a single exon. [6] [9]

The predicted promoter region (GXP_180875) for TMEM81 is 1158 bp long and extends from 205,084,360 to 205,085,517 on the reverse strand. [10]

Protein

Schematic illustration of the TMEM81 peptide Schematic illustration of the TMEM81 peptide.png
Schematic illustration of the TMEM81 peptide

The TMEM81 precursor peptide is 255 amino acids long with a predicted molecular weight of 28.5 kDa and pI = 8.92. [11]

The protein contains a helical transmembrane region, an extracellular immunoglobulin domain, and an N-linked glycosylation site. A disulfide bridge is predicted to form between residues Cys104 and Cys156. [11]

Protein composition

Illustration of the human TMEM81 peptide created using Protter Protter TMM81 HUMAN.png
Illustration of the human TMEM81 peptide created using Protter

The mature form (signal peptide removed) of TMEM81 has a slightly increased valine and somewhat decreased methionine composition relative to average proteins. [13] TMEM81 also contains three charge runs, each of which are three amino acids long:

ChargeAmino acidsLocation
+ Arg-Arg-Lys 71–73
- Asp-Asp-Glu 131–133
+Lys-Lys-Lys221–223

Secondary structure

The extracellular region of TMEM81 is predicted to be composed of beta sheets while the intracellular region likely assumes an alpha helix conformation. The transmembrane region of TMEM81 is helical. [14] An alignment of mature TMEM81 peptide sequences in H. sapiens, M. musculus and G. gallus was used to predict the secondary structure of TMEM81 using Ali2D. [15]

Secondary structure of TMEM81 (predicted by Ali2D).png

In predication results given above, blue indicates beta strands while red indicates alpha helices. Color saturation is proportional to the confidence of the predication.

Tertiary structure

TMEM81 predicted tertiary structure (Phyre2) C5f4tA .2.big (1).png
TMEM81 predicted tertiary structure (Phyre2)

The tertiary structure of TMEM81 has been predicted using izumo sperm-egg fusion protein 1 as a template. The image on the right depicts a model of residues 19 to 152 with 97.3% confidence with 56% coverage obtained using Phyre2. [16] The red-to-blue color gradation indicates the N- to C-terminus directionality of the structure.

Post-translational modifications

Experimental evidence has been found for an N-glycosylation site located at Asn45 indicating that TMEM81 is a glycoprotein. [14] Several tyrosine residues within TMEM81 have been predicted to undergo sulfation. [17]

Subcellular location

TMEM81 is predicted to be localized to the plasma membrane. [6] However, immunohistochemistry experiments using TMEM81-specific antibodies found localization to intermediate filaments [18] and microfilaments. [19]

Expression

Expression in humans

RNA-seq experiments from the GTEx project found that TMEM81 is ubiquitously expressed in humans but shows enhanced expression in the cerebellum and cerebellar hemisphere. [20] Other tissues and organs showing somewhat enhanced mRNA expression include the testis and spleen.

Expression in rodents

In mice (M. musculus) and rats (R. norvegicus), TMEM81 shows enhanced expression in the testes and relatively low expression in other tissues. [21] [22] Additionally, TMEM81 expression is not localized to the cerebellum in mice. [23]

TMEM81 shows monoallelic expression in both H. sapiens and M. musculus. [24]

Protein expression

In both H. sapiens and M. musculus, TMEM81 is present at a concentration of just under 1 ppm. [25] [26] Relative to other proteins, TMEM81 is present at slightly below the median protein concentration level.

Clinical Significance

Methylation changes in TMEM81 are associated with an increased risk of intermittent explosive disorder. [27] Additionally, SNPs located in TMEM81 affect thrombopoiesis, mean platelet volume, [28] and have been implicated in Meniere’s disease. [29]

Cancer

The 1q32.1 region showed copy number gain with a frequency of 68.9% in a study of 46 breast cancers [30] and was gained in a case of extraventricular central neurocytoma. [31] TMEM81 also has been implicated in the development of hepatocellular carcinoma. [32]

Homology

No paralogs of the TMEM81 gene exist in humans. Orthologs of the gene have been found in various lineages of gnathostomes with the most distantly orthologs found among chondrichthyes. TMEM81 orthologs have not been detected among agnatha, lancelets, tunicates, or invertebrates.

Taxonomic nameCommon nameDate of divergence (mya) [33] NCBI Accession #Length (aa)Identity (%) [34]
Homo sapiensHuman0 NP_976310 255100
Mus musculusMouse89 NP_083301.1 25969.8
Tursiops truncatus Dolphin94 XP_019773842.1 25181.4
Loxodonta africana Elephant102 XP_023404078.1 27670.6
Ornithorhynchus anatinus Platypus180 XP_001507541.1 28154.4
Aptenodytes forsteri Penguin318 XP_009271191.1 26445.7
Notechis scutatus Snake318 XP_026532625.1 24141.9
Melopsittacus undulatus Budgerigar318 XP_005140927.2 29736.9
Microcaecilia unicolor Caecilian 352 XP_030077474.1 26638.1
Latimeria chalumnae Coelacanth 414 XP_005989300.1 25434.4
Amphiprion ocellaris Clownfish433 XP_023128675.1 25624.9
Rhincodon typus Whale shark465 XP_020374416.1 25729.2

Related Research Articles

<span class="mw-page-title-main">TMEM98</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 98 is a single-pass membrane protein that in humans is encoded by the TMEM98 gene. The function of this protein is currently unknown. TMEM98 is also known as UNQ536/PRO1079.

<span class="mw-page-title-main">TMEM8B</span> Protein-coding gene in humans

Transmembrane protein 8B is a protein that in humans is encoded by the TMEM8B gene. It encodes for a transmembrane protein that is 338 amino acids long, and is located on human chromosome 9. Aliases associated with this gene include C9orf127, NAG-5, and NGX61.

<span class="mw-page-title-main">TMEM242</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 242 (TMEM242) is a protein that in humans is encoded by the TMEM242 gene. The tmem242 gene is located on chromosome 6, on the long arm, in band 2 section 5.3. This protein is also commonly called C6orf35, BM033, and UPF0463 Transmembrane Protein C6orf35. The tmem242 gene is 35,238 base pairs long, and the protein is 141 amino acids in length. The tmem242 gene contains 4 exons. The function of this protein is not well understood by the scientific community. This protein contains a DUF1358 domain.

<span class="mw-page-title-main">TMEM229B</span> Gene of the species Homo sapiens

Transmembrane protein 229b is a protein that in humans is encoded by the TMEM229b gene.

<span class="mw-page-title-main">TMEM106A</span> Protein-coding gene in the species Homo sapiens

TMEM106A is a gene that encodes the transmembrane protein 106A (TMEM106A) in Homo sapiens. It is located at 17q21.31 on the plus strand next to cancer-related genes NBR1 and BRCA1. The TMEM106A gene contains a domain of unknown function, DUF1356.

<span class="mw-page-title-main">Protein FAM46B</span> Protein-coding gene in the species Homo sapiens

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.

TMEM156 is a gene that encodes the transmembrane protein 156 (TMEM156) in Homo sapiens. It has the clone name of FLJ23235.

<span class="mw-page-title-main">TMEM176B</span> Protein-coding gene in the species Homo sapiens

Transmembrane Protein 176B, or TMEM176B is a transmembrane protein that in humans is encoded by the TMEM176B gene. It is thought to play a role in the process of maturation of dendritic cells.

<span class="mw-page-title-main">Transmembrane protein 44</span>

Transmembrane protein 44 is a protein that in humans is encoded by the TMEM44 gene.

<span class="mw-page-title-main">TMEM44</span> Protein-coding gene in the species Homo sapiens

TMEM44 is a protein that in humans is encoded by the TMEM44 gene. DKFZp686O18124 is a synonym of TMEM44.

<span class="mw-page-title-main">TMEM171</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 171 (TMEM171) is a protein that in humans is encoded by the TMEM171 gene.

<span class="mw-page-title-main">Transmembrane protein 179</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">TMEM128</span>

TMEM128, also known as Transmembrane Protein 128, is a protein that in humans is encoded by the TMEM128 gene. TMEM128 has three variants, varying in 5' UTR's and start codon location. TMEM128 contains four transmembrane domains and is localized in the Endoplasmic Reticulum membrane. TMEM128 contains a variety of regulation at the gene, transcript, and protein level. While the function of TMEM128 is poorly understood, it interacts with several proteins associated with the cell cycle, signal transduction, and memory.

<span class="mw-page-title-main">LSMEM2</span> Protein-coding gene in the species Homo sapiens

Leucine rich single-pass membrane protein 2 is a single-pass membrane protein rich in leucine, that in humans is encoded by the LSMEM2 gene. The LSMEM2 protein is conserved in mammals, birds, and reptiles. In humans, LSMEM2 is found to be highly expressed in the heart, skeletal muscle and tongue.

TMEM275 is a protein that in humans is encoded by the TMEM275 gene. TMEM275 has two, highly-conserved, helical trans-membrane regions. It is predicted to reside within the plasma membrane or the endoplasmic reticulum's membrane.

<span class="mw-page-title-main">TMEM169</span> Gene

Transmembrane protein 169 (TMEM169) in humans is encoded by TMEM169 gene. The aliases of TMEM169 include FLJ34263, DKFZp781L2456, and LOC92691. TMEM169 has the highest expression in the brain, particularly the fetal brain. TMEM169 has homologs mammals, reptiles, amphibians, birds, fish, chordates and invertebrates. The most distantly related homolog of TMEM169 is Anopheles albimanus.

<span class="mw-page-title-main">TMEM101</span>

Transmembrane protein 101 (TMEM101) is a protein that in humans is encoded by the TMEM101 gene. The TMEM101 protein has been demonstrated to activate the NF-κB signaling pathway. High levels of expression of TMEM101 have been linked to breast cancer.

<span class="mw-page-title-main">TMEM212</span> Protein-coding gene in the species Homo sapiens

Transmembrane protein 212 is a protein that in humans is encoded by the TMEM212 gene. The protein consists of 5 transmembrane domains and localizes in the plasma membrane and endoplasmic reticulum. TMEM212 has orthologs in vertebrates but not invertebrates. TMEM212 has been associated with sporadic Parkinson's disease, facial processing, and adiposity in African Americans.

<span class="mw-page-title-main">TEDDM1</span> Protein-coding gene in the species Homo sapiens

Transmembrane epididymal protein 1 is a transmembrane protein encoded by the TEDDM1 gene. TEDDM1 is also commonly known as TMEM45C and encodes 273 amino acids that contains six alpha-helix transmembrane regions. The protein contains a 118 amino acid length family of unknown function. While the exact function of TEDDM1 is not understood, it is predicted to be an integral component of the plasma membrane.


<span class="mw-page-title-main">TMEM82</span> Transmembrane Protein 82

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

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000174529 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000048174 - 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. "I-TASSER (Iterative Threading ASSEmbly Refinement". Zhang Lab.
  6. 1 2 3 4 "TMEM81". GeneCards. Weizmann Institute of Science.
  7. "Symbol report for TMEM81". GeneNames. HUGO Gene Nomenclature Committee (HGNC).
  8. "TMEM81". BioCyc. SRI International.
  9. "Gene: TMEM81". Ensembl Genome Browser. European Bioinformatics Institute (EMBL-EBI).
  10. "Genomes and Annotation: ElDorado". Genomatix Software Suite. Genomatix GmbH.
  11. 1 2 "TMEM81 - Proteomics". neXtProt. Swiss Institute of Bioinformatics.
  12. "Protter". ETH Zurich Wollscheid Lab.
  13. "Statistical Analysis of Protein Structure". European Bioinformatics Institute (EMBL-EBI).
  14. 1 2 "Homo sapiens transmembrane protein 81 (TMEM81), mRNA". NCBI Nucleotide Database. National Center for Biotechnology Information. 12 December 2020.
  15. "Ali2D". MPI Bioinformatics Toolkit. Max Planck Institute for Developmental Biology.
  16. "Phyre2". Protein Homology/analogY Recognition Engine V 2.0. Imperial College London.
  17. "Sulfinator". Expasy. Swiss Institute of Bioinformatics.
  18. "TMEM81 Subcellular". The Human Protein Atlas. SciLifeLab, Uppsala University, KTH Royal Institute of Technology.
  19. "Anti-TMEM81 antibody produced in rabbit". MilliporeSigma. Merck Group.
  20. "Gene Page TMEM81". GTEx Portal. Broad Institute of MIT and Harvard.
  21. "Tmem81 transmembrane protein 81 [ Mus musculus (house mouse) ]". NCBI Gene Database. National Center for Biotechnology Information (NCBI).
  22. "Tmem81 transmembrane protein 81 [ Rattus norvegicus (Norway rat) ]". NCBI Gene Database. National Center for Biotechnology Information (NCBI).
  23. "TMEM81 Brain". The Human Protein Atlas. SciLifeLab, Uppsala University, KTH Royal Institute of Technology.
  24. "dbMAE". dbMAE: the database of autosomal monoallelic expression. Gimelbrant Lab.
  25. "TMEM81 Homo sapiens protein". PAXdb: Protein Abundance Database. Swiss Institute of Bioinformatics, University of Zurich.
  26. "Tmem81 Mus musculus protein". PAXdb: Protein Abundance Database. Swiss Institute of Bioinformatics, University of Zurich.
  27. Montalvo-Ortiz JL, Zhang H, Chen C, Liu C, Coccaro EF (January 2018). "Genome-Wide DNA Methylation Changes Associated with Intermittent Explosive Disorder: A Gene-Based Functional Enrichment Analysis". The International Journal of Neuropsychopharmacology. 21 (1): 12–20. doi:10.1093/ijnp/pyx087. PMC   5789263 . PMID   29106553.
  28. Shameer K, Denny JC, Ding K, Jouni H, Crosslin DR, de Andrade M, et al. (January 2014). "A genome- and phenome-wide association study to identify genetic variants influencing platelet count and volume and their pleiotropic effects". Human Genetics. 133 (1): 95–109. doi:10.1007/s00439-013-1355-7. PMC   3880605 . PMID   24026423.
  29. Campbell CA (2010). \Identification of a genetic contribution to Meniere's disease (Ph.D. thesis). University of Iowa, USA).
  30. Kawauchi S, Furuya T, Ikemoto K, Nakao M, Yamamoto S, Oka M, Sasaki K (October 2010). "DNA copy number aberrations associated with aneuploidy and chromosomal instability in breast cancers". Oncology Reports. 24 (4): 875–83. doi: 10.3892/or.2010.875 . PMID   20811667.
  31. Myung JK, Cho HJ, Park CK, Chung CK, Choi SH, Kim SK, Park SH (April 2013). "Clinicopathological and genetic characteristics of extraventricular neurocytomas". Neuropathology. 33 (2): 111–121. doi:10.1111/j.1440-1789.2012.01330.x. PMID   22672632. S2CID   2024518.
  32. Chen J, Qian Z, Li F, Li J, Lu Y (January 2017). "Integrative Analysis of Microarray Data to Reveal Regulation Patterns in the Pathogenesis of Hepatocellular Carcinoma". Gut and Liver. 11 (1): 112–120. doi:10.5009/gnl16063. PMC   5221868 . PMID   27458175.
  33. "TimeTree". Temple University.
  34. "Standard Protein BLAST". BLAST. National Center for Biotechnology Information.