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TMEM261
Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9.[1]TMEM261 is also known as C9ORF123, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123.[2]

Gene Features

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TMEM261 is located at 9p24.1,its length is 91,891 base pairs (bp) on the reverse strand.[2]Its neighbouring gene is PTPRD located at 9p23-p24.3 also on the reverse strand and encodes protein tyrosine phosphatase receptor type delta.[1][2] TMEM261 has 2 exons and 1 intron, and 6 transcript variants; the largest mRNA transcript variant consisting of 742bp with a protein 129 amino acids (aa) in length and 13,500 Daltons (Da) in size, and the smallest coding transcript variant being 381bp with a protein 69aa long and 6,100 Da in size.[3][4]

Annotated features of TMEM261 protein including topology and important sites for phosphorylation and Myristoylation as well DUF4536 and transmembrane helical domains.

Protein Features

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TMEM261 is a protein of 112aa with a molecular weight of 11,800 Da.[5] The isoelectric is predicted to be 10.2Cite error: The <ref> tag has too many names (see the help page)., whilst its posttranslational modification value is 9.9[4].

Structure

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Some proteins found to interact with TMEM261

TMEM261 contains a domain of unknown function, DUF4536 (pfam15055), predicted as a helical membrane spanning domain about 45aa (Cys 47- Ser 92) in length with no known domain relationships.[6][7] Two further transmembrane helical domains are predicted of lengths 18aa (Val 52-Ala 69) and 23aa (Pro 81-Ala 102]).Cite error: The <ref> tag has too many names (see the help page).[8]There is also a low complexity region spanning 25aa (Thr 14-Ala 39).[9] The tertiary structure for TMEM261 has not yet been determined. However, its secondary structure is mostly composed of coiled-coil regions with beta strands and alpha helices found within the transmembrane and domain of unknown function reigons. The N-terminal region of TMEM261 is composed of a disordered region[10] [11] which contains the low complexity region[9] that is not highly conserved amongst orthologues[12][13].

Modifications

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A N-myristoylation domain is shown to be present in most TMEM261 protein variants.[4] Post-translational modifications include myristoylation of the N-terminal Glycine residue (Gly2)[4][14] of the TMEM261 protein as well as phosphorylation of Threonine 31.[15]

Interactions

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Proteins shown to interact with TMEM261 include NAAA (protein-protein interaction), QTRT1 (RNA-protein interaction),ZC4H2(DNA-protein interaction)[16] and ZNF454(DNA-protein interaction)[17][18]. It has also shown to interact with APP(protein-protein interaction)[19],ARHGEF38(protein-protein interaction)[20] and HNRNPD(RNA-protein interaction)[21].[22]

Tissue expression of TMEM261 showing tissue enriched gene (TEG) expression [23]

Additional transcription factor binding sites (DNA-protein interaction) predicted include one binding site for MEF2C a monocyte-specific enhancement factor that is involved in muscle-cell regulation particularly in the cardiovascular system [2][24] and two binding sites for GATA1 which is a globin transcription factor 1 involved in erythroblast development regulation[25][26]. [27]

Expression

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TMEM261 shows ubiquitous expression in humans detected in almost all tissue types[28][29] and shows tissue-enriched gene (TEG) expression when compared to housekeeping gene (HKG) expression[23]. Its highest expression is seen in the heart (overall relative expression 94%) particularly in heart fibroblast cells, thymus (overall relative expression 90%), and thyroid (overall relative expression 93%) particularly in thyroid glandular cells.[23][28]Staining intensity of cancer cells showed intermediate to high expression in breast, colorectal, ovarian, skin, urothelial, head and neck cells. [28].


Function

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Currently the function for TMEM261 is unknown. However, gene amplification and rearrangements of its locus have been associated with various cancers including colorectal cancer[30], breast cancer[31] and lymphomas[32][33].

Evolution

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Orthologues

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The orthologues and homologues of TMEM261 are limited to vertebrates, its oldest homologue dates to that of the cartilaginous fishes[34] which diverged from Homo sapiens 462.5 million years ago [35]. The primary structure of TMEM261 shows higher overall conservation in mammals, however high conservation of the domain of unknown function (DUF4536) to the C-terminus region is seen in all orthologues, including distant homologues. The secondary structure of TMEM261 shows conservation across most orthologues.[12][13]

Organism Scientific Name Accession Number Date of Divergence from Humans (million years) Amino acids (aa) Identity (%) Class
Humans Homo sapiens NP_219500.1 0 112 100 Mammalia
Gorilla Gorilla gorilla XP_004047847.1 8.8 112 99 Mammalia
Olive Baboon Papio anubis XP_003911767.1 29 112 84 Mammalia
Sunda Flying Lemur Galeopterus variegatus XP_008587957.1 81.5 112 68 Mammalia
Lesser Egyptian Jerboa Jaculus Jaculus XP_004653029.1 92.3 109 56 Mammalia
Naked Mole Rat Heterocephalus glaber XP_004898193.1 92.3 114 45 Mammalia
White Rhinoceros Ceratotherium simum simum XP_004436891.1 94.2 112 66 Mammalia
Nine-banded armadillo Dasypus novemcinctus XP_004459147.1 104.4 112 59 Mammalia
Green Sea Turtle Chelonia mydas XP_007056940.1 296 85 49 Reptilia
Zebra Finch Taeniopygia Guttata XP_002187613.2 296 72 47 Aves
Western Clawed Frog Xenopus tropicalis XP_002943025.1 371.2 85 45 Amphibia
Haplochromis burtoni Haplochromis burtoni XP_005928614.1 400.1 91 51 Actinopterygii
Australian Ghost Shark Callorhinchus milii XP_007884223.1 426.5 86 43 Chondrichthyes

Paralogues

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TMEM261 has no known paralogs[34].

References

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  1. ^ a b "Entrez Protein: TMEM261".
  2. ^ a b c d "GeneCards:TMEM261 Gene". Cite error: The named reference "GeneCards" was defined multiple times with different content (see the help page).
  3. ^ Thierry-Mieg, D; Thierry-Mieg, J. (2006). "AceView: a comprehensive cDNA-supported gene and transcripts annotation". Genome Biology. 7 (Suppl 1): S12.1–14. doi:10.1186/gb-2006-7-s1-s12. PMC 1810549. PMID 16925834.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  4. ^ a b c d "AceView:Homo sapiens gene C9orf123".
  5. ^ "Ensemble:Transcript TMEM261-003".
  6. ^ "NCBI Conserved Domains: DUF4536".
  7. ^ "EMBL-EBI Interpro: Transmembrane protein 261 (Q96GE9)".
  8. ^ "Q96GE9 - TM261_HUMAN". UniProt. UniProt Consortium.
  9. ^ a b "Vega: Transcript: C9orf123-003".
  10. ^ "PHYRE: Protein Homology/analogY Recognition Engine". PHYRE.
  11. ^ Kelley, LA; Sternberg, MJE (2009). "Protein structure prediction on the Web: a case study using the Phyre server". MJE. 4 (3): 363–371. doi:10.1038/nprot.2009.2. hdl:10044/1/18157. PMID 19247286. S2CID 12497300.
  12. ^ a b "ClustalW".
  13. ^ a b Thompson, Julie D; Higgins, Desmond G; Gibson, Toby J (1994). "CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice". Nucleic Acids Res. 22 (22): 4673–4680. doi:10.1093/nar/22.22.4673. PMC 308517. PMID 308517.
  14. ^ Gallo, Vincenzo. "Myristoylation : Proteins Post-translational Modifications". http://flipper.diff.org/. University of Turin. {{cite web}}: External link in |website= (help)
  15. ^ "Nextprot:TMEM261 » Transmembrane protein 261".
  16. ^ Dash, A; et al. (2002). "Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens". Am J Pathol. 161 (5): 1743–1748. doi:10.1016/S0002-9440(10)64451-3. PMC 1850797. PMID 12414521. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  17. ^ Rovillain, E; et al. (2011). "An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence". BMC Genomics. 12 (355): 355. doi:10.1186/1471-2164-12-355. PMC 3161017. PMID 21740549. {{cite journal}}: Explicit use of et al. in: |first1= (help)CS1 maint: unflagged free DOI (link)
  18. ^ "c9orf123 protein (Homo Sapiens)- STRING Network View". STRING - Known and Predicted Protein-Protein Interactions.
  19. ^ Oláh, J; et al. (2011). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein". J Biol Chem. 286 (39): 34088–34100. doi:10.1074/jbc.M111.243907. PMC 3190826. PMID 21832049. {{cite journal}}: Explicit use of et al. in: |first1= (help)CS1 maint: unflagged free DOI (link)
  20. ^ Huttlin, E L; et al. (2014). "High-Throughput Proteomic Mapping of Human Interaction Networks via Affinity-Purification Mass Spectrometry (Pre-Publication)". Pre-Publication. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  21. ^ Lehner, B; Sanderson, C M (2004). "A protein interaction framework for human mRNA degradation". Genome Res. 14 (7): 1315–1323. doi:10.1101/gr.2122004. PMC 442147. PMID 15231747.
  22. ^ "9ORF123 chromosome 9 open reading frame 123". BioGRID: Database of Protein and Genetic Interactions. TyersLab.
  23. ^ a b c She X, Rohl CA, Castle JC, Kulkarni AV, Johnson JM, Chen R (2009). "Definition, conservation and epigenetics of housekeeping and tissue-enriched genes". BMC Genomics. 10: 269. doi:10.1186/1471-2164-10-269. PMC 2706266. PMID 19534766.{{cite journal}}: CS1 maint: unflagged free DOI (link)
  24. ^ "GeneCards:MEF2C Gene".
  25. ^ Welch, J J; et al. (2004). "Global regulation of erythroid gene expression by transcription factor GATA-1". Blood. 104 (10): 3136–3147. doi:10.1182/blood-2004-04-1603. PMID 15297311. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  26. ^ Merryweather-Clarke, A T; et al. (2011). "Global gene expression analysis of human erythroid progenitors". Blood. 117 (13): e96-108. doi:10.1182/blood-2010-07-290825. PMID 21270440. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  27. ^ "Genomatics- NGS Data Analysis and Personalised Medicine". Genomatix. Genomatix Software GmbH.
  28. ^ a b c "The Human Protein Atlas:TMEM261".
  29. ^ "EST profile: TMEM261". UniGene. National Library of Medicine.
  30. ^ Gaspar, C (2008). "Cross-Species Comparison of Human and Mouse Intestinal Polyps Reveals Conserved Mechanisms in Adenomatous Polyposis Coli (APC)-Driven Tumorigenesis". Am J Pathol. 172 (5): 1363–1380. doi:10.2353/ajpath.2008.070851. PMC 2329845. PMID 18403596.
  31. ^ Wu, J (2012). "Identification and functional analysis of 9p24 amplified genes in human breast cancer". Oncogene. 31 (3): 333–341. doi:10.1038/onc.2011.227. PMC 3886828. PMID 21666724.
  32. ^ Twa, D D W; et al. (2014). "Genomic Rearrangements Involving Programmed Death Ligands Are Recurrent in Primary Mediastinal Large B-Cell Lymphoma". Blood. 123 (13): 2062–2065. doi:10.1182/blood-2013-10-535443. PMID 24497532. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  33. ^ Green, M R; et al. (2010). "Integrative Analysis Reveals Selective 9p24.1 Amplification, Increased PD-1 Ligand Expression, and Further Induction via JAK2 in Nodular Sclerosing Hodgkin Lymphoma and Primary Mediastinal Large B-Cell Lymphoma". Blood. 116 (17): 3268–3277. doi:10.1182/blood-2010-05-282780. PMC 2995356. PMID 20628145. {{cite journal}}: Explicit use of et al. in: |first1= (help)
  34. ^ a b "NCBI BLAST:Basic Local Alignment Search Tool".
  35. ^ Hedges, S. Blaire; Dudley, Joel; Kumar, Sudhir (22 September 2006). "TimeTree: a public knowledge-base of divergence times among organisms" (PDF). Bioinformatics. 22 (23): 2971–2972. doi:10.1093/bioinformatics/btl505. PMID 17021158.


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Further Reading

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