Biology: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 and DMAC1, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123[2] and Distal membrane-arm assembly complex protein 1[3].
Gene Features
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 primary 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.[4][5]
Protein Features
TMEM261 is a protein consisting out of 112 amino acids, with a molecular weight of 11.8 kDa.[6] The isoelectric point is predicted to be 10.2,[7] whilst its posttranslational modification value is 9.9.[5]
Structure
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.[8][9] Two further transmembrane helical domains are predicted of lengths 18aa (Val 52-Ala 69) and 23aa (Pro 81-Ala 102]).[10][11] There is also a low complexity region spanning 25aa (Thr 14-Ala 39).[12] The tertiary structure for TMEM261 has not yet been determined. However, its protein secondary structure is mostly composed of coiled-coil regions with beta strands and alpha helices found within the transmembrane and domain of unknown function regions. The N-terminal region of TMEM261 is composed of a disordered region[13][14] which contains the low complexity region[12] that is not highly conserved amongst orthologues.[15][16]
Modifications
A N-myristoylation domain is shown to be present in most TMEM261 protein variants.[5] Post-translational modifications include myristoylation of the N-terminal Glycine residue (Gly2)[5][17] of the TMEM261 protein as well as phosphorylation of Threonine 31.[18]
Interactions
Proteins shown to interact with TMEM261 include NAAA (protein-protein interaction), QTRT1 (RNA-protein interaction),ZC4H2(DNA-protein interaction)[19] and ZNF454(DNA-protein interaction).[20][21] It has also shown to interact with APP(protein-protein interaction),[22] ARHGEF38(protein-protein interaction)[23] and HNRNPD(RNA-protein interaction).[24][25]
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][27] and two binding sites for GATA1 which is a globin transcription factor 1 involved in erythroblast development regulation.[28][29][30]
Expression
TMEM261 shows ubiquitous expression in humans and is detected in almost all tissue types.[31][32] It shows tissue-enriched gene (TEG) expression when compared to housekeeping gene (HKG) expression.[26] 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.[26][31] Staining intensity of cancer cells showed intermediate to high expression in breast, colorectal, ovarian, skin, urothelial, head and neck cells.[31]
Function
Currently the function for TMEM261 is unknown.[33] However, gene amplification and rearrangements of its locus have been associated with various cancers including colorectal cancer,[34] breast cancer[35] and lymphomas.[36][37]
Evolution
Orthologues
The orthologues and homologues of TMEM261 are limited to vertebrates, its oldest homologue dates to that of the cartilaginous fishes[38] which diverged from Homo sapiens 462.5 million years ago.[39] The protein 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 protein structure of TMEM261 shows conservation across most orthologues.[15][16]
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
TMEM261 has no known paralogs.[38]
References
- ↑ 1.0 1.1 "Entrez Protein: TMEM261". https://www.ncbi.nlm.nih.gov/gene/90871.
- ↑ 2.0 2.1 2.2 2.3 "GeneCards: PTPRD". https://www.genecards.org/cgi-bin/carddisp.pl?gene=PTPRD&search=ec5eebdfa3e88e99844e476b922bd273.
- ↑ "DMAC1 - Distal membrane-arm assembly complex protein 1 - Homo sapiens (Human) - DMAC1 gene & protein" (in en). https://www.uniprot.org/uniprot/Q96GE9.
- ↑ Thierry-Mieg, D; Thierry-Mieg, J. (2006). "AceView: a comprehensive cDNA-supported gene and transcripts annotation". Genome Biology 7 (Suppl 1): S12. doi:10.1186/gb-2006-7-s1-s12. PMID 16925834.
- ↑ 5.0 5.1 5.2 5.3 "AceView:Homo sapiens gene C9orf123". https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go.
- ↑ "Ensemble:Transcript TMEM261-003". http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000137038;r=9:7796490-7888380;t=ENST00000358227.
- ↑ "PI:Isoelectric point determination". http://workbench.sdsc.edu/.
- ↑ "NCBI Conserved Domains: DUF4536". https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=259192.
- ↑ "EMBL-EBI Interpro: Transmembrane protein 261 (Q96GE9)". http://www.ebi.ac.uk/s4/summary/molecular?term=TMEM261&classification=9606&tid=nameOrgENSG00000137038.
- ↑ "Phobius: A combined transmembrane topology and signal peptide predictor". http://phobius.sbc.su.se/.
- ↑ "Q96GE9 - TM261_HUMAN". UniProt Consortium. https://www.uniprot.org/uniprot/Q96GE9.
- ↑ 12.0 12.1 "Vega: Transcript: C9orf123-003". http://vega.sanger.ac.uk/Homo_sapiens/Transcript/ProteinSummary?db=core;g=OTTHUMG00000019539;r=9:7796490-7888380;t=OTTHUMT00000051705.
- ↑ "PHYRE: Protein Homology/analogY Recognition Engine". http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index.
- ↑ Kelley, LA; Sternberg, MJE (2009). "Protein structure prediction on the Web: a case study using the Phyre server". MJE 4: 363–371. doi:10.1038/nprot.2009.2. PMID 19247286. http://www.nature.com/nprot/journal/v4/n3/full/nprot.2009.2.html.
- ↑ 15.0 15.1 "ClustalW". http://workbench.sdsc.edu/.
- ↑ 16.0 16.1 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. PMID 7984417.
- ↑ Gallo, Vincenzo. "Myristoylation : Proteins Post-translational Modifications". University of Turin. http://flipper.diff.org/app/pathways/info/4026.
- ↑ "Nextprot:TMEM261 » Transmembrane protein 261". http://www.nextprot.org/db/entry/NX_Q96GE9/sequence.
- ↑ "Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens.". Am J Pathol 161 (5): 1743–1748. 2002. doi:10.1016/S0002-9440(10)64451-3. PMID 12414521.
- ↑ "An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence.". BMC Genomics 12 (355). 2011. doi:10.1186/1471-2164-12-355. PMID 21740549.
- ↑ "c9orf123 protein (Homo Sapiens)- STRING Network View". http://string-db.org/newstring_cgi/show_input_page.pl?UserId=65EMVhw9LAhY&sessionId=N5_gHtjz1Wbz.
- ↑ "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein.". J Biol Chem 286 (39): 34088–34100. 2011. doi:10.1074/jbc.M111.243907. PMID 21832049. PMC 3190826. http://www.jbc.org/content/286/39/34088.long.
- ↑ "High-Throughput Proteomic Mapping of Human Interaction Networks via Affinity-Purification Mass Spectrometry (Pre-Publication)". Pre-Publication. 2014. http://thebiogrid.org/166968/publication/high-throughput-proteomic-mapping-of-human-interaction-networks-via-affinity-purification-mass-spectrometry.html.
- ↑ 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. PMID 15231747. PMC 442147. http://genome.cshlp.org/content/14/7/1315.long.
- ↑ "9ORF123 chromosome 9 open reading frame 123". TyersLab. http://thebiogrid.org/124777/summary/homo-sapiens/c9orf123.html.
- ↑ 26.0 26.1 26.2 "Definition, conservation and epigenetics of housekeeping and tissue-enriched genes". BMC Genomics 10: 269. 2009. doi:10.1186/1471-2164-10-269. PMID 19534766.
- ↑ "GeneCards:MEF2C Gene". https://www.genecards.org/cgi-bin/carddisp.pl?gene=MEF2C&search=b74dc542dd9d720d31835d8b921cab5f.
- ↑ "Global regulation of erythroid gene expression by transcription factor GATA-1.". Blood 104 (10): 3136–3147. 2004. doi:10.1182/blood-2004-04-1603. PMID 15297311. http://www.bloodjournal.org/content/104/10/3136?sso-checked=true.
- ↑ "Global gene expression analysis of human erythroid progenitors". Blood 117 (13): e96-108. 2011. doi:10.1182/blood-2010-07-290825. PMID 21270440. http://www.bloodjournal.org/content/117/13/e96.long.
- ↑ "Genomatics- NGS Data Analysis and Personalised Medicine". Genomatix Software GmbH. https://www.genomatix.de/.
- ↑ 31.0 31.1 31.2 "The Human Protein Atlas:TMEM261". http://www.proteinatlas.org/ENSG00000137038-TMEM261/tissue.
- ↑ "EST profile: TMEM261". UniGene. National Library of Medicine. https://www.ncbi.nlm.nih.gov/UniGene/clust.cgi?UGID=132138&TAXID=9606&SEARCH=c9orf123.
- ↑ "Identification and functional analysis of 9p24 amplified genes in human breast cancer". Oncogene 31 (3): 333–341. 2012. doi:10.1038/onc.2011.227. PMID 21666724. PMC 3886828. http://www.nature.com/onc/journal/v31/n3/full/onc2011227a.html.
- ↑ 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. PMID 18403596.
- ↑ 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. PMID 21666724. PMC 3886828. http://www.nature.com/onc/journal/v31/n3/full/onc2011227a.html.
- ↑ "Genomic Rearrangements Involving Programmed Death Ligands Are Recurrent in Primary Mediastinal Large B-Cell Lymphoma". Blood 123 (13): 2062–2065. 2014. doi:10.1182/blood-2013-10-535443. PMID 24497532. http://www.bloodjournal.org/content/123/13/2062.long?sso-checked=true.
- ↑ "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. 2010. doi:10.1182/blood-2010-05-282780. PMID 20628145. PMC 2995356. http://www.bloodjournal.org/content/116/17/3268.long.
- ↑ 38.0 38.1 "NCBI BLAST:Basic Local Alignment Search Tool". http://blast.ncbi.nlm.nih.gov/Blast.cgi.
- ↑ Hedges, S. Blaire; Dudley, Joel; Kumar, Sudhir (22 September 2006). "TimeTree: a public knowledge-base of divergence times among organisms". Bioinformatics 22 (23): 2971–2972. doi:10.1093/bioinformatics/btl505. PMID 17021158. http://kumarlab.net/pdf_new/HedgesKumar06.pdf.
External links
- PubMed
- NCBI gene record
- GeneCards
- UCSC Genome Browser
- Expasy Bioinformatics Resource Portal
- SDSC Biology Workbench
- Uniprot
- HUGO
Further reading
- Nicholas K. Tonks (2006). "Protein tyrosine phosphatases: from genes, to function, to disease". Cancer Cell 7: 833–846. doi:10.1038/nrm2039.
- "Global gene expression analysis of human erythroid progenitors.". Blood 117 (13): e96-108. 2011. doi:10.1182/blood-2010-07-290825. PMID 21270440.
- "Global regulation of erythroid gene expression by transcription factor GATA-1". Blood 104 (10): 3136–3147. 2004. doi:10.1182/blood-2004-04-1603. PMID 15297311.
- "Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition.". Cancer Cell 14 (1): 23–35. 2008. doi:10.1016/j.ccr.2008.05.016. PMID 18598941.