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''TMEM261'' is located at 9p24.1,its length is 91,891 [[base pairs]] (bp) on the reverse strand.<ref name = "GeneCards">{{cite web|title=GeneCards:TMEM261 Gene|url=http://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM261&search=b6dd0fe61f84418762b84e0f9a3a0892}}</ref>Its neighbouring gene is ''[[PTPRD]]'' located at 9p23-p24.3 also on the reverse strand and encodes [[protein tyrosine phosphatase]] receptor type delta.<ref name = "entrez">{{cite web|title=Entrez Protein: TMEM261|url=http://www.ncbi.nlm.nih.gov/gene/90871}}</ref><ref name = GeneCards>{{cite web|title=GeneCards: PTPRD|url=http://www.genecards.org/cgi-bin/carddisp.pl?gene=PTPRD&search=ec5eebdfa3e88e99844e476b922bd273}}</ref> |
''TMEM261'' is located at 9p24.1,its length is 91,891 [[base pairs]] (bp) on the reverse strand.<ref name = "GeneCards">{{cite web|title=GeneCards:TMEM261 Gene|url=http://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM261&search=b6dd0fe61f84418762b84e0f9a3a0892}}</ref>Its neighbouring gene is ''[[PTPRD]]'' located at 9p23-p24.3 also on the reverse strand and encodes [[protein tyrosine phosphatase]] receptor type delta.<ref name = "entrez">{{cite web|title=Entrez Protein: TMEM261|url=http://www.ncbi.nlm.nih.gov/gene/90871}}</ref><ref name = GeneCards>{{cite web|title=GeneCards: PTPRD|url=http://www.genecards.org/cgi-bin/carddisp.pl?gene=PTPRD&search=ec5eebdfa3e88e99844e476b922bd273}}</ref> |
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''TMEM261'' has 2 [[exons]] and 1 [[intron]], and 6 [[primary transcript|transcript]] variants |
''TMEM261'' has 2 [[exons]] and 1 [[intron]], and 6 [[primary transcript|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.<ref>{{cite journal|last=Thierry-Mieg|first=D|author2=Thierry-Mieg, J.|title=AceView: a comprehensive cDNA-supported gene and transcripts annotation|journal=Genome Biology|year=2006|volume=7|issue=Suppl 1|pages=S12.1–14|doi=10.1186/gb-2006-7-s1-s12|pmid=16925834|pmc=1810549}}</ref><ref name = "AceView">{{cite web|title=AceView:Homo sapiens gene C9orf123|url=http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go}}</ref> |
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[[File:TMEM261 features.jpg|thumb|Annotated features of TMEM261 protein including topology and important sites for phosphorylation and Myristoylation as well DUF4536 and transmembrane helical domains.]] |
[[File:TMEM261 features.jpg|thumb|Annotated features of TMEM261 protein including topology and important sites for phosphorylation and Myristoylation as well DUF4536 and transmembrane helical domains.]] |
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==Protein Features== |
==Protein Features== |
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TMEM261 is a protein of 112aa with a [[molecular weight]] of |
TMEM261 is a protein of 112aa with a [[molecular weight]] of 11,800 Da.<ref name = "Ensemble">{{cite web|title=Ensemble:Transcript TMEM261-003|url=http://www.ensembl.org/Homo_sapiens/Transcript/Summary?db=core;g=ENSG00000137038;r=9:7796490-7888380;t=ENST00000358227}}</ref> The isoelectric is predicted to be 10.2<ref name = SDSC Biology WorkBench>{{cite web|title=PI:Isoelectric point determination|url=http://workbench.sdsc.edu/}}</ref>, whilst its [[posttranslational modification]] value is 9.9<ref name = "AceView">{{cite web|title=AceView:Homo sapiens gene C9orf123|url=http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go}}</ref>. |
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==== Structure ==== |
==== Structure ==== |
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[[File:TMEM261interactions.jpg|thumb|Some proteins found to interact with TMEM261]] |
[[File:TMEM261interactions.jpg|thumb|Some proteins found to interact with TMEM261]] |
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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.<ref name="conserved domains">{{cite web | title = NCBI Conserved Domains: DUF4536| url =http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=259192}}</ref><ref name="EMBL-EBI>{{cite web | title = EMBL-EBI Interpro: Transmembrane protein 261 (Q96GE9)| url =http://www.ebi.ac.uk/s4/summary/molecular?term=TMEM261&classification=9606&tid=nameOrgENSG00000137038}}</ref> Two further transmembrane helical domains are predicted of lengths 18aa ([[Val]]52-[[Ala]]69) and 23aa ([[Pro]]81- |
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.<ref name="conserved domains">{{cite web | title = NCBI Conserved Domains: DUF4536| url =http://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=259192}}</ref><ref name="EMBL-EBI>{{cite web | title = EMBL-EBI Interpro: Transmembrane protein 261 (Q96GE9)| url =http://www.ebi.ac.uk/s4/summary/molecular?term=TMEM261&classification=9606&tid=nameOrgENSG00000137038}}</ref> Two further transmembrane helical domains are predicted of lengths 18aa ([[Val]] 52-[[Ala]] 69) and 23aa ([[Pro]] 81-[[Ala]] 102]).<ref name=Bioinformatics Centre Stockholm>{{cite web | title = Phobius: A combined transmembrane topology and signal peptide predictor| url =http://phobius.sbc.su.se/}}</ref><ref>{{cite web|title=Q96GE9 - TM261_HUMAN|url=http://www.uniprot.org/uniprot/Q96GE9|website=UniProt|publisher=UniProt Consortium}}</ref>There is also a low complexity region spanning 25aa ([[Thr]] 14-[[Ala]] 39).<ref name="Vega Genome Browser 58>{{cite web | title = Vega: Transcript: C9orf123-003| url =http://vega.sanger.ac.uk/Homo_sapiens/Transcript/ProteinSummary?db=core;g=OTTHUMG00000019539;r=9:7796490-7888380;t=OTTHUMT00000051705}}</ref> The [[protein tertiary structure|tertiary structure]] for TMEM261 has not yet been determined. However, its [[Protein secondary structure|secondary structure]] is mostly composed of [[Coiled-coil|coiled-coil]] regions with [[Beta strand|beta strands]] and [[Alpha helices|alpha helices]] found within the [[transmembrane]] and [[domain of unknown function]] reigons. The N-terminal region of TMEM261 is composed of a disordered region<ref>{{cite web|title=PHYRE: Protein Homology/analogY Recognition Engine|url=http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index|website=PHYRE}}</ref> <ref>{{cite journal|last1=Kelley|first1=LA|last2=Sternberg|first2= MJE|title=Protein structure prediction on the Web: a case study using the Phyre server|journal=MJE|date=2009|volume=4|issue=3|pages=363–371|doi=10.1038/nprot.2009.2|pmid=19247286|hdl=10044/1/18157|s2cid=12497300|url=http://www.nature.com/nprot/journal/v4/n3/full/nprot.2009.2.html}}</ref> which contains the low complexity region<ref name="Vega Genome Browser 58>{{cite web | title = Vega: Transcript: C9orf123-003| url =http://vega.sanger.ac.uk/Homo_sapiens/Transcript/ProteinSummary?db=core;g=OTTHUMG00000019539;r=9:7796490-7888380;t=OTTHUMT00000051705}}</ref> that is not highly conserved amongst orthologues<ref name = "SDSC Biology ">{{cite web|title= ClustalW|url=http://workbench.sdsc.edu/}}</ref><ref name= Thompson>{{cite journal|last1=Thompson|first1=Julie D|last2=Higgins|first2=Desmond G|last3=Gibson|first3=Toby J|title=CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice.|journal=Nucleic Acids Res|date=1994|volume=22|issue=22|pages=4673–4680|doi=10.1093/nar/22.22.4673|pmid=308517|pmc=308517}}</ref>. |
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==== Modifications ==== |
==== Modifications ==== |
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A N-myristoylation domain is shown to be present in most TMEM261 protein variants.<ref name = "AceView">{{cite web|title=AceView:Homo sapiens gene C9orf123|url=http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go}}</ref> Post-translational modifications include [[myristoylation]] of the [[N-terminal]] [[Glycine]] residue ([[Gly]]2)<ref name = "AceView">{{cite web|title=AceView:Homo sapiens gene C9orf123|url=http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go}}</ref><ref>{{cite web|last1=Gallo|first1=Vincenzo|title=Myristoylation : Proteins Post-translational Modifications|url=http://flipper.diff.org/app/pathways/info/4026|website=http://flipper.diff.org/|publisher=University of Turin}}</ref> of the TMEM261 protein as well as [[phosphorylation]] of [[Threonine]] 31.<ref name = "Nextprot">{{cite web|title=Nextprot:TMEM261 » |
A N-myristoylation domain is shown to be present in most TMEM261 protein variants.<ref name = "AceView">{{cite web|title=AceView:Homo sapiens gene C9orf123|url=http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go}}</ref> Post-translational modifications include [[myristoylation]] of the [[N-terminal]] [[Glycine]] residue ([[Gly]]2)<ref name = "AceView">{{cite web|title=AceView:Homo sapiens gene C9orf123|url=http://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go}}</ref><ref>{{cite web|last1=Gallo|first1=Vincenzo|title=Myristoylation : Proteins Post-translational Modifications|url=http://flipper.diff.org/app/pathways/info/4026|website=http://flipper.diff.org/|publisher=University of Turin}}</ref> of the TMEM261 protein as well as [[phosphorylation]] of [[Threonine]] 31.<ref name = "Nextprot">{{cite web|title=Nextprot:TMEM261 » Transmembrane protein 261|url=http://www.nextprot.org/db/entry/NX_Q96GE9/sequence}}</ref> <br /> |
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==== Interactions ==== |
==== Interactions ==== |
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Proteins shown to interact with TMEM261 include [http://www.genecards.org/cgi-bin/carddisp.pl?gene=NAAA NAAA], [http://www.genecards.org/cgi-bin/carddisp.pl?gene=QTRT1&search=d6edd4112f517825968a5a6978882712 QTRT1],[http://www.genecards.org/cgi-bin/carddisp.pl?gene=ZC4H2&search=79ba8f7afa868106306bf83d200ba523 ZC4H2]<ref>{{cite journal|last1=Dash|first1=A et al.|title=Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens.|journal=Am J Pathol.|date=2002|volume=161|issue=5|pages= |
Proteins shown to interact with TMEM261 include [http://www.genecards.org/cgi-bin/carddisp.pl?gene=NAAA NAAA] ([[protein-protein interaction]]), [http://www.genecards.org/cgi-bin/carddisp.pl?gene=QTRT1&search=d6edd4112f517825968a5a6978882712 QTRT1] ([https://www.lifetechnologies.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/methods-detecting-protein-rna-interactions.html RNA-protein interaction]),[http://www.genecards.org/cgi-bin/carddisp.pl?gene=ZC4H2&search=79ba8f7afa868106306bf83d200ba523 ZC4H2]([[DNA-protein interaction]])<ref>{{cite journal|last1=Dash|first1=A et al.|title=Changes in differential gene expression because of warm ischemia time of radical prostatectomy specimens.|journal=Am J Pathol.|date=2002|volume=161|issue=5|pages=1743–1748|doi=10.1016/S0002-9440(10)64451-3|pmid=12414521|pmc=1850797}}</ref> and [http://www.genecards.org/cgi-bin/carddisp.pl?gene=ZNF454&search=68835d4da3192d71bcf7818742536191 ZNF454](DNA-protein interaction)<ref>{{cite journal|last1=Rovillain|first1=E et al.|title=An RNA interference screen for identifying downstream effectors of the p53 and pRB tumour suppressor pathways involved in senescence.|journal=BMC Genomics.|date=2011|volume=12|issue=355|page=355|doi=10.1186/1471-2164-12-355|pmid=21740549|pmc=3161017}}</ref><ref>{{cite web|title=c9orf123 protein (Homo Sapiens)- STRING Network View|url=http://string-db.org/newstring_cgi/show_input_page.pl?UserId=65EMVhw9LAhY&sessionId=N5_gHtjz1Wbz|website=STRING - Known and Predicted Protein-Protein Interactions}}</ref>. It has also shown to interact with [http://www.genecards.org/cgi-bin/carddisp.pl?gene=APP APP](protein-protein interaction)<ref>{{cite journal|last1=Oláh|first1=J et al.|title=Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein.|journal=J Biol Chem.|date=2011|volume=286|issue=39|pages=34088–34100|doi=10.1074/jbc.M111.243907|pmid=21832049|pmc=3190826|url=http://www.jbc.org/content/286/39/34088.long}}</ref>,[http://www.genecards.org/cgi-bin/carddisp.pl?gene=ARHGEF38&search=1bcacaca34542f4b438e308c6b02cfd2 ARHGEF38](protein-protein interaction)<ref>{{cite journal|last1=Huttlin|first1=E L et al.|title=High-Throughput Proteomic Mapping of Human Interaction Networks via Affinity-Purification Mass Spectrometry (Pre-Publication)|journal=Pre-Publication|date=2014|url=http://thebiogrid.org/166968/publication/high-throughput-proteomic-mapping-of-human-interaction-networks-via-affinity-purification-mass-spectrometry.html}}</ref> and [http://www.genecards.org/cgi-bin/carddisp.pl?gene=HNRNPD&search=c4b9dd1c49f01a5dfb3c401f24182f32 HNRNPD]([https://www.lifetechnologies.com/us/en/home/life-science/protein-biology/protein-biology-learning-center/protein-biology-resource-library/pierce-protein-methods/methods-detecting-protein-rna-interactions.html RNA-protein interaction])<ref>{{cite journal|last1=Lehner|first1=B|last2=Sanderson|first2=C M|title=A protein interaction framework for human mRNA degradation.|journal=Genome Res.|date=2004|volume=14|issue=7|pages=1315–1323|doi=10.1101/gr.2122004|pmid=15231747|pmc=442147|url=http://genome.cshlp.org/content/14/7/1315.long}}</ref>.<ref>{{cite web|title=9ORF123 chromosome 9 open reading frame 123|url=http://thebiogrid.org/124777/summary/homo-sapiens/c9orf123.html|website=BioGRID: Database of Protein and Genetic Interactions|publisher=TyersLab}}</ref> |
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[[File:Tissueexpression.jpg|thumb|Tissue expression of TMEM261 showing tissue enriched gene (TEG) expression <ref name="She X et al.">{{cite journal |vauthors=She X, Rohl CA, Castle JC, Kulkarni AV, Johnson JM, Chen R |title=Definition, conservation and epigenetics of housekeeping and tissue-enriched genes |journal=BMC Genomics |volume=10 |issue= |pages=269 |year=2009 |pmid=19534766 |pmc=2706266 |doi=10.1186/1471-2164-10-269 |url=}}</ref>]]Additional [[transcription factor]] binding sites (DNA-protein interaction) predicted include one binding site for [http://www.genecards.org/cgi-bin/carddisp.pl?gene=MEF2C&search=b74dc542dd9d720d31835d8b921cab5f MEF2C] a [[monocyte]]-specific [[Transcription factor|enhancement factor]] that is involved in [[Muscle cell|muscle-cell]] regulation particularly in the [[cardiovascular system]] <ref name = "GeneCards">{{cite web|title=GeneCards:TMEM261 Gene|url=http://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM261&search=b6dd0fe61f84418762b84e0f9a3a0892}}</ref><ref>{{cite web|title=GeneCards:MEF2C Gene|url=http://www.genecards.org/cgi-bin/carddisp.pl?gene=MEF2C&search=b74dc542dd9d720d31835d8b921cab5f}}</ref> and two binding sites for [http://www.genecards.org/cgi-bin/carddisp.pl?gene=GATA1&search=a9de4a756db711a75e3c928b363bde71 GATA1] which is a globin transcription factor 1 involved in [[erythroblast]] development regulation<ref>{{cite journal|last1=Welch|first1=J J et al.|title=Global regulation of erythroid gene expression by transcription factor GATA-1.|journal=Blood|date=2004|volume=104|issue=10|pages=3136–3147|doi=10.1182/blood-2004-04-1603|pmid=15297311|url=http://www.bloodjournal.org/content/104/10/3136?sso-checked=true}}</ref><ref>{{cite journal|last1=Merryweather-Clarke|first1=A T et al.|title=Global gene expression analysis of human erythroid progenitors|journal=Blood|date=2011|volume=117|issue=13|pages=e96-108|doi=10.1182/blood-2010-07-290825|pmid=21270440|url=http://www.bloodjournal.org/content/117/13/e96.long}}</ref>. <ref>{{cite web|title=Genomatics- NGS Data Analysis and Personalised Medicine|url=https://www.genomatix.de/|website=Genomatix|publisher=Genomatix Software GmbH}}</ref> |
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[[File:Tissueexpression.jpg|thumb|Tissue expression of TMEM261 showing tissue enriched gene (TEG) expression <ref>{{vcite2 journal |vauthors=She X, Rohl CA, Castle JC, Kulkarni AV, Johnson JM, Chen R |title=Definition, conservation and epigenetics of housekeeping and tissue-enriched genes |journal=BMC Genomics |volume=10 |issue= |pages=269 |year=2009 |pmid=19534766 |pmc=2706266 |doi=10.1186/1471-2164-10-269 |url=}}</ref>]] |
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==Expression== |
==Expression== |
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''TMEM261'' shows ubiquitous expression in humans detected in almost all tissue types |
''TMEM261'' shows ubiquitous expression in humans detected in almost all tissue types<ref name = "The Human Protein Atlas">{{cite web|title=The Human Protein Atlas:TMEM261| url=http://www.proteinatlas.org/ENSG00000137038-TMEM261/tissue}}</ref><ref name=UniGene>{{cite web|title=EST profile: TMEM261|url=http://www.ncbi.nlm.nih.gov/UniGene/clust.cgi?UGID=132138&TAXID=9606&SEARCH=c9orf123|work=UniGene|publisher=National Library of Medicine}}</ref> and shows [http://www.biomedcentral.com/1471-2164/10/269 tissue-enriched gene] (TEG) expression when compared to [[Housekeeping gene|housekeeping gene]] (HKG) expression<ref name= "She X et al."/>. 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.<ref name= "She X et al."/><ref name = "The Human Protein Atlas">{{cite web|title=The Human Protein Atlas:TMEM261| url=http://www.proteinatlas.org/ENSG00000137038-TMEM261/tissue}}</ref>Staining intensity of [[cancer]] cells showed intermediate to high expression in [[breast]], [[colorectal]], [[ovarian]], [[skin]], [[urothelial]], [[head]] and [[neck]] cells. <ref name = "The Human Protein Atlas">{{cite web|title=The Human Protein Atlas:TMEM261| url=http://www.proteinatlas.org/ENSG00000137038-TMEM261/tissue}}</ref>. |
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==Function== |
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Currently the function for TMEM261 is unknown. However, [[Gene duplication|gene amplification]] and rearrangements of its locus have been associated with various cancers including [[colorectal cancer]]<ref>{{cite journal|last1=Gaspar|first1=C|title=Cross-Species Comparison of Human and Mouse Intestinal Polyps Reveals Conserved Mechanisms in Adenomatous Polyposis Coli (APC)-Driven Tumorigenesis|journal=Am J Pathol|date=2008|volume=172|issue=5|pages=1363–1380|doi=10.2353/ajpath.2008.070851|pmid=18403596 |pmc=2329845}}</ref>, |
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[[breast cancer]]<ref>{{cite journal|last1=Wu|first1=J|title=Identification and functional analysis of 9p24 amplified genes in human breast cancer|journal=Oncogene|date=2012|volume=31|issue=3|pages=333–341|doi=10.1038/onc.2011.227|pmid=21666724|pmc=3886828|url=http://www.nature.com/onc/journal/v31/n3/full/onc2011227a.html}}</ref> and [[lymphomas]]<ref>{{cite journal|last1=Twa|first1=D D W et al.|title=Genomic Rearrangements Involving Programmed Death Ligands Are Recurrent in Primary Mediastinal Large B-Cell Lymphoma|journal=Blood|date=2014|volume=123|issue=13|pages=2062–2065|doi=10.1182/blood-2013-10-535443|pmid=24497532|url=http://www.bloodjournal.org/content/123/13/2062.long?sso-checked=true}}</ref><ref>{{cite journal|last1=Green|first1=M R et al.|title=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|journal=Blood|date=2010|volume=116|issue=17|pages=3268–3277|doi=10.1182/blood-2010-05-282780|pmid=20628145|pmc=2995356|url=http://www.bloodjournal.org/content/116/17/3268.long}}</ref>. |
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==Evolution== |
==Evolution== |
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==== Orthologues ==== |
==== Orthologues ==== |
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The [[orthologues]] and [[homologues]] of TMEM261 are limited to [[vertebrates]], |
The [[orthologues]] and [[homologues]] of TMEM261 are limited to [[vertebrates]], its oldest homologue dates to that of the [[cartilaginous fishes]]<ref name = "NCBI BLAST">{{cite web|title= NCBI BLAST:Basic Local Alignment Search Tool|url=http://blast.ncbi.nlm.nih.gov/Blast.cgi}}</ref> which diverged from [[Homo sapiens]] 462.5 million years ago <ref>{{cite journal|last1=Hedges|first1=S. Blaire|last2=Dudley|first2=Joel|last3=Kumar|first3=Sudhir|title=TimeTree: a public knowledge-base of divergence times among organisms|journal=Bioinformatics|date=22 September 2006|volume=22|issue=23|pages=2971–2972|doi=10.1093/bioinformatics/btl505|pmid=17021158|url=http://kumarlab.net/pdf_new/HedgesKumar06.pdf}}</ref>. The [[Protein primary structure|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 secondary structure|secondary structure]] of TMEM261 shows conservation across most orthologues.<ref name = "SDSC Biology ">{{cite web|title= ClustalW|url=http://workbench.sdsc.edu/}}</ref><ref name= Thompson/> |
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==Further Reading== |
==Further Reading== |
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*{{cite journal | author=Nicholas K. Tonks|title=Protein tyrosine phosphatases: from genes, to function, to disease|journal=Cancer Cell |volume=7 |pages= |
*{{cite journal | author=Nicholas K. Tonks|title=Protein tyrosine phosphatases: from genes, to function, to disease|journal=Cancer Cell |volume=7 |pages= 833–846 |year= 2006 |issue=11|doi=10.1038/nrm2039|pmid=17057753|s2cid=1302726| author-separator=,}} |
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*{{cite journal | author=Merryweather-Clarke AT et al.|title=Global gene expression analysis of human erythroid progenitors. |journal=Blood |volume=117 |issue= 13 |pages= e96-108 |year= 2011 |pmid= 21270440 |doi= 10.1182/blood-2010-07-290825 | author-separator=,}} |
*{{cite journal | author=Merryweather-Clarke AT et al.|title=Global gene expression analysis of human erythroid progenitors. |journal=Blood |volume=117 |issue= 13 |pages= e96-108 |year= 2011 |pmid= 21270440 |doi= 10.1182/blood-2010-07-290825 | author-separator=,}} |
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*{{cite journal | author=Welch JJ, Watts JA, Vakoc CR, et al.|title=Global regulation of erythroid gene expression by transcription factor GATA-1 |journal=Blood |volume=104 |issue= 10 |pages= |
*{{cite journal | author=Welch JJ, Watts JA, Vakoc CR, et al.|title=Global regulation of erythroid gene expression by transcription factor GATA-1 |journal=Blood |volume=104 |issue= 10 |pages= 3136–3147 |year= 2004 |pmid= 15297311 |doi=10.1182/blood-2004-04-1603| author-separator=,}} |
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*{{cite journal | author=Nickeleit I et al.|title=Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition.|journal=Cancer Cell |volume=14 |issue= 1 |pages= |
*{{cite journal | author=Nickeleit I et al.|title=Argyrin a reveals a critical role for the tumor suppressor protein p27(kip1) in mediating antitumor activities in response to proteasome inhibition.|journal=Cancer Cell |volume=14 |issue= 1 |pages= 23–35 |year= 2008 |pmid= 18598941|doi=10.1016/j.ccr.2008.05.016|hdl=11858/00-001M-0000-0012-DB84-4| author-separator=,}} |
Latest revision as of 01:49, 10 May 2021
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
[edit]
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]
Protein Features
[edit]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
[edit]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
[edit]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
[edit]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]
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
[edit]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
[edit]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
[edit]Orthologues
[edit]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
[edit]TMEM261 has no known paralogs[34].
References
[edit]- ^ a b "Entrez Protein: TMEM261".
- ^ a b c d "GeneCards:TMEM261 Gene". Cite error: The named reference "GeneCards" was defined multiple times with different content (see the help page).
- ^ 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) - ^ a b c d "AceView:Homo sapiens gene C9orf123".
- ^ "Ensemble:Transcript TMEM261-003".
- ^ "NCBI Conserved Domains: DUF4536".
- ^ "EMBL-EBI Interpro: Transmembrane protein 261 (Q96GE9)".
- ^ "Q96GE9 - TM261_HUMAN". UniProt. UniProt Consortium.
- ^ a b "Vega: Transcript: C9orf123-003".
- ^ "PHYRE: Protein Homology/analogY Recognition Engine". PHYRE.
- ^ 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.
- ^ a b "ClustalW".
- ^ 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.
- ^ Gallo, Vincenzo. "Myristoylation : Proteins Post-translational Modifications". http://flipper.diff.org/. University of Turin.
{{cite web}}
: External link in
(help)|website=
- ^ "Nextprot:TMEM261 » Transmembrane protein 261".
- ^ 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.
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(help) - ^ 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.
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(help)CS1 maint: unflagged free DOI (link) - ^ "c9orf123 protein (Homo Sapiens)- STRING Network View". STRING - Known and Predicted Protein-Protein Interactions.
- ^ 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.
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(help)CS1 maint: unflagged free DOI (link) - ^ Huttlin, E L; et al. (2014). "High-Throughput Proteomic Mapping of Human Interaction Networks via Affinity-Purification Mass Spectrometry (Pre-Publication)". Pre-Publication.
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(help) - ^ 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.
- ^ "9ORF123 chromosome 9 open reading frame 123". BioGRID: Database of Protein and Genetic Interactions. TyersLab.
- ^ 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) - ^ "GeneCards:MEF2C Gene".
- ^ 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}}
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(help) - ^ 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}}
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(help) - ^ "Genomatics- NGS Data Analysis and Personalised Medicine". Genomatix. Genomatix Software GmbH.
- ^ a b c "The Human Protein Atlas:TMEM261".
- ^ "EST profile: TMEM261". UniGene. National Library of Medicine.
- ^ 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.
- ^ 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.
- ^ 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}}
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(help) - ^ 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}}
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(help) - ^ a b "NCBI BLAST:Basic Local Alignment Search Tool".
- ^ 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.
External Links
[edit]- PubMed
- NCBI gene record
- GeneCards
- UCSC Genome Browser
- Expasy Bioinformatics Resource Portal
- SDSC Biology Workbench
Further Reading
[edit]- Nicholas K. Tonks (2006). "Protein tyrosine phosphatases: from genes, to function, to disease". Cancer Cell. 7 (11): 833–846. doi:10.1038/nrm2039. PMID 17057753. S2CID 1302726.
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ignored (help) - Welch JJ, Watts JA, Vakoc CR; 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.
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ignored (help)CS1 maint: multiple names: authors list (link) - Nickeleit I; et al. (2008). "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. doi:10.1016/j.ccr.2008.05.016. hdl:11858/00-001M-0000-0012-DB84-4. PMID 18598941.
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