DMAC1

{{Short description|Protein-coding gene in the species Mus musculus}}

Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9.{{cite web|title=Entrez Protein: TMEM261|url=https://www.ncbi.nlm.nih.gov/gene/90871}} TMEM261 is also known as C9ORF123 and DMAC1, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123 and Distal membrane-arm assembly complex protein 1.{{Cite web|url=https://www.uniprot.org/uniprot/Q96GE9|title=DMAC1 - Distal membrane-arm assembly complex protein 1 - Homo sapiens (Human) - DMAC1 gene & protein|website=www.uniprot.org|language=en|access-date=2018-07-30}}

Gene features

TMEM261 is located at 9p24.1, its length is 91,891 base pairs (bp) on the reverse strand. Its neighbouring gene is PTPRD located at 9p23-p24.3 also on the reverse strand and encodes protein tyrosine phosphatase receptor type delta.{{cite web|title=GeneCards: PTPRD|url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=PTPRD&search=ec5eebdfa3e88e99844e476b922bd273}}

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.{{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|doi-access=free}}{{cite web|title=AceView:Homo sapiens gene C9orf123|url=https://www.ncbi.nlm.nih.gov/IEB/Research/Acembly/av.cgi?db=human&term=c9orf123&submit=Go}}

File:TMEM261 features.jpg

Protein features

TMEM261 is a protein consisting out of 112 amino acids, with a molecular weight of 11.8 kDa.{{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}} The isoelectric point is predicted to be 10.2,{{cite web|title=PI:Isoelectric point determination|url=http://workbench.sdsc.edu/}} whilst its posttranslational modification value is 9.9.

= Structure =

File:TMEM261interactions.jpg

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.{{cite web | title = NCBI Conserved Domains: DUF4536| url =https://www.ncbi.nlm.nih.gov/Structure/cdd/cddsrv.cgi?uid=259192}}{{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}} Two further transmembrane helical domains are predicted of lengths 18aa (Val 52-Ala 69) and 23aa (Pro 81-Ala 102]).{{cite web | title = Phobius: A combined transmembrane topology and signal peptide predictor| url =http://phobius.sbc.su.se/}}{{cite web|title=Q96GE9 - TM261_HUMAN|url=https://www.uniprot.org/uniprot/Q96GE9|website=UniProt|publisher=UniProt Consortium}} There is also a low complexity region spanning 25aa (Thr 14-Ala 39).{{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}} 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{{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}}{{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=Nature Protocols|date=2009|volume=4|issue=3|pages=363–371|doi=10.1038/nprot.2009.2|pmid=19247286|hdl=10044/1/18157|s2cid=12497300|hdl-access=free}} which contains the low complexity region that is not highly conserved amongst orthologues.{{cite web|title= ClustalW|url=http://workbench.sdsc.edu/}}{{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|pmc=308517|doi=10.1093/nar/22.22.4673|pmid=7984417}}

= Modifications =

A N-myristoylation domain is shown to be present in most TMEM261 protein variants. Post-translational modifications include myristoylation of the N-terminal Glycine residue (Gly2){{cite web|last1=Gallo|first1=Vincenzo|title=Myristoylation : Proteins Post-translational Modifications|url=http://flipper.diff.org/app/pathways/info/4026|website=flipper.diff.org|publisher=University of Turin}} of the TMEM261 protein as well as phosphorylation of Threonine 31.{{cite web|title=Nextprot:TMEM261 » Transmembrane protein 261|url=http://www.nextprot.org/db/entry/NX_Q96GE9/sequence}}

= Interactions =

Proteins shown to interact with TMEM261 include [https://www.genecards.org/cgi-bin/carddisp.pl?gene=NAAA NAAA] (protein-protein interaction), [https://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]),[https://www.genecards.org/cgi-bin/carddisp.pl?gene=ZC4H2&search=79ba8f7afa868106306bf83d200ba523 ZC4H2](DNA-protein interaction){{cite journal|vauthors=Dash 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}} and [https://www.genecards.org/cgi-bin/carddisp.pl?gene=ZNF454&search=68835d4da3192d71bcf7818742536191 ZNF454](DNA-protein interaction).{{cite journal|vauthors=Rovillain 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|pages=355|doi=10.1186/1471-2164-12-355|pmid=21740549|pmc=3161017 |doi-access=free }}{{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}} It has also shown to interact with [https://www.genecards.org/cgi-bin/carddisp.pl?gene=APP APP](protein-protein interaction),{{cite journal|vauthors=Oláh 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|doi-access=free }} [https://www.genecards.org/cgi-bin/carddisp.pl?gene=ARHGEF38&search=1bcacaca34542f4b438e308c6b02cfd2 ARHGEF38](protein-protein interaction){{cite journal|vauthors=Huttlin EL 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}} and [https://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]).{{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}}{{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}}

File:Tissueexpression.jpgAdditional transcription factor binding sites (DNA-protein interaction) predicted include one binding site for [https://www.genecards.org/cgi-bin/carddisp.pl?gene=MEF2C&search=b74dc542dd9d720d31835d8b921cab5f MEF2C] a monocyte-specific enhancement factor that is involved in muscle-cell regulation particularly in the cardiovascular system{{cite web|title=GeneCards:MEF2C Gene |url=https://www.genecards.org/cgi-bin/carddisp.pl?gene=MEF2C&search=b74dc542dd9d720d31835d8b921cab5f}} and two binding sites for [https://www.genecards.org/cgi-bin/carddisp.pl?gene=GATA1&search=a9de4a756db711a75e3c928b363bde71 GATA1] which is a globin transcription factor 1 involved in erythroblast development regulation.{{cite journal|vauthors=Welch JJ 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|pmid=15297311 |url=http://www.bloodjournal.org/content/104/10/3136?sso-checked=true|doi=10.1182/blood-2004-04-1603|doi-access=free}}{{cite journal|vauthors=Merryweather-Clarke AT 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|doi-access=free}}{{cite web|title=Genomatics- NGS Data Analysis and Personalised Medicine|url=https://www.genomatix.de/|website=Genomatix|publisher=Genomatix Software GmbH|access-date=2015-05-07|archive-date=2001-02-24|archive-url=https://web.archive.org/web/20010224072831/http://www.genomatix.de/|url-status=dead}}

Expression

TMEM261 shows ubiquitous expression in humans and is detected in almost all tissue types.{{cite web|title=The Human Protein Atlas:TMEM261| url=http://www.proteinatlas.org/ENSG00000137038-TMEM261/tissue}}{{cite web|title=EST profile: TMEM261|url=https://www.ncbi.nlm.nih.gov/UniGene/clust.cgi?UGID=132138&TAXID=9606&SEARCH=c9orf123|work=UniGene|publisher=National Library of Medicine}} It shows [http://www.biomedcentral.com/1471-2164/10/269 tissue-enriched gene] (TEG) expression when compared to housekeeping gene (HKG) expression. 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. Staining intensity of cancer cells showed intermediate to high expression in breast, colorectal, ovarian, skin, urothelial, head and neck cells.

Function

Currently the function for TMEM261 is unknown.{{cite journal|vauthors=Wu J et al.|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}} However, gene amplification and rearrangements of its locus have been associated with various cancers including colorectal cancer,{{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}}

breast cancer{{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}} and lymphomas.{{cite journal|vauthors=Twa DD 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|doi-access=free}}{{cite journal|vauthors=Green MR 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}}

Evolution

= Orthologues =

The orthologues and homologues of TMEM261 are limited to vertebrates, its oldest homologue dates to that of the cartilaginous fishes{{cite web|title= NCBI BLAST:Basic Local Alignment Search Tool|url=http://blast.ncbi.nlm.nih.gov/Blast.cgi}} which diverged from Homo sapiens 462.5 million years ago.{{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|date=22 September 2006|volume=22|issue=23|pages=2971–2972|doi=10.1093/bioinformatics/btl505|url=http://kumarlab.net/pdf_new/HedgesKumar06.pdf|pmid=17021158|journal=Bioinformatics|access-date=7 May 2015|archive-url=https://web.archive.org/web/20150505113900/http://kumarlab.net/pdf_new/HedgesKumar06.pdf|archive-date=5 May 2015|url-status=dead|doi-access=free}} 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.

Organism	Scientific Name	Accession Number	Date of Divergence from Humans (million years)	Amino acids (aa)	Identity (%)	Class
class="wikitable"
Humans	Homo sapiens	[https://www.ncbi.nlm.nih.gov/protein/NP_219500.1 NP_219500.1]	0	112	100	Mammalia
Gorilla	Gorilla gorilla	[https://www.ncbi.nlm.nih.gov/protein/XP_004047847.1 XP_004047847.1]	8.8	112	99	Mammalia
Olive baboon	Papio anubis	[https://www.ncbi.nlm.nih.gov/protein/XP_003911767.1 XP_003911767.1]	29	112	84	Mammalia
Sunda flying lemur	Galeopterus variegatus	[https://www.ncbi.nlm.nih.gov/protein/XP_008587957.1 XP_008587957.1]	81.5	112	68	Mammalia
Lesser Egyptian jerboa	Jaculus Jaculus	[https://www.ncbi.nlm.nih.gov/protein/XP_004653029.1 XP_004653029.1]	92.3	109	56	Mammalia
Naked mole rat	Heterocephalus glaber	[https://www.ncbi.nlm.nih.gov/protein/XP_004898193.1 XP_004898193.1]	92.3	114	45	Mammalia
White rhinoceros	Ceratotherium simum simum	[https://www.ncbi.nlm.nih.gov/protein/XP_004436891.1 XP_004436891.1]	94.2	112	66	Mammalia
Nine-banded armadillo	Dasypus novemcinctus	[https://www.ncbi.nlm.nih.gov/protein/XP_004459147.1 XP_004459147.1]	104.4	112	59	Mammalia
Green sea turtle	Chelonia mydas	[https://www.ncbi.nlm.nih.gov/protein/XP_007056940.1 XP_007056940.1]	296	85	49	Reptilia
Zebra finch	Taeniopygia Guttata	[https://www.ncbi.nlm.nih.gov/protein/XP_002187613.2 XP_002187613.2]	296	72	47	Aves
Western clawed frog	Xenopus tropicalis	[https://www.ncbi.nlm.nih.gov/protein/XP_002943025.1 XP_002943025.1]	371.2	85	45	Amphibia
Haplochromis burtoni	Haplochromis burtoni	[https://www.ncbi.nlm.nih.gov/protein/XP_005928614.1 XP_005928614.1]	400.1	91	51	Actinopterygii
Australian ghost shark	Callorhinchus milii	[https://www.ncbi.nlm.nih.gov/protein/XP_007884223.1 XP_007884223.1]	426.5	86	43	Chondrichthyes

= Paralogues =

TMEM261 has no known paralogs.

References

External links

[https://www.ncbi.nlm.nih.gov.ezp1.lib.umn.edu/pubmed/?term=tmem261 PubMed]{{Dead link|date=November 2019 |bot=InternetArchiveBot |fix-attempted=yes }}
[https://www.ncbi.nlm.nih.gov/nuccore/NM_033428.1 NCBI gene record]
[https://www.genecards.org/cgi-bin/carddisp.pl?gene=TMEM261&search=b6dd0fe61f84418762b84e0f9a3a0892/ GeneCards]
[https://genome.ucsc.edu/cgi-bin/hgTracks?db=hg19&position=chr9%3A7798199-7800148&hgsid=426081123_Rw46kZ3CniQWvyf4FzjzEiQdx33z/ UCSC Genome Browser]
[http://www.expasy.org/ Expasy Bioinformatics Resource Portal]
[http://workbench.sdsc.edu/ SDSC Biology Workbench]
[https://www.uniprot.org/uniprot/Q96GE9/ Uniprot]
[https://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC:30536/ HUGO] {{Webarchive|url=https://web.archive.org/web/20150924042128/http://www.genenames.org/cgi-bin/gene_symbol_report?hgnc_id=HGNC%3A30536%2F |date=2015-09-24 }}