DMAC1

Dmac1
Identifiers
Aliases	Tmem2611700027K24Rik3110001D03Riktransmembrane protein 261distal membrane arm assembly complex 1
External IDs	HomoloGene: 12054 GeneCards: [1]
Gene location (Human) Chr. Chromosome 4 (human) Band 4|4 C3 Start 75,195,591 bp End 75,196,542 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in interventricular septum endocardial cushion superior cervical ganglion internal carotid artery external carotid artery atrioventricular valve dermis maxillary prominence medial ganglionic eminence atrium n/a More reference expression data BioGPS n/a
Gene ontology Molecular function molecular function Cellular component membrane integral component of membrane mitochondrion mitochondrial inner membrane mitochondrial respiratory chain complex I Biological process mitochondrial respiratory chain complex I assembly Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 66928 n/a Ensembl ENSMUSG00000028398 n/a UniProt Q9CQ00 n/a RefSeq (mRNA) NM_025849 n/a RefSeq (protein) NP_080125 n/a Location (UCSC) Chr 4: 75.2 – 75.2 Mb n/a PubMed search n/a
Wikidata
View/Edit Human

Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9. 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.

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.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.

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

Protein features

TMEM261 is a protein consisting out of 112 amino acids, with a molecular weight of 11.8 kDa. The isoelectric point is predicted to be 10.2, whilst its posttranslational modification value is 9.9.

Structure

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. Two further transmembrane helical domains are predicted of lengths 18aa (Val 52-Ala 69) and 23aa (Pro 81-Ala 102]). There is also a low complexity region spanning 25aa (Thr 14-Ala 39). 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 which contains the low complexity region that is not highly conserved amongst orthologues.

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) of the TMEM261 protein as well as phosphorylation of Threonine 31.

Interactions

Proteins shown to interact with TMEM261 include NAAA (protein-protein interaction), QTRT1 (RNA-protein interaction),ZC4H2(DNA-protein interaction) and ZNF454(DNA-protein interaction). It has also shown to interact with APP(protein-protein interaction),ARHGEF38(protein-protein interaction) and HNRNPD(RNA-protein interaction).

Tissue expression of TMEM261 showing tissue enriched gene (TEG) expression

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 and two binding sites for GATA1 which is a globin transcription factor 1 involved in erythroblast development regulation.

Expression

TMEM261 shows ubiquitous expression in humans and is detected in almost all tissue types. It shows 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. However, gene amplification and rearrangements of its locus have been associated with various cancers including colorectal cancer,breast cancer and lymphomas.

Evolution

Orthologues

The orthologues and homologues of TMEM261 are limited to vertebrates, its oldest homologue dates to that of the cartilaginous fishes which diverged from Homo sapiens 462.5 million years ago. 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.

Paralogues

TMEM261 has no known paralogs.

External links

• PubMed
• NCBI gene record
• GeneCards
• UCSC Genome Browser
• Expasy Bioinformatics Resource Portal
• SDSC Biology Workbench
• Uniprot
• HUGO Archived 2015-09-24 at the Wayback Machine

Further reading

• 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.
• Merryweather-Clarke AT, et al. (2011). "Global gene expression analysis of human erythroid progenitors" (PDF). Blood. 117 (13): e96-108. doi:10.1182/blood-2010-07-290825. PMID 21270440. S2CID 1021801.
• 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.
• 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-DB83-6. PMID 18598941.