DMAC1

TMEM261 is located at 9p24.1, its length is 91,891 base pairs (bp) on the reverse strand.[3] Its neighbouring gene is PTPRD located at 9p23-p24.3 also on the reverse strand and encodes protein tyrosine phosphatase receptor type delta.[2][3] 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.[5][6]

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

TMEM261 is a protein consisting out of 112 amino acids, with a molecular weight of 11.8 kDa.[7] The isoelectric point is predicted to be 10.2,[8] whilst its posttranslational modification value is 9.9.[6]

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.[9][10] Two further transmembrane helical domains are predicted of lengths 18aa (Val 52-Ala 69) and 23aa (Pro 81-Ala 102]).[11][12] There is also a low complexity region spanning 25aa (Thr 14-Ala 39).[13] 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[14][15] which contains the low complexity region[13] that is not highly conserved amongst orthologues.[16][17]

Interactions

Proteins shown to interact with TMEM261 include NAAA (protein-protein interaction), QTRT1 (RNA-protein interaction),ZC4H2(DNA-protein interaction)[20] and ZNF454(DNA-protein interaction).[21][22] It has also shown to interact with APP(protein-protein interaction),[23] ARHGEF38(protein-protein interaction)[24] and HNRNPD(RNA-protein interaction).[25][26]

Tissue expression of TMEM261 showing tissue enriched gene (TEG) expression [27]

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[3][28] and two binding sites for GATA1 which is a globin transcription factor 1 involved in erythroblast development regulation.[29][30][31]

TMEM261 shows ubiquitous expression in humans and is detected in almost all tissue types.[32][33] It shows tissue-enriched gene (TEG) expression when compared to housekeeping gene (HKG) expression.[27] 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.[27][32] Staining intensity of cancer cells showed intermediate to high expression in breast, colorectal, ovarian, skin, urothelial, head and neck cells.[32]

Currently the function for TMEM261 is unknown.[34] However, gene amplification and rearrangements of its locus have been associated with various cancers including colorectal cancer,[35] breast cancer[36] and lymphomas.[37][38]

• 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

• 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.