DMAC1

DMAC1
Identifiers
AliasesDMAC1, C9orf123, TMEM261, transmembrane protein 261, distal membrane arm assembly complex 1, distal membrane arm assembly component 1
External IDsOMIM: 617261; MGI: 1914178; GeneCards: DMAC1
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

90871

66928

Ensembl

ENSG00000137038

ENSMUSG00000028398

UniProt

Q96GE9

Q9CQ00

RefSeq (mRNA)

NM_033428
NM_001318058
NM_001318059

NM_025849

RefSeq (protein)

NP_001304987
NP_001304988
NP_219500

NP_080125

Location (UCSC)Chr 9: 7.8 – 7.89 MbChr 4: 75.2 – 75.2 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

Distal membrane-arm assembly complex protein 1 is a protein that in humans is encoded by the DMAC1 gene (previously TMEM261). 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.

OrganismScientific nameAccession numberDate of Divergence from Humans (million years)Amino acids (aa)Identity (%)Class
HumansHomo sapiensNP_219500.10112100Mammalia
GorillaGorilla gorillaXP_004047847.18.811299Mammalia
Olive baboonPapio anubisXP_003911767.12911284Mammalia
Sunda flying lemurGaleopterus variegatusXP_008587957.181.511268Mammalia
Lesser Egyptian jerboaJaculus JaculusXP_004653029.192.310956Mammalia
Naked mole ratHeterocephalus glaberXP_004898193.192.311445Mammalia
White rhinocerosCeratotherium simum simumXP_004436891.194.211266Mammalia
Nine-banded armadilloDasypus novemcinctusXP_004459147.1104.411259Mammalia
Green sea turtleChelonia mydasXP_007056940.12968549Reptilia
Zebra finchTaeniopygia GuttataXP_002187613.22967247Aves
Western clawed frogXenopus tropicalisXP_002943025.1371.28545Amphibia
Haplochromis burtoniHaplochromis burtoniXP_005928614.1400.19151Actinopterygii
Australian ghost sharkCallorhinchus miliiXP_007884223.1426.58643Chondrichthyes

Paralogues

TMEM261 has no known paralogs.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000137038 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000028398 – Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. 1 2 "Entrez Protein: TMEM261".
  6. 1 2 3 4 "GeneCards: PTPRD".
  7. ↑ "DMAC1 - Distal membrane-arm assembly complex protein 1 - Homo sapiens (Human) - DMAC1 gene & protein". UniProt. Retrieved 2018-07-30.
  8. ↑ Thierry-Mieg D, Thierry-Mieg J (2006). "AceView: a comprehensive cDNA-supported gene and transcripts annotation". Genome Biology. 7 Suppl 1 (Suppl 1): S12.1–14. doi:10.1186/gb-2006-7-s1-s12. PMC 1810549. PMID 16925834.
  9. 1 2 3 4 Thierry-Mieg D, Thierry-Mieg J. "AceView:Homo sapiens gene C9orf123".
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  12. ↑ NIH/NLM/NCBI/IEB/CDD group. "NCBI Conserved Domains: DUF4536".
  13. ↑ European Bioinformatics Institute. "EMBL-EBI Interpro: Transmembrane protein 261 (Q96GE9)".
  14. ↑ "Phobius: A combined transmembrane topology and signal peptide predictor".
  15. ↑ "Q96GE9 - TM261_HUMAN". UniProt. UniProt Consortium.
  16. 1 2 "Vega: Transcript: C9orf123-003".
  17. ↑ Kelley L. "PHYRE: Protein Homology/analogY Recognition Engine". PHYRE.
  18. ↑ Kelley LA, Sternberg MJ (2009). "Protein structure prediction on the Web: a case study using the Phyre server". Nature Protocols. 4 (3): 363–371. doi:10.1038/nprot.2009.2. hdl:10044/1/18157. PMID 19247286. S2CID 12497300.
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  21. ↑ Gallo V. "Myristoylation : Proteins Post-translational Modifications". flipper.diff.org. University of Turin.
  22. ↑ Nextprot:TMEM261 » Transmembrane protein 261 (Report). doi:10.25504/fairsharing.ceeffa.
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  25. ↑ "c9orf123 protein (Homo Sapiens)- STRING Network View". STRING - Known and Predicted Protein-Protein Interactions.
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  27. ↑ Huttlin EL, et al. (2014). "High-Throughput Proteomic Mapping of Human Interaction Networks via Affinity-Purification Mass Spectrometry (Pre-Publication)". Pre-Publication.
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  31. ↑ "GeneCards:MEF2C Gene".
  32. ↑ Welch JJ, Watts JA, Vakoc CR, Yao Y, Wang H, Hardison RC, et al. (November 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.
  33. ↑ Merryweather-Clarke AT, Atzberger A, Soneji S, Gray N, Clark K, Waugh C, et al. (March 2011). "Global gene expression analysis of human erythroid progenitors". Blood. 117 (13): e96–108. doi:10.1182/blood-2010-07-290825. PMID 21270440.
  34. ↑ "Genomatics- NGS Data Analysis and Personalised Medicine". Genomatix. Genomatix Software GmbH. Archived from the original on 2001-02-24. Retrieved 2015-05-07.
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  38. ↑ Gaspar C, Cardoso J, Franken P, Molenaar L, Morreau H, Möslein G, et al. (May 2008). "Cross-species comparison of human and mouse intestinal polyps reveals conserved mechanisms in adenomatous polyposis coli (APC)-driven tumorigenesis". The American Journal of Pathology. 172 (5): 1363–1380. doi:10.2353/ajpath.2008.070851. PMC 2329845. PMID 18403596.
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Further reading