DMAC1
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 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 in length and 13,500 daltons in size, and the smallest coding transcript variant being 381bp with a protein 69aa long and 6,100 Da in size.
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
TMEM261 contains a domain of unknown function, DUF4536, predicted as a helical membrane spanning domain about 45aa in length with no known domain relationships. Two further transmembrane helical domains are predicted of lengths 18aa and 23aa. There is also a low complexity region spanning 25aa. 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 of the TMEM261 protein as well as phosphorylation of Threonine 31.Interactions
Proteins shown to interact with TMEM261 include , , and . It has also shown to interact with , and .Additional transcription factor binding sites predicted include one binding site for a monocyte-specific enhancement factor that is involved in muscle-cell regulation particularly in the cardiovascular system and two binding sites for 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 expression when compared to housekeeping gene expression. Its highest expression is seen in the heart particularly in heart fibroblast cells, thymus, and thyroid 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 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 | Amino acids | Identity | Class |
| Humans | Homo sapiens | 0 | 112 | 100 | Mammalia | |
| Gorilla | Gorilla gorilla | 8.8 | 112 | 99 | Mammalia | |
| Olive baboon | Papio anubis | 29 | 112 | 84 | Mammalia | |
| Sunda flying lemur | Galeopterus variegatus | 81.5 | 112 | 68 | Mammalia | |
| Lesser Egyptian jerboa | Jaculus Jaculus | 92.3 | 109 | 56 | Mammalia | |
| Naked mole rat | Heterocephalus glaber | 92.3 | 114 | 45 | Mammalia | |
| White rhinoceros | Ceratotherium simum simum | 94.2 | 112 | 66 | Mammalia | |
| Nine-banded armadillo | Dasypus novemcinctus | 104.4 | 112 | 59 | Mammalia | |
| Green sea turtle | Chelonia mydas | 296 | 85 | 49 | Reptilia | |
| Zebra finch | Taeniopygia Guttata | 296 | 72 | 47 | Aves | |
| Western clawed frog | Xenopus tropicalis | 371.2 | 85 | 45 | Amphibia | |
| Haplochromis burtoni | Haplochromis burtoni | 400.1 | 91 | 51 | Actinopterygii | |
| Australian ghost shark | Callorhinchus milii | 426.5 | 86 | 43 | Chondrichthyes |