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| Aliases | Tmem2611700027K24Rik3110001D03Riktransmembrane protein 261distal membrane arm assembly complex 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | HomoloGene: 12054 GeneCards: | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Transmembrane protein 261 is a protein that in humans is encoded by the TMEM261 gene located on chromosome 9. [2] TMEM261 is also known as C9ORF123 and DMAC1, Chromosome 9 Open Reading Frame 123 and Transmembrane Protein C9orf123 [3] and Distal membrane-arm assembly complex protein 1. [4]
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]
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]
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]
A N-myristoylation domain is shown to be present in most TMEM261 protein variants. [6] Post-translational modifications include myristoylation of the N-terminal Glycine residue (Gly2) [6] [18] of the TMEM261 protein as well as phosphorylation of Threonine 31. [19]
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]
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]
The orthologues and homologues of TMEM261 are limited to vertebrates, its oldest homologue dates to that of the cartilaginous fishes [39] which diverged from Homo sapiens 462.5 million years ago. [40] 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. [16] [17]
| Organism | Scientific Name | Accession Number | Date of Divergence from Humans (million years) | Amino acids (aa) | Identity (%) | Class |
|---|---|---|---|---|---|---|
| Humans | Homo sapiens | NP_219500.1 | 0 | 112 | 100 | Mammalia |
| Gorilla | Gorilla gorilla | XP_004047847.1 | 8.8 | 112 | 99 | Mammalia |
| Olive baboon | Papio anubis | XP_003911767.1 | 29 | 112 | 84 | Mammalia |
| Sunda flying lemur | Galeopterus variegatus | XP_008587957.1 | 81.5 | 112 | 68 | Mammalia |
| Lesser Egyptian jerboa | Jaculus Jaculus | XP_004653029.1 | 92.3 | 109 | 56 | Mammalia |
| Naked mole rat | Heterocephalus glaber | XP_004898193.1 | 92.3 | 114 | 45 | Mammalia |
| White rhinoceros | Ceratotherium simum simum | XP_004436891.1 | 94.2 | 112 | 66 | Mammalia |
| Nine-banded armadillo | Dasypus novemcinctus | XP_004459147.1 | 104.4 | 112 | 59 | Mammalia |
| Green sea turtle | Chelonia mydas | XP_007056940.1 | 296 | 85 | 49 | Reptilia |
| Zebra finch | Taeniopygia Guttata | XP_002187613.2 | 296 | 72 | 47 | Aves |
| Western clawed frog | Xenopus tropicalis | XP_002943025.1 | 371.2 | 85 | 45 | Amphibia |
| Haplochromis burtoni | Haplochromis burtoni | XP_005928614.1 | 400.1 | 91 | 51 | Actinopterygii |
| Australian ghost shark | Callorhinchus milii | XP_007884223.1 | 426.5 | 86 | 43 | Chondrichthyes |
TMEM261 has no known paralogs. [39]
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