Uncharacterized protein C9orf84, also known as C9orf84, is a protein that in humans is encoded by the C9orf84 gene, which stands for Chromosome 9 open reading frame 84.
The chromosomal locus of C9orf84 is 9q31.3, which it shares with at least 115 other protein encoding genes, and it is located on the negative strand.[1][2] In humans it contains 34 exons, and it is 108,834 base pairs long, including introns and exons. C9orf84 is located between the protein encoding genes GNG10 and UGCG. When this gene is transcribed in humans, it most often forms a mRNA which is 4,721 base pairs long and contains 26 exons. There are at least 13 alternate splice forms of C9orf84, with more predicted.[3]
Protein
C9orf84 in humans has at least 6 alternate isoforms, with at least 10 more predicted.[4] The primarily used sequence in humans is C9orf84 Isoform 1. This isoform is 1444 aa long, contains 26 exons, has a predicted molecular weight of 165.190 kDa, and a predicted pI of 5.10.[5]
C9orf84 has been show to undergo phosphorylation.[6] It is predicted that C9orf84 undergoes several other post-translational modifications, including glycosylation and o-linked glycosylation, and it contains leucine-rich nuclear export signals.[7][8][9] Compared to the generic reference set swp23s.q, the primary structure of the protein is deficient in the amino acid grouping AGP (alanine, glycine, proline), and contains more acidic amino acids (glutamate, aspartate) than basic amino acids (lysine, arginine).[10] This is true for the protein in all vertebrates. In the human Isoform 1, there have been 220 identified single nucleotide polymorphisms detected in the coding region, but none have currently been linked to human disease.[11] The secondary structure of this protein is predicted to be mainly alpha-helices in roughly the first two thirds of the protein, and coils in the last third.[12] It is predicted that this protein is localized in the nucleus.[13]
Expression
C9orf84 is ubiquitously expressed in most tissues with higher than average expression in the testes, the kidney, the thymus, and the adrenal gland.[14][15]
The promoter for C9orf84 Isoform 1 in humans is 639 bp long and overlaps with the 5’ untranslated region of the gene. There are four alternate promoters that promote different transcript variants.[16]
= Interactions
=
C9orf84 has been experimentally determined, through a two hybrid pooling approach, to interact with methionine aminopeptidase, a protein encoded by the maP3 gene in Bacillus anthracis.[17]
Several of the most common and most conserved transcription factor binding sites families that are predicted to be found in C9orf84’s promoter region are ETS1 factors, Ccaat/Enhancer Binding Proteins, and Lymphoid enhancer-binding factor 1.[18]ETS1, Ccaat-enhancer-binding proteins, and Lymphoid enhancer-binding factor 1 are all related to immunity.
Evolutionary History
C9orf84 is the only gene in the human genome with its particular sequence.[19] This gene is found in all vertebrates, and some invertebrates. The most distant ortholog detectable by NCBI BLAST is in Nematostella vectensis (starlet sea anemone).[20] The closest plant ortholog to C9orf84 is the SHOC1 protein in Arabidopsis thaliana.[21] C9orf84 is not very well conserved even among mammals.
Clinical Significance
C9orf84 is highly upregulated in psoriasis patients with lesional skin as opposed to psoriasis patients with non-lesional skin and non-psoriasis patients.[22]
↑"BLAST". National Center for Biotechnology Information.
↑Macaisne N, Novatchkova M, Peirera L, Vezon D, Jolivet S, Froger N, Chelysheva L, Grelon M, Mercier R (September 2008). "SHOC1, an XPF endonuclease-related protein, is essential for the formation of class I meiotic crossovers". Current Biology. 18 (18): 1432–7. doi:10.1016/j.cub.2008.08.041. PMID18812090.
↑Nair RP, Duffin KC, Helms C, Ding J, Stuart PE, Goldgar D, Gudjonsson JE, Li Y, Tejasvi T, Feng BJ, Ruether A, Schreiber S, Weichenthal M, Gladman D, Rahman P, Schrodi SJ, Prahalad S, Guthery SL, Fischer J, Liao W, Kwok PY, Menter A, Lathrop GM, Wise CA, Begovich AB, Voorhees JJ, Elder JT, Krueger GG, Bowcock AM, Abecasis GR (February 2009). "Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways". Nature Genetics. 41 (2): 199–204. doi:10.1038/ng.311. PMC2745122. PMID19169254.