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Chromosome 18 open reading frame 63 is a protein that in humans is encoded by the C18orf63 gene. This protein is not yet well understood by the scientific community. Research has been conducted suggesting that C18orf63 could be a potential biomarker form for early stage pancreatic cancer and breast cancer.

Gene
This gene is located at band 22, sub-band 3, on the long arm of chromosome 18. It is composed of 5065 base pairs spanning from 74,315,875 to 74,359,187 bp on chromosome 18. The gene has a total of 14 exons. C18orf63 is also known by the alias DKFZP78G0119. No isoforms exist for this gene.

Expression
C18orf63 has high expression in the testis. There is low expression in the kidneys, heart, liver, lung, and pelvis. There is no phenotype associated with this gene.

Promoter
The promoter region for C18orf63 is 1163 bp long starting at 74,314,813 bp and ending at 74,315,975 bp. The promoter ID is GXP_4417391.

Protein


The C18orf63 protein is composed up of 685 amino acids and has a molecular weight of 77230.50 Da, with a predicted isoelectric point of 9.83. No isoforms exist for this protein. This protein is rich in glutamine, isoleucine, lysine, and serine when compared to the average protein and lacks in aspartic acid and glycine.

Structure
In the predicted protein structure there are a number of beta turns, beta strands and alpha helices. For C18orf63 48.6% of the protein is expected to form alpha helices and 28.6% of the structure is expected to be composed of beta strands.

Domains and Motifs
The protein contains one domain of unknown function, DUF 4709, spanning from the 7th amino acid to the 280th amino acid. Motifs that are predicted to exist include an N-terminal motif, RxxL motif, KEN conserving motif, Wxxx motif, and a RVxPx motif. There is also a bipartite nuclear localization signal at the end of the protein sequence.

Post-Translational Modifications
Post-translational modifications the protein is predicted to undergo includes SUMOylation, PKC and CK2 phosphorylation, N-glycosylation, amiditation, and cleavage. There are six total PKC phosphorylation sites and 2 CK2 phosphorylation sites, 2 SUMOylation sites, and 2 N-glycosylation sites.

Subcellular Location
Due to the nuclear localization signal at the end of the protein sequence, C18orf63 is predicted to be targeted to the nucleus. C18orf63 has also been predicted to be targeted to the mitochondria in addition to the nucleus.

Orhologs
Orthologs have been found in most eukaryotes, with the exception of the class Amphibia. No human paralogs exist for C18orf63. The most distant homolog detectable is Mizuhopecten yessoensis, sharing a 37% identity with the human protein sequence. The only homologus domain was the domain of unknown function, it was found to be highly conserved in all orthologs. The table below shows some examples of various orthologs for this protein.



Rate of Evolution
C18orf63 is a mildly slow evolving protein. The protein evolves faster than Cytochorme C but slower than Betaglobin.

Interacting proteins
Transcription factors of interest predicted to bind to the regulatory sequence include p53 tumor suppressors, SRY testis determining factors, Y-box binding transcription factors, and glucocorticoid responsive elements. The JUN protein was found to interact with C18orf63 through antibait co-immunoprecipitation. The JUN protein binds to the USP28 promoter in colorectal cancer cells and is involved in the activation of these cancer cells.