C6orf58

While there are 3 splice variants of C6orf58, only one encodes a good protein. In humans, C6orf58 expressed sequence tags were primarily detected in the larynx and trachea.{{cite web|title=EST Profile Hs.226268|url=https://www.ncbi.nlm.nih.gov/UniGene/ESTProfileViewer.cgi?uglist=Hs.226268|publisher=NCBI|access-date=30 April 2012}} Transcripts were only detected during the adult stage of development. Experimental microarray data, however, reveals additional regions of C6orf58 expression, namely in the salivary gland, thyroid, and small intestine.{{cite journal |vauthors=Dezso Z, Nikolsky Y, Sviridov E, Shi W, Serebriyskaya T, Dosymbekov D, Bugrim A, Rakhmatulin E, Brennan RJ, Guryanov A, Li K, Blake J, Samaha RR, Nikolskaya T | title = A comprehensive functional analysis of tissue specificity of human gene expression | journal = BMC Biol. | volume = 6 | pages = 49 | year = 2008 | pmid = 19014478 | pmc = 2645369 | doi = 10.1186/1741-7007-6-49 | doi-access = free }} Arsenic may also regulate expression as it increases methylation of the C6orf58 promoter.{{cite journal |vauthors=Smeester L, Rager JE, Bailey KA, Guan X, Smith N, García-Vargas G, Del Razo LM, Drobná Z, Kelkar H, Stýblo M, Fry RC | title = Epigenetic changes in individuals with arsenicosis | journal = Chem. Res. Toxicol. | volume = 24 | issue = 2 | pages = 165–7 | year = 2011 | pmid = 21291286 | pmc = 3042796 | doi = 10.1021/tx1004419 }}

File:GEO Profiles Tissue Expression Graph.png experiment of various tissues shows C6orf58 expression to be limited.]]

Genes within 500 Kilobases of C6orf58 include RSPO3, C6orf174, KIAA0408, RPL17P23, ECHDC1, RPL5P18, YWHAZP4, LOC100420743, LOC100421513, MRPS17P5, and THEMIS.

A selected set of homologous sequences are listed below, with sequence identity being calculated in comparison to the human reference sequence.

Mass spectrometry has shown that the observed molecular weight of UPF0762 is 32kDa.{{cite journal |vauthors=Mangum JE, Crombie FA, Kilpatrick N, Manton DJ, Hubbard MJ | title = Surface integrity governs the proteome of hypomineralized enamel | journal = J. Dent. Res. | volume = 89 | issue = 10 | pages = 1160–5 |date=October 2010 | pmid = 20651090 | doi = 10.1177/0022034510375824 | s2cid = 21703818 | url = https://zenodo.org/record/894336 }} It remains unclear why the observed molecular weight is less than predicted, even after accounting for cleavage of the signal peptide. Attachment of a sugar at the site of N-linked glycosylation would also increase the molecular weight.

UPF0762 shows high homology in primates and orthologous proteins can be traced back as far as trichoplax adhaerens. The list of proteins below is not a comprehensive listing of UPF0762 orthologs. Sequence identity and similarity were determined using BLAST{{cite journal |vauthors=Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ | title = Basic local alignment search tool | journal = J. Mol. Biol. | volume = 215 | issue = 3 | pages = 403–10 | year = 1990 | pmid = 2231712 | doi = 10.1016/S0022-2836(05)80360-2 | s2cid = 14441902 }} with the reference human sequence as the query.

DUF781 is the singular domain of the protein and spans 318 of the protein's 330 amino acids. DUF781 has been linked to liver development in zebrafish.{{cite journal |vauthors=Chang C, Hu M, Zhu Z, Lo LJ, Chen J, Peng J | title = liver-enriched gene 1a and 1b encode novel secretory proteins essential for normal liver development in zebrafish | journal = PLOS ONE | volume = 6 | issue = 8 | pages = e22910 | year = 2011 | pmid = 21857963 | pmc = 3153479 | doi = 10.1371/journal.pone.0022910 | bibcode = 2011PLoSO...622910C | doi-access = free }}

Observed post-translational modifications include N-linked glycosylation at amino acid 69.{{cite journal |vauthors=Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA | title = Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry | journal = J. Proteome Res. | volume = 5 | issue = 6 | pages = 1493–503 |date=June 2006 | pmid = 16740002 | doi = 10.1021/pr050492k }} A signal peptide, which is predicted to direct the protein to the endoplasmic reticulum for secretion,{{cite web|last=Caboche|first=Michel|title=Predotar|url=http://urgi.versailles.inra.fr/predotar/predotar.html|access-date=7 May 2012|archive-url=https://web.archive.org/web/20090228020939/http://urgi.versailles.inra.fr/predotar/predotar.html|archive-date=28 February 2009|url-status=dead}} is cleaved from the first 20 amino acids of the peptide sequence. The missense mutation S18F detected in hepatocellular carcinoma{{cite journal |vauthors=Li M, Zhao H, Zhang X, Wood LD, Anders RA, Choti MA, Pawlik TM, Daniel HD, Kannangai R, Offerhaus GJ, Velculescu VE, Wang L, Zhou S, Vogelstein B, Hruban RH, Papadopoulos N, Cai J, Torbenson MS, Kinzler KW | title = Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma | journal = Nat. Genet. | volume = 43 | issue = 9 | pages = 828–9 | year = 2011 | pmid = 21822264 | pmc = 3163746 | doi = 10.1038/ng.903 }} significantly reduces the predicted cleavage score of the signal peptide.{{cite journal |vauthors=Petersen TN, Brunak S, von Heijne G, Nielsen H | title = SignalP 4.0: discriminating signal peptides from transmembrane regions | journal = Nat. Methods | volume = 8 | issue = 10 | pages = 785–6 | year = 2011 | pmid = 21959131 | doi = 10.1038/nmeth.1701 | s2cid = 16509924 | doi-access = free }}

File:C6orf58 protein structure.png

Human C6orf58 has been reported to interact with the enzyme ribonucleotide reductase as encoded by the vaccinia virus through a yeast two-hybrid screen.{{cite journal |vauthors=Zhang L, Villa NY, Rahman MM, Smallwood S, Shattuck D, Neff C, Dufford M, Lanchbury JS, Labaer J, McFadden G | title = Analysis of vaccinia virus-host protein-protein interactions: validations of yeast two-hybrid screenings | journal = J. Proteome Res. | volume = 8 | issue = 9 | pages = 4311–8 | year = 2009 | pmid = 19637933 | pmc = 2738428 | doi = 10.1021/pr900491n }}

Statistical analysis has shown C6orf58 to be associated with pancreatic cancer survival time.{{cite journal |vauthors=Wu TT, Gong H, Clarke EM | title = A transcriptome analysis by lasso penalized Cox regression for pancreatic cancer survival | journal = J Bioinform Comput Biol | volume = 9 | pages = 63–73 | year = 2011 | issue = Suppl 1 | pmid = 22144254 | doi = 10.1142/s0219720011005744}} In addition, a missense mutation at amino acid 18 has been observed in liver cancer cells where serine becomes phenylalanine. Analysis of the mutated protein sequence for a signal peptide shows cleavability at the regular amino acid 20 is lost. DUF781's association with liver development and the missense mutation's association with liver cancer is a correlation that remains to be investigated.

File:Problem set 4 SignalP Final3.tif

{{reflist|2}}

• {{UCSC gene info|C6orf58}}