C6orf58 is a human gene located at locus 6q22.33 of chromosome 6 and encodes for UPF0762, a protein which is subsequently secreted after cleavage of a signal peptide.[1] DUF781, which is the singular identifiable domain in UPF0762, is tied to liver development in an orthologous protein in zebrafish.[2] The function of the human UPF0762 remains unknown.[3]
Gene and mRNA
editGenomic DNA Length (base pairs) | Exons | Mature mRNA Length (base pairs) | Splice variants | Signal peptide CDS (base pair) | Mature Peptide CDS (base pair) | 5'-UTR (base pair) | 3'-UTR (base pair) |
---|---|---|---|---|---|---|---|
14644[1] | 6[1] | 1200[1] | 3 [3] | 13-72[1] | 73-1002[1] | 1-12[1] | 1003-1200[1] |
Expression
editWhile there are 3 splice variants of C6orf58, only one encodes a good protein.[3] In humans, C6orf58 expressed sequence tags were primarily detected in the larynx and trachea.[4] Transcripts were only detected during the adult stage of development.[4] Experimental microarray data, however, reveals additional regions of C6orf58 expression, namely in the salivary gland, thyroid, and small intestine.[5] Arsenic may also regulate expression as it increases methylation of the C6orf58 promoter.[6]
Gene Neighborhood
editGenes within 500 Kilobases of C6orf58 include RSPO3, C6orf174, KIAA0408, RPL17P23, ECHDC1, RPL5P18, YWHAZP4, LOC100420743, LOC100421513, MRPS17P5, and THEMIS.
Homology
editA selected set of homologous sequences are listed below, with sequence identity being calculated in comparison to the human reference sequence.
Species | Common Name | Accession Number | Sequence Length (base pairs) | Sequence Identity |
---|---|---|---|---|
Nomascus leucogenys | Northern white-cheeked gibbon | XM_003255689.1 | 1190 | .97 |
Macaca mulatta | Rhesus monkey | NM_001194318.1 | 1190 | .95 |
Oryctolagus cuniculus | European rabbit | XM_002714721.1 | 1014 | .79 |
Loxodonta africana | African bush elephant | XM_003404026.1 | 1020 | .78 |
Cavia porcellus | Guinea pig | XM_003468475.1 | 1017 | .76 |
Equus caballus | Horse | XM_001917090.1 | 990 | .77 |
Protein
editProperties
editAmino acid length (amino acids) | Signal Peptide Length (amino acids) | Molecular Weight of Precursor Protein | Molecular Weight of Signal Peptide (Predicted) | Molecular Weight of Mature Peptide(predicted) | Molecular Weight(observed) | Isoelectric Point (Predicted) | N-linked glycosylation Site |
---|---|---|---|---|---|---|---|
330[1] | 20[1] | 37.9 kDa[7] | 2.1 kDa[7] | 35.8 kDa[7] | 32 kDa[8] | 5.78[7] | Amino acid 69 |
Mass spectrometry has shown that the observed molecular weight of UPF0762 is 32kDa.[8] 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.
Homology
editUPF0762 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[9] with the reference human sequence as the query.
Species | Common Name | Accession Number | Sequence Length (amino acids) | Sequence Identity (%) | Sequence Similarity (%) |
---|---|---|---|---|---|
Pan troglodytes | Chimpanzee | XP_518733.2 | 330 | 1 | 1 |
Pongo abelii | Sumatran orangutan | XP_002817388.1 | 330 | .98 | .99 |
Callithrix jacchus | Marmoset | XP_002746989.1 | 330 | .87 | .93 |
Canis lupus | Gray wolf | XP_851589.1 | 310 | .7 | .82 |
Taeniopygia guttata | Zebra finch | XP_002190886.1 | 364 | .43 | .63 |
Gallus gallus | Red junglefowl | XP_419749.3 | 371 | .42 | .6 |
Xenopus tropicalis | Western clawed frog | XP_002940437.1 | 178 | 0.29 | 0.51 |
Trichoplax adhaerens | N/A | XP_002111384 | 381 | .34 | .49 |
Conserved domains
editDUF781 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.[2]
Post-translational modifications
editObserved post-translational modifications include N-linked glycosylation at amino acid 69.[10] A signal peptide, which is predicted to direct the protein to the endoplasmic reticulum for secretion[11], is cleaved from the first 20 amino acids of the peptide sequence[1] . The missense mutation S18F detected in hepatocellular carcinoma[12] significantly reduces the predicted cleavage score of the signal peptide.[13]
Interactions
editHuman C6orf58 has been reported to interact with the enzyme ribonucleotide reductase as encoded by the vaccinia virus through a yeast two-hybrid screen.[14]
Pathology
editStatistical analysis has shown C6orf58 to be associated with pancreatic cancer survival time.[15] In addition, a missense mutation at amino acid 18 has been observed in liver cancer cells where serine becomes phenylalanine.[12] Analysis of the mutated protein sequence for a signal peptide shows cleavability at the regular amino acid 20 is lost.[13] DUF781's association with liver development and the missense mutation's association with liver cancer is a correlation that remains to be investigated.
References
edit- ^ a b c d e f g h i j k "Homo sapiens chromosome 6 open reading frame 58 (C6orf58), mRNA". National Center for Biotechnology Information. Retrieved 26 April 2012.
- ^ a b Chang C, Hu M, Zhu Z, Lo LJ, Chen J, Peng J (2011). "liver-enriched gene 1a and 1b encode novel secretory proteins essential for normal liver development in zebrafish". PLoS ONE. 6 (8): e22910. doi:10.1371/journal.pone.0022910. PMC 3153479. PMID 21857963.
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: CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link) - ^ a b c Thierry-Mieg, Danielle. "AceView: integrative annotation of cDNA-supported genes in human, mouse, rat, worm and Arabidopsis". NCBI. Retrieved 30 April 2012.
- ^ a b "EST Profile Hs.226268". NCBI. Retrieved 30 April 2012.
- ^ Dezso, Z (2008 Nov 12). "A comprehensive functional analysis of tissue specificity of human gene expression". BMC biology. 6: 49. PMID 19014478.
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ignored (help)CS1 maint: multiple names: authors list (link) - ^ Altschul, SF (1990 Oct 5). [BLAST "Basic local alignment search tool"]. Journal of molecular biology. 215 (3): 403–10. PMID 2231712. Retrieved 8 May 2012.
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suggested) (help) - ^ Ramachandran P, Boontheung P, Xie Y, Sondej M, Wong DT, Loo JA (2006). "Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry". J. Proteome Res. 5 (6): 1493–503. doi:10.1021/pr050492k. PMID 16740002.
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ignored (help)CS1 maint: multiple names: authors list (link) - ^ Caboche, Michel. "Predotar". Predotar. Retrieved 7 May 2012.
- ^ a b Li, M (2011 Aug 7). "Inactivating mutations of the chromatin remodeling gene ARID2 in hepatocellular carcinoma". Nature genetics. 43 (9): 828–9. PMID 21822264.
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suggested) (help) - ^ a b Petersen, TN (2011 Sep 29). "SignalP 4.0: discriminating signal peptides from transmembrane regions". Nature methods. 8 (10): 785–6. PMID 21959131.
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