C6orf58

C6orf58 is a humanis_associated_with::gene located at locus 6q22.33 of is_associated_with::chromosome 6 and encodes for UPF0762, a is_associated_with::protein which is subsequently secreted after cleavage of a is_associated_with::signal peptide. DUF781, which is the singular identifiable domain in UPF0762, is tied to is_associated_with::liver development in an orthologous protein in is_associated_with::zebrafish. The function of the human UPF0762 is not yet well characterized.

Expression
While there are 3 splice variants of C6orf58, only one encodes a good protein. In humans, C6orf58 is_associated_with::expressed sequence tags were primarily detected in the is_associated_with::larynx and trachea. Transcripts were only detected during the is_associated_with::adult stage of development. Experimental is_associated_with::microarray data, however, reveals additional regions of C6orf58 expression, namely in the is_associated_with::salivary gland, is_associated_with::thyroid, and is_associated_with::small intestine. Arsenic may also regulate expression as it increases is_associated_with::methylation of the C6orf58 promoter.

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

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

Properties
is_associated_with::Mass spectrometry has shown that the observed molecular weight of UPF0762 is 32kDa. 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 is_associated_with::N-linked glycosylation would also increase the molecular weight.

Homology
UPF0762 shows high homology in primates and orthologous proteins can be traced back as far as is_associated_with::trichoplax adhaerens. The list of proteins below is not a comprehensive listing of UPF0762 orthologs. Sequence identity and similarity were determined using BLAST with the reference human sequence as the query.

Conserved domains
DUF781 is the singular domain of the protein and spans 318 of the protein's 330 is_associated_with::amino acids. DUF781 has been linked to is_associated_with::liver development in is_associated_with::zebrafish.

Post-translational modifications
Observed is_associated_with::post-translational modifications include is_associated_with::N-linked glycosylation at amino acid 69. A signal peptide, which is predicted to direct the protein to the is_associated_with::endoplasmic reticulum for secretion, is cleaved from the first 20 amino acids of the peptide sequence. The is_associated_with::missense mutation S18F detected in is_associated_with::hepatocellular carcinoma significantly reduces the predicted cleavage score of the signal peptide.



Interactions
Human C6orf58 has been reported to interact with the is_associated_with::enzyme is_associated_with::ribonucleotide reductase as encoded by the is_associated_with::vaccinia virus through a is_associated_with::yeast two-hybrid screen.

Pathology
Statistical analysis has shown C6orf58 to be associated with is_associated_with::pancreatic cancer survival time. In addition, a is_associated_with::missense mutation at amino acid 18 has been observed in liver cancer cells where is_associated_with::serine becomes is_associated_with::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.