C8orf34 is a protein that, in Homo sapiens, is encoded by the C8orf34 gene. Aliases for C8orf34 include vestibule-1 or VEST-1. Within the cell, C8orf34 is localized to the nucleus and nucleoli where it may play a role in the regulation of gene expression as well as the cell cycle.
Gene
The C8orf34 gene is located on the positive-sense strand of chromosome 8 at locus 8q13.2. On the NCBI genome assembly GRCh38.p12, it spans from 68330373 to 68819023. It is 635 kbp in length and contains 14 exons. Among the seven possible transcripts for C8orf34, the longest is 2452 base pairs, encoding for 538 amino acids.
Gene neighbors
Several gene loci lie near the C8orf34 gene along chromosome 8. While many of these are non-functional pseudogenes, a few of these gene neighbors are functional and protein-coding. The nearest protein-encoding gene to C8orf34 is PREX2, a guanine-nucleotide exchange factor for the Rac family of G proteins. This protein is involved in insulin signalling pathways. Mutations in and overexpression of the PREX2 gene have been observed in some cancers.
Gene expression
Within the cell, C8orf34 is expressed primarily in the nucleus. C8orf34 protein lacks a signal peptide to allow it to sort outside of the nuclear membrane or to other organelles. An analysis via PSORT II concluded that C8orf34 is localized to the nucleus 94.1% reliability. This nuclear localization suggests that C8orf34 protein may have a function related to the expression and regulation of genes in the nucleus. Alternatively, it may be involved in the maintenance and protection of the cell's genetic material.
C8orf34 is expressed in a wide array of tissues, including the kidney, stomach, thymus, pituitary gland, ear, and brain. In the brain, C8orf34 is expressed in the dentate gyrus, epithalamus, and medulla. In the mouse brain, an orthologous C8orf34 is expressed highly in the granule layer of the dentate gyrus, the somatosensory areas of the cerebral cortex and in the amygdala.
Regulation of expression
Several different transcription factors regulate the expression of the C8orf34 gene. Many of these transcription factors are related to regulation of the cell's progression through the cell cycle and longevity, suggesting that C8orf34 performs a function related to these processes.
Protein
The protein product of the C8orf34 gene is 538 amino acids in length, with a predicted molecular weight of 59kDa and an isoelectric point of 5.9. At the cellular level, several pieces of evidence support the conclusion that C8orf34 plays a role in gene expression regulation and regulation of the cell cycle.
Domains
C8orf34 has a domain entitled "Dimerization-anchoring domain of cAMP-dependent protein kinase regulatory subunit" that spans residues 94 to 133. Proteins with this domain are subunits of a multimer protein kinase. The negatively-charged region within the middle of the protein may indicate the site of a coordination with a metal ion, a common structure in proteins that interact with DNA, including zinc-finger proteins.
Post-translational modifications
C8orf34 protein undergoes few modifications following translation. C8orf34 protein is not cleaved after translation. There are eight sites along the protein that are likely candidates for glycosylation and 27 probable sites for phosphorylation. There are four predicted SUMOylation sites in C8orf34. Each of these post-translational modifications is expected to have some effect on the protein. O-glycosylation may influence the sorting of a protein and the protein's conformation. In some cases, glycosylation may play a role in adhesion and immunological processes. Phosphorylation of amino acid residues may serve to activate or deactivate the functional domain of C8orf34. SUMOylation sites are residues that SUMO (small ubiquitin-like modifier) proteins can bind to modify the protein's function. SUMO proteins may modify proteins to perform many functions, including nuclear-cytosolic transport, transcriptional regulation, progressing through the cell cycle, and even apoptosis.
Structure
The secondary structure of C8orf34 is predicted to consist mostly of free random coils with alpha helices being the dominant organized structure. Alpha helices are a common motif in proteins that regulate gene expression and may support this function in C8orf34. The structure prediction and analysis application Phyre2 reported that a portion of C8orf34 has close structural similarity with the yeast methyltransferase H3K4, an enzyme that influences gene expression by catalyzing methylation of DNA.