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C8orf34
Identifiers
Aliases	C8orf34, VEST-1, VEST1, chromosome 8 open reading frame 34
External IDs	MGI: 2444149; HomoloGene: 14194; GeneCards: C8orf34; OMA:C8orf34 - orthologs
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 A2 Start 11,414,105 bp End 11,975,901 bp
Orthologs Species Human Mouse Entrez 116328 320492 Ensembl ENSG00000165084 ENSMUSG00000057715 UniProt Q49A92 Q8BZJ8 RefSeq (mRNA) NM_001195639 NM_052958 NM_001160369 NM_001160370 NM_001160371 NM_177173 NM_001310451 NM_001374633 NM_001374634 RefSeq (protein) NP_001182568 NP_443190 NP_001336405 NP_001336406 NP_001336407 NP_001336408 NP_001336409 NP_001153841 NP_001153842 NP_001153843 NP_001297380 NP_796147 NP_001361562 NP_001361563 NP_001387218 NP_001387220 Location (UCSC) n/a Chr 1: 11.41 – 11.98 Mb PubMed search
Wikidata
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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.

Function

Software-based predictions and experimental results yield several possibilities as to the function of C8orf34. The high frequency of alpha helices may indicate a few things about C8orf34's function. Alpha helices are commonly found in DNA-binding motifs of proteins, including helix-turn-helix motifs and zinc finger motifs. As C8orf34 is localized to the nucleus, the presence of alpha helices further supports the possibility that it is involved in gene regulation and expression. The protein kinase dimerization domain within C8orf34 in combination with its presence in the nucleus may indicate that it is a type of histone kinase.

Homology

C8orf34 has been carried across evolutionary events and is observed being expressed as an orthologous protein in several animal clades. There are no observed paralogs for C8orf34 within the human genome as the result of a gene duplication event.

Orthologs

Orthologs of C8orf34 exist in many species. C8orf34 seems to have appeared first in cnidarians, with sea anemones holding its most distant ortholog. An ortholog most similar in structure and function to human C8orf34 likely arose in aquatic chordates, as there appears to be a higher level of identity beginning with sharks. There is no similar homolog of C8orf34 present in arthropods. This clade may have evolved to no longer need C8orf34 for whatever function it served. Alternatively, arthropod species may have a substitute for C8orf34 that performs a similar function.

Protein interactions

Yeast two hybrid experimentation has revealed that C8orf34 interacts with a number of proteins insular to the nucleus. The protein has been shown to interact with ubiquitin C, a precursor protein to polyubiquitin, which functions to lead various effects in the cell cycle depending on the residues it conjugates to. C8orf34 has also demonstrated interactions with MTUS2 (microtubule associated tumor suppressor candidate 2). There is not much information available about this protein candidate, but it is likely to be involved in tumor-suppression functions and cell cycle regulation. C8orf34 also interacts with MCM7 (mini chromosome maintenance complex component 7), part of a protein complex that functions in the Initiation of eukaryotic genome replication during the cell cycle. C8orf34's interactions with these proteins support the conclusion that it is involved in transcription regulation and cell cycle progression.

Clinical significance

Studies have determined that C8orf34 has associations with several diseases. Mutations within C8orf34 are associated with risk for diarrhea and neutropenia in patients receiving chemotherapy. A translocation causing a fusion of the C8orf34 gene with the MET protooncogene has been found in tissue sample of patients with papillary renal carcinoma. A Japanese patent application currently cites a procedure claimed to be able to scan for mutations in C8orf34 as a method for the detection of a congenital disease causing hardness of hearing.

References

1. ^ GRCm38: Ensembl release 89: ENSMUSG00000057715 – Ensembl, May 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. Reference, Genetics Home. "C8orf34 gene". Genetics Home Reference. National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2019-05-05.
5. "GRCh38.p12 - Genome - Assembly - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-03.
6. ^ "C8orf34 chromosome 8 open reading frame 34 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-02-26.
7. ^ "PREX2 phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 2 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-03.
8. Pandiella, Atanasio; Montero, Juan Carlos (1 September 2013). "Molecular Pathways: P-Rex in Cancer". Clinical Cancer Research. 19 (17): 4564–4569. doi:10.1158/1078-0432.CCR-12-1662.
9. "LOC105375888 uncharacterized LOC105375888 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-03.
10. "LOC107986951 uncharacterized LOC107986951 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-03.
11. "LOC108004543 8q13.2-q13.3 proximal HERV-mediated recombination region [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-05-03.
12. "PSORT II Prediction". psort.hgc.jp. Retrieved 2019-05-06.
13. "Microarray Data :: Allen Brain Atlas: Human Brain". human.brain-map.org. Retrieved 2019-05-06.
14. "EST Profile - Hs.491941". www.ncbi.nlm.nih.gov. Retrieved 2019-04-22.
15. "Brain Map - brain-map.org". portal.brain-map.org. Retrieved 2019-04-22.
16. The proteomics protocols handbook. Walker, John M., 1948-. Totowa, N.J.: Humana Press. 2005. ISBN 978-1592598908. OCLC 272404489.{{cite book}}: CS1 maint: others (link)
17. "Genomatix: MatInspector Input". www.genomatix.de. Retrieved 2019-05-06.
18. Segil N, Roberts SB, Heintz N (December 1991). "Mitotic phosphorylation of the Oct-1 homeodomain and regulation of Oct-1 DNA binding activity". Science. 254 (5039): 1814–6. Bibcode:1991Sci...254.1814S. doi:10.1126/science.1684878. PMID 1684878.
19. "STAT3 - Signal transducer and activator of transcription 3 - Homo sapiens (Human) - STAT3 gene & protein". www.uniprot.org. Retrieved 2019-05-04.
20. Zuo J, Rungger D, Voellmy R (August 1995). "Multiple layers of regulation of human heat shock transcription factor 1". Molecular and Cellular Biology. 15 (8): 4319–30. doi:10.1128/MCB.15.8.4319. PMC 230671. PMID 7623826.
21. Morris JF, Hromas R, Rauscher FJ (March 1994). "Characterization of the DNA-binding properties of the myeloid zinc finger protein MZF1: two independent DNA-binding domains recognize two DNA consensus sequences with a common G-rich core". Molecular and Cellular Biology. 14 (3): 1786–95. doi:10.1128/MCB.14.3.1786. PMC 358536. PMID 8114711.
22. "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2019-05-06.
23. "Dimerization-anchoring domain of cAMP-dependent PK regulatory subunit superfamily". supfam.org. Retrieved 2019-05-06.
24. Canaves JM, Taylor SS (January 2002). "Classification and phylogenetic analysis of the cAMP-dependent protein kinase regulatory subunit family". Journal of Molecular Evolution. 54 (1): 17–29. Bibcode:2002JMolE..54...17C. doi:10.1007/s00239-001-0013-1. PMID 11734894. S2CID 26668215.
25. Berg JM, Shi Y (February 1996). "The galvanization of biology: a growing appreciation for the roles of zinc". Science. 271 (5252): 1081–5. Bibcode:1996Sci...271.1081B. doi:10.1126/science.271.5252.1081. PMID 8599083. S2CID 23883052.
26. "SUMOplot™ Analysis Program | Abgent". www.abgent.com. Retrieved 2019-05-06.
27. Van den Steen P, Rudd PM, Dwek RA, Opdenakker G (January 1998). "Concepts and principles of O-linked glycosylation". Critical Reviews in Biochemistry and Molecular Biology. 33 (3): 151–208. doi:10.1080/10409239891204198. PMID 9673446.
28. Hanisch FG (February 2001). "O-glycosylation of the mucin type". Biological Chemistry. 382 (2): 143–9. doi:10.1515/BC.2001.022. PMID 11308013. S2CID 25029487.
29. Johnson LN, Barford D (June 1993). "The effects of phosphorylation on the structure and function of proteins". Annual Review of Biophysics and Biomolecular Structure. 22 (1): 199–232. doi:10.1146/annurev.bb.22.060193.001215. PMID 8347989.
30. Hay RT (April 2005). "SUMO: a history of modification". Molecular Cell. 18 (1): 1–12. doi:10.1016/j.molcel.2005.03.012. PMID 15808504.
31. Cheng TS, Chang LK, Howng SL, Lu PJ, Lee CI, Hong YR (February 2006). "SUMO-1 modification of centrosomal protein hNinein promotes hNinein nuclear localization". Life Sciences. 78 (10): 1114–20. doi:10.1016/j.lfs.2005.06.021. PMID 16154161.
32. "I-TASSER results". zhanglab.ccmb.med.umich.edu. Retrieved 2019-05-06.
33. "NPS@ : SOPMA secondary structure prediction". npsa-prabi.ibcp.fr. Retrieved 2019-05-06.
34. Walter P, Roberts K, Raff M, Lewis J, Johnson A, Alberts B (2002). "DNA-Binding Motifs in Gene Regulatory Proteins". Molecular Biology of the Cell (4th ed.).
35. "Phyre 2 Results for c8orf34__". www.sbg.bio.ic.ac.uk. Retrieved 2019-05-06.
36. Hsu PL, Li H, Lau HT, Leonen C, Dhall A, Ong SE, Chatterjee C, Zheng N (August 2018). "Crystal Structure of the COMPASS H3K4 Methyltransferase Catalytic Module". Cell. 174 (5): 1106–1116.e9. doi:10.1016/j.cell.2018.06.038. PMC 6108940. PMID 30100181.
37. Brändén, Carl-Ivar, 1934- (1999). Introduction to protein structure. Tooze, John. (2nd ed.). New York: Garland Pub. ISBN 978-0815323044. OCLC 39508201.{{cite book}}: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link)
38. Matthews HR, Huebner VD (1984). "Nuclear protein kinases". Molecular and Cellular Biochemistry. 59 (1–2): 81–99. doi:10.1007/bf00231306. PMID 6323962. S2CID 25765323.
39. ^ "BLAST: Basic Local Alignment Search Tool". blast.ncbi.nlm.nih.gov. Retrieved 2019-05-04.
40. "TimeTree :: The Timescale of Life". timetree.org. Retrieved 2019-05-04.
41. "C8orf34 Result Summary | BioGRID". thebiogrid.org. Retrieved 2019-05-06.
42. Jiang K, Wang J, Liu J, Ward T, Wordeman L, Davidson A, Wang F, Yao X (August 2009). "TIP150 interacts with and targets MCAK at the microtubule plus ends". EMBO Reports. 10 (8): 857–65. doi:10.1038/embor.2009.94. PMC 2699393. PMID 19543227.
43. Zheng D, Ye S, Wang X, Zhang Y, Yan D, Cai X, Gao W, Shan H, Gao Y, Chen J, Hu Z, Li H, Li J (June 2017). "Pre-RC Protein MCM7 depletion promotes mitotic exit by Inhibiting CDK1 activity". Scientific Reports. 7 (1): 2854. Bibcode:2017NatSR...7.2854Z. doi:10.1038/s41598-017-03148-3. PMC 5460140. PMID 28588300.
44. Han JY, Shin ES, Lee YS, Ghang HY, Kim SY, Hwang JA, Kim JY, Lee JS (October 2013). "A genome-wide association study for irinotecan-related severe toxicities in patients with advanced non-small-cell lung cancer". The Pharmacogenomics Journal. 13 (5): 417–22. doi:10.1038/tpj.2012.24. PMID 22664479.
45. Stransky N, Cerami E, Schalm S, Kim JL, Lengauer C (September 2014). "The landscape of kinase fusions in cancer". Nature Communications. 5 (1): 4846. Bibcode:2014NatCo...5.4846S. doi:10.1038/ncomms5846. PMC 4175590. PMID 25204415.
46. JP application 2006158349, Usami, Shinichi; Abe, Satoko & Yamaguchi, Toshikazu, "Method for detecting gene mutation defining hardness of hearing", published 2006-06-22, assigned to BML Inc. 

• Human genes
• Uncharacterized proteins