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C8orf34

From Wikipedia, the free encyclopedia
C8orf34
Identifiers
AliasesC8orf34, VEST-1, VEST1, chromosome 8 open reading frame 34
External IDsMGI: 2444149; HomoloGene: 14194; GeneCards: C8orf34; OMA:C8orf34 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

116328

320492

Ensembl

ENSG00000165084

ENSMUSG00000057715

UniProt

Q49A92

Q8BZJ8

RefSeq (mRNA)

NM_001195639
NM_052958

RefSeq (protein)
Location (UCSC)n/aChr 1: 11.41 – 11.98 Mb
PubMed search[2][3]
Wikidata
View/Edit HumanView/Edit Mouse

C8orf34 is a protein that, in Homo sapiens, is encoded by the C8orf34 gene.[4] 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

[edit]

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.[5] 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.[6]

Location of C8orf34 on human chromosome 8.

Gene neighbors

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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.[7] This protein is involved in insulin signalling pathways. Mutations in and overexpression of the PREX2 gene have been observed in some cancers.[8]

Gene neighbors and areas of interest
Gene Location Function NCBI Gene ID
PREX2 67951918...68237033 facilitates the exchange of GDP for GTP on Rac1 (a GTPase) 80243[7]
LOC105375888 68082051...68095535 uncharacterized 105375888[9]
LOC107986951 68849606...68858076 uncharacterized 107986951[10]
LOC108004543 68973432...68976574 non-coding, known to undergo non-allelic homologous recombination (NAHR) with another region 108004543[11]

Gene expression

[edit]

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.[12] 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.

Microarray data from 6 individuals showing the expression of C8orf34 in different regions of the brain. Areas of high expression are shown in red while areas of low expression are noted in green.[13]

C8orf34 is expressed in a wide array of tissues, including the kidney, stomach, thymus, pituitary gland, ear, and brain.[6][14] In the brain, C8orf34 is expressed in the dentate gyrus, epithalamus, and medulla.[15] 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.[16]

Regulation of expression

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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.[17]

Transcription factor Function
OCT1 Involved in the cell cycle regulation of histone H2B gene transcription and in the transcription of other cellular housekeeping genes.[18]
STAT3 Involved in the expression of genes that progress cell cycle from G1 to S phase. Acts as a regulator of inflammatory response by regulating differentiation of naive CD4+ T-cells into T-helper Th17 or regulatory T-cells (Treg).[19]
HSF1 Rapidly induced after temperature stress and binds heat shock promoter elements (HSE). This protein plays a role in the regulation of lifespan.[20]
MZF1 Expressed in hematopoietic progenitor cells that are committed to myeloid lineage differentiation. It contains 13 C2H2 zinc fingers arranged in two domains that are separated by a short glycine- and proline-rich sequence.[21]

Protein

[edit]

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.[22] 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

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C8orf34 has a domain entitled "Dimerization-anchoring domain of cAMP-dependent protein kinase regulatory subunit" that spans residues 94 to 133.[23] Proteins with this domain are subunits of a multimer protein kinase.[24] 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.[25]

Post-translational modifications

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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.[26] 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.[27] In some cases, glycosylation may play a role in adhesion and immunological processes.[28] Phosphorylation of amino acid residues may serve to activate or deactivate the functional domain of C8orf34.[29] SUMOylation sites are residues that SUMO (small ubiquitin-like modifier) proteins can bind to modify the protein's function.[30] SUMO proteins may modify proteins to perform many functions, including nuclear-cytosolic transport, transcriptional regulation, progressing through the cell cycle, and even apoptosis.[31]

I-TASSER-predicted three-dimensional structure of C8orf34.[32]

Structure

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The secondary structure of C8orf34 is predicted to consist mostly of free random coils with alpha helices being the dominant organized structure.[33] Alpha helices are a common motif in proteins that regulate gene expression and may support this function in C8orf34.[34] 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.[35][36]

Function

[edit]

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.[37] 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.[38]

Homology

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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.[39]

Orthologs

[edit]

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.[39] 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.

Organism Scientific Name NCBI Accession[39] Identity % Seq Length Est Time of Divergence (MYA)[40]
Human Homo sapiens NP_443190.2 100.00% 538 0.00
Gorilla Gorilla gorilla gorilla XP_004047177.2 99.44% 538 9.06
Chimpanzee Pan troglodytes NP_001186058.1 99.26% 538 6.65
Dog Canis lupus familiaris NP_001182595.1 91.59% 451 96.00
Mouse Mus musculus NP_001153841.1 90.71% 462 90.00
Chinchilla Chinchilla lanigera XP_013373625.1 90.48% 456 90.00
Cat Felis catus XP_019678323.2 88.13% 537 96.00
Horse Equus caballus XP_023504264.1 86.43% 534 96.00
Thirteen-lined ground squirrel Ictidomys tridecemlineatus XP_021580557.1 85.53% 538 90.00
Chicken Gallus gallus XP_025003758.1 83.73% 620 312.00
American Alligator Alligator mississippiensis XP_019354134.1 82.20% 678 312.00
White-throat sparrow Zonotrichia albicollis XP_026647522.1 79.78% 657 312.00
Western clawed frog Xenopus tropicalis XP_002935369.2 77.23% 621 352.00
Common box turtle Terrapene mexicana triunguis XP_026503128.1 77.21% 414 312.00
Australian ghostshark Callorhinchus milii XP_007885522.1 70.80% 709 473.00
Zebrafish Danio rerio XP_005162763.1 70.65% 626 435.00
Lamp Shell Lingula anatina XP_013381780.1 30.73% 517 797.00
C. teleta Capitella teleta ELU06153.1 29.00% 516 797.00
Eastern Oytster Crassostrea virginica XP_022341487.1 26.91% 500 797.00
Exaiptasia (sea anemone) Exaiptasia pallida XP_020895362.1 26.65% 548 824.00

Protein interactions

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Yeast two hybrid experimentation has revealed that C8orf34 interacts with a number of proteins insular to the nucleus.[41] 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.[42] 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.[43] C8orf34's interactions with these proteins support the conclusion that it is involved in transcription regulation and cell cycle progression.

Clinical significance

[edit]

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.[44] 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.[45] 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.[46]

References

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  1. ^ a b c 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. ^ a b "C8orf34 chromosome 8 open reading frame 34 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-02-26.
  7. ^ a b "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.[permanent dead link]
  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. ^ a b c "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. 
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