Wikipedia

C18orf63

Chromosome 18 open reading frame 63 is a protein which in humans is encoded by the C18orf63 gene.[5] This protein is not yet well understood by the scientific community. Research has been conducted suggesting that C18orf63 could be a potential biomarker for early stage pancreatic cancer and breast cancer.[6][7]

C18orf63
Identifiers
AliasesC18orf63, DKFZP781G0119, chromosome 18 open reading frame 63
External IDsMGI: 4936900; HomoloGene: 124404; GeneCards: C18orf63; OMA:C18orf63 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

644041

100503964

Ensembl

ENSG00000206043

ENSMUSG00000117781

UniProt

Q68DL7

A0A494BAC1

RefSeq (mRNA)

NM_001174123

NM_001370919

RefSeq (protein)

NP_001167594

NP_001357848

Location (UCSC)Chr 18: 74.32 – 74.36 MbChr 18: 84.82 – 84.85 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

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This gene is located at band 22, sub-band 3, on the long arm of chromosome 18. It is composed of 5065 base pairs spanning from 74,315,875 to 74,359,187 bp on chromosome 18.[5] The gene has a total of 14 exons.[5] C18orf63 is also known by the alias DKFZP78G0119.[8] No isoforms exist for this gene.[5]

 
NCBI GEO Expression Profile for C18orf63

Expression

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C18orf63 has high expression in the testis.[5] The gene shows low expression in the kidneys, liver, lung, and pelvis.[9] There is no phenotype associated with this gene.[5][10]

Promoter

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The promoter region for C18orf63 is 1163 bp long starting at 74,314,813 bp and ending at 74,315,975 bp.[11] The promoter ID is GXP_4417391. The presence of multiple y-box binding transcription factors and SRY transcription factor binding sites suggest that C18orf63 is involved in male sex determination.[12]

Protein

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Amino acid composition of the average protein (left) and Amino acid composition of C18orf63 (right)

The C18orf63 protein is composed up of 685 amino acids and has a molecular weight of 77230.50 Da, with a predicted isoelectric point of 9.83.[5][13] No isoforms exist for this protein.[14] This protein is rich in glutamine, isoleucine, lysine, and serine when compared to the average protein, but lacks in aspartic acid and glycine.[15][16]

Structure

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Partial 3D structure for C18orf63

In the predicted secondary structure for this protein there are a number of beta turns, beta strands and alpha helices. For C18orf63 48.6% of the protein is expected to form alpha helices and 28.6% of the structure is expected to be composed of beta strands.[17][18]

Domains and Motifs

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Motifs and Domains for C18orf63

The protein contains one domain of unknown function, DUF 4709, spanning from the 7th amino acid to the 280th amino acid.[19] Motifs that are predicted to exist include an N-terminal motif, RxxL motif, and KEN conserving motif, which all signal for protein degradation.[20] Another motif that is predicted to exist is a Wxxx motif, which facilitates entrance of PTS1 cargo proteins into the organellar lumen, and a RVxPx motif which allows protein transport from the trans-Golgi network to the plasma membrane of the cilia.[21][22] There is also a bipartite nuclear localization signal at the end of the protein sequence.[23] There is no trans-membrane domain present, indicating that C18orf63 is not a trans-membrane protein.[24]

Post-Translational Modifications

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Post-translational modifications the protein is predicted to undergo include SUMOylation, PKC and CK2 phosphorylation, N-glycosylation, amiditation, and cleavage.[25][26][27][28] There are six total PKC phosphorylation sites and 2 CK2 phosphorylation sites, 2 SUMOylation sites, and 2 N-glycosylation sites. There are no signal peptides present in this sequence.[28]

Subcellular Location

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Due to the nuclear localization signal at the end of the protein sequence, C18orf63 is predicted to be nuclear. C18orf63 has also been predicted to be targeted to the mitochondria in addition to the nucleus.[29][30][31]

Homology

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Orthologs

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Orthologs have been found in most eukaryotes, with the exception of the class Amphibia.[14] No human paralogs exist for C18orf63.[14][32] The most distant homolog detectable is Mizuhopecten yessoensis, sharing a 37% identity with the human protein sequence. The domain of unknown function was the only homologous domain present in the protein sequence, it was found to be highly conserved in all orthologs. The table below shows some examples of various orthologs for this protein.

Table of Orthologs for C18orf63
Genus Species Common Name Accession Number Sequence Length Sequence Identity Sequence Similarity
Mammalia Galeopterus variegatus Flying lemur XP_008582575.1 677 78% 87%
Fukomys damarensis Damara mole-rat XP_019061329.1 654 70% 81%
Equus przewalskii Przewalski's horse XP_008534756.1 751 76% 83%
Loxodonta africana African bush elephant XP_023399495.1 676 73% 83%
Chinchilla lanigera Long-tailed chinchilla XP_005373135.1 679 74% 83%
Aves Corvus cornix Hooded crow XP_019138065.2 743 52% 69%
Sturnus vulgaris Common starling XP_014726419.1 742 51% 68%
Struthio camelus Southern ostrich XP_009668441.1 741 44% 62%
Phaethon lepturus White-tailed tropicbird XP_010287785.1 740 44% 60%
Nestor notabillis Kea XP_010018784.1 741 43% 60%
Reptillia Ophiophagus hannah King cobra ETE73844.1 671 55% 69%
Anolis carolinensis Carolina anole XP_008106943.1 719 48% 66%
Pogona vitticeps Central bearded dragon XP_020657479.1 676 52% 70%
Chrysemys picta Painted turtle XP_008162704.1 770 45% 60%
Fish Callorhinchus milii Australian ghostshark XP_007901438.1 738 57% 74%
Rhincodon typus Whale shark XP_020370482.1 712 41% 55%
Salmo salar Atlantic salmon XP_0140366110.1 626 43% 60%
Invertebrates Stylophora pistillata Coral XP_022802513.1 721 33% 57%
Acanthaster planci Crown of thorns starfish XP_022082271.1 750 37% 56%
Mizuhopecten yessoensis Scallop OWF48219.1 260 37% 57%
 
Rate of evolution for C18orf63 when compared to betaglobin, fibrinogen alpha, and cytochrome c

Rate of Evolution

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C18orf63 is a mildly slow evolving protein. The protein evolves faster than Cytochorme C but slower than Betaglobin.[14]

Interacting proteins

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Transcription factors of interest predicted to bind to the regulatory sequence include p53 tumor suppressors, SRY testis determining factors, Y-box binding transcription factors, and glucocorticoid responsive elements.[11] The JUN protein was found to interact with C18orf63 through anti-bait co-immunoprecipitation.[33] The JUN protein binds to the USP28 promoter in colorectal cancer cells and is involved in the activation of these cancer cells.[34][35]

Clinical significance

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Mutations

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A variety of missense mutations occur in the human population for this protein. In the regulatory sequence missense mutations occur at two transcription factor binding sites.[32] Transcription factors affected are glucocorticoid responsive elements and E2F-myc cell cycle regulars. There are eleven common mutations that occur that affect the protein sequence itself.[32] None of these mutations affect predicted post-translational modifications the protein sequence undergoes.

Disease association

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C18orf63 has been associated with personality disorders, obesity, and type two diabetes through a genome-wide association study.[36][37][38] Currently research has not shown if C18orf63 plays a direct role in any of these diseases.

References

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  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000206043 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000117781 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b c d e f g "C18orf63 chromosome 18 open reading frame 63 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-02-19.
  6. ^ Zheng H, Zhao C, Qian M, Roy S, Soherwardy A, Roy D, Kuruc M (30 September 2015). New Proteomic Workflows Combine Albumin Depletion and On- Bead Digestion, for Quantitative Cancer Serum (PDF). Biotech Support Group (Report). Application Report. Rutgers Center for Integrative Proteomics.
  7. ^ Kuruc M (April 2016). The Commonality of the Cancer Serum Proteome Phenotype as analyzed by LC-MS/MS, and Its Application to Monitor Dysregulated Wellness. American Association for Cancer Research Annual Meeting 2016. New Orleans LA, USA. doi:10.13140/rg.2.2.23237.65765.
  8. ^ "C18orf63 Gene". GeneCards. Retrieved 2018-02-19.
  9. ^ github.com/gxa/atlas/graphs/contributors, EMBL-EBI Expression Atlas development team. "Search results < Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-04-26. {{cite web}}: |last= has generic name (help)
  10. ^ Cosmic. "C18orf63 Gene - COSMIC". cancer.sanger.ac.uk. Retrieved 2018-04-27.
  11. ^ a b "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Archived from the original on 2001-02-24. Retrieved 2018-04-27.
  12. ^ "SRY gene". Genetics Home Reference. Retrieved 2018-05-05.
  13. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2018-04-26.
  14. ^ a b c d "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2018-04-26.
  15. ^ EMBL-EBI. "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-05-01.
  16. ^ "Amino Acid Frequency". www.tiem.utk.edu. Archived from the original on 2017-04-29. Retrieved 2018-05-01.
  17. ^ Kumar TA. "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2018-05-01.
  18. ^ "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2018-05-01.
  19. ^ "uncharacterized protein C18orf63 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-04-26.
  20. ^ Morgan DO (June 2013). "The D box meets its match". Molecular Cell. 50 (5): 609–10. doi:10.1016/j.molcel.2013.05.023. PMC 3702177. PMID 23746347.
  21. ^ Neuhaus A, Kooshapur H, Wolf J, Meyer NH, Madl T, Saidowsky J, Hambruch E, Lazam A, Jung M, Sattler M, Schliebs W, Erdmann R (January 2014). "A novel Pex14 protein-interacting site of human Pex5 is critical for matrix protein import into peroxisomes". The Journal of Biological Chemistry. 289 (1): 437–48. doi:10.1074/jbc.M113.499707. PMC 3879566. PMID 24235149.
  22. ^ Ou Y, Zhang Y, Cheng M, Rattner JB, Dobrinski I, van der Hoorn FA (2012). "Targeting of CRMP-2 to the primary cilium is modulated by GSK-3β". PLOS ONE. 7 (11): e48773. Bibcode:2012PLoSO...748773O. doi:10.1371/journal.pone.0048773. PMC 3504062. PMID 23185275.
  23. ^ Nakai K, Horton P (January 1999). "PSORT: a program for detecting sorting signals in proteins and predicting their subcellular localization". Trends in Biochemical Sciences. 24 (1): 34–6. doi:10.1016/S0968-0004(98)01336-X. PMID 10087920.
  24. ^ Möller S, Croning MD, Apweiler R (July 2001). "Evaluation of methods for the prediction of membrane spanning regions". Bioinformatics. 17 (7): 646–53. doi:10.1093/bioinformatics/17.7.646. PMID 11448883.
  25. ^ "Motif Scan". myhits.isb-sib.ch. Retrieved 2018-04-27.
  26. ^ "NetAcet 1.0 Server". www.cbs.dtu.dk. Retrieved 2018-04-27.
  27. ^ "NetNGlyc 1.0 Server". www.cbs.dtu.dk. Retrieved 2018-04-27.
  28. ^ a b Petersen TN, Brunak S, von Heijne G, Nielsen H (September 2011). "SignalP 4.0: discriminating signal peptides from transmembrane regions". Nature Methods. 8 (10): 785–6. doi:10.1038/nmeth.1701. PMID 21959131. S2CID 16509924.
  29. ^ "Cell atlas - C18orf63 - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2018-05-01.
  30. ^ "PSORT: Protein Subcellular Localization Prediction Tool". www.genscript.com. Retrieved 2018-05-01.
  31. ^ "TargetP 1.1 Server". www.cbs.dtu.dk. Retrieved 2018-05-01.
  32. ^ a b c "Human BLAT Search". genome.ucsc.edu. Retrieved 2018-04-27.
  33. ^ Li X, Wang W, Wang J, Malovannaya A, Xi Y, Li W, Guerra R, Hawke DH, Qin J, Chen J (January 2015). "Proteomic analyses reveal distinct chromatin-associated and soluble transcription factor complexes". Molecular Systems Biology. 11 (1): 775. doi:10.15252/msb.20145504. PMC 4332150. PMID 25609649.
  34. ^ "JUN - Transcription factor AP-1 - Homo sapiens (Human) - JUN gene & protein". www.uniprot.org. Retrieved 2018-05-01.
  35. ^ Serra RW, Fang M, Park SM, Hutchinson L, Green MR (March 2014). "A KRAS-directed transcriptional silencing pathway that mediates the CpG island methylator phenotype". eLife. 3: e02313. doi:10.7554/eLife.02313. PMC 3949416. PMID 24623306.
  36. ^ Terracciano A, Sanna S, Uda M, Deiana B, Usala G, Busonero F, Maschio A, Scally M, Patriciu N, Chen WM, Distel MA, Slagboom EP, Boomsma DI, Villafuerte S, Sliwerska E, Burmeister M, Amin N, Janssens AC, van Duijn CM, Schlessinger D, Abecasis GR, Costa PT (June 2010). "Genome-wide association scan for five major dimensions of personality". Molecular Psychiatry. 15 (6): 647–56. doi:10.1038/mp.2008.113. PMC 2874623. PMID 18957941.
  37. ^ Comuzzie AG, Cole SA, Laston SL, Voruganti VS, Haack K, Gibbs RA, Butte NF (2012). "Novel genetic loci identified for the pathophysiology of childhood obesity in the Hispanic population". PLOS ONE. 7 (12): e51954. Bibcode:2012PLoSO...751954C. doi:10.1371/journal.pone.0051954. PMC 3522587. PMID 23251661.
  38. ^ Saxena R, Voight BF, Lyssenko V, Burtt NP, de Bakker PI, Chen H, Roix JJ, Kathiresan S, Hirschhorn JN, Daly MJ, Hughes TE, Groop L, Altshuler D, Almgren P, Florez JC, Meyer J, Ardlie K, Bengtsson Boström K, Isomaa B, Lettre G, Lindblad U, Lyon HN, Melander O, Newton-Cheh C, Nilsson P, Orho-Melander M, Råstam L, Speliotes EK, Taskinen MR, Tuomi T, Guiducci C, Berglund A, Carlson J, Gianniny L, Hackett R, Hall L, Holmkvist J, Laurila E, Sjögren M, Sterner M, Surti A, Svensson M, Svensson M, Tewhey R, Blumenstiel B, Parkin M, Defelice M, Barry R, Brodeur W, Camarata J, Chia N, Fava M, Gibbons J, Handsaker B, Healy C, Nguyen K, Gates C, Sougnez C, Gage D, Nizzari M, Gabriel SB, Chirn GW, Ma Q, Parikh H, Richardson D, Ricke D, Purcell S (June 2007). "Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels". Science. 316 (5829): 1331–6. Bibcode:2007Sci...316.1331.. doi:10.1126/science.1142358. PMID 17463246. S2CID 26332244.
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