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Chromosome 18 open reading frame 63 is a protein that in humans is encoded by the C18orf63 gene.[1] This protein is not yet well understood by the scientific community. Research has been conducted suggesting that C18orf63 could be a potential biomarker form for early stage pancreatic cancer and breast cancer.[2][3]

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.[4] The gene has a total of 14 exons.[1] C18orf63 is also known by the alias DKFZP78G0119.[5] No isoforms exist for this gene.[1]

 
NCBI GEO Expression Profile for C18orf63

Expression

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C18orf63 has high expression in the testis.[1] There is low expression in the kidneys, heart, liver, lung, and pelvis.[6] There is no phenotype associated with this gene.[1][7]

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.[8] The promoter ID is GXP_4417391.

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.[1][9] No isoforms exist for this protein.[10] This protein is rich in glutamine, isoleucine, lysine, and serine when compared to the average protein and lacks in aspartic acid and glycine.[11][12]

Structure

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Partial 3D structure for C18orf63

In the predicted protein structure 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.[13][14]

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.[15] Motifs that are predicted to exist include an N-terminal motif, RxxL motif, KEN conserving motif, Wxxx motif, and a RVxPx motif. There is also a bipartite nuclear localization signal at the end of the protein sequence.[16]

Post-Translational Modifications

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Post-translational modifications the protein is predicted to undergo includes SUMOylation, PKC and CK2 phosphorylation, N-glycosylation, amiditation, and cleavage.[17][18][19][20] There are six total PKC phosphorylation sites and 2 CK2 phosphorylation sites, 2 SUMOylation sites, and 2 N-glycosylation sites.

Subcellular Location

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Due to the nuclear localization signal at the end of the protein sequence, C18orf63 is predicted to be targeted to the nucleus. C18orf63 has also been predicted to be targeted to the mitochondria in addition to the nucleus. [21][22][23]

Homology

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Orhologs

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Orthologs have been found in most eukaryotes, with the exception of the class Amphibia.[10] No human paralogs exist for C18orf63.[10][24] The most distant homolog detectable is Mizuhopecten yessoensis, sharing a 37% identity with the human protein sequence. The only homologus domain was the domain of unknown function, 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.[10]

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.[8] The JUN protein was found to interact with C18orf63 through antibait co-immunoprecipitation.[25] The JUN protein binds to the USP28 promoter in colorectal cancer cells and is involved in the activation of these cancer cells. [26][27]

References

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  1. ^ a b c d e f "C18orf63 chromosome 18 open reading frame 63 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-02-19.
  2. ^ 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.
  3. ^ 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 of Cancer Research Annual Meeting 2016. New Orleans LA, USA. doi:10.13140/rg.2.2.23237.65765.
  4. ^ "C18orf63 chromosome 18 open reading frame 63 [Homo sapiens (human)] - Gene - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-02-19.
  5. ^ "C18orf63 Gene". GeneCards. Retrieved 2018-02-19.
  6. ^ 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)CS1 maint: extra punctuation (link)
  7. ^ Cosmic. "C18orf63 Gene - COSMIC". cancer.sanger.ac.uk. Retrieved 2018-04-27.
  8. ^ a b "Genomatix - NGS Data Analysis & Personalized Medicine". www.genomatix.de. Retrieved 2018-04-27.
  9. ^ "ExPASy - Compute pI/Mw tool". web.expasy.org. Retrieved 2018-04-26.
  10. ^ a b c d "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2018-04-26.
  11. ^ EMBL-EBI. "SAPS < Sequence Statistics < EMBL-EBI". www.ebi.ac.uk. Retrieved 2018-05-01.
  12. ^ "Amino Acid Frequency". www.tiem.utk.edu. Retrieved 2018-05-01.
  13. ^ Kumar TA. "CFSSP: Chou & Fasman Secondary Structure Prediction Server". www.biogem.org. Retrieved 2018-05-01.
  14. ^ "I-TASSER server for protein structure and function prediction". zhanglab.ccmb.med.umich.edu. Retrieved 2018-05-01.
  15. ^ "uncharacterized protein C18orf63 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2018-04-26.
  16. ^ 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.
  17. ^ "Motif Scan". myhits.isb-sib.ch. Retrieved 2018-04-27.
  18. ^ "NetAcet 1.0 Server". www.cbs.dtu.dk. Retrieved 2018-04-27.
  19. ^ "NetNGlyc 1.0 Server". www.cbs.dtu.dk. Retrieved 2018-04-27.
  20. ^ 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.
  21. ^ "Cell atlas - C18orf63 - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2018-05-01.
  22. ^ "PSORT: Protein Subcellular Localization Prediction Tool". www.genscript.com. Retrieved 2018-05-01.
  23. ^ "TargetP 1.1 Server". www.cbs.dtu.dk. Retrieved 2018-05-01.
  24. ^ "Human BLAT Search". genome.ucsc.edu. Retrieved 2018-04-27.
  25. ^ 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. PMC 4332150. PMID 25609649.
  26. ^ "JUN - Transcription factor AP-1 - Homo sapiens (Human) - JUN gene & protein". www.uniprot.org. Retrieved 2018-05-01.
  27. ^ 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.{{cite journal}}: CS1 maint: unflagged free DOI (link)
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