Biology:C3orf67
![]() Generic protein structure example |
Chromosome 3 open reading frame 67 or C3orf67 is a protein that in humans is encoded by the gene C3orf67.[1][2] The function of C3orf67 is not yet fully understood.
Gene
C3orf67 is located at 3p14.2 on the reverse strand ranging from 58716417 to 59050045 base pairs.[3][1] The accession number is NP_001338459.1.[4]
Protein
Primary sequence and isoforms
The coding sequence is 402-2681 base pairs of 3135 base pairs,[3] making up 759 amino acids.[1][4] C3orf67 has six validated isoforms.[1] Isoform one is the most complete with 16 exons.[3] C3orf67 weighs 84.35 kilodaltons.[5]
Domains and motifs
There are three functional domains identified for C3orf67[6]
Post-translational modifications
File:Conserved PTM map.tif Several post-translational modifications have been predicted for C3orf67 in conserved regions using various bioinformatic prediction tools[7][8][9][10][11][12][13][14]
- Two nuclear export signals
- Three sumoylation sites
- Two o-glycosylation sites
- One phosphorylation site
- One tyrosine sulfation site
Secondary structure
The beginning of C3orf67 is predicted to consist of a series of beta strands and a couple alpha helices that coincide with the DUF667 domain. There are also alpha helices predicted in regions that correspond to the CM_mono2 and OCRE domains.[15][16][17]
Tertiary structure
The DUF667 region is predicted to form a tube-like structure from a series of beta sheets.[17]
Homology and Evolution
Paralogs
There are no known paralogs of C3orf67.
Orthologs
Orthologs have been identified for C3orf67 in species ranging from fungus, plants, hemichordates, parasites, fish, reptiles, birds, invertebrates, and mammals.
Species | Common Name | Date of Divergence (MYA) | Accession Number | Sequence Length (aa) | % Identity |
Orbicella faveolata | Mountainous star coral | 824 | XP_020630732.1 / XP_020630739.1 | 849 | 32.20% |
Exaiptasia pallida | Pale anemone | 824 | XP_020899564.1 | 797 | 32.00% |
Acanthaster planci | Crown-of-thorns starfish | 684 | XP_022107809.1 | 976 | 31.60% |
Stylophora pistillata | Smooth cauliflower coral | 824 | XP_022782397.1 | 825 | 30.80% |
Crassostrea gigas | Pacific oyster | 797 | XP_011453705.1 | 950 | 29.50% |
Lingula anatina | Lamp shell | 797 | XP_013404893.1 | 1077 | 29.30% |
Octopus bimaculoides | California two-spotted octopus | 797 | XP_014778712.1 | 902 | 29.10% |
Saccoglossus kowalevskii | Acorn worm | 684 | XP_006821003.1 | 596 | 23.30% |
Amphimedon queenslandica | Sponge | 951.8 | XP_011402616.1 | 508 | 22.70% |
Distant homologs
Species | Common Name | Date of Divergence (MYA) | Accession Number | Sequence Length (aa) | % Identity |
Trichinella spiralis | Trichina worm | 797 | XP_003374081.1 | 393 | 12.60% |
Spizellomyces punctatus | Unknown | 1105 | XP_016608387.1 | 183 | 8.20% |
Selaginella moellendorffii | Spikemoss | 1496 | XP_002989784.1 | 209 | 6.00% |
Expression
Promoter
The promoter is well conserved across humans, gibbons, baboons, orangutans, cats, squirrels, alpacas, rabbits and mice.[18] There are several high quality transcription factor binding sites.[19] There are also several stem-loop structures that are predicted to be formed in the promoter region, some of which overlap with transcription factor binding sites.[20]
Expression
C3orf67 is prominently expressed in the liver, tonsils, trachea, ovaries, testis, placenta, and colon. In other tissues it is expressed at low levels.[21] An increase in expression has been linked to small cell lung cancer.[22]
Function
The protein has been identified as one of seventeen (17) genes that may play a novel role in the intersection of tumor promotion and DNA-damaging stress and may be linked to carcinogenesis.[23]
Interacting Proteins
Transcription factors
There are three notable transcription factors that are known to be involved in the regulation of cell growth or immune responses:
- V$SMAD3.01[19]
- V$EBF1.01[25]
- V$IK2.01[27]
- Ikaros 2 is a potential regulator for lymphocyte differentiation.[28]
Other interacting proteins
Several other proteins have been predicted to interact with C3orf67:
- CLK1[29]
- Phosphorylates serine/arginine-rich proteins involved in pre-mRNA processing in the nucleus.[30]
- CDK16 (gene)[31]
- A protein kinase thought to play a role in signal transduction cascades in differentiated cells, exocytosis, and transport of secretory cargo from the ER.[32]
- MARS2[33]
- Mitochondrial methionyl-tRNA synthetase.[34]
- AARS2[33]
- mitochondrial alanyl-tRNA synthetase.[34]
- C12orf60[35]
References
- ↑ 1.0 1.1 1.2 1.3 "NCBI Gene". https://www.ncbi.nlm.nih.gov/gene?LinkName=nuccore_gene&from_uid=1191017729.
- ↑ "C3orf67". https://www.genecards.org/cgi-bin/carddisp.pl?gene=C3orf67.
- ↑ 3.0 3.1 3.2 NCBI Nucleotide. May 2019. https://www.ncbi.nlm.nih.gov/nuccore/NM_001351530.1.
- ↑ 4.0 4.1 "NCBI Protein". https://www.ncbi.nlm.nih.gov/protein/NP_001338459.1.
- ↑ "Protein Molecular Weight Calculator". https://www.sciencegateway.org/tools/proteinmw.htm.
- ↑ "MOTIF: Searching Protein Sequence Motifs". http://www.genome.jp/tools/motif/.
- ↑ "DictyOGlyc 1.1 Server" (in en). http://www.cbs.dtu.dk/services/DictyOGlyc/.
- ↑ "GPS-SUMO: Prediction of SUMOylation Sites & SUMO-interaction Motifs". http://sumosp.biocuckoo.org/online.php.
- ↑ "ExPASy - Sulfinator tool" (in en-US). https://web.expasy.org/sulfinator/.
- ↑ "SUMOplot™ Analysis Program | Abgent" (in en). http://www.abgent.com/sumoplot.
- ↑ "C3orf67 (human)". https://www.phosphosite.org/proteinAction.action?id=2264321&showAllSites=true.
- ↑ "NetOGlyc 4.0 Server" (in en). http://www.cbs.dtu.dk/services/NetOGlyc/.
- ↑ "YinOYang 1.2 Server" (in en). http://www.cbs.dtu.dk/services/YinOYang/.
- ↑ "NetPhos 3.1 Server" (in en). http://www.cbs.dtu.dk/services/NetPhos/.
- ↑ "JPred: A Protein Secondary Structure Prediction Server" (in en). http://www.compbio.dundee.ac.uk/jpred/.
- ↑ Kelley, Lawrence. "PHYRE2 Protein Fold Recognition Server". http://www.sbg.bio.ic.ac.uk/phyre2/html/page.cgi?id=index.
- ↑ 17.0 17.1 "SWISS-MODEL | Workspace" (in en). https://swissmodel.expasy.org/interactive.
- ↑ "Human BLAT Search". https://genome.ucsc.edu/cgi-bin/hgBlat.
- ↑ 19.0 19.1 "Genomatix: Matrix Library information" (in en-US). https://www.genomatix.de/cgi-bin/matbase/matbase.pl?s=ef479d78b72cd422e7b38360cea871c4;NAME=MATRIXID_41a78c8600cf8a089c042a11aacd2ef7;ML=110.
- ↑ "RNA Folding Form | mfold.rit.albany.edu" (in en). http://unafold.rna.albany.edu/?q=mfold/rna-folding-form.
- ↑ "A comprehensive functional analysis of tissue specificity of human gene expression". BMC Biology 6: 49. November 2008. doi:10.1186/1741-7007-6-49. PMID 19014478.
- ↑ "PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer" (in En). Scientific Reports 3 (1): 1911. 2013-05-29. doi:10.1038/srep01911. PMID 23714854. Bibcode: 2013NatSR...3E1911S.
- ↑ "Synergistic Gene Expression Signature Observed in TK6 Cells upon Co-Exposure to UVC-Irradiation and Protein Kinase C-Activating Tumor Promoters". PLOS ONE 10 (10): e0139850. 2 October 2015. doi:10.1371/journal.pone.0139850. PMID 26431317. Bibcode: 2015PLoSO..1039850G.
- ↑ "Human Smad3 and Smad4 are sequence-specific transcription activators". Molecular Cell 1 (4): 611–7. March 1998. doi:10.1016/S1097-2765(00)80061-1. PMID 9660945.
- ↑ "Genomatix: Matrix Library information" (in en-US). https://www.genomatix.de/cgi-bin/matbase/matbase.pl?s=ef479d78b72cd422e7b38360cea871c4;NAME=MATRIXID_333a51744ffdaf7158e710eeafb0ff9d;ML=110.
- ↑ "Early B cell factor 1 regulates B cell gene networks by activation, repression, and transcription- independent poising of chromatin". Immunity 32 (5): 714–25. May 2010. doi:10.1016/j.immuni.2010.04.013. PMID 20451411.
- ↑ "Genomatix: Matrix Library information" (in en-US). https://www.genomatix.de/cgi-bin/matbase/matbase.pl?s=ef479d78b72cd422e7b38360cea871c4;NAME=MATRIXID_4727fdb43b1487897e8922c5900f1d08;ML=110.
- ↑ "The Ikaros gene encodes a family of functionally diverse zinc finger DNA-binding proteins". Molecular and Cellular Biology 14 (12): 8292–303. December 1994. doi:10.1128/MCB.14.12.8292. PMID 7969165.
- ↑ "SR protein kinases promote splicing of nonconsensus introns" (in En). Nature Structural & Molecular Biology 22 (8): 611–7. August 2015. doi:10.1038/nsmb.3057. PMID 26167880.
- ↑ "Antibodypedia - CLK1 antibodies". https://www.antibodypedia.com/gene/34923/CLK1.
- ↑ "Cyclin-dependent kinase 16/PCTAIRE kinase 1 is activated by cyclin Y and is essential for spermatogenesis". Molecular and Cellular Biology 32 (4): 868–79. February 2012. doi:10.1128/MCB.06261-11. PMID 22184064.
- ↑ "Antibodypedia - CDK16 antibodies". https://www.antibodypedia.com/gene/374/CDK16.
- ↑ 33.0 33.1 "Rare recessive loss-of-function methionyl-tRNA synthetase mutations presenting as a multi-organ phenotype". BMC Medical Genetics 14: 106. October 2013. doi:10.1186/1471-2350-14-106. PMID 24103465.
- ↑ 34.0 34.1 "STRING: functional protein association networks" (in en). https://string-db.org/cgi/network.pl?taskId=76hl8pAxLuaX.
- ↑ "Candidate luminal B breast cancer genes identified by genome, gene expression and DNA methylation profiling". PLOS ONE 9 (1): e81843. 2014-01-09. doi:10.1371/journal.pone.0081843. PMID 24416132. Bibcode: 2014PLoSO...981843C.