CCDC60
Coiled-coil domain containing 60 (CCDC60) is a human protein that is most highly expressed in the trachea, salivary glands, bladder, cervix, and epididymis.[1]
Gene
editThe gene that encodes CCDC60 is located on the plus strand of chromosome 12 (12q24.23) and contains 14 exons.[2] The gene spans positions 119334712-119541047.[3] The first record of the gene that encodes CCDC60 in the NCBI nucleotide database originated from a data set containing 15,000 human and mouse full-length cDNA sequences.[2]
Protein
edit
CCDC60 is made up of 550 amino acids.[5] The computational isoelectric point of CCDC60 is 9.17 and the computational molecular weight is approximately 63kDa.[6] Western blots of RT-4 and U-251 cell lines support the predicted molecular weight.[7] The predicted sub-cellular location of CCDC60 is the mitochondria.[8] The secondary structure of CCDC60 contains a namesake coiled-coil domain in addition to predicted alpha helices and coils.[9]
Regulation
editGene Expression
editThe expression of CCDC60 is tissue-specific. CCDC60 is most highly expressed in the trachea, salivary glands, bladder, cervix, and epididymis.[1] CCDC60 is also expressed in epithelial cells of the upper respiratory system.[10] RNA seq data shows relatively high levels of expression in the prostate, moderate expression in the lungs and ovaries, and low expression in the colon, adrenal gland, and brain.[11]
Transcription Factors
editThere are many candidate transcription factors that bind to the promoter region of the gene that encodes CCDC60.[12]
| Family | Description |
|---|---|
| CAAT | CCAAT binding factor |
| XBBF | X-box binding factor |
| MZF1 | Myeloid zinc finger 1 factor |
| EGRF | Wilms tumor supressor |
| KLFS | Krueppel-like factor 2 (lung) (LKLF) |
| ZFO2 | C2H2 zinc finger transcription factor 2 |
| CALM | Calmodulin-binding transcription activator (CAMTA1, CAMTA2) |
| SORY | SRY (sex determining region Y) |
| SAL1 | Spalt-like transcription factor 1 |
| VTBP | Vertebrate TATA binding protein factor |
| RUSH | SWI/SNF related, actin dependent regulator of chromatin, subfamily a, member 3 |
| ETSF | Human and murine ETS1 factors |
| HAND | Twist subfamily of class B bHLH transcription factor |
| HESF | Basic helix-loop-helix protein known as Dec2, Sharp1 or BHLHE41 |
| ZFHX | Two-handed zinc finger homeodomain transcription factor |
| CART | Cart-1 (cartilage homeoprotein 1) |
| HEAT | Heat shock factor 2 |
Post-Translational Modification
editCCDC60 is a candidate for phosphorylation by Protein kinase C.[13] The initial methionine residue is predicted to be cleaved from the polypeptide after translation.[14]
Evolutionary History
editOrthologs
editThe most distantly related organism that a likely ortholog to Human CCDC60 can be found in is Amphimedon queenslandica, a sea sponge. Orthologs to Human CCDC60 are not found in any prokaryotes. Interestingly, there are no known orthologs in arthropods, although there are many other invertebrates that possess likely orthologs.
Paralogs
editThere are no known paralogs of CCDC60.
Protein Interactions
editThere are several binary protein interactions involving CCDC60 that have been experimentally verified.[17]
| Protein | Function[18] | Interaction |
| UPF3B | Involved in nonsense-mediated decay (NMD) of mRNAs containing premature stop codons by associating with the nuclear exon junction complex (EJC) and serving as link between the EJC core and NMD machinery. | Physical Association[19] |
| ZNF593 | Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity. | Physical Association[19] |
| FAM32A | Isoform 1, but not isoform 2 or isoform 3, may induce G2 arrest and apoptosis. | Physical Association[19] |
| RBM42 | Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA. | Physical Association[19] |
| DCP1B | May play a role in the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. | Physical Association[19] |
| EGFR | Receptor tyrosine kinase binding ligands of the EGF family and activating several signaling cascades to convert extracellular cues into appropriate cellular responses. | Physical Association[20] |
| FAM204A | Unknown function. | Physical Association[19] |
| APP | Functions as a cell surface receptor and performs physiological functions on the surface of neurons relevant to neurite growth, neuronal adhesion and axonogenesis. | Direct Interaction[21] |
| MTUS2 | Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules. | Direct Interaction[22] |
| B9D1 | Component of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. | Direct Interaction[23] |
Clinical Significance
editMutations in CCDC60 have been associated with decreased walking speed.[24] Additionally, CCDC60 is one of many candidate genes that has been associated with diagnosis of schizophrenia in genome-wide study.[25]
References
edit- ^ a b She, Xinwei; Rohl, Carol A; Castle, John C; Kulkarni, Amit V; Johnson, Jason M; Chen, Ronghua (2009). "Definition, conservation and epigenetics of housekeeping and tissue-enriched genes". BMC Genomics. 10 (1): 269. doi:10.1186/1471-2164-10-269. ISSN 1471-2164. PMC 2706266. PMID 19534766.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ a b "Homo sapiens coiled-coil domain containing 60 (CCDC60), mRNA". 2018-12-29.
{{cite journal}}: Cite journal requires|journal=(help) - ^ Kent, W. J. (2002-05-16). "The Human Genome Browser at UCSC". Genome Research. 12 (6): 996–1006. doi:10.1101/gr.229102. ISSN 1088-9051. PMC 186604. PMID 12045153.
- ^ Kelley, Lawrence A. Mezulis, Stefans Yates, Christopher M. Wass, Mark N. Sternberg, Michael J. E. (2015). The Phyre2 web portal for protein modeling, prediction and analysis. OCLC 922582332.
{{cite book}}: CS1 maint: multiple names: authors list (link) - ^ "coiled-coil domain-containing protein 60 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-03-04.
- ^ Bjellqvist, Bengt; Hughes, Graham J.; Pasquali, Christian; Paquet, Nicole; Ravier, Florence; Sanchez, Jean-Charles; Frutiger, Séverine; Hochstrasser, Denis (1993). "The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences". Electrophoresis. 14 (1): 1023–1031. doi:10.1002/elps.11501401163. ISSN 0173-0835. PMID 8125050. S2CID 38041111.
- ^ "Anti-CCDC60 antibody produced in rabbit HPA039048". Immunohistochemistry, Western. Retrieved 2019-05-12.
- ^ Emanuelsson, Olof; Nielsen, Henrik; Brunak, Søren; von Heijne, Gunnar (2000). "Predicting Subcellular Localization of Proteins Based on their N-terminal Amino Acid Sequence". Journal of Molecular Biology. 300 (4): 1005–1016. doi:10.1006/jmbi.2000.3903. ISSN 0022-2836. PMID 10891285.
- ^ Klausen, Michael Schantz; Jespersen, Martin Closter; Nielsen, Henrik; Jensen, Kamilla Kjaergaard; Jurtz, Vanessa Isabell; Soenderby, Casper Kaae; Sommer, Morten Otto Alexander; Winther, Ole; Nielsen, Morten (2018-04-30). "NetSurfP-2.0: improved prediction of protein structural features by integrated deep learning". dx.doi.org. doi:10.1101/311209. S2CID 215797127. Retrieved 2019-04-26.
- ^ "CCDC60 Top Ten Tissues". Genevisible.
- ^ "Experiment < Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-05-12.
- ^ Cartharius, K.; Frech, K.; Grote, K.; Klocke, B.; Haltmeier, M.; Klingenhoff, A.; Frisch, M.; Bayerlein, M.; Werner, T. (2005-04-28). "MatInspector and beyond: promoter analysis based on transcription factor binding sites". Bioinformatics. 21 (13): 2933–2942. doi:10.1093/bioinformatics/bti473. ISSN 1367-4803. PMID 15860560.
- ^ Blom, Nikolaj; Sicheritz-Pontén, Thomas; Gupta, Ramneek; Gammeltoft, Steen; Brunak, Søren (2004). "Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence". Proteomics. 4 (6): 1633–1649. doi:10.1002/pmic.200300771. ISSN 1615-9853. PMID 15174133. S2CID 18810164.
- ^ Charpilloz, Christophe; Veuthey, Anne-Lise; Chopard, Bastien; Falcone, Jean-Luc (2014-03-28). "Motifs tree: a new method for predicting post-translational modifications". Bioinformatics. 30 (14): 1974–1982. doi:10.1093/bioinformatics/btu165. ISSN 1460-2059. PMID 24681905.
- ^ "TimeTree - The Timescale of Life". TimeTree. Retrieved 12 May 2019.
- ^ "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2019-05-12.
- ^ "PSICQUIC View". www.ebi.ac.uk. Retrieved 2019-05-12.
- ^ "UniProt". www.uniprot.org. Retrieved 2019-05-12.
- ^ a b c d e f Huttlin, Edward L.; Bruckner, Raphael J.; Paulo, Joao A.; Cannon, Joe R.; Ting, Lily; Baltier, Kurt; Colby, Greg; Gebreab, Fana; Gygi, Melanie P. (2017). "Architecture of the human interactome defines protein communities and disease networks". Nature. 545 (7655): 505–509. doi:10.1038/nature22366. ISSN 1476-4687. PMC 5531611. PMID 28514442.
- ^ Yao, Zhong; Darowski, Katelyn; St-Denis, Nicole; Wong, Victoria; Offensperger, Fabian; Villedieu, Annabel; Amin, Shahreen; Malty, Ramy; Aoki, Hiroyuki (2017-01-19). "A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome". Molecular Cell. 65 (2): 347–360. doi:10.1016/j.molcel.2016.12.004. ISSN 1097-4164. PMC 5663465. PMID 28065597.
- ^ Oláh, Judit; Vincze, Orsolya; Virók, Dezsõ; Simon, Dóra; Bozsó, Zsolt; Tõkési, Natália; Horváth, István; Hlavanda, Emma; Kovács, János (2011-09-30). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088–34100. doi:10.1074/jbc.M111.243907. ISSN 1083-351X. PMC 3190826. PMID 21832049.
- ^ Vidal, Marc; Roth, Frederick P.; Hao, Tong; Hill, David E.; Calderwood, Michael A.; Tavernier, Jan; De Las Rivas, Javier; Aloy, Patrick; Iakoucheva, Lilia M. (2014-11-20). "A Proteome-Scale Map of the Human Interactome Network". Cell. 159 (5): 1212–1226. doi:10.1016/j.cell.2014.10.050. ISSN 0092-8674. PMC 4266588. PMID 25416956.
- ^ Dowdle, William E.; Robinson, Jon F.; Kneist, Andreas; Sirerol-Piquer, M. Salomé; Frints, Suzanna G. M.; Corbit, Kevin C.; Zaghloul, Norann A.; Zaghloul, Norran A.; van Lijnschoten, Gesina (2011-07-15). "Disruption of a ciliary B9 protein complex causes Meckel syndrome". American Journal of Human Genetics. 89 (1): 94–110. doi:10.1016/j.ajhg.2011.06.003. ISSN 1537-6605. PMC 3135817. PMID 21763481.
- ^ Lunetta, Kathryn L; D'Agostino, Ralph B; Karasik, David; Benjamin, Emelia J; Guo, Chao-Yu; Govindaraju, Raju; Kiel, Douglas P; Kelly-Hayes, Margaret; Massaro, Joseph M (2007). "Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study". BMC Medical Genetics. 8 (Suppl 1): S13. doi:10.1186/1471-2350-8-s1-s13. ISSN 1471-2350. PMC 1995604. PMID 17903295.
{{cite journal}}: CS1 maint: unflagged free DOI (link) - ^ Kirov, G; Zaharieva, I; Georgieva, L; Moskvina, V; Nikolov, I; Cichon, S; Hillmer, A; Toncheva, D; Owen, M J (2008-03-11). "A genome-wide association study in 574 schizophrenia trios using DNA pooling". Molecular Psychiatry. 14 (8): 796–803. doi:10.1038/mp.2008.33. ISSN 1359-4184. PMID 18332876. S2CID 7969539.