Ccdc60

Coiled-coil domain containing 60 is a protein that in humans is encoded by the CCDC60 gene that is most highly expressed in the trachea, salivary glands, bladder, cervix, and epididymis.[5]

CCDC60
Identifiers
AliasesCCDC60, coiled-coil domain containing 60
External IDsMGI: 2141043 HomoloGene: 18624 GeneCards: CCDC60
Gene location (Human)
Chr.Chromosome 12 (human)[1]
Band12q24.23Start119,334,712 bp[1]
End119,541,040 bp[1]
Orthologs
SpeciesHumanMouse
Entrez

160777

269693

Ensembl

ENSG00000183273

ENSMUSG00000043913

UniProt

Q8IWA6

Q8C4J0

RefSeq (mRNA)

NM_178499

NM_177759
NM_001360004
NM_001360005

RefSeq (protein)

NP_848594

NP_808427
NP_001346933
NP_001346934

Location (UCSC)Chr 12: 119.33 – 119.54 MbChr 5: 116.12 – 116.29 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Gene

The gene that encodes CCDC60 is located on the plus strand of chromosome 12 (12q24.23) and contains 14 exons.[6] The gene spans positions 119334712-119541047.[7] 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.[6]

Protein
Predicted structure of CCDC60.[8]

CCDC60 is made up of 550 amino acids.[9] The computational isoelectric point of CCDC60 is 9.17 and the computational molecular weight is approximately 63kDa.[10] Western blots of RT-4 and U-251 cell lines support the predicted molecular weight.[11] The predicted subcellular location of CCDC60 is the mitochondria.[12] The secondary structure of CCDC60 contains a namesake coiled-coil domain in addition to predicted alpha helices and coils.[13]

Regulation

Gene expression

The expression of CCDC60 is tissue-specific. CCDC60 is most highly expressed in the trachea, salivary glands, bladder, cervix, and epididymis.[5] CCDC60 is also expressed in epithelial cells of the upper respiratory system.[14] 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.[15]

Transcription factors

There are many candidate transcription factors that bind to the promoter region of the gene that encodes CCDC60.[16]

Candidate Transcription Factor Binding Sites
Family Description
CAAT CCAAT binding factor
XBBF X-box binding factor
MZF1 Myeloid zinc finger 1 factor
EGRF Wilms tumor suppressor
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

CCDC60 is a candidate for phosphorylation by Protein kinase C.[17] The initial methionine residue is predicted to be cleaved from the polypeptide after translation.[18]

Evolutionary history

Orthologs

The most distantly related organism in which 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.

CCDC60 Orthologs
Organism Taxonomic Group Divergence (MYA)[19] Accession Number Sequence Length Shared Sequence Identity[20]
Human Hominidae 0 NP_848594.2 550 100%
Philippine tarsier Tarsiidae 67 XP_008067500.1 559 77.29%
Gray mouse lemur Lemuriformes 73 XP_012612137.1 548 77.60%
Yellow-bellied marmot Rodentia 90 XP_027779037.1 559 76.32%
Sea otter Carnivora 96 XP_022373045.1 548 84.90%
Florida Manatee Placentalia 105 XP_004379174.1 551 83.64%
Common wombat Marsupialia 159 XP_027721296.1 564 62.86%
Southern Ostrich Aves 312 XP_009685824.1 489 37.03%
Bald eagle Aves 320 XP_010573943.1 661 32.02%
High Himilaya Frog Amphibia 352 XP_018413991.1 540 37.31%
Western clawed frog Amphibia 352 XP_012824143.1 657 32.70%
Yellowhead Catfish Osteichthyes 435 XP_027018543.1 577 26.93%
Whale Shark Chondrichthyes 473 XP_020385120.1 672 34.87%
Sea Vase Ascidiacea 676 XP_009860110.2 818 28.31%
Acorn Worm Hemichordata 684 XP_006811258.1 733 27.87%
Pacific Purple Sea Urchin Echinoidea 684 XP_011683370.1 791 23.76%
California two-spot octopus Mollusca 797 XP_014780749.1 689 27.05%
Mountainous Star Coral Cnidaria 824 XP_020617162.1 864 31.28%
Trichoplax Placozoa 948 XP_002117053.1 1247 34.84%
Sponge Porifera 952 XP_011405574.2 569 22.87%

Paralogs

There are no known paralogs of CCDC60.

Protein interactions

There are several binary protein interactions involving CCDC60 that have been experimentally verified.[21]

Interacting Proteins
Protein Function[22] 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[23]
ZNF593 Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity. Physical Association[23]
FAM32A Isoform 1, but not isoform 2 or isoform 3, may induce G2 arrest and apoptosis. Physical Association[23]
RBM42 Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA. Physical Association[23]
DCP1B May play a role in the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay. Physical Association[23]
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[24]
FAM204A Unknown function. Physical Association[23]
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[25]
MTUS2 Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules. Direct Interaction[26]
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[27]

Clinical significance

Mutations in CCDC60 have been associated with decreased walking speed.[28] Additionally, CCDC60 is one of many candidate genes that has been associated with diagnosis of schizophrenia in genome-wide study.[29]

References
  1. GRCh38: Ensembl release 89: ENSG00000183273 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000043913 - 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. She X, Rohl CA, Castle JC, Kulkarni AV, Johnson JM, Chen R (June 2009). "Definition, conservation and epigenetics of housekeeping and tissue-enriched genes". BMC Genomics. 10 (1): 269. doi:10.1186/1471-2164-10-269. PMC 2706266. PMID 19534766.
  6. "Homo sapiens coiled-coil domain containing 60 (CCDC60), mRNA". 2018-12-29. Cite journal requires |journal= (help)
  7. Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D (June 2002). "The human genome browser at UCSC". Genome Research. 12 (6): 996–1006. doi:10.1101/gr.229102. PMC 186604. PMID 12045153.
  8. Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJ (June 2015). "The Phyre2 web portal for protein modeling, prediction and analysis". Nature Protocols. 10 (6): 845–58. doi:10.1038/nprot.2015.053. PMC 5298202. PMID 25950237.
  9. "coiled-coil domain-containing protein 60 [Homo sapiens] - Protein - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2019-03-04.
  10. Bjellqvist B, Hughes GJ, Pasquali C, Paquet N, Ravier F, Sanchez JC, Frutiger S, Hochstrasser D (October 1993). "The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences". Electrophoresis. 14 (10): 1023–31. doi:10.1002/elps.11501401163. PMID 8125050. S2CID 38041111.
  11. "Anti-CCDC60 antibody produced in rabbit HPA039048". Immunohistochemistry, Western. Retrieved 2019-05-12.
  12. Emanuelsson O, Nielsen H, Brunak S, von Heijne G (July 2000). "Predicting subcellular localization of proteins based on their N-terminal amino acid sequence". Journal of Molecular Biology. 300 (4): 1005–16. doi:10.1006/jmbi.2000.3903. PMID 10891285.
  13. Klausen MS, Jespersen MC, Nielsen H, Jensen KK, Jurtz VI, Sønderby CK, Sommer MO, Winther O, Nielsen M, Petersen B, Marcatili P (June 2019). "NetSurfP-2.0: Improved prediction of protein structural features by integrated deep learning". Proteins. 87 (6): 520–527. bioRxiv 10.1101/311209. doi:10.1002/prot.25674. PMID 30785653. S2CID 216629401.
  14. "CCDC60 Top Ten Tissues". Genevisible.
  15. "Experiment < Expression Atlas < EMBL-EBI". www.ebi.ac.uk. Retrieved 2019-05-12.
  16. Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, Klingenhoff A, Frisch M, Bayerlein M, Werner T (July 2005). "MatInspector and beyond: promoter analysis based on transcription factor binding sites". Bioinformatics. 21 (13): 2933–42. doi:10.1093/bioinformatics/bti473. PMID 15860560.
  17. Blom N, Sicheritz-Pontén T, Gupta R, Gammeltoft S, Brunak S (June 2004). "Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence". Proteomics. 4 (6): 1633–49. doi:10.1002/pmic.200300771. PMID 15174133. S2CID 18810164.
  18. Charpilloz C, Veuthey AL, Chopard B, Falcone JL (July 2014). "Motifs tree: a new method for predicting post-translational modifications" (PDF). Bioinformatics. 30 (14): 1974–82. doi:10.1093/bioinformatics/btu165. PMID 24681905.
  19. "TimeTree - The Timescale of Life". TimeTree. Archived from the original on 13 May 2019. Retrieved 12 May 2019.
  20. "Protein BLAST: search protein databases using a protein query". blast.ncbi.nlm.nih.gov. Retrieved 2019-05-12.
  21. "PSICQUIC View". www.ebi.ac.uk. Retrieved 2019-05-12.
  22. "UniProt". www.uniprot.org. Retrieved 2019-05-12.
  23. Huttlin EL, Bruckner RJ, Paulo JA, Cannon JR, Ting L, Baltier K, et al. (May 2017). "Architecture of the human interactome defines protein communities and disease networks". Nature. 545 (7655): 505–509. Bibcode:2017Natur.545..505H. doi:10.1038/nature22366. PMC 5531611. PMID 28514442.
  24. Yao Z, Darowski K, St-Denis N, Wong V, Offensperger F, Villedieu A, et al. (January 2017). "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. PMC 5663465. PMID 28065597.
  25. Oláh J, Vincze O, Virók D, Simon D, Bozsó Z, Tõkési N, Horváth I, Hlavanda E, Kovács J, Magyar A, Szũcs M, Orosz F, Penke B, Ovádi J (September 2011). "Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein". The Journal of Biological Chemistry. 286 (39): 34088–100. doi:10.1074/jbc.M111.243907. PMC 3190826. PMID 21832049.
  26. Rolland T, Taşan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, et al. (November 2014). "A proteome-scale map of the human interactome network". Cell. 159 (5): 1212–1226. doi:10.1016/j.cell.2014.10.050. PMC 4266588. PMID 25416956.
  27. Dowdle WE, Robinson JF, Kneist A, Sirerol-Piquer MS, Frints SG, Corbit KC, Zaghloul NA, Zaghloul NA, van Lijnschoten G, Mulders L, Verver DE, Zerres K, Reed RR, Attié-Bitach T, Johnson CA, García-Verdugo JM, Katsanis N, Bergmann C, Reiter JF (July 2011). "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. PMC 3135817. PMID 21763481.
  28. Lunetta KL, D'Agostino RB, Karasik D, Benjamin EJ, Guo CY, Govindaraju R, Kiel DP, Kelly-Hayes M, Massaro JM, Pencina MJ, Seshadri S, Murabito JM (September 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 (Suppl 1): S13. doi:10.1186/1471-2350-8-s1-s13. PMC 1995604. PMID 17903295.
  29. Kirov G, Zaharieva I, Georgieva L, Moskvina V, Nikolov I, Cichon S, Hillmer A, Toncheva D, Owen MJ, O'Donovan MC (August 2009). "A genome-wide association study in 574 schizophrenia trios using DNA pooling". Molecular Psychiatry. 14 (8): 796–803. doi:10.1038/mp.2008.33. PMID 18332876. S2CID 7969539.
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