Ccdc60

Last updated
CCDC60
Identifiers
Aliases CCDC60 , coiled-coil domain containing 60
External IDs MGI: 2141043; HomoloGene: 18624; GeneCards: CCDC60; OMA:CCDC60 - orthologs
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
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 Mb Chr 5: 116.26 – 116.43 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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]

Contents

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. CCDC60 Structure.png
Predicted structure of CCDC60.

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
FamilyDescription
CAATCCAAT binding factor
XBBFX-box binding factor
MZF1Myeloid zinc finger 1 factor
EGRFWilms tumor suppressor
KLFSKrueppel-like factor 2 (lung) (LKLF)
ZFO2C2H2 zinc finger transcription factor 2
CALMCalmodulin-binding transcription activator (CAMTA1, CAMTA2)
SORYSRY (sex determining region Y)
SAL1Spalt-like transcription factor 1
VTBPVertebrate TATA binding protein factor
RUSHSWI/SNF related, actin dependent regulator of chromatin, subfamily a, member 3
ETSFHuman and murine ETS1 factors
HANDTwist subfamily of class B bHLH transcription factor
HESFBasic helix-loop-helix protein known as Dec2, Sharp1 or BHLHE41
ZFHXTwo-handed zinc finger homeodomain transcription factor
CARTCart-1 (cartilage homeoprotein 1)
HEATHeat 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
OrganismTaxonomic GroupDivergence (MYA) [19] Accession NumberSequence LengthShared Sequence Identity [20]
Human Hominidae 0 NP_848594.2 550100%
Philippine tarsier Tarsiidae 67 XP_008067500.1 55977.29%
Gray mouse lemur Lemuriformes 73 XP_012612137.1 54877.60%
Yellow-bellied marmot Rodentia 90 XP_027779037.1 55976.32%
Sea otter Carnivora 96 XP_022373045.1 54884.90%
Florida Manatee Placentalia 105 XP_004379174.1 55183.64%
Common wombat Marsupialia 159 XP_027721296.1 56462.86%
Southern Ostrich Aves 312 XP_009685824.1 48937.03%
Bald eagle Aves 320 XP_010573943.1 66132.02%
High Himalaya Frog Amphibia 352 XP_018413991.1 54037.31%
Western clawed frog Amphibia 352 XP_012824143.1 65732.70%
Yellowhead Catfish Osteichthyes 435 XP_027018543.1 57726.93%
Whale Shark Chondrichthyes 473 XP_020385120.1 67234.87%
Sea Vase Ascidiacea 676 XP_009860110.2 81828.31%
Acorn Worm Hemichordata 684 XP_006811258.1 73327.87%
Pacific Purple Sea UrchinEchinoidea684 XP_011683370.1 79123.76%
California two-spot octopus Mollusca 797 XP_014780749.1 68927.05%
Mountainous Star Coral Cnidaria 824 XP_020617162.1 86431.28%
Trichoplax Placozoa 948 XP_002117053.1 124734.84%
Sponge Porifera 952 XP_011405574.2 56922.87%

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
ProteinFunction [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]
FAM204AUnknown 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]
MTUS2Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules.Direct Interaction [26]
B9D1Component 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. 1 2 3 GRCh38: Ensembl release 89: ENSG00000183273 Ensembl, May 2017
  2. 1 2 3 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. 1 2 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. 1 2 "Homo sapiens coiled-coil domain containing 60 (CCDC60), mRNA". 2018-12-29.{{cite journal}}: Cite journal requires |journal= (help)
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  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.
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  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.
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  21. "PSICQUIC View". www.ebi.ac.uk. Retrieved 2019-05-12.
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  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.
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  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.
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  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.