Ccdc60 Explained

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.^[1]

Gene

The 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.

Protein

CCDC60 is made up of 550 amino acids.^[4] The computational isoelectric point of CCDC60 is 9.17 and the computational molecular weight is approximately 63kDa.^[5] Western blots of RT-4 and U-251 cell lines support the predicted molecular weight.^[6] The predicted subcellular location of CCDC60 is the mitochondria.^[7] The secondary structure of CCDC60 contains a namesake coiled-coil domain in addition to predicted alpha helices and coils.^[8]

Regulation

Gene expression

The expression of CCDC60 is tissue-specific. CCDC60 is most highly expressed in the trachea, salivary glands, bladder, cervix, and epididymis. CCDC60 is also expressed in epithelial cells of the upper respiratory system.^[9] 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.^[10]

Transcription factors

There are many candidate transcription factors that bind to the promoter region of the gene that encodes CCDC60.^[11]

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.^[12] The initial methionine residue is predicted to be cleaved from the polypeptide after translation.^[13]

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.

Organism

Taxonomic Group	Divergence (MYA)^[14]	Accession Number	Sequence Length	Shared Sequence Identity^[15]
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.^[16]

Protein

Function^[17]	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^[18]
ZNF593	Negatively modulates the DNA binding activity of Oct-2 and therefore its transcriptional regulatory activity.	Physical Association
FAM32A	Isoform 1, but not isoform 2 or isoform 3, may induce G2 arrest and apoptosis.	Physical Association
RBM42	Binds (via the RRM domain) to the 3'-untranslated region (UTR) of CDKN1A mRNA.	Physical Association
DCP1B	May play a role in the degradation of mRNAs, both in normal mRNA turnover and in nonsense-mediated mRNA decay.	Physical Association
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^[19]
FAM204A	Unknown function.	Physical Association
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^[20]
MTUS2	Binds microtubules. Together with MAPRE1 may target the microtubule depolymerase KIF2C to the plus-end of microtubules.	Direct Interaction^[21]
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^[22]

Clinical significance

Mutations in CCDC60 have been associated with decreased walking speed.^[23] Additionally, CCDC60 is one of many candidate genes that has been associated with diagnosis of schizophrenia in genome-wide study.^[24]

Notes and References

1. She X, Rohl CA, Castle JC, Kulkarni AV, Johnson JM, Chen R . Definition, conservation and epigenetics of housekeeping and tissue-enriched genes . BMC Genomics . 10 . 1 . 269 . June 2009 . 19534766 . 2706266 . 10.1186/1471-2164-10-269 . free .
2. 2018-12-29. Homo sapiens coiled-coil domain containing 60 (CCDC60), mRNA. en-US.
3. Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D . The human genome browser at UCSC . Genome Research . 12 . 6 . 996–1006 . June 2002 . 12045153 . 186604 . 10.1101/gr.229102 .
4. Web site: coiled-coil domain-containing protein 60 [Homo sapiens] - Protein - NCBI]. www.ncbi.nlm.nih.gov. 2019-03-04.
5. Bjellqvist B, Hughes GJ, Pasquali C, Paquet N, Ravier F, Sanchez JC, Frutiger S, Hochstrasser D . The focusing positions of polypeptides in immobilized pH gradients can be predicted from their amino acid sequences . Electrophoresis . 14 . 10 . 1023–31 . October 1993 . 8125050 . 10.1002/elps.11501401163 . 38041111 .
6. Web site: Anti-CCDC60 antibody produced in rabbit HPA039048. Immunohistochemistry, Western. 2019-05-12.
7. Emanuelsson O, Nielsen H, Brunak S, von Heijne G . Predicting subcellular localization of proteins based on their N-terminal amino acid sequence . Journal of Molecular Biology . 300 . 4 . 1005–16 . July 2000 . 10891285 . 10.1006/jmbi.2000.3903 .
8. Klausen MS, Jespersen MC, Nielsen H, Jensen KK, Jurtz VI, Sønderby CK, Sommer MO, Winther O, Nielsen M, Petersen B, Marcatili P . NetSurfP-2.0: Improved prediction of protein structural features by integrated deep learning . Proteins . 87 . 6 . 520–527 . June 2019 . 30785653 . 10.1002/prot.25674 . 10.1101/311209 . 216629401 .
9. Web site: CCDC60 Top Ten Tissues. Genevisible.
10. Web site: Experiment < Expression Atlas < EMBL-EBI. www.ebi.ac.uk. 2019-05-12.
11. Cartharius K, Frech K, Grote K, Klocke B, Haltmeier M, Klingenhoff A, Frisch M, Bayerlein M, Werner T . MatInspector and beyond: promoter analysis based on transcription factor binding sites . Bioinformatics . 21 . 13 . 2933–42 . July 2005 . 15860560 . 10.1093/bioinformatics/bti473 . free .
12. Blom N, Sicheritz-Pontén T, Gupta R, Gammeltoft S, Brunak S . Prediction of post-translational glycosylation and phosphorylation of proteins from the amino acid sequence . Proteomics . 4 . 6 . 1633–49 . June 2004 . 15174133 . 10.1002/pmic.200300771 . 18810164 .
13. Charpilloz C, Veuthey AL, Chopard B, Falcone JL . Motifs tree: a new method for predicting post-translational modifications . Bioinformatics . 30 . 14 . 1974–82 . July 2014 . 24681905 . 10.1093/bioinformatics/btu165 . free .
14. Web site: TimeTree - The Timescale of Life. TimeTree. https://web.archive.org/web/20190513131853/http://timetree.org/. 13 May 2019. 12 May 2019. dead.
15. Web site: Protein BLAST: search protein databases using a protein query. blast.ncbi.nlm.nih.gov. 2019-05-12.
16. Web site: PSICQUIC View. www.ebi.ac.uk. 2019-05-12.
17. Web site: UniProt. www.uniprot.org. 2019-05-12.
18. Huttlin EL, Bruckner RJ, Paulo JA, Cannon JR, Ting L, Baltier K, Colby G, Gebreab F, Gygi MP, Parzen H, Szpyt J, Tam S, Zarraga G, Pontano-Vaites L, Swarup S, White AE, Schweppe DK, Rad R, Erickson BK, Obar RA, Guruharsha KG, Li K, Artavanis-Tsakonas S, Gygi SP, Harper JW . 6 . Architecture of the human interactome defines protein communities and disease networks . Nature . 545 . 7655 . 505–509 . May 2017 . 28514442 . 5531611 . 10.1038/nature22366 . 2017Natur.545..505H .
19. Yao Z, Darowski K, St-Denis N, Wong V, Offensperger F, Villedieu A, Amin S, Malty R, Aoki H, Guo H, Xu Y, Iorio C, Kotlyar M, Emili A, Jurisica I, Neel BG, Babu M, Gingras AC, Stagljar I . 6 . A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome . Molecular Cell . 65 . 2 . 347–360 . January 2017 . 28065597 . 5663465 . 10.1016/j.molcel.2016.12.004 .
20. 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 . Interactions of pathological hallmark proteins: tubulin polymerization promoting protein/p25, beta-amyloid, and alpha-synuclein . The Journal of Biological Chemistry . 286 . 39 . 34088–100 . September 2011 . 21832049 . 3190826 . 10.1074/jbc.M111.243907 . free .
21. Rolland T, Taşan M, Charloteaux B, Pevzner SJ, Zhong Q, Sahni N, Yi S, Lemmens I, Fontanillo C, Mosca R, Kamburov A, Ghiassian SD, Yang X, Ghamsari L, Balcha D, Begg BE, Braun P, Brehme M, Broly MP, Carvunis AR, Convery-Zupan D, Corominas R, Coulombe-Huntington J, Dann E, Dreze M, Dricot A, Fan C, Franzosa E, Gebreab F, Gutierrez BJ, Hardy MF, Jin M, Kang S, Kiros R, Lin GN, Luck K, MacWilliams A, Menche J, Murray RR, Palagi A, Poulin MM, Rambout X, Rasla J, Reichert P, Romero V, Ruyssinck E, Sahalie JM, Scholz A, Shah AA, Sharma A, Shen Y, Spirohn K, Tam S, Tejeda AO, Trigg SA, Twizere JC, Vega K, Walsh J, Cusick ME, Xia Y, Barabási AL, Iakoucheva LM, Aloy P, De Las Rivas J, Tavernier J, Calderwood MA, Hill DE, Hao T, Roth FP, Vidal M . 6 . A proteome-scale map of the human interactome network . English . Cell . 159 . 5 . 1212–1226 . November 2014 . 25416956 . 4266588 . 10.1016/j.cell.2014.10.050 .
22. 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 . Disruption of a ciliary B9 protein complex causes Meckel syndrome . American Journal of Human Genetics . 89 . 1 . 94–110 . July 2011 . 21763481 . 3135817 . 10.1016/j.ajhg.2011.06.003 .
23. 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 . 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 . September 2007 . 17903295 . 1995604 . 10.1186/1471-2350-8-s1-s13 . free .
24. Kirov G, Zaharieva I, Georgieva L, Moskvina V, Nikolov I, Cichon S, Hillmer A, Toncheva D, Owen MJ, O'Donovan MC . A genome-wide association study in 574 schizophrenia trios using DNA pooling . Molecular Psychiatry . 14 . 8 . 796–803 . August 2009 . 18332876 . 10.1038/mp.2008.33 . 7969539 . free .