CCDC8_HUMAN
ID CCDC8_HUMAN Reviewed; 538 AA.
AC Q9H0W5; Q8TB26;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 2.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Coiled-coil domain-containing protein 8;
GN Name=CCDC8;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [4]
RP INTERACTION WITH OBSL1, TISSUE SPECIFICITY, AND INVOLVEMENT IN 3M3.
RX PubMed=21737058; DOI=10.1016/j.ajhg.2011.05.028;
RA Hanson D., Murray P.G., O'Sullivan J., Urquhart J., Daly S., Bhaskar S.S.,
RA Biesecker L.G., Skae M., Smith C., Cole T., Kirk J., Chandler K.,
RA Kingston H., Donnai D., Clayton P.E., Black G.C.;
RT "Exome sequencing identifies CCDC8 mutations in 3-M syndrome, Suggesting
RT that CCDC8 Contributes in a Pathway with CUL7 and OBSL1 to Control Human
RT Growth.";
RL Am. J. Hum. Genet. 89:148-153(2011).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-142 AND SER-146, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [6]
RP INVOLVEMENT IN 3M3.
RX PubMed=23018678; DOI=10.1530/jme-12-0034;
RA Hanson D., Murray P.G., Coulson T., Sud A., Omokanye A., Stratta E.,
RA Sakhinia F., Bonshek C., Wilson L.C., Wakeling E., Temtamy S.A., Aglan M.,
RA Rosser E.M., Mansour S., Carcavilla A., Nampoothiri S., Khan W.I.,
RA Banerjee I., Chandler K.E., Black G.C., Clayton P.E.;
RT "Mutations in CUL7, OBSL1 and CCDC8 in 3-M syndrome lead to disordered
RT growth factor signalling.";
RL J. Mol. Endocrinol. 49:267-275(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP FUNCTION, IDENTIFICATION IN THE 3M COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=24793695; DOI=10.1016/j.molcel.2014.03.047;
RA Yan J., Yan F., Li Z., Sinnott B., Cappell K.M., Yu Y., Mo J., Duncan J.A.,
RA Chen X., Cormier-Daire V., Whitehurst A.W., Xiong Y.;
RT "The 3M complex maintains microtubule and genome integrity.";
RL Mol. Cell 54:791-804(2014).
RN [10]
RP FUNCTION.
RX PubMed=24793696; DOI=10.1016/j.molcel.2014.03.046;
RA Li Z., Pei X.H., Yan J., Yan F., Cappell K.M., Whitehurst A.W., Xiong Y.;
RT "CUL9 mediates the functions of the 3M complex and ubiquitylates survivin
RT to maintain genome integrity.";
RL Mol. Cell 54:805-819(2014).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 494-510 IN COMPLEX WITH ANKRA2,
RP INTERACTION WITH ANKRA2, MUTAGENESIS OF PRO-503 AND THR-504, AND MOTIF.
RX PubMed=25752541; DOI=10.1016/j.str.2015.02.001;
RA Nie J., Xu C., Jin J., Aka J.A., Tempel W., Nguyen V., You L., Weist R.,
RA Min J., Pawson T., Yang X.J.;
RT "Ankyrin repeats of ANKRA2 recognize a PxLPxL motif on the 3M syndrome
RT protein CCDC8.";
RL Structure 23:700-712(2015).
CC -!- FUNCTION: Core component of the 3M complex, a complex required to
CC regulate microtubule dynamics and genome integrity. It is unclear how
CC the 3M complex regulates microtubules, it could act by controlling the
CC level of a microtubule stabilizer (PubMed:24793695, PubMed:24793696).
CC Required for localization of CUL7 to the centrosome (PubMed:24793695).
CC {ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:24793696}.
CC -!- SUBUNIT: Component of the 3M complex, composed of core components CUL7,
CC CCDC8 and OBSL1 (PubMed:21737058, PubMed:24793695). Interacts (via
CC PxLPxI/L motif) with ANKRA2 (via ankyrin repeats); may link the 3M
CC complex to histone deacetylases including HDAC4 and HDAC5
CC (PubMed:25752541). {ECO:0000269|PubMed:21737058,
CC ECO:0000269|PubMed:24793695, ECO:0000269|PubMed:25752541}.
CC -!- INTERACTION:
CC Q9H0W5; Q9H9E1: ANKRA2; NbExp=4; IntAct=EBI-5236005, EBI-10215533;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:24793695}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:24793695}.
CC -!- TISSUE SPECIFICITY: Widely expressed with low levels in spleen,
CC skeletal muscle, small intestine, kidney and liver.
CC {ECO:0000269|PubMed:21737058}.
CC -!- DOMAIN: The PxLPxI/L motif mediates interaction with ankyrin repeats of
CC ANKRA2. {ECO:0000269|PubMed:25752541}.
CC -!- DISEASE: 3M syndrome 3 (3M3) [MIM:614205]: A disorder characterized by
CC poor postnatal growth and distinctive facial features, including
CC triangular facies, frontal bossing, fleshy tipped nose, and fleshy
CC lips. Other features may include skeletal anomalies and prominent
CC heels. {ECO:0000269|PubMed:21737058, ECO:0000269|PubMed:23018678}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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DR EMBL; AL136609; CAB66544.1; -; mRNA.
DR EMBL; BC025243; AAH25243.1; -; mRNA.
DR CCDS; CCDS12685.1; -.
DR RefSeq; NP_114429.2; NM_032040.4.
DR PDB; 4LG6; X-ray; 1.80 A; B=494-510.
DR PDBsum; 4LG6; -.
DR AlphaFoldDB; Q9H0W5; -.
DR SMR; Q9H0W5; -.
DR BioGRID; 123838; 648.
DR CORUM; Q9H0W5; -.
DR DIP; DIP-60183N; -.
DR ELM; Q9H0W5; -.
DR IntAct; Q9H0W5; 19.
DR MINT; Q9H0W5; -.
DR STRING; 9606.ENSP00000303158; -.
DR CarbonylDB; Q9H0W5; -.
DR iPTMnet; Q9H0W5; -.
DR PhosphoSitePlus; Q9H0W5; -.
DR BioMuta; CCDC8; -.
DR DMDM; 116241287; -.
DR EPD; Q9H0W5; -.
DR jPOST; Q9H0W5; -.
DR MassIVE; Q9H0W5; -.
DR MaxQB; Q9H0W5; -.
DR PaxDb; Q9H0W5; -.
DR PeptideAtlas; Q9H0W5; -.
DR PRIDE; Q9H0W5; -.
DR ProteomicsDB; 80331; -.
DR Antibodypedia; 31453; 152 antibodies from 23 providers.
DR DNASU; 83987; -.
DR Ensembl; ENST00000307522.5; ENSP00000303158.3; ENSG00000169515.8.
DR GeneID; 83987; -.
DR KEGG; hsa:83987; -.
DR MANE-Select; ENST00000307522.5; ENSP00000303158.3; NM_032040.5; NP_114429.2.
DR UCSC; uc002pep.4; human.
DR CTD; 83987; -.
DR DisGeNET; 83987; -.
DR GeneCards; CCDC8; -.
DR GeneReviews; CCDC8; -.
DR HGNC; HGNC:25367; CCDC8.
DR HPA; ENSG00000169515; Tissue enhanced (ovary).
DR MalaCards; CCDC8; -.
DR MIM; 614145; gene.
DR MIM; 614205; phenotype.
DR neXtProt; NX_Q9H0W5; -.
DR OpenTargets; ENSG00000169515; -.
DR Orphanet; 2616; 3M syndrome.
DR PharmGKB; PA134931534; -.
DR VEuPathDB; HostDB:ENSG00000169515; -.
DR eggNOG; ENOG502S9UD; Eukaryota.
DR GeneTree; ENSGT01030000234522; -.
DR HOGENOM; CLU_025577_0_0_1; -.
DR InParanoid; Q9H0W5; -.
DR OMA; RFSWFRK; -.
DR OrthoDB; 1181293at2759; -.
DR PhylomeDB; Q9H0W5; -.
DR TreeFam; TF335054; -.
DR PathwayCommons; Q9H0W5; -.
DR Reactome; R-HSA-8951664; Neddylation.
DR SignaLink; Q9H0W5; -.
DR BioGRID-ORCS; 83987; 7 hits in 1078 CRISPR screens.
DR GeneWiki; CCDC8; -.
DR GenomeRNAi; 83987; -.
DR Pharos; Q9H0W5; Tbio.
DR PRO; PR:Q9H0W5; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q9H0W5; protein.
DR Bgee; ENSG00000169515; Expressed in kidney epithelium and 162 other tissues.
DR Genevisible; Q9H0W5; HS.
DR GO; GO:1990393; C:3M complex; IDA:UniProtKB.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:LIFEdb.
DR GO; GO:0000226; P:microtubule cytoskeleton organization; IMP:UniProtKB.
DR GO; GO:0007088; P:regulation of mitotic nuclear division; IMP:UniProtKB.
DR InterPro; IPR026523; PNMA.
DR Pfam; PF14893; PNMA; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Coiled coil; Cytoplasm; Cytoskeleton; Dwarfism;
KW Phosphoprotein; Reference proteome.
FT CHAIN 1..538
FT /note="Coiled-coil domain-containing protein 8"
FT /id="PRO_0000089401"
FT REGION 58..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 349..366
FT /evidence="ECO:0000255"
FT COILED 514..535
FT /evidence="ECO:0000255"
FT MOTIF 500..506
FT /note="PxLPxI/L motif; mediates interaction with ANKRA2"
FT /evidence="ECO:0000269|PubMed:25752541"
FT COMPBIAS 297..311
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..369
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 377..392
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..420
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 146
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 261
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163,
FT ECO:0007744|PubMed:24275569"
FT VARIANT 296
FT /note="G -> R (in dbSNP:rs11880658)"
FT /id="VAR_061587"
FT VARIANT 383
FT /note="H -> Y (in dbSNP:rs34186470)"
FT /id="VAR_061588"
FT VARIANT 507
FT /note="K -> N (in dbSNP:rs2279517)"
FT /id="VAR_020272"
FT MUTAGEN 503
FT /note="P->A: Decreased interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:25752541"
FT MUTAGEN 504
FT /note="T->A: Decreased interaction with ANKRA2."
FT /evidence="ECO:0000269|PubMed:25752541"
FT CONFLICT 515
FT /note="A -> V (in Ref. 1; CAB66544)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 538 AA; 59374 MW; EB33975190CD9E81 CRC64;
MLQIGEDVDY LLIPREVRLA GGVWRVISKP ATKEAEFRER LTQFLEEEGR TLEDVARIME
KSTPHPPQPP KKPKEPRVRR RVQQMVTPPP RLVVGTYDSS NASDSEFSDF ETSRDKSRQG
PRRGKKVRKM PVSYLGSKFL GSDLESEDDE ELVEAFLRRQ EKQPSAPPAR RRVNLPVPMF
EDNLGPQLSK ADRWREYVSQ VSWGKLKRRV KGWAPRAGPG VGEARLASTA VESAGVSSAP
EGTSPGDRLG NAGDVCVPQA SPRRWRPKIN WASFRRRRKE QTAPTGQGAD IEADQGGEAA
DSQREEAIAD QREGAAGNQR AGAPADQGAE AADNQREEAA DNQRAGAPAE EGAEAADNQR
EEAADNQRAE APADQRSQGT DNHREEAADN QRAEAPADQG SEVTDNQREE AVHDQRERAP
AVQGADNQRA QARAGQRAEA AHNQRAGAPG IQEAEVSAAQ GTTGTAPGAR ARKQVKTVRF
QTPGRFSWFC KRRRAFWHTP RLPTLPKRVP RAGEARNLRV LRAEARAEAE QGEQEDQL
