CDK8_HUMAN
ID CDK8_HUMAN Reviewed; 464 AA.
AC P49336; Q5VUF3; Q6ISB5;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Cyclin-dependent kinase 8;
DE EC=2.7.11.22;
DE EC=2.7.11.23;
DE AltName: Full=Cell division protein kinase 8;
DE AltName: Full=Mediator complex subunit CDK8;
DE AltName: Full=Mediator of RNA polymerase II transcription subunit CDK8;
DE AltName: Full=Protein kinase K35;
GN Name=CDK8;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=7568034; DOI=10.1073/pnas.92.19.8871;
RA Tassan J.-P., Jaquenoud M., Leopold P., Schultz S.J., Nigg E.A.;
RT "Identification of human cyclin-dependent kinase 8, a putative protein
RT kinase partner for cyclin C.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:8871-8875(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR
RP COMPLEX.
RX PubMed=9734358; DOI=10.1016/s1097-2765(00)80131-8;
RA Sun X., Zhang Y., Cho H., Rickert P., Lees E., Lane W.S., Reinberg D.;
RT "NAT, a human complex containing Srb polypeptides that functions as a
RT negative regulator of activated transcription.";
RL Mol. Cell 2:213-222(1998).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE SMCC
RP COMPLEX.
RX PubMed=10024883; DOI=10.1016/s1097-2765(00)80178-1;
RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E.,
RA Qin J., Roeder R.G.;
RT "A novel human SRB/MED-containing cofactor complex, SMCC, involved in
RT transcription regulation.";
RL Mol. Cell 3:97-108(1999).
RN [7]
RP ERRATUM OF PUBMED:10024883.
RA Gu W., Malik S., Ito M., Yuan C.-X., Fondell J.D., Zhang X., Martinez E.,
RA Qin J., Roeder R.G.;
RL Mol. Cell 3:541-541(1999).
RN [8]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-173.
RX PubMed=10993082; DOI=10.1038/35024111;
RA Akoulitchev S., Chuikov S., Reinberg D.;
RT "TFIIH is negatively regulated by cdk8-containing mediator complexes.";
RL Nature 407:102-106(2000).
RN [9]
RP FUNCTION, AND INTERACTION WITH MAML1.
RX PubMed=15546612; DOI=10.1016/j.molcel.2004.10.014;
RA Fryer C.J., White J.B., Jones K.A.;
RT "Mastermind recruits CycC:CDK8 to phosphorylate the Notch ICD and
RT coordinate activation with turnover.";
RL Mol. Cell 16:509-520(2004).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND IDENTIFICATION IN THE MEDIATOR
RP COMPLEX.
RX PubMed=15175163; DOI=10.1016/j.molcel.2004.05.006;
RA Sato S., Tomomori-Sato C., Parmely T.J., Florens L., Zybailov B.,
RA Swanson S.K., Banks C.A.S., Jin J., Cai Y., Washburn M.P., Conaway J.W.,
RA Conaway R.C.;
RT "A set of consensus mammalian mediator subunits identified by
RT multidimensional protein identification technology.";
RL Mol. Cell 14:685-691(2004).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY, IDENTIFICATION IN THE MEDIATOR
RP COMPLEX, AND ASSOCIATION OF THE MEDIATOR COMPLEX WITH RNA POLYMERASE II.
RX PubMed=15989967; DOI=10.1016/j.molcel.2005.05.015;
RA Zhang X., Krutchinsky A., Fukuda A., Chen W., Yamamura S., Chait B.T.,
RA Roeder R.G.;
RT "MED1/TRAP220 exists predominantly in a TRAP/Mediator subpopulation
RT enriched in RNA polymerase II and is required for ER-mediated
RT transcription.";
RL Mol. Cell 19:89-100(2005).
RN [12]
RP INTERACTION WITH CTNNB1; GLI3; MED1; MED6; MED12 AND MED23.
RX PubMed=17000779; DOI=10.1128/mcb.00443-06;
RA Zhou H., Kim S., Ishii S., Boyer T.G.;
RT "Mediator modulates Gli3-dependent Sonic hedgehog signaling.";
RL Mol. Cell. Biol. 26:8667-8682(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [14]
RP INVOLVEMENT IN IDDHBA, VARIANTS IDDHBA LEU-27; GLY-29; SER-30; LEU-62;
RP LEU-97; GLN-178; GLY-193 AND MET-223, CHARACTERIZATION OF VARIANTS IDDHBA
RP LEU-27; GLY-29; SER-30; LEU-62; GLN-178; GLY-193 AND MET-223, FUNCTION, AND
RP MUTAGENESIS OF ASP-173.
RX PubMed=30905399; DOI=10.1016/j.ajhg.2019.02.006;
RG Deciphering Developmental Disorders Study;
RA Calpena E., Hervieu A., Kaserer T., Swagemakers S.M.A., Goos J.A.C.,
RA Popoola O., Ortiz-Ruiz M.J., Barbaro-Dieber T., Bownass L., Brilstra E.H.,
RA Brimble E., Foulds N., Grebe T.A., Harder A.V.E., Lees M.M., Monaghan K.G.,
RA Newbury-Ecob R.A., Ong K.R., Osio D., Reynoso Santos F.J.,
RA Ruzhnikov M.R.Z., Telegrafi A., van Binsbergen E., van Dooren M.F.,
RA van der Spek P.J., Blagg J., Twigg S.R.F., Mathijssen I.M.J., Clarke P.A.,
RA Wilkie A.O.M.;
RT "De Novo Missense Substitutions in the Gene Encoding CDK8, a Regulator of
RT the Mediator Complex, Cause a Syndromic Developmental Disorder.";
RL Am. J. Hum. Genet. 104:709-720(2019).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 1-403 IN COMPLEX WITH CCNC AND
RP INHIBITOR.
RX PubMed=21806996; DOI=10.1016/j.jmb.2011.07.020;
RA Schneider E.V., Bottcher J., Blaesse M., Neumann L., Huber R., Maskos K.;
RT "The structure of CDK8/CycC implicates specificity in the CDK/cyclin family
RT and reveals interaction with a deep pocket binder.";
RL J. Mol. Biol. 412:251-266(2011).
RN [16]
RP VARIANTS [LARGE SCALE ANALYSIS] ASN-189 AND CYS-424.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Component of the Mediator complex, a coactivator involved in
CC regulated gene transcription of nearly all RNA polymerase II-dependent
CC genes. Mediator functions as a bridge to convey information from gene-
CC specific regulatory proteins to the basal RNA polymerase II
CC transcription machinery. Mediator is recruited to promoters by direct
CC interactions with regulatory proteins and serves as a scaffold for the
CC assembly of a functional pre-initiation complex with RNA polymerase II
CC and the general transcription factors. Phosphorylates the CTD (C-
CC terminal domain) of the large subunit of RNA polymerase II (RNAp II),
CC which may inhibit the formation of a transcription initiation complex.
CC Phosphorylates CCNH leading to down-regulation of the TFIIH complex and
CC transcriptional repression. Recruited through interaction with MAML1 to
CC hyperphosphorylate the intracellular domain of NOTCH, leading to its
CC degradation. {ECO:0000269|PubMed:10993082, ECO:0000269|PubMed:15546612,
CC ECO:0000269|PubMed:30905399}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC Evidence={ECO:0000269|PubMed:10993082};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22; Evidence={ECO:0000269|PubMed:10993082};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho-
CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA-
CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.23;
CC Evidence={ECO:0000269|PubMed:10993082};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- SUBUNIT: Component of the Mediator complex, which is composed of MED1,
CC MED4, MED6, MED7, MED8, MED9, MED10, MED11, MED12, MED13, MED13L,
CC MED14, MED15, MED16, MED17, MED18, MED19, MED20, MED21, MED22, MED23,
CC MED24, MED25, MED26, MED27, MED29, MED30, MED31, CCNC, CDK8 and
CC CDC2L6/CDK11. The MED12, MED13, CCNC and CDK8 subunits form a distinct
CC module termed the CDK8 module. Mediator containing the CDK8 module is
CC less active than Mediator lacking this module in supporting
CC transcriptional activation. Individual preparations of the Mediator
CC complex lacking one or more distinct subunits have been variously
CC termed ARC, CRSP, DRIP, PC2, SMCC and TRAP. The cylin/CDK pair formed
CC by CCNC/CDK8 also associates with the large subunit of RNA polymerase
CC II. Interacts with CTNNB1, GLI3 and MAML1.
CC {ECO:0000269|PubMed:10024883, ECO:0000269|PubMed:15175163,
CC ECO:0000269|PubMed:15546612, ECO:0000269|PubMed:15989967,
CC ECO:0000269|PubMed:17000779, ECO:0000269|PubMed:21806996,
CC ECO:0000269|PubMed:9734358}.
CC -!- INTERACTION:
CC P49336; P24863: CCNC; NbExp=37; IntAct=EBI-394377, EBI-395261;
CC P49336; Q01094: E2F1; NbExp=3; IntAct=EBI-394377, EBI-448924;
CC P49336-2; P02489: CRYAA; NbExp=3; IntAct=EBI-11039720, EBI-6875961;
CC P49336-2; Q14204: DYNC1H1; NbExp=3; IntAct=EBI-11039720, EBI-356015;
CC P49336-2; Q92876: KLK6; NbExp=3; IntAct=EBI-11039720, EBI-2432309;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P49336-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P49336-2; Sequence=VSP_029970;
CC -!- DISEASE: Intellectual developmental disorder with hypotonia and
CC behavioral abnormalities (IDDHBA) [MIM:618748]: An autosomal dominant
CC neurodevelopmental disorder with onset in infancy. IDDHBA is
CC characterized by hypotonia, global developmental delay, learning
CC disability, and behavioral abnormalities, such as autistic features and
CC attention deficit-hyperactivity disorder. Additional variable features
CC may include non-specific facial dysmorphism, congenital heart defects,
CC ocular anomalies, and poor feeding. {ECO:0000269|PubMed:30905399}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; X85753; CAA59754.1; -; mRNA.
DR EMBL; AL159159; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL590108; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471075; EAX08386.1; -; Genomic_DNA.
DR EMBL; CH471075; EAX08387.1; -; Genomic_DNA.
DR EMBL; BC069634; AAH69634.1; -; mRNA.
DR EMBL; BC104492; AAI04493.1; -; mRNA.
DR EMBL; BC105950; AAI05951.1; -; mRNA.
DR EMBL; BC107601; AAI07602.1; -; mRNA.
DR CCDS; CCDS9317.1; -. [P49336-1]
DR PIR; I37227; I37227.
DR RefSeq; NP_001251.1; NM_001260.2. [P49336-1]
DR RefSeq; NP_001305297.1; NM_001318368.1. [P49336-2]
DR PDB; 3RGF; X-ray; 2.20 A; A=1-403.
DR PDB; 4CRL; X-ray; 2.40 A; A=1-403.
DR PDB; 4F6S; X-ray; 2.60 A; A=1-403.
DR PDB; 4F6U; X-ray; 2.10 A; A=1-403.
DR PDB; 4F6W; X-ray; 2.39 A; A=1-403.
DR PDB; 4F70; X-ray; 3.00 A; A=1-403.
DR PDB; 4F7J; X-ray; 2.60 A; A=1-403.
DR PDB; 4F7L; X-ray; 2.90 A; A=1-403.
DR PDB; 4F7N; X-ray; 2.65 A; A=1-403.
DR PDB; 4F7S; X-ray; 2.20 A; A=1-403.
DR PDB; 4G6L; X-ray; 2.70 A; A=1-403.
DR PDB; 5BNJ; X-ray; 2.64 A; A=1-403.
DR PDB; 5CEI; X-ray; 2.24 A; A=1-403.
DR PDB; 5FGK; X-ray; 2.36 A; A=1-362.
DR PDB; 5HBE; X-ray; 2.38 A; A=1-362.
DR PDB; 5HBH; X-ray; 2.50 A; A=1-362.
DR PDB; 5HBJ; X-ray; 3.00 A; A=1-362.
DR PDB; 5HNB; X-ray; 2.35 A; A=1-362.
DR PDB; 5HVY; X-ray; 2.39 A; A=1-403.
DR PDB; 5I5Z; X-ray; 2.60 A; A=1-362.
DR PDB; 5ICP; X-ray; 2.18 A; A=1-362.
DR PDB; 5IDN; X-ray; 2.26 A; A=1-364.
DR PDB; 5IDP; X-ray; 2.65 A; A=1-364.
DR PDB; 5XQX; X-ray; 2.30 A; A=1-371.
DR PDB; 5XS2; X-ray; 2.04 A; A=1-371.
DR PDB; 6QTG; X-ray; 2.70 A; A=1-403.
DR PDB; 6QTJ; X-ray; 2.48 A; A=1-403.
DR PDB; 6R3S; X-ray; 2.19 A; A=1-403.
DR PDB; 6T41; X-ray; 2.45 A; A=1-404.
DR PDB; 6TPA; X-ray; 2.80 A; A=1-403.
DR PDB; 6Y0A; X-ray; 2.19 A; A=1-403.
DR PDBsum; 3RGF; -.
DR PDBsum; 4CRL; -.
DR PDBsum; 4F6S; -.
DR PDBsum; 4F6U; -.
DR PDBsum; 4F6W; -.
DR PDBsum; 4F70; -.
DR PDBsum; 4F7J; -.
DR PDBsum; 4F7L; -.
DR PDBsum; 4F7N; -.
DR PDBsum; 4F7S; -.
DR PDBsum; 4G6L; -.
DR PDBsum; 5BNJ; -.
DR PDBsum; 5CEI; -.
DR PDBsum; 5FGK; -.
DR PDBsum; 5HBE; -.
DR PDBsum; 5HBH; -.
DR PDBsum; 5HBJ; -.
DR PDBsum; 5HNB; -.
DR PDBsum; 5HVY; -.
DR PDBsum; 5I5Z; -.
DR PDBsum; 5ICP; -.
DR PDBsum; 5IDN; -.
DR PDBsum; 5IDP; -.
DR PDBsum; 5XQX; -.
DR PDBsum; 5XS2; -.
DR PDBsum; 6QTG; -.
DR PDBsum; 6QTJ; -.
DR PDBsum; 6R3S; -.
DR PDBsum; 6T41; -.
DR PDBsum; 6TPA; -.
DR PDBsum; 6Y0A; -.
DR AlphaFoldDB; P49336; -.
DR SMR; P49336; -.
DR BioGRID; 107458; 215.
DR ComplexPortal; CPX-1969; Cyclin C-CDK8 complex.
DR ComplexPortal; CPX-3232; CKM complex variant 1.
DR CORUM; P49336; -.
DR DIP; DIP-32595N; -.
DR IntAct; P49336; 197.
DR MINT; P49336; -.
DR STRING; 9606.ENSP00000370938; -.
DR BindingDB; P49336; -.
DR ChEMBL; CHEMBL5719; -.
DR DrugBank; DB03496; Alvocidib.
DR DrugCentral; P49336; -.
DR GuidetoPHARMACOLOGY; 1980; -.
DR GlyGen; P49336; 3 sites, 1 O-linked glycan (3 sites).
DR iPTMnet; P49336; -.
DR PhosphoSitePlus; P49336; -.
DR BioMuta; CDK8; -.
DR DMDM; 1345718; -.
DR EPD; P49336; -.
DR jPOST; P49336; -.
DR MassIVE; P49336; -.
DR MaxQB; P49336; -.
DR PaxDb; P49336; -.
DR PeptideAtlas; P49336; -.
DR PRIDE; P49336; -.
DR ProteomicsDB; 55991; -. [P49336-1]
DR ProteomicsDB; 55992; -. [P49336-2]
DR Antibodypedia; 7248; 461 antibodies from 37 providers.
DR DNASU; 1024; -.
DR Ensembl; ENST00000381527.8; ENSP00000370938.3; ENSG00000132964.12. [P49336-1]
DR GeneID; 1024; -.
DR KEGG; hsa:1024; -.
DR MANE-Select; ENST00000381527.8; ENSP00000370938.3; NM_001260.3; NP_001251.1.
DR UCSC; uc001uqr.2; human. [P49336-1]
DR CTD; 1024; -.
DR DisGeNET; 1024; -.
DR GeneCards; CDK8; -.
DR HGNC; HGNC:1779; CDK8.
DR HPA; ENSG00000132964; Low tissue specificity.
DR MalaCards; CDK8; -.
DR MIM; 603184; gene.
DR MIM; 618748; phenotype.
DR neXtProt; NX_P49336; -.
DR OpenTargets; ENSG00000132964; -.
DR PharmGKB; PA26315; -.
DR VEuPathDB; HostDB:ENSG00000132964; -.
DR eggNOG; KOG0666; Eukaryota.
DR GeneTree; ENSGT00940000157104; -.
DR HOGENOM; CLU_000288_181_6_1; -.
DR InParanoid; P49336; -.
DR OMA; VYLHRNW; -.
DR OrthoDB; 642369at2759; -.
DR PhylomeDB; P49336; -.
DR TreeFam; TF101025; -.
DR BRENDA; 2.7.11.22; 2681.
DR BRENDA; 2.7.11.23; 2681.
DR PathwayCommons; P49336; -.
DR Reactome; R-HSA-1989781; PPARA activates gene expression.
DR Reactome; R-HSA-2122947; NOTCH1 Intracellular Domain Regulates Transcription.
DR Reactome; R-HSA-212436; Generic Transcription Pathway.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants.
DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR SignaLink; P49336; -.
DR SIGNOR; P49336; -.
DR BioGRID-ORCS; 1024; 41 hits in 1043 CRISPR screens.
DR ChiTaRS; CDK8; human.
DR GeneWiki; Cyclin-dependent_kinase_8; -.
DR GenomeRNAi; 1024; -.
DR Pharos; P49336; Tchem.
DR PRO; PR:P49336; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P49336; protein.
DR Bgee; ENSG00000132964; Expressed in adrenal tissue and 206 other tissues.
DR ExpressionAtlas; P49336; baseline and differential.
DR Genevisible; P49336; HS.
DR GO; GO:0016592; C:mediator complex; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; IMP:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; ATP-binding;
KW Autism spectrum disorder; Disease variant; Intellectual disability; Kinase;
KW Nucleotide-binding; Nucleus; Reference proteome; Repressor;
KW Serine/threonine-protein kinase; Transcription; Transcription regulation;
KW Transferase.
FT CHAIN 1..464
FT /note="Cyclin-dependent kinase 8"
FT /id="PRO_0000085797"
FT DOMAIN 21..335
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..15
FT /note="Interaction with CCNC"
FT REGION 361..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..398
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 412..464
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 151
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 27..35
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 370
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_029970"
FT VARIANT 27
FT /note="V -> L (in IDDHBA; decreased protein kinase
FT activity)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083786"
FT VARIANT 29
FT /note="R -> G (in IDDHBA; decreased protein kinase
FT activity; dbSNP:rs1593218885)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083787"
FT VARIANT 30
FT /note="G -> S (in IDDHBA; decreased protein kinase
FT activity; dbSNP:rs1593218890)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083788"
FT VARIANT 62
FT /note="S -> L (in IDDHBA; decreased protein kinase
FT activity; dbSNP:rs1565977796)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083789"
FT VARIANT 97
FT /note="F -> L (in IDDHBA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083790"
FT VARIANT 178
FT /note="R -> Q (in IDDHBA; decreased protein kinase
FT activity; dbSNP:rs1418353379)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083791"
FT VARIANT 189
FT /note="D -> N (in a lung neuroendocrine carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041980"
FT VARIANT 193
FT /note="V -> G (in IDDHBA; decreased protein kinase
FT activity)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083792"
FT VARIANT 223
FT /note="I -> M (in IDDHBA; decreased protein kinase
FT activity; dbSNP:rs1593310364)"
FT /evidence="ECO:0000269|PubMed:30905399"
FT /id="VAR_083793"
FT VARIANT 424
FT /note="R -> C (in a colorectal adenocarcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041981"
FT MUTAGEN 173
FT /note="D->A: Abrogates kinase activity and TFIIH-dependent
FT transcriptional repression."
FT /evidence="ECO:0000269|PubMed:10993082,
FT ECO:0000269|PubMed:30905399"
FT HELIX 3..12
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 16..19
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 26..30
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 33..44
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 49..58
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 61..72
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 83..87
FT /evidence="ECO:0007829|PDB:5XS2"
FT TURN 88..91
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 92..98
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 101..103
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 104..115
FT /evidence="ECO:0007829|PDB:5XS2"
FT TURN 116..118
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 125..144
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 154..156
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:5XS2"
FT TURN 164..167
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:5XS2"
FT TURN 174..178
FT /evidence="ECO:0007829|PDB:6TPA"
FT HELIX 179..181
FT /evidence="ECO:0007829|PDB:5ICP"
FT STRAND 186..188
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 202..205
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 213..229
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 249..259
FT /evidence="ECO:0007829|PDB:5XS2"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 268..272
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 276..282
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 285..288
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 293..299
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 307..315
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 320..322
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 326..330
FT /evidence="ECO:0007829|PDB:5XS2"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:5XS2"
FT STRAND 337..339
FT /evidence="ECO:0007829|PDB:5XS2"
FT TURN 345..348
FT /evidence="ECO:0007829|PDB:5XS2"
SQ SEQUENCE 464 AA; 53284 MW; 00CBAB6CE354605F CRC64;
MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA LKQIEGTGIS
MSACREIALL RELKHPNVIS LQKVFLSHAD RKVWLLFDYA EHDLWHIIKF HRASKANKKP
VQLPRGMVKS LLYQILDGIH YLHANWVLHR DLKPANILVM GEGPERGRVK IADMGFARLF
NSPLKPLADL DPVVVTFWYR APELLLGARH YTKAIDIWAI GCIFAELLTS EPIFHCRQED
IKTSNPYHHD QLDRIFNVMG FPADKDWEDI KKMPEHSTLM KDFRRNTYTN CSLIKYMEKH
KVKPDSKAFH LLQKLLTMDP IKRITSEQAM QDPYFLEDPL PTSDVFAGCQ IPYPKREFLT
EEEPDDKGDK KNQQQQQGNN HTNGTGHPGN QDSSHTQGPP LKKVRVVPPT TTSGGLIMTS
DYQRSNPHAA YPNPGPSTSQ PQSSMGYSAT SQQPPQYSHQ THRY
