CDK8_MOUSE
ID CDK8_MOUSE Reviewed; 464 AA.
AC Q8R3L8;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 20-MAR-2007, sequence version 3.
DT 03-AUG-2022, entry version 151.
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;
GN Name=Cdk8;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Brain, and Mammary tumor;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 44-464 (ISOFORM 3).
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
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 (By similarity). {ECO:0000250|UniProtKB:P49336}.
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 -!- 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;
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 -!- 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 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q8R3L8; A2AGH6: Med12; NbExp=3; IntAct=EBI-5745402, EBI-5744969;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8R3L8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8R3L8-2; Sequence=VSP_023673, VSP_023674;
CC Name=3;
CC IsoId=Q8R3L8-3; Sequence=VSP_023675;
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; AC113316; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC025046; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; BC132551; AAI32552.1; -; mRNA.
DR EMBL; BC132553; AAI32554.1; -; mRNA.
DR EMBL; AK131948; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS19869.1; -. [Q8R3L8-1]
DR RefSeq; NP_705827.2; NM_153599.3. [Q8R3L8-1]
DR RefSeq; XP_006504899.1; XM_006504836.3. [Q8R3L8-3]
DR AlphaFoldDB; Q8R3L8; -.
DR SMR; Q8R3L8; -.
DR BioGRID; 234457; 4.
DR ComplexPortal; CPX-3266; CKM complex variant 1.
DR DIP; DIP-59235N; -.
DR IntAct; Q8R3L8; 7.
DR STRING; 10090.ENSMUSP00000031640; -.
DR BindingDB; Q8R3L8; -.
DR ChEMBL; CHEMBL4296068; -.
DR PhosphoSitePlus; Q8R3L8; -.
DR EPD; Q8R3L8; -.
DR MaxQB; Q8R3L8; -.
DR PaxDb; Q8R3L8; -.
DR PRIDE; Q8R3L8; -.
DR ProteomicsDB; 281352; -. [Q8R3L8-1]
DR ProteomicsDB; 281353; -. [Q8R3L8-2]
DR ProteomicsDB; 281354; -. [Q8R3L8-3]
DR Antibodypedia; 7248; 461 antibodies from 37 providers.
DR DNASU; 264064; -.
DR Ensembl; ENSMUST00000031640; ENSMUSP00000031640; ENSMUSG00000029635. [Q8R3L8-1]
DR GeneID; 264064; -.
DR KEGG; mmu:264064; -.
DR UCSC; uc009and.1; mouse. [Q8R3L8-1]
DR UCSC; uc009ane.1; mouse. [Q8R3L8-2]
DR CTD; 1024; -.
DR MGI; MGI:1196224; Cdk8.
DR VEuPathDB; HostDB:ENSMUSG00000029635; -.
DR eggNOG; KOG0666; Eukaryota.
DR GeneTree; ENSGT00940000157104; -.
DR HOGENOM; CLU_000288_181_6_1; -.
DR InParanoid; Q8R3L8; -.
DR OMA; VYLHRNW; -.
DR OrthoDB; 642369at2759; -.
DR PhylomeDB; Q8R3L8; -.
DR TreeFam; TF101025; -.
DR Reactome; R-MMU-212436; Generic Transcription Pathway.
DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR BioGRID-ORCS; 264064; 3 hits in 76 CRISPR screens.
DR ChiTaRS; Cdk8; mouse.
DR PRO; PR:Q8R3L8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q8R3L8; protein.
DR Bgee; ENSMUSG00000029635; Expressed in metanephric proximal tubule and 254 other tissues.
DR ExpressionAtlas; Q8R3L8; baseline and differential.
DR Genevisible; Q8R3L8; MM.
DR GO; GO:0016592; C:mediator complex; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO: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; ISS: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 Activator; Alternative splicing; ATP-binding; Kinase; Nucleotide-binding;
KW Nucleus; Reference proteome; Repressor; Serine/threonine-protein kinase;
KW Transcription; Transcription regulation; Transferase.
FT CHAIN 1..464
FT /note="Cyclin-dependent kinase 8"
FT /id="PRO_0000280443"
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 /evidence="ECO:0000250"
FT REGION 358..464
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 358..372
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..392
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 1..259
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023673"
FT VAR_SEQ 216..220
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_023675"
FT VAR_SEQ 260..263
FT /note="GFPA -> MYFT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_023674"
SQ SEQUENCE 464 AA; 53210 MW; D8E350486ADA3F8D CRC64;
MDYDFKVKLS SERERVEDLF EYEGCKVGRG TYGHVYKAKR KDGKDDKDYA LKQIEGTGIS
MSACREIALL RELKHPNVIS LLKVFLSHAD 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
EEEPDEKGDK KTQQQQQGNN HTNGTGHPGN QDSGHAQGPP LKKVRVVPPT TTSGGLIMTS
DYQRSNPHAA YPNPGPSTSQ PQSSMGYSAT SQQPPQYSHQ THRY
