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 24-JAN-2024, entry version 159. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; CHEMBL5169178; -. DR GlyGen; Q8R3L8; 3 sites, 1 O-linked glycan (3 sites). DR PhosphoSitePlus; Q8R3L8; -. DR EPD; Q8R3L8; -. DR MaxQB; Q8R3L8; -. DR PaxDb; 10090-ENSMUSP00000031640; -. DR ProteomicsDB; 281352; -. [Q8R3L8-1] DR ProteomicsDB; 281353; -. [Q8R3L8-2] DR ProteomicsDB; 281354; -. [Q8R3L8-3] DR Pumba; Q8R3L8; -. DR Antibodypedia; 7248; 528 antibodies from 37 providers. DR DNASU; 264064; -. DR Ensembl; ENSMUST00000031640.15; ENSMUSP00000031640.9; ENSMUSG00000029635.16. [Q8R3L8-1] DR GeneID; 264064; -. DR KEGG; mmu:264064; -. DR UCSC; uc009and.1; mouse. [Q8R3L8-1] DR UCSC; uc009ane.1; mouse. [Q8R3L8-2] DR AGR; MGI:1196224; -. 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; YFKNGGP; -. DR OrthoDB; 46620at2759; -. DR PhylomeDB; Q8R3L8; -. DR TreeFam; TF101025; -. DR Reactome; R-MMU-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR BioGRID-ORCS; 264064; 3 hits in 81 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 258 other cell types or tissues. DR ExpressionAtlas; Q8R3L8; baseline and differential. DR GO; GO:1990508; C:CKM complex; ISO:MGI. 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:0000151; C:ubiquitin ligase complex; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IEA:UniProtKB-EC. DR GO; GO:0004672; F:protein kinase activity; ISS:UniProtKB. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central. DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:UniProtKB-EC. DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:Ensembl. DR GO; GO:0090209; P:negative regulation of triglyceride metabolic process; IEA:Ensembl. DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0016567; P:protein ubiquitination; IEA:Ensembl. DR CDD; cd07868; STKc_CDK8; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1. DR PANTHER; PTHR24056:SF243; CYCLIN-DEPENDENT KINASE 8; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; Q8R3L8; MM. 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 //