ID CDK8_DROME Reviewed; 454 AA. AC Q9VT57; P91642; Q8MS41; DT 02-FEB-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 2. DT 02-SEP-2026, entry version 186. 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 Short=DmCdk8; DE AltName: Full=Mediator complex subunit Cdk8; DE AltName: Full=Mediator of RNA polymerase II transcription subunit Cdk8; GN Name=Cdk8; ORFNames=CG10572; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida; OC Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota; OC Aparaglossata; Panorpida; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227 {ECO:0000312|EMBL:AAF50197.2}; RN [1] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION, SUBCELLULAR LOCATION, RP AND DEVELOPMENTAL STAGE. RC TISSUE=Embryo {ECO:0000269|PubMed:8730095}; RX PubMed=8730095; DOI=10.1091/mbc.7.4.505; RA Leclerc V., Tassan J.-P., O'Farrell P.H., Nigg E.A., Leopold P.; RT "Drosophila Cdk8, a kinase partner of cyclin C that interacts with the RT large subunit of RNA polymerase II."; RL Mol. Biol. Cell 7:505-513(1996). RN [2] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132}; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., RA Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [3] {ECO:0000305} RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [4] {ECO:0000305} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley {ECO:0000269|PubMed:12537569}; RC TISSUE=Embryo {ECO:0000269|PubMed:12537569}; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [5] RP FUNCTION, AND INTERACTION WITH CYCC; KTO AND SKD. RX PubMed=17290221; DOI=10.1038/sj.emboj.7601566; RA Loncle N., Boube M., Joulia L., Boschiero C., Werner M., Cribbs D.L., RA Bourbon H.-M.; RT "Distinct roles for Mediator Cdk8 module subunits in Drosophila RT development."; RL EMBO J. 26:1045-1054(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. May phosphorylate 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 Required for leg and eye development and macrochaete specification or CC differentiation. {ECO:0000269|PubMed:17290221, CC ECO:0000269|PubMed:8730095}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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:0000250|UniProtKB:P49336, ECO:0000303|PubMed:8730095}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.22; CC Evidence={ECO:0000250|UniProtKB:P49336, ECO:0000303|PubMed:8730095}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed CC RNA polymerase] + ADP + H(+); 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; CC Evidence={ECO:0000250|UniProtKB:P49336}; CC -!- SUBUNIT: Component of the Cdk8 module of the Mediator complex, composed CC of CycC, Cdk8, kto and skd. CC -!- INTERACTION: CC Q9VT57; P25008: CycC; NbExp=2; IntAct=EBI-163640, EBI-195485; CC Q9VT57; Q27368: E2f1; NbExp=2; IntAct=EBI-163640, EBI-108384; CC Q9VT57; Q9VW47: kto; NbExp=2; IntAct=EBI-163640, EBI-139710; CC Q9VT57; Q7KTX8: skd; NbExp=2; IntAct=EBI-163640, EBI-110730; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:8730095}. CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically during CC developmental periods of maximal cell division; most abundant in early CC embryos and low levels in larvae, pupae and adults. CC {ECO:0000269|PubMed:8730095}. 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; U33015; AAB38385.1; -; mRNA. DR EMBL; AE014296; AAF50197.2; -; Genomic_DNA. DR EMBL; AY119111; AAM50971.1; -; mRNA. DR RefSeq; NP_536735.2; NM_080487.4. DR AlphaFoldDB; Q9VT57; -. DR SMR; Q9VT57; -. DR BioGRID; 64544; 50. DR ComplexPortal; CPX-7701; CKM complex. DR DIP; DIP-38574N; -. DR FunCoup; Q9VT57; 2351. DR IntAct; Q9VT57; 52. DR MINT; Q9VT57; -. DR STRING; 7227.FBpp0076098; -. DR PaxDb; 7227-FBpp0076098; -. DR PeptideAtlas; Q9VT57; -. DR EnsemblMetazoa; FBtr0076369; FBpp0076098; FBgn0015618. DR GeneID; 39157; -. DR KEGG; dme:Dmel_CG10572; -. DR AGR; FB:FBgn0015618; -. DR CTD; 1024; -. DR FlyBase; FBgn0015618; Cdk8. DR VEuPathDB; VectorBase:FBgn0015618; -. DR eggNOG; KOG0666; Eukaryota. DR HOGENOM; CLU_000288_181_6_1; -. DR InParanoid; Q9VT57; -. DR OMA; SEMPRMD; -. DR OrthoDB; 6284126at2759; -. DR PhylomeDB; Q9VT57; -. DR BRENDA; 2.7.11.23; 1994. DR Reactome; R-DME-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription. DR Reactome; R-DME-9841922; MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis. DR SignaLink; Q9VT57; -. DR BioGRID-ORCS; 39157; 0 hits in 3 CRISPR screens. DR GenomeRNAi; 39157; -. DR PRO; PR:Q9VT57; -. DR Proteomes; UP000000803; Chromosome 3L. DR Bgee; FBgn0015618; Expressed in T neuron T5a (Drosophila) in embryonic/larval optic lobe (Drosophila) and 32 other cell types or tissues. DR ExpressionAtlas; Q9VT57; baseline and differential. DR GO; GO:1990508; C:CKM complex; IDA:FlyBase. DR GO; GO:0016592; C:mediator complex; IDA:FlyBase. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISS:FlyBase. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:FlyBase. DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IEA:UniProtKB-EC. DR GO; GO:0022416; P:chaeta development; IMP:FlyBase. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; IMP:UniProtKB. DR GO; GO:0036011; P:imaginal disc-derived leg segmentation; IMP:FlyBase. DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB. DR GO; GO:0045498; P:sex comb development; IMP:FlyBase. DR GO; GO:0034472; P:snRNA 3'-end processing; IDA:FlyBase. DR CDD; cd07842; STKc_CDK8_like; 1. DR FunFam; 1.10.510.10:FF:000088; cyclin-dependent kinase 8 isoform X1; 1. DR FunFam; 3.30.200.20:FF:000122; cyclin-dependent kinase 8 isoform X1; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR050108; CDK. 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:SF495; CYCLIN-DEPENDENT KINASE 8-RELATED; 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. PE 1: Evidence at protein level; KW Activator; ATP-binding; Kinase; Nucleotide-binding; Nucleus; KW Phosphoprotein; Reference proteome; Repressor; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase. FT CHAIN 1..454 FT /note="Cyclin-dependent kinase 8" FT /id="PRO_0000085798" FT DOMAIN 21..335 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 342..454 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 373..400 FT /note="Low complexity" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 424..454 FT /note="Low complexity" 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:0000250|UniProtKB:P49336, FT ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 52 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000250|UniProtKB:P49336, FT ECO:0000255|PROSITE-ProRule:PRU00159" FT CONFLICT 9 FT /note="T -> A (in Ref. 1; AAB38385)" FT /evidence="ECO:0000305" FT CONFLICT 15 FT /note="K -> N (in Ref. 1; AAB38385)" FT /evidence="ECO:0000305" FT CONFLICT 37 FT /note="K -> R (in Ref. 1; AAB38385)" FT /evidence="ECO:0000305" FT CONFLICT 40 FT /note="W -> R (in Ref. 1; AAB38385)" FT /evidence="ECO:0000305" FT CONFLICT 70 FT /note="L -> W (in Ref. 1; AAB38385)" FT /evidence="ECO:0000305" FT CONFLICT 185 FT /note="K -> R (in Ref. 4; AAM50971)" FT /evidence="ECO:0000305" FT CONFLICT 321 FT /note="N -> I (in Ref. 1; AAB38385)" FT /evidence="ECO:0000305" FT CONFLICT 336 FT /note="Q -> R (in Ref. 1; AAB38385)" FT /evidence="ECO:0000305" SQ SEQUENCE 454 AA; 53682 MW; D73F6219E2A03C98 CRC64; MDYDFKMKTQ IERTKVEDLF NYEGCKVGRG TYGHVYKAKW KETSDGKEYA LKQIDGTGLS MSACREIALL RELKHQNVIT LIRVFLSHND RKVFLLIDYA EHDLWHIIKF HRAAKATKKQ VVVPRGMVKS LLYQILDGIH YLHSNWVLHR DLKPANILVM GDGNERGRVK IADMGFARLF NAPLKPLADL DPVVVTFWYR APELLLGARH YTKAIDIWAI GCIFAELLTS EPIFHCRQED IKTSNPYHHD QLDRIFNVMG FPQDKDWEDI KKMPEHHTLT KDFKRSTYST CSLAKYMERH KIKPDSKAFH LLQKLLLMDP NKRITSEQAM QDQYFQEEPQ PTQDVFAGCP IPYPKREFLT DDDQEDKSDN KRQQQQQQQQ QQQQQQQQQQ QQQQQQQQQQ MNAEPNAKRV RLSGAGNQQD FHHQQQQQQQ QQQQQQQQQQ QMMFNQQQNF QRFN //