CDK8_DROME
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 03-AUG-2022, entry version 171.
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; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; 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=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:0000250|UniProtKB:P49336, ECO:0000303|PubMed:8730095};
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:0000250|UniProtKB:P49336,
CC ECO:0000303|PubMed:8730095};
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;
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 -!- 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}.
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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 DIP; DIP-38574N; -.
DR IntAct; Q9VT57; 5.
DR MINT; Q9VT57; -.
DR STRING; 7227.FBpp0076098; -.
DR PaxDb; Q9VT57; -.
DR EnsemblMetazoa; FBtr0076369; FBpp0076098; FBgn0015618.
DR GeneID; 39157; -.
DR KEGG; dme:Dmel_CG10572; -.
DR CTD; 1024; -.
DR FlyBase; FBgn0015618; Cdk8.
DR VEuPathDB; VectorBase:FBgn0015618; -.
DR eggNOG; KOG0666; Eukaryota.
DR GeneTree; ENSGT00940000158213; -.
DR HOGENOM; CLU_000288_181_6_1; -.
DR InParanoid; Q9VT57; -.
DR OMA; VYLHRNW; -.
DR OrthoDB; 642369at2759; -.
DR PhylomeDB; Q9VT57; -.
DR BRENDA; 2.7.11.23; 1994.
DR Reactome; R-DME-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
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 secondary oocyte and 23 other tissues.
DR ExpressionAtlas; Q9VT57; baseline and differential.
DR Genevisible; Q9VT57; DM.
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:UniProtKB-KW.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0016301; F:kinase activity; IDA:FlyBase.
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: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:0010508; P:positive regulation of autophagy; 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 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; 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 356..372
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 373..406
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 417..454
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: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
