ID   CDK12_DROME             Reviewed;        1157 AA.
AC   Q9VP22; Q8T9E1; Q95SE1;
DT   26-MAY-2009, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   26-FEB-2020, entry version 159.
DE   RecName: Full=Cyclin-dependent kinase 12;
DE            EC=2.7.11.22;
DE            EC=2.7.11.23;
DE   AltName: Full=Cell division protein kinase 12;
DE            Short=dCdk12;
GN   Name=Cdk12; ORFNames=CG7597;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC   Neoptera; Holometabola; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
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   [2]
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   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Embryo, and Ovary;
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley;
RA   Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL   Submitted (JAN-2009) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-106; THR-184; SER-190;
RP   SER-192; THR-217; SER-280; THR-283; SER-291; SER-301; SER-314; SER-353;
RP   THR-365; SER-487; SER-492; SER-730; SER-743; SER-747 AND SER-755, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Embryo;
RX   PubMed=18327897; DOI=10.1021/pr700696a;
RA   Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT   "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL   J. Proteome Res. 7:1675-1682(2008).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-553, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY.
RX   PubMed=17372656; DOI=10.1039/b617545g;
RA   Bodenmiller B., Mueller L.N., Pedrioli P.G.A., Pflieger D., Juenger M.A.,
RA   Eng J.K., Aebersold R., Tao W.A.;
RT   "An integrated chemical, mass spectrometric and computational strategy for
RT   (quantitative) phosphoproteomics: application to Drosophila melanogaster
RT   Kc167 cells.";
RL   Mol. Biosyst. 3:275-286(2007).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH
RP   CYCK.
RX   PubMed=20952539; DOI=10.1101/gad.1968210;
RA   Bartkowiak B., Liu P., Phatnani H.P., Fuda N.J., Cooper J.J., Price D.H.,
RA   Adelman K., Lis J.T., Greenleaf A.L.;
RT   "CDK12 is a transcription elongation-associated CTD kinase, the metazoan
RT   ortholog of yeast Ctk1.";
RL   Genes Dev. 24:2303-2316(2010).
CC   -!- FUNCTION: Cyclin-dependent kinase which displays CTD kinase activity:
CC       hyperphosphorylates the C-terminal heptapeptide repeat domain (CTD) of
CC       the largest RNA polymerase II subunit, thereby acting as a key
CC       regulator of transcription elongation. {ECO:0000269|PubMed:20952539}.
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:20952539};
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:20952539};
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:20952539};
CC   -!- SUBUNIT: Interacts with cyclin CycK. {ECO:0000269|PubMed:20952539}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20952539}. Chromosome
CC       {ECO:0000269|PubMed:20952539}. Note=Localizes to active genes.
CC   -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC       protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAL28383.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR   EMBL; AE014296; AAF51738.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN12171.1; -; Genomic_DNA.
DR   EMBL; AY060835; AAL28383.1; ALT_INIT; mRNA.
DR   EMBL; AY069806; AAL39951.1; -; mRNA.
DR   EMBL; BT058001; ACM16711.1; -; mRNA.
DR   RefSeq; NP_001262167.1; NM_001275238.1.
DR   RefSeq; NP_649325.2; NM_141068.4.
DR   RefSeq; NP_730643.1; NM_168912.2.
DR   SMR; Q9VP22; -.
DR   BioGrid; 65630; 2.
DR   IntAct; Q9VP22; 11.
DR   STRING; 7227.FBpp0078013; -.
DR   iPTMnet; Q9VP22; -.
DR   PaxDb; Q9VP22; -.
DR   PRIDE; Q9VP22; -.
DR   EnsemblMetazoa; FBtr0078357; FBpp0078013; FBgn0037093.
DR   EnsemblMetazoa; FBtr0078358; FBpp0078014; FBgn0037093.
DR   EnsemblMetazoa; FBtr0332716; FBpp0304962; FBgn0037093.
DR   GeneID; 40385; -.
DR   KEGG; dme:Dmel_CG7597; -.
DR   UCSC; CG7597-RA; d. melanogaster.
DR   CTD; 51755; -.
DR   FlyBase; FBgn0037093; Cdk12.
DR   eggNOG; KOG0600; Eukaryota.
DR   eggNOG; ENOG410XPIR; LUCA.
DR   GeneTree; ENSGT00940000157852; -.
DR   HOGENOM; CLU_007431_0_0_1; -.
DR   InParanoid; Q9VP22; -.
DR   KO; K08819; -.
DR   OMA; QKKTHRR; -.
DR   OrthoDB; 925637at2759; -.
DR   PhylomeDB; Q9VP22; -.
DR   Reactome; R-DME-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR   Reactome; R-DME-6798695; Neutrophil degranulation.
DR   SignaLink; Q9VP22; -.
DR   GenomeRNAi; 40385; -.
DR   PRO; PR:Q9VP22; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0037093; Expressed in female gonad and 32 other tissues.
DR   ExpressionAtlas; Q9VP22; baseline and differential.
DR   Genevisible; Q9VP22; DM.
DR   GO; GO:0005694; C:chromosome; IBA:GO_Central.
DR   GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IBA:GO_Central.
DR   GO; GO:0008024; C:cyclin/CDK positive transcription elongation factor complex; IBA:GO_Central.
DR   GO; GO:0000790; C:nuclear chromatin; IBA:GO_Central.
DR   GO; GO:0000228; C:nuclear chromosome; IDA:UniProtKB.
DR   GO; GO:0019908; C:nuclear cyclin-dependent protein kinase holoenzyme complex; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0005700; C:polytene chromosome; IDA:FlyBase.
DR   GO; GO:0005703; C:polytene chromosome puff; IDA:FlyBase.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0030332; F:cyclin binding; IPI:UniProtKB.
DR   GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; ISS:FlyBase.
DR   GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA:UniProtKB.
DR   GO; GO:0008134; F:transcription factor binding; IBA:GO_Central.
DR   GO; GO:0044212; F:transcription regulatory region DNA binding; IBA:GO_Central.
DR   GO; GO:0070816; P:phosphorylation of RNA polymerase II C-terminal domain; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:FlyBase.
DR   GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IBA:GO_Central.
DR   GO; GO:0006468; P:protein phosphorylation; ISS:FlyBase.
DR   GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; 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   ATP-binding; Chromosome; Kinase; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase.
FT   CHAIN           1..1157
FT                   /note="Cyclin-dependent kinase 12"
FT                   /id="PRO_0000372859"
FT   DOMAIN          804..1098
FT                   /note="Protein kinase"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   NP_BIND         810..818
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   NP_BIND         891..896
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   ACT_SITE        936
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT                   ECO:0000255|PROSITE-ProRule:PRU10027"
FT   BINDING         833
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         1118
FT                   /note="ATP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         106
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         184
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         190
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         192
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         217
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         280
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         283
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         291
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         301
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         314
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         353
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         365
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         487
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         492
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         553
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:17372656"
FT   MOD_RES         730
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         743
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         747
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   MOD_RES         755
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:18327897"
FT   CONFLICT        188
FT                   /note="A -> V (in Ref. 3; AAL39951)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        1099
FT                   /note="R -> K (in Ref. 3; AAL28383)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   1157 AA;  128333 MW;  B37ADCFBCAB4E9F3 CRC64;
     MHASSAAATA LVEYSDVSSE DFSDQEAGDL DADAGKGAGN IKKPKPAPDN QFSKGRLDAK
     PDKEGYDNYR SRRAEDSSDP VAAGSRQTSS SEATNPREEP SQASNTSKDE LWGREIYMSS
     DSIDTDELEA EMKRQKRKKQ KKEKHKHKSK KKSKKRKKKR AKSYSSIDSM SDNDINALLD
     RRYTPPTAPS KSNERTVSAA PSSFTPHNLK ESSSPATPPP VRRPNTNSNY YGESSLETAN
     SALGSNLQVT VTNKQSISNR LRSPPPSSRS SGNGPRFGNS PRTPPPSHYS SSGGGGVGSG
     SVVRDSRSSR YVNSPHKEDV SAHHRSSHDH GYQGRYSGAG SSSHDTRKVK RLSPELDRYN
     HQPSTPPHKR RKFSDGREVG LGNFEHSRHH SGKYERYSRD RYSRRSSRSP SVQHSRSRQS
     PSGGLSSGSN AFRHGGSHKH KYGTTVSSTP SHTTRTSKRA SGTGTSGDRY SRSPRTSSRY
     MESSPPSPVG ASGSHHYHHR RSPRMRQRTR GDSRRRSPSS ASSESSASRS RSPTSRDLKH
     KREEYIKKIS ETSLFAELVK DRHKRQKALK EIIERQEENS NSNSNGALTI NDNSSSVDGN
     TPNAADGRSA PGSGTPAAAS TTSNGLQALG SKPDLDLNNI PMPNKQNDSV VSNPASNADV
     PDSVAQLKQP LLVPPFSASK NNIKPKSLTS LPLPPGMNVL DLAGARSPSP GQKKESDEKN
     VTSSGSANKS VLNLPMPPVI PGSEELSGDD DVIDSPEDFD APAVGTVHGH GGGPGTTRQR
     PVILNRRDSR NNVRDWGERC VDVFEMIAQI GEGTYGQVYK ARDHHTNDMV ALKKVRLEHE
     KEGFPITAVR EIKILRQLNH RNIVNLHEIV TDKQDAVEFR KDKGSFYLVF EYMDHDLMGL
     LESGMVDFNE ENNASIMKQL LDGLNYCHKK NFLHRDIKCS NILMNNRGKV KLADFGLARL
     YNADDRERPY TNKVITLWYR PPELLLGEER YGPSIDVWSC GCILGELFVK RPLFQANAEM
     AQLETISKIC GSPVPAVWPN VIKLPLFHTL KQKKTHRRRL REDFEFMPAP ALDLLDKMLD
     LDPDKRITAE DALRSPWLRK INPDEMPTPQ LPTWQDCHEL WSKKRRRQMR EQQESLPPTV
     IASTKYQQHG ATMVGDA
//