CDK9_HUMAN
ID CDK9_HUMAN Reviewed; 372 AA.
AC P50750; Q5JU24; Q5JU25; Q5U006; Q96TF1;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 3.
DT 03-AUG-2022, entry version 235.
DE RecName: Full=Cyclin-dependent kinase 9;
DE EC=2.7.11.22 {ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:20980437};
DE EC=2.7.11.23 {ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:28426094};
DE AltName: Full=C-2K;
DE AltName: Full=Cell division cycle 2-like protein kinase 4;
DE AltName: Full=Cell division protein kinase 9 {ECO:0000303|PubMed:10903437};
DE AltName: Full=Serine/threonine-protein kinase PITALRE {ECO:0000303|PubMed:8170997};
DE AltName: Full=Tat-associated kinase complex catalytic subunit;
GN Name=CDK9 {ECO:0000303|PubMed:10903437, ECO:0000312|HGNC:HGNC:1780};
GN Synonyms=CDC2L4, TAK;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8170997; DOI=10.1073/pnas.91.9.3834;
RA Grana X., de Luca A., Sang N., Fu Y., Claudio P.P., Rosenblatt J.,
RA Morgan D.O., Giordano A.;
RT "PITALRE, a nuclear CDC2-related protein kinase that phosphorylates the
RT retinoblastoma protein in vitro.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:3834-3838(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT ALA-231.
RX PubMed=7695608; DOI=10.1006/bbrc.1995.1375;
RA Best J.L., Presky D.H., Swerlick R.A., Burns D.K., Chu W.;
RT "Cloning of a full-length cDNA sequence encoding a cdc2-related protein
RT kinase from human endothelial cells.";
RL Biochem. Biophys. Res. Commun. 208:562-568(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ALA-231.
RX PubMed=10903437; DOI=10.1016/s0378-1119(00)00215-8;
RA Liu H., Rice A.P.;
RT "Genomic organization and characterization of promoter function of the
RT human CDK9 gene.";
RL Gene 252:51-59(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NIEHS SNPs program;
RL Submitted (JUN-2002) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
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 [8]
RP INTERACTION WITH HIV TAT.
RX PubMed=9491887; DOI=10.1016/s0092-8674(00)80939-3;
RA Wei P., Garber M.E., Fang S.-M., Fischer W.H., Jones K.A.;
RT "A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat
RT and mediates its high-affinity, loop-specific binding to TAR RNA.";
RL Cell 92:451-462(1998).
RN [9]
RP FUNCTION.
RX PubMed=9857195; DOI=10.1093/emboj/17.24.7395;
RA Wada T., Takagi T., Yamaguchi Y., Watanabe D., Handa H.;
RT "Evidence that P-TEFb alleviates the negative effect of DSIF on RNA
RT polymerase II-dependent transcription in vitro.";
RL EMBO J. 17:7395-7403(1998).
RN [10]
RP IDENTIFICATION IN A COMPLEX WITH CCNT1 AND CCNT2.
RX PubMed=9499409; DOI=10.1101/gad.12.5.755;
RA Peng J.-M., Zhu Y., Milton J.T., Price D.H.;
RT "Identification of multiple cyclin subunits of human P-TEFb.";
RL Genes Dev. 12:755-762(1998).
RN [11]
RP FUNCTION, AND IDENTIFICATION IN A COMPLEX WITH HTATSF1; CCNT1; RNA POL II;
RP SUPT5H AND NCL.
RX PubMed=10393184; DOI=10.1093/emboj/18.13.3688;
RA Parada C.A., Roeder R.G.;
RT "A novel RNA polymerase II-containing complex potentiates Tat-enhanced HIV-
RT 1 transcription.";
RL EMBO J. 18:3688-3701(1999).
RN [12]
RP FUNCTION, AND INTERACTION WITH CCNK.
RX PubMed=10574912; DOI=10.1074/jbc.274.49.34527;
RA Fu T.J., Peng J., Lee G., Price D.H., Flores O.;
RT "Cyclin K functions as a CDK9 regulatory subunit and participates in RNA
RT polymerase II transcription.";
RL J. Biol. Chem. 274:34527-34530(1999).
RN [13]
RP FUNCTION.
RX PubMed=10912001; DOI=10.1016/s1097-2765(00)80272-5;
RA Wada T., Orphanides G., Hasegawa J., Kim D.-K., Shima D., Yamaguchi Y.,
RA Fukuda A., Hisatake K., Oh S., Reinberg D., Handa H.;
RT "FACT relieves DSIF/NELF-mediated inhibition of transcriptional elongation
RT and reveals functional differences between P-TEFb and TFIIH.";
RL Mol. Cell 5:1067-1072(2000).
RN [14]
RP FUNCTION.
RX PubMed=10757782; DOI=10.1128/mcb.20.9.2970-2983.2000;
RA Ivanov D., Kwak Y.T., Guo J., Gaynor R.B.;
RT "Domains in the SPT5 protein that modulate its transcriptional regulatory
RT properties.";
RL Mol. Cell. Biol. 20:2970-2983(2000).
RN [15]
RP PHOSPHORYLATION BY PKA, AUTOPHOSPHORYLATION, PHOSPHORYLATION AT SER-347;
RP THR-350; SER-353; THR-354 AND SER-357, INTERACTION WITH HIV TAT, AND
RP MUTAGENESIS OF 347-SER--SER-357 AND ASP-167.
RX PubMed=10958691; DOI=10.1128/mcb.20.18.6958-6969.2000;
RA Garber M.E., Mayall T.P., Suess E.M., Meisenhelder J., Thompson N.E.,
RA Jones K.A.;
RT "CDK9 autophosphorylation regulates high-affinity binding of the human
RT immunodeficiency virus type 1 tat-P-TEFb complex to TAR RNA.";
RL Mol. Cell. Biol. 20:6958-6969(2000).
RN [16]
RP FUNCTION, AND MUTAGENESIS OF ASP-167 AND THR-186.
RX PubMed=11145967; DOI=10.1074/jbc.m010908200;
RA Kim J.B., Sharp P.A.;
RT "Positive transcription elongation factor B phosphorylates hSPT5 and RNA
RT polymerase II carboxyl-terminal domain independently of cyclin-dependent
RT kinase-activating kinase.";
RL J. Biol. Chem. 276:12317-12323(2001).
RN [17]
RP FUNCTION.
RX PubMed=11112772; DOI=10.1074/jbc.m006130200;
RA Ping Y.-H., Rana T.M.;
RT "DSIF and NELF interact with RNA polymerase II elongation complex and HIV-1
RT Tat stimulates P-TEFb-mediated phosphorylation of RNA polymerase II and
RT DSIF during transcription elongation.";
RL J. Biol. Chem. 276:12951-12958(2001).
RN [18]
RP FUNCTION.
RX PubMed=11575923; DOI=10.1006/jmbi.2001.4991;
RA Lavoie S.B., Albert A.L., Handa H., Vincent M., Bensaude O.;
RT "The peptidyl-prolyl isomerase Pin1 interacts with hSpt5 phosphorylated by
RT Cdk9.";
RL J. Mol. Biol. 312:675-685(2001).
RN [19]
RP FUNCTION, AND INTERACTION WITH CCNK/CYCLIN K.
RX PubMed=11884399; DOI=10.1074/jbc.m200117200;
RA Lin X., Taube R., Fujinaga K., Peterlin B.M.;
RT "P-TEFb containing cyclin K and Cdk9 can activate transcription via RNA.";
RL J. Biol. Chem. 277:16873-16878(2002).
RN [20]
RP INTERACTION WITH AFF4.
RX PubMed=12065898; DOI=10.1007/bf02256070;
RA Estable M.C., Naghavi M.H., Kato H., Xiao H., Qin J., Vahlne A.,
RA Roeder R.G.;
RT "MCEF, the newest member of the AF4 family of transcription factors
RT involved in leukemia, is a positive transcription elongation factor-b-
RT associated protein.";
RL J. Biomed. Sci. 9:234-245(2002).
RN [21]
RP SUBCELLULAR LOCATION.
RX PubMed=12115727; DOI=10.1002/jcp.10130;
RA Napolitano G., Licciardo P., Carbone R., Majello B., Lania L.;
RT "CDK9 has the intrinsic property to shuttle between nucleus and cytoplasm,
RT and enhanced expression of cyclin T1 promotes its nuclear localization.";
RL J. Cell. Physiol. 192:209-215(2002).
RN [22]
RP FUNCTION.
RX PubMed=11809800; DOI=10.1128/mcb.22.4.1079-1093.2002;
RA Bourgeois C.F., Kim Y.K., Churcher M.J., West M.J., Karn J.;
RT "Spt5 cooperates with human immunodeficiency virus type 1 Tat by preventing
RT premature RNA release at terminator sequences.";
RL Mol. Cell. Biol. 22:1079-1093(2002).
RN [23]
RP FUNCTION AS MYOD1 KINASE, CATALYTIC ACTIVITY, AND INTERACTION WITH MYOD1
RP AND CCNT2.
RX PubMed=12037670; DOI=10.1038/sj.onc.1205493;
RA Simone C., Stiegler P., Bagella L., Pucci B., Bellan C., De Falco G.,
RA De Luca A., Guanti G., Puri P.L., Giordano A.;
RT "Activation of MyoD-dependent transcription by cdk9/cyclin T2.";
RL Oncogene 21:4137-4148(2002).
RN [24]
RP INTERACTION WITH SUPT5H.
RX PubMed=12718890; DOI=10.1016/s1097-2765(03)00101-1;
RA Kwak Y.T., Guo J., Prajapati S., Park K.-J., Surabhi R.M., Miller B.,
RA Gehrig P., Gaynor R.B.;
RT "Methylation of SPT5 regulates its interaction with RNA polymerase II and
RT transcriptional elongation properties.";
RL Mol. Cell 11:1055-1066(2003).
RN [25]
RP FUNCTION.
RX PubMed=15564463; DOI=10.1128/jvi.78.24.13522-13533.2004;
RA Zhou M., Deng L., Lacoste V., Park H.U., Pumfery A., Kashanchi F.,
RA Brady J.N., Kumar A.;
RT "Coordination of transcription factor phosphorylation and histone
RT methylation by the P-TEFb kinase during human immunodeficiency virus type 1
RT transcription.";
RL J. Virol. 78:13522-13533(2004).
RN [26]
RP FUNCTION.
RX PubMed=14701750; DOI=10.1128/mcb.24.2.787-795.2004;
RA Fujinaga K., Irwin D., Huang Y., Taube R., Kurosu T., Peterlin B.M.;
RT "Dynamics of human immunodeficiency virus transcription: P-TEFb
RT phosphorylates RD and dissociates negative effectors from the
RT transactivation response element.";
RL Mol. Cell. Biol. 24:787-795(2004).
RN [27]
RP IDENTIFICATION IN INACTIVE 7SK SNRNP COMPLEX, AND PHOSPHORYLATION AT
RP THR-186.
RX PubMed=15965233; DOI=10.1074/jbc.m502712200;
RA Li Q., Price J.P., Byers S.A., Cheng D., Peng J., Price D.H.;
RT "Analysis of the large inactive P-TEFb complex indicates that it contains
RT one 7SK molecule, a dimer of HEXIM1 or HEXIM2, and two P-TEFb molecules
RT containing Cdk9 phosphorylated at threonine 186.";
RL J. Biol. Chem. 280:28819-28826(2005).
RN [28]
RP FUNCTION, AND INTERACTION WITH BRD4.
RX PubMed=16109376; DOI=10.1016/j.molcel.2005.06.027;
RA Jang M.K., Mochizuki K., Zhou M., Jeong H.S., Brady J.N., Ozato K.;
RT "The bromodomain protein Brd4 is a positive regulatory component of P-TEFb
RT and stimulates RNA polymerase II-dependent transcription.";
RL Mol. Cell 19:523-534(2005).
RN [29]
RP FUNCTION, AND INTERACTION WITH BRD4.
RX PubMed=16109377; DOI=10.1016/j.molcel.2005.06.029;
RA Yang Z., Yik J.H., Chen R., He N., Jang M.K., Ozato K., Zhou Q.;
RT "Recruitment of P-TEFb for stimulation of transcriptional elongation by the
RT bromodomain protein Brd4.";
RL Mol. Cell 19:535-545(2005).
RN [30]
RP FUNCTION IN CYTOKINE SIGNALING, AND INTERACTION WITH STAT3.
RX PubMed=17956865; DOI=10.1074/jbc.m706458200;
RA Hou T., Ray S., Brasier A.R.;
RT "The functional role of an interleukin 6-inducible CDK9.STAT3 complex in
RT human gamma-fibrinogen gene expression.";
RL J. Biol. Chem. 282:37091-37102(2007).
RN [31]
RP IDENTIFICATION IN THE 7SK SNRNP COMPLEX.
RX PubMed=17643375; DOI=10.1016/j.molcel.2007.06.027;
RA Jeronimo C., Forget D., Bouchard A., Li Q., Chua G., Poitras C.,
RA Therien C., Bergeron D., Bourassa S., Greenblatt J., Chabot B.,
RA Poirier G.G., Hughes T.R., Blanchette M., Price D.H., Coulombe B.;
RT "Systematic analysis of the protein interaction network for the human
RT transcription machinery reveals the identity of the 7SK capping enzyme.";
RL Mol. Cell 27:262-274(2007).
RN [32]
RP ACETYLATION AT LYS-44, IDENTIFICATION IN COMPLEX WITH NCOR1; HEXIM1 AND
RP HDAC3, AND MUTAGENESIS OF LYS-44.
RX PubMed=17452463; DOI=10.1128/mcb.00857-06;
RA Fu J., Yoon H.-G., Qin J., Wong J.;
RT "Regulation of P-TEFb elongation complex activity by CDK9 acetylation.";
RL Mol. Cell. Biol. 27:4641-4651(2007).
RN [33]
RP PHOSPHORYLATION AT THR-186, DEPHOSPHORYLATION BY PPP1CA, P-TEFB/7SK SNRNP
RP COMPLEX, SUBUNIT, INTERACTION WITH BRD4, AND ACTIVITY REGULATION.
RX PubMed=18483222; DOI=10.1101/gad.1636008;
RA Chen R., Liu M., Li H., Xue Y., Ramey W.N., He N., Ai N., Luo H., Zhu Y.,
RA Zhou N., Zhou Q.;
RT "PP2B and PP1alpha cooperatively disrupt 7SK snRNP to release P-TEFb for
RT transcription in response to Ca2+ signaling.";
RL Genes Dev. 22:1356-1368(2008).
RN [34]
RP PHOSPHORYLATION AT THR-186, AND DEPHOSPHORYLATION BY PPM1A AND PPM1B.
RX PubMed=18829461; DOI=10.1074/jbc.m807495200;
RA Wang Y., Dow E.C., Liang Y.Y., Ramakrishnan R., Liu H., Sung T.L., Lin X.,
RA Rice A.P.;
RT "Phosphatase PPM1A regulates phosphorylation of Thr-186 in the Cdk9 T-
RT loop.";
RL J. Biol. Chem. 283:33578-33584(2008).
RN [35]
RP IDENTIFICATION IN COMPLEX WITH LARP7 IN 7SK SNRNP COMPLEX.
RX PubMed=18249148; DOI=10.1016/j.molcel.2008.01.003;
RA He N., Jahchan N.S., Hong E., Li Q., Bayfield M.A., Maraia R.J., Luo K.,
RA Zhou Q.;
RT "A La-related protein modulates 7SK snRNP integrity to suppress P-TEFb-
RT dependent transcriptional elongation and tumorigenesis.";
RL Mol. Cell 29:588-599(2008).
RN [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT SER-35 (ISOFORM 2), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [37]
RP ACETYLATION AT LYS-44 AND LYS-48 BY PCAF/KAT2B AND GCN5/KAT2A, ACTIVITY
RP REGULATION BY ACETYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=18250157; DOI=10.1128/mcb.01557-07;
RA Sabo A., Lusic M., Cereseto A., Giacca M.;
RT "Acetylation of conserved lysines in the catalytic core of cyclin-dependent
RT kinase 9 inhibits kinase activity and regulates transcription.";
RL Mol. Cell. Biol. 28:2201-2212(2008).
RN [38]
RP FUNCTION IN CYTOKINE SIGNALING, AND INTERACTION WITH RELA/P65.
RX PubMed=18362169; DOI=10.1128/mcb.01152-07;
RA Nowak D.E., Tian B., Jamaluddin M., Boldogh I., Vergara L.A., Choudhary S.,
RA Brasier A.R.;
RT "RelA Ser276 phosphorylation is required for activation of a subset of NF-
RT kappaB-dependent genes by recruiting cyclin-dependent kinase 9/cyclin T1
RT complexes.";
RL Mol. Cell. Biol. 28:3623-3638(2008).
RN [39]
RP FUNCTION IN HISTONE REGULATION.
RX PubMed=19844166; DOI=10.4161/cc.8.22.9890;
RA Pirngruber J., Shchebet A., Johnsen S.A.;
RT "Insights into the function of the human P-TEFb component CDK9 in the
RT regulation of chromatin modifications and co-transcriptional mRNA
RT processing.";
RL Cell Cycle 8:3636-3642(2009).
RN [40]
RP FUNCTION IN HISTONE H2B UBIQUITINATION.
RX PubMed=19575011; DOI=10.1038/embor.2009.108;
RA Pirngruber J., Shchebet A., Schreiber L., Shema E., Minsky N.,
RA Chapman R.D., Eick D., Aylon Y., Oren M., Johnsen S.A.;
RT "CDK9 directs H2B monoubiquitination and controls replication-dependent
RT histone mRNA 3'-end processing.";
RL EMBO Rep. 10:894-900(2009).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347 AND THR-350,
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35 (ISOFORM 2), AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [42]
RP FUNCTION IN DNA REPAIR, AND INTERACTION WITH KU70/XRCC6.
RX PubMed=20493174; DOI=10.1016/j.bbrc.2010.05.092;
RA Liu H., Herrmann C.H., Chiang K., Sung T.L., Moon S.H., Donehower L.A.,
RA Rice A.P.;
RT "55K isoform of CDK9 associates with Ku70 and is involved in DNA repair.";
RL Biochem. Biophys. Res. Commun. 397:245-250(2010).
RN [43]
RP FUNCTION IN CDK9/CYCLIN K COMPLEX DURING REPLICATION STRESS.
RX PubMed=20930849; DOI=10.1038/embor.2010.153;
RA Yu D.S., Zhao R., Hsu E.L., Cayer J., Ye F., Guo Y., Shyr Y., Cortez D.;
RT "Cyclin-dependent kinase 9-cyclin K functions in the replication stress
RT response.";
RL EMBO Rep. 11:876-882(2010).
RN [44]
RP FUNCTION IN CARDIAC HYPERTROPHY, AND IDENTIFICATION IN COMPLEX WITH
RP CCNT1/CYCLIN-T1; EP300 AND GATA4.
RX PubMed=20081228; DOI=10.1074/jbc.m109.070458;
RA Sunagawa Y., Morimoto T., Takaya T., Kaichi S., Wada H., Kawamura T.,
RA Fujita M., Shimatsu A., Kita T., Hasegawa K.;
RT "Cyclin-dependent kinase-9 is a component of the p300/GATA4 complex
RT required for phenylephrine-induced hypertrophy in cardiomyocytes.";
RL J. Biol. Chem. 285:9556-9568(2010).
RN [45]
RP IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=20471948; DOI=10.1016/j.molcel.2010.04.013;
RA He N., Liu M., Hsu J., Xue Y., Chou S., Burlingame A., Krogan N.J.,
RA Alber T., Zhou Q.;
RT "HIV-1 Tat and host AFF4 recruit two transcription elongation factors into
RT a bifunctional complex for coordinated activation of HIV-1 transcription.";
RL Mol. Cell 38:428-438(2010).
RN [46]
RP IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=20159561; DOI=10.1016/j.molcel.2010.01.026;
RA Lin C., Smith E.R., Takahashi H., Lai K.C., Martin-Brown S., Florens L.,
RA Washburn M.P., Conaway J.W., Conaway R.C., Shilatifard A.;
RT "AFF4, a component of the ELL/P-TEFb elongation complex and a shared
RT subunit of MLL chimeras, can link transcription elongation to leukemia.";
RL Mol. Cell 37:429-437(2010).
RN [47]
RP FUNCTION IN AR KINASE, CATALYTIC ACTIVITY, AND INTERACTION WITH AR.
RX PubMed=20980437; DOI=10.1210/me.2010-0238;
RA Gordon V., Bhadel S., Wunderlich W., Zhang J., Ficarro S.B., Mollah S.A.,
RA Shabanowitz J., Hunt D.F., Xenarios I., Hahn W.C., Conaway M., Carey M.F.,
RA Gioeli D.;
RT "CDK9 regulates AR promoter selectivity and cell growth through serine 81
RT phosphorylation.";
RL Mol. Endocrinol. 24:2267-2280(2010).
RN [48]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [49]
RP IDENTIFICATION IN THE SEC COMPLEX.
RX PubMed=22195968; DOI=10.1016/j.molcel.2011.12.008;
RA Smith E.R., Lin C., Garrett A.S., Thornton J., Mohaghegh N., Hu D.,
RA Jackson J., Saraf A., Swanson S.K., Seidel C., Florens L., Washburn M.P.,
RA Eissenberg J.C., Shilatifard A.;
RT "The little elongation complex regulates small nuclear RNA transcription.";
RL Mol. Cell 44:954-965(2011).
RN [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-186, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [51]
RP ACTIVITY REGULATION BY CDKI-71.
RX PubMed=21484792; DOI=10.1002/ijc.26127;
RA Liu X., Shi S., Lam F., Pepper C., Fischer P.M., Wang S.;
RT "CDKI-71, a novel CDK9 inhibitor, is preferentially cytotoxic to cancer
RT cells compared to flavopiridol.";
RL Int. J. Cancer 130:1216-1226(2012).
RN [52]
RP FUNCTION AS RPB1/POLR2A CTD KINASE, CATALYTIC ACTIVITY, POLYUBIQUITINATION
RP BY UBR5, AND INTERACTION WITH UBR5 AND TFIIS/TCEA1.
RX PubMed=21127351; DOI=10.1074/jbc.m110.176628;
RA Cojocaru M., Bouchard A., Cloutier P., Cooper J.J., Varzavand K.,
RA Price D.H., Coulombe B.;
RT "Transcription factor IIS cooperates with the E3 ligase UBR5 to
RT ubiquitinate the CDK9 subunit of the positive transcription elongation
RT factor B.";
RL J. Biol. Chem. 286:5012-5022(2011).
RN [53]
RP PHOSPHORYLATION AT THR-186, ACTIVITY REGULATION, DEGRADATION BY THE
RP PROTEASOME, AND MUTAGENESIS OF THR-186.
RX PubMed=21448926; DOI=10.1002/jcp.22760;
RA Ramakrishnan R., Rice A.P.;
RT "Cdk9 T-loop phosphorylation is regulated by the calcium signaling
RT pathway.";
RL J. Cell. Physiol. 227:609-617(2012).
RN [54]
RP PHOSPHORYLATION AT SER-175, DEPHOSPHORYLATION AT SER-175 BY PP1, AND
RP MUTAGENESIS OF SER-175.
RX PubMed=21533037; DOI=10.1371/journal.pone.0018985;
RA Ammosova T., Obukhov Y., Kotelkin A., Breuer D., Beullens M., Gordeuk V.R.,
RA Bollen M., Nekhai S.;
RT "Protein phosphatase-1 activates CDK9 by dephosphorylating Ser175.";
RL PLoS ONE 6:E18985-E18985(2011).
RN [55]
RP REVIEW ON NELF AND DSIF KINASE ACTIVITY.
RX PubMed=16885020; DOI=10.1016/j.molcel.2006.06.014;
RA Peterlin B.M., Price D.H.;
RT "Controlling the elongation phase of transcription with P-TEFb.";
RL Mol. Cell 23:297-305(2006).
RN [56]
RP REVIEW ON CYTOKINE SIGNALING.
RX PubMed=18728388; DOI=10.4161/cc.7.17.6594;
RA Brasier A.R.;
RT "Expanding role of cyclin dependent kinases in cytokine inducible gene
RT expression.";
RL Cell Cycle 7:2661-2666(2008).
RN [57]
RP REVIEW ON TRANSCRIPTION REGULATION, AND INHIBITORS.
RX PubMed=19029809; DOI=10.4161/cc.7.23.7122;
RA Romano G., Giordano A.;
RT "Role of the cyclin-dependent kinase 9-related pathway in mammalian gene
RT expression and human diseases.";
RL Cell Cycle 7:3664-3668(2008).
RN [58]
RP REVIEW ON TRANSCRIPTION REGULATION, AND INHIBITORS.
RX PubMed=18423896; DOI=10.1016/j.tips.2008.03.003;
RA Wang S., Fischer P.M.;
RT "Cyclin-dependent kinase 9: a key transcriptional regulator and potential
RT drug target in oncology, virology and cardiology.";
RL Trends Pharmacol. Sci. 29:302-313(2008).
RN [59]
RP ACTIVITY REGULATION, AND GENE FAMILY.
RX PubMed=19238148; DOI=10.1038/nrc2602;
RA Malumbres M., Barbacid M.;
RT "Cell cycle, CDKs and cancer: a changing paradigm.";
RL Nat. Rev. Cancer 9:153-166(2009).
RN [60]
RP REVIEW ON CARDIAC HYPERTROPHY, AND INHIBITORS.
RX PubMed=19757441; DOI=10.1002/med.20172;
RA Krystof V., Chamrad I., Jorda R., Kohoutek J.;
RT "Pharmacological targeting of CDK9 in cardiac hypertrophy.";
RL Med. Res. Rev. 30:646-666(2010).
RN [61]
RP REVIEW ON GENOME INTEGRITY MAINTENANCE.
RX PubMed=21200140; DOI=10.4161/cc.10.1.14364;
RA Yu D.S., Cortez D.;
RT "A role for cdk9-cyclin k in maintaining genome integrity.";
RL Cell Cycle 10:28-32(2011).
RN [62]
RP INTERACTION WITH HERPES SIMPLEX VIRUS 1 PROTEIN ICP22.
RX PubMed=23029222; DOI=10.1371/journal.pone.0045749;
RA Guo L., Wu W.J., Liu L.D., Wang L.C., Zhang Y., Wu L.Q., Guan Y., Li Q.H.;
RT "Herpes simplex virus 1 ICP22 inhibits the transcription of viral gene
RT promoters by binding to and blocking the recruitment of P-TEFb.";
RL PLoS ONE 7:E45749-E45749(2012).
RN [63]
RP INTERACTION WITH BRD4 AND JMJD6.
RX PubMed=24360279; DOI=10.1016/j.cell.2013.10.056;
RA Liu W., Ma Q., Wong K., Li W., Ohgi K., Zhang J., Aggarwal A.,
RA Rosenfeld M.G.;
RT "Brd4 and JMJD6-associated anti-pause enhancers in regulation of
RT transcriptional pause release.";
RL Cell 155:1581-1595(2013).
RN [64]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-347, PHOSPHORYLATION [LARGE
RP SCALE ANALYSIS] AT THR-54 (ISOFORM 2), AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [65]
RP INTERACTION WITH HSF1.
RX PubMed=27189267; DOI=10.1038/srep26294;
RA Pan X.Y., Zhao W., Zeng X.Y., Lin J., Li M.M., Shen X.T., Liu S.W.;
RT "Heat shock factor 1 mediates latent HIV reactivation.";
RL Sci. Rep. 6:26294-26294(2016).
RN [66]
RP FUNCTION, CATALYTIC ACTIVITY, ACETYLATION AT LYS-48, DEACETYLATION BY
RP SIRT7, AND MUTAGENESIS OF LYS-48.
RX PubMed=28426094; DOI=10.1093/nar/gkx053;
RA Blank M.F., Chen S., Poetz F., Schnoelzer M., Voit R., Grummt I.;
RT "SIRT7-dependent deacetylation of CDK9 activates RNA polymerase II
RT transcription.";
RL Nucleic Acids Res. 45:2675-2686(2017).
RN [67]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=29335245; DOI=10.15252/embr.201744311;
RA Brauns-Schubert P., Schubert F., Wissler M., Weiss M., Schlicher L.,
RA Bessler S., Safavi M., Miething C., Borner C., Brummer T., Maurer U.;
RT "CDK9-mediated phosphorylation controls the interaction of TIP60 with the
RT transcriptional machinery.";
RL EMBO Rep. 19:244-256(2018).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 1-345 IN COMPLEX WITH HIV-1 TAT
RP AND CCNT1, AND PHOSPHORYLATION AT THR-186.
RX PubMed=20535204; DOI=10.1038/nature09131;
RA Tahirov T.H., Babayeva N.D., Varzavand K., Cooper J.J., Sedore S.C.,
RA Price D.H.;
RT "Crystal structure of HIV-1 Tat complexed with human P-TEFb.";
RL Nature 465:747-751(2010).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (2.48 ANGSTROMS) OF 2-330 IN COMPLEX WITH INHIBITOR
RP FLAVOPIRIDOL; ATP AND CCNT1, PHOSPHORYLATION AT THR-186 SER-347; THR-362
RP AND THR-363, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF THR-186.
RX PubMed=18566585; DOI=10.1038/emboj.2008.121;
RA Baumli S., Lolli G., Lowe E.D., Troiani S., Rusconi L., Bullock A.N.,
RA Debreczeni J.E., Knapp S., Johnson L.N.;
RT "The structure of P-TEFb (CDK9/cyclin T1), its complex with flavopiridol
RT and regulation by phosphorylation.";
RL EMBO J. 27:1907-1918(2008).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 2-330 IN COMPLEX WITH INHIBITOR
RP DRB, AND PHOSPHORYLATION AT THR-186.
RX PubMed=20851342; DOI=10.1016/j.chembiol.2010.07.012;
RA Baumli S., Endicott J.A., Johnson L.N.;
RT "Halogen bonds form the basis for selective P-TEFb inhibition by DRB.";
RL Chem. Biol. 17:931-936(2010).
RN [71]
RP X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 2-330 IN COMPLEX WITH CCNT1;
RP INHIBITORS ROSCOVITINE AND CR8, PHOSPHORYLATION AT THR-186, AND ACTIVITY
RP REGULATION.
RX PubMed=21779453; DOI=10.1177/1947601910369817;
RA Bettayeb K., Baunbaek D., Delehouze C., Loaec N., Hole A.J., Baumli S.,
RA Endicott J.A., Douc-Rasy S., Benard J., Oumata N., Galons H., Meijer L.;
RT "CDK inhibitors roscovitine and CR8 trigger Mcl-1 down-regulation and
RT apoptotic cell death in neuroblastoma cells.";
RL Genes Cancer 1:369-380(2010).
RN [72]
RP VARIANT [LARGE SCALE ANALYSIS] LEU-59.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
RN [73]
RP VARIANT CYS-225.
RX PubMed=30237576; DOI=10.1038/s41436-018-0138-x;
RA Maddirevula S., Alzahrani F., Al-Owain M., Al Muhaizea M.A., Kayyali H.R.,
RA AlHashem A., Rahbeeni Z., Al-Otaibi M., Alzaidan H.I., Balobaid A.,
RA El Khashab H.Y., Bubshait D.K., Faden M., Yamani S.A., Dabbagh O.,
RA Al-Mureikhi M., Jasser A.A., Alsaif H.S., Alluhaydan I., Seidahmed M.Z.,
RA Alabbasi B.H., Almogarri I., Kurdi W., Akleh H., Qari A., Al Tala S.M.,
RA Alhomaidi S., Kentab A.Y., Salih M.A., Chedrawi A., Alameer S., Tabarki B.,
RA Shamseldin H.E., Patel N., Ibrahim N., Abdulwahab F., Samira M., Goljan E.,
RA Abouelhoda M., Meyer B.F., Hashem M., Shaheen R., AlShahwan S.,
RA Alfadhel M., Ben-Omran T., Al-Qattan M.M., Monies D., Alkuraya F.S.;
RT "Autozygome and high throughput confirmation of disease genes candidacy.";
RL Genet. Med. 21:736-742(2019).
CC -!- FUNCTION: Protein kinase involved in the regulation of transcription
CC (PubMed:10574912, PubMed:10757782, PubMed:11145967, PubMed:11575923,
CC PubMed:11809800, PubMed:11884399, PubMed:14701750, PubMed:16109376,
CC PubMed:16109377, PubMed:20930849, PubMed:28426094, PubMed:29335245).
CC Member of the cyclin-dependent kinase pair (CDK9/cyclin-T) complex,
CC also called positive transcription elongation factor b (P-TEFb), which
CC facilitates the transition from abortive to productive elongation by
CC phosphorylating the CTD (C-terminal domain) of the large subunit of RNA
CC polymerase II (RNAP II) POLR2A, SUPT5H and RDBP (PubMed:10574912,
CC PubMed:10757782, PubMed:11145967, PubMed:11575923, PubMed:11809800,
CC PubMed:11884399, PubMed:14701750, PubMed:16109376, PubMed:16109377,
CC PubMed:20930849, PubMed:28426094). This complex is inactive when in the
CC 7SK snRNP complex form (PubMed:10574912, PubMed:10757782,
CC PubMed:11145967, PubMed:11575923, PubMed:11809800, PubMed:11884399,
CC PubMed:14701750, PubMed:16109376, PubMed:16109377, PubMed:20930849,
CC PubMed:28426094). Phosphorylates EP300, MYOD1, RPB1/POLR2A and AR and
CC the negative elongation factors DSIF and NELFE (PubMed:9857195,
CC PubMed:10912001, PubMed:11112772, PubMed:12037670, PubMed:20081228,
CC PubMed:20980437, PubMed:21127351). Regulates cytokine inducible
CC transcription networks by facilitating promoter recognition of target
CC transcription factors (e.g. TNF-inducible RELA/p65 activation and IL-6-
CC inducible STAT3 signaling) (PubMed:17956865, PubMed:18362169). Promotes
CC RNA synthesis in genetic programs for cell growth, differentiation and
CC viral pathogenesis (PubMed:10393184, PubMed:11112772). P-TEFb is also
CC involved in cotranscriptional histone modification, mRNA processing and
CC mRNA export (PubMed:15564463, PubMed:19575011, PubMed:19844166).
CC Modulates a complex network of chromatin modifications including
CC histone H2B monoubiquitination (H2Bub1), H3 lysine 4 trimethylation
CC (H3K4me3) and H3K36me3; integrates phosphorylation during transcription
CC with chromatin modifications to control co-transcriptional histone mRNA
CC processing (PubMed:15564463, PubMed:19575011, PubMed:19844166). The
CC CDK9/cyclin-K complex has also a kinase activity towards CTD of RNAP II
CC and can substitute for CDK9/cyclin-T P-TEFb in vitro (PubMed:21127351).
CC Replication stress response protein; the CDK9/cyclin-K complex is
CC required for genome integrity maintenance, by promoting cell cycle
CC recovery from replication arrest and limiting single-stranded DNA
CC amount in response to replication stress, thus reducing the breakdown
CC of stalled replication forks and avoiding DNA damage (PubMed:20493174).
CC In addition, probable function in DNA repair of isoform 2 via
CC interaction with KU70/XRCC6 (PubMed:20493174). Promotes cardiac myocyte
CC enlargement (PubMed:20081228). RPB1/POLR2A phosphorylation on 'Ser-2'
CC in CTD activates transcription (PubMed:21127351). AR phosphorylation
CC modulates AR transcription factor promoter selectivity and cell growth.
CC DSIF and NELF phosphorylation promotes transcription by inhibiting
CC their negative effect (PubMed:9857195, PubMed:10912001,
CC PubMed:11112772). The phosphorylation of MYOD1 enhances its
CC transcriptional activity and thus promotes muscle differentiation
CC (PubMed:12037670). Catalyzes phosphorylation of KAT5, promoting KAT5
CC recruitment to chromatin and histone acetyltransferase activity
CC (PubMed:29335245). {ECO:0000269|PubMed:10393184,
CC ECO:0000269|PubMed:10574912, ECO:0000269|PubMed:10757782,
CC ECO:0000269|PubMed:10912001, ECO:0000269|PubMed:11112772,
CC ECO:0000269|PubMed:11145967, ECO:0000269|PubMed:11575923,
CC ECO:0000269|PubMed:11809800, ECO:0000269|PubMed:11884399,
CC ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:14701750,
CC ECO:0000269|PubMed:15564463, ECO:0000269|PubMed:16109376,
CC ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:17956865,
CC ECO:0000269|PubMed:18362169, ECO:0000269|PubMed:19575011,
CC ECO:0000269|PubMed:19844166, ECO:0000269|PubMed:20081228,
CC ECO:0000269|PubMed:20493174, ECO:0000269|PubMed:20930849,
CC ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351,
CC ECO:0000269|PubMed:28426094, ECO:0000269|PubMed:29335245,
CC ECO:0000269|PubMed:9857195}.
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:12037670, ECO:0000269|PubMed:20980437,
CC ECO:0000269|PubMed:29335245};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:20980437,
CC ECO:0000269|PubMed:29335245};
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:12037670,
CC ECO:0000269|PubMed:20980437};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000269|PubMed:12037670, ECO:0000269|PubMed:20980437};
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:21127351, ECO:0000269|PubMed:28426094};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10217;
CC Evidence={ECO:0000269|PubMed:21127351, ECO:0000269|PubMed:28426094};
CC -!- ACTIVITY REGULATION: Inhibited by CDKI-71, CR8, GPC-286199, AG-024322,
CC flavopiridol (alvocidib), RBG-286147, anilinopyrimidine 32,
CC arylazopyrazole 31b, indirubin 3'-monoxime, meriolin 3,P276-00,
CC olomoucine II, pyrazolotriazine, meriolin, variolin, thiazolyl-
CC pyrimidine, thiazolyl-pyrimidine, indirubin-30-monoxime, ZK 304709, AG-
CC 012986, AT7519, R547, RGB-286638, imidazole pyrimidine, EXEL-3700,
CC EXEL-8647, 5,6-dichloro-1-b-ribofur-anosyl-benzimidazole (DRB), P276-
CC 00, roscovitine (seliciclib, CYC202) and SNS-032 (BMS-387032).
CC Activation by Thr-186 phosphorylation is calcium Ca(2+) signaling
CC pathway-dependent; actively inactivated by dephosphorylation mediated
CC by PPP1CA, PPM1A and PPM1B. Reversibly repressed by acetylation at Lys-
CC 44 and Lys-48. {ECO:0000269|PubMed:18250157,
CC ECO:0000269|PubMed:18483222, ECO:0000269|PubMed:19238148,
CC ECO:0000269|PubMed:21448926, ECO:0000269|PubMed:21484792,
CC ECO:0000269|PubMed:21779453}.
CC -!- SUBUNIT: Component of the super elongation complex (SEC), at least
CC composed of EAF1, EAF2, CDK9, MLLT3/AF9, AFF (AFF1 or AFF4), the P-TEFb
CC complex and ELL (ELL, ELL2 or ELL3). Associates with CCNT1/cyclin-T1,
CC CCNT2/cyclin-T2 (isoform A and isoform B) or CCNK/cyclin-K to form
CC active P-TEFb. P-TEFb forms a complex with AFF4/AF5Q31 and is part of
CC the super elongation complex (SEC). Component of a complex which is
CC composed of at least 5 members: HTATSF1/Tat-SF1, P-TEFb complex, RNA
CC pol II, SUPT5H and NCL/nucleolin. Associates with UBR5 and forms a
CC transcription regulatory complex composed of CDK9, RNAP II, UBR5 and
CC TFIIS/TCEA1 that can stimulate target gene transcription (e.g. gamma
CC fibrinogen/FGG) by recruiting their promoters. Component of the 7SK
CC snRNP inactive complex which is composed of at least 8 members: P-TEFb
CC (composed of CDK9 and CCNT1/cyclin-T1), HEXIM1, HEXIM2, LARP7, BCDIN3,
CC SART3 proteins and 7SK and U6 snRNAs. This inactive 7SK snRNP complex
CC can also interact with NCOR1 and HDAC3, probably to regulate CDK9
CC acetylation. Release of P-TEFb from P-TEFb/7SK snRNP complex requires
CC both PP2B to transduce calcium Ca(2+) signaling in response to stimuli
CC (e.g. UV or hexamethylene bisacetamide (HMBA)) and PPP1CA to
CC dephosphorylate Thr-186. This released P-TEFb remains inactive in the
CC pre-initiation complex with BRD4 until new Thr-186 phosphorylation
CC occurs after the synthesis of a short RNA (PubMed:10393184,
CC PubMed:10574912, PubMed:12037670, PubMed:11884399, PubMed:12065898,
CC PubMed:12718890, PubMed:15965233, PubMed:16109376, PubMed:17452463,
CC PubMed:17643375, PubMed:18249148, PubMed:18483222, PubMed:18566585,
CC PubMed:20159561, PubMed:20471948, PubMed:21127351, PubMed:21779453,
CC PubMed:22195968, PubMed:9491887). Interacts with BRD4; to target
CC chromatin binding (PubMed:16109376, PubMed:16109377, PubMed:18483222).
CC Interacts with JMJD6 (PubMed:24360279). Interacts with activated
CC nuclear STAT3 and RELA/p65 (PubMed:17956865, PubMed:18362169). Binds to
CC AR and MYOD1 (PubMed:12037670, PubMed:20980437). Forms a complex
CC composed of CDK9, CCNT1/cyclin-T1, EP300 and GATA4 that stimulates
CC hypertrophy in cardiomyocytes (PubMed:20081228). The large PER complex
CC involved in the repression of transcriptional termination is composed
CC of at least PER2, CDK9, DDX5, DHX9, NCBP1 and POLR2A (By similarity).
CC Interacts with HSF1 (PubMed:27189267). Interacts with TBX21 (By
CC similarity). Isoform 3: binds to KU70/XRCC6 (PubMed:20535204).
CC Interacts with WDR43 (By similarity). {ECO:0000250|UniProtKB:Q99J95,
CC ECO:0000269|PubMed:10393184, ECO:0000269|PubMed:10574912,
CC ECO:0000269|PubMed:11884399, ECO:0000269|PubMed:12037670,
CC ECO:0000269|PubMed:12065898, ECO:0000269|PubMed:12718890,
CC ECO:0000269|PubMed:15965233, ECO:0000269|PubMed:16109376,
CC ECO:0000269|PubMed:16109377, ECO:0000269|PubMed:17452463,
CC ECO:0000269|PubMed:17643375, ECO:0000269|PubMed:17956865,
CC ECO:0000269|PubMed:18249148, ECO:0000269|PubMed:18362169,
CC ECO:0000269|PubMed:18483222, ECO:0000269|PubMed:18566585,
CC ECO:0000269|PubMed:20081228, ECO:0000269|PubMed:20159561,
CC ECO:0000269|PubMed:20471948, ECO:0000269|PubMed:20535204,
CC ECO:0000269|PubMed:20980437, ECO:0000269|PubMed:21127351,
CC ECO:0000269|PubMed:21779453, ECO:0000269|PubMed:22195968,
CC ECO:0000269|PubMed:24360279, ECO:0000269|PubMed:27189267,
CC ECO:0000269|PubMed:9491887}.
CC -!- SUBUNIT: (Microbial infection) Interacts with the acidic/proline-rich
CC region of HIV-1 and HIV-2 Tat via T-loop region and is thus required
CC for HIV to hijack host transcription machinery during its replication
CC through cooperative binding to viral TAR RNA (PubMed:10958691,
CC PubMed:9491887). Interacts with herpes simplex virus 1 protein ICP22;
CC this interaction inhibits the positive transcription elongation factor
CC b (P-TEFb) (PubMed:23029222). {ECO:0000269|PubMed:10958691,
CC ECO:0000269|PubMed:23029222, ECO:0000269|PubMed:9491887}.
CC -!- INTERACTION:
CC P50750; Q13535: ATR; NbExp=3; IntAct=EBI-1383449, EBI-968983;
CC P50750; Q8WXE1: ATRIP; NbExp=3; IntAct=EBI-1383449, EBI-747353;
CC P50750; O60885-1: BRD4; NbExp=9; IntAct=EBI-1383449, EBI-9345088;
CC P50750; O60563: CCNT1; NbExp=26; IntAct=EBI-1383449, EBI-2479671;
CC P50750; O60583: CCNT2; NbExp=6; IntAct=EBI-1383449, EBI-2836757;
CC P50750; O60583-1: CCNT2; NbExp=2; IntAct=EBI-1383449, EBI-9077118;
CC P50750; O60583-2: CCNT2; NbExp=3; IntAct=EBI-1383449, EBI-9077112;
CC P50750; Q16543: CDC37; NbExp=5; IntAct=EBI-1383449, EBI-295634;
CC P50750; Q9HAW4: CLSPN; NbExp=3; IntAct=EBI-1383449, EBI-1369377;
CC P50750; Q13451: FKBP5; NbExp=6; IntAct=EBI-1383449, EBI-306914;
CC P50750; O94992: HEXIM1; NbExp=12; IntAct=EBI-1383449, EBI-2832510;
CC P50750; P07900: HSP90AA1; NbExp=3; IntAct=EBI-1383449, EBI-296047;
CC P50750; P08238: HSP90AB1; NbExp=3; IntAct=EBI-1383449, EBI-352572;
CC P50750; Q6NYC1: JMJD6; NbExp=5; IntAct=EBI-1383449, EBI-8464037;
CC P50750; Q4G0J3: LARP7; NbExp=12; IntAct=EBI-1383449, EBI-2371923;
CC P50750; P53041: PPP5C; NbExp=3; IntAct=EBI-1383449, EBI-716663;
CC P50750; P40763: STAT3; NbExp=2; IntAct=EBI-1383449, EBI-518675;
CC P50750; P04608: tat; Xeno; NbExp=8; IntAct=EBI-1383449, EBI-6164389;
CC P50750-2; P28799: GRN; NbExp=3; IntAct=EBI-12029902, EBI-747754;
CC P50750-2; P28799-2: GRN; NbExp=3; IntAct=EBI-12029902, EBI-25860013;
CC P50750-2; Q6XYB7-2: LBX2; NbExp=3; IntAct=EBI-12029902, EBI-12029900;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Nucleus, PML body.
CC Note=Accumulates on chromatin in response to replication stress.
CC Complexed with CCNT1 in nuclear speckles, but uncomplexed form in the
CC cytoplasm. The translocation from nucleus to cytoplasm is XPO1/CRM1-
CC dependent. Associates with PML body when acetylated.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P50750-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P50750-2; Sequence=VSP_016288;
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: By replication stress, in chromatin. Probably degraded by
CC the proteasome upon Thr-186 dephosphorylation.
CC -!- PTM: Autophosphorylation at Thr-186, Ser-347, Thr-350, Ser-353, Thr-354
CC and Ser-357 triggers kinase activity by promoting cyclin and substrate
CC binding (e.g. HIV TAT) upon conformational changes. Thr-186
CC phosphorylation requires the calcium Ca(2+) signaling pathway,
CC including CaMK1D and calmodulin. This inhibition is relieved by Thr-29
CC dephosphorylation. However, phosphorylation at Thr-29 is inhibitory
CC within the HIV transcription initiation complex. Phosphorylation at
CC Ser-175 inhibits kinase activity. Can be phosphorylated on either Thr-
CC 362 or Thr-363 but not on both simultaneously (PubMed:18566585).
CC {ECO:0000269|PubMed:10958691, ECO:0000269|PubMed:15965233,
CC ECO:0000269|PubMed:18483222, ECO:0000269|PubMed:18566585,
CC ECO:0000269|PubMed:18829461, ECO:0000269|PubMed:20535204,
CC ECO:0000269|PubMed:20851342, ECO:0000269|PubMed:21448926,
CC ECO:0000269|PubMed:21533037, ECO:0000269|PubMed:21779453}.
CC -!- PTM: Dephosphorylation of Thr-186 by PPM1A and PPM1B blocks CDK9
CC activity and may lead to CDK9 proteasomal degradation. However, PPP1CA-
CC mediated Thr-186 dephosphorylation is required to release P-TEFb from
CC its inactive P-TEFb/7SK snRNP complex. Dephosphorylation of C-terminus
CC Thr and Ser residues by protein phosphatase-1 (PP1) triggers CDK9
CC activity, contributing to the activation of HIV-1 transcription.
CC -!- PTM: N6-acetylation of Lys-44 promotes kinase activity, whereas
CC acetylation of both Lys-44 and Lys-48 mediated by PCAF/KAT2B and
CC GCN5/KAT2A reduces kinase activity (PubMed:17452463, PubMed:18250157).
CC The acetylated form associates with PML bodies in the nuclear matrix
CC and with the transcriptionally silent HIV-1 genome; deacetylated upon
CC transcription stimulation (PubMed:17452463, PubMed:18250157).
CC Deacetylated by SIRT7, promoting the kinase activity and subsequent
CC 'Ser-2' phosphorylation of the C-terminal domain (CTD) of RNA
CC polymerase II (PubMed:28426094). {ECO:0000269|PubMed:17452463,
CC ECO:0000269|PubMed:18250157, ECO:0000269|PubMed:28426094}.
CC -!- PTM: Polyubiquitinated and thus activated by UBR5. This ubiquitination
CC is promoted by TFIIS/TCEA1 and favors 'Ser-2' phosphorylation of
CC RPB1/POLR2A CTD. {ECO:0000269|PubMed:21127351}.
CC -!- DISEASE: Note=Chronic activation of CDK9 causes cardiac myocyte
CC enlargement leading to cardiac hypertrophy and confers predisposition
CC to heart failure.
CC -!- MISCELLANEOUS: CDK9 inhibition contributes to the anticancer activity
CC of most CDK inhibitors under clinical investigation (PubMed:18423896
CC and PubMed:21779453). As a retroviruses target during the hijack of
CC host transcription (e.g. HIV), CDK9 inhibitors might become specific
CC antiretroviral agents (PubMed:18423896). May be a target for cardiac
CC hypertrophy future treatments (PubMed:19757441 and PubMed:18423896).
CC May also be a target in anti-inflammatory therapy in innate immunity
CC and systemic inflammation (PubMed:18728388).
CC {ECO:0000305|PubMed:18423896, ECO:0000305|PubMed:18728388}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cdk9/";
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; L25676; AAA35668.1; -; mRNA.
DR EMBL; X80230; CAA56516.1; -; mRNA.
DR EMBL; AF255306; AAF72183.1; -; Genomic_DNA.
DR EMBL; BT019903; AAV38706.1; -; mRNA.
DR EMBL; AF517840; AAM54039.1; -; Genomic_DNA.
DR EMBL; AL162586; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001968; AAH01968.1; -; mRNA.
DR CCDS; CCDS6879.1; -. [P50750-1]
DR PIR; A55262; A55262.
DR RefSeq; NP_001252.1; NM_001261.3. [P50750-1]
DR PDB; 3BLH; X-ray; 2.48 A; A=2-330.
DR PDB; 3BLQ; X-ray; 2.90 A; A=2-330.
DR PDB; 3BLR; X-ray; 2.80 A; A=2-330.
DR PDB; 3LQ5; X-ray; 3.00 A; A=2-330.
DR PDB; 3MI9; X-ray; 2.10 A; A=1-345.
DR PDB; 3MIA; X-ray; 3.00 A; A=1-345.
DR PDB; 3MY1; X-ray; 2.80 A; A=2-330.
DR PDB; 3TN8; X-ray; 2.95 A; A=2-330.
DR PDB; 3TNH; X-ray; 3.20 A; A=2-330.
DR PDB; 3TNI; X-ray; 3.23 A; A=2-330.
DR PDB; 4BCF; X-ray; 3.01 A; A=2-330.
DR PDB; 4BCG; X-ray; 3.08 A; A=2-330.
DR PDB; 4BCH; X-ray; 2.96 A; A=2-330.
DR PDB; 4BCI; X-ray; 3.10 A; A=2-330.
DR PDB; 4BCJ; X-ray; 3.16 A; A=2-330.
DR PDB; 4EC8; X-ray; 3.60 A; A=2-372.
DR PDB; 4EC9; X-ray; 3.21 A; A=2-372.
DR PDB; 4IMY; X-ray; 2.94 A; A/C/E=1-330.
DR PDB; 4OGR; X-ray; 3.00 A; A/E/I=1-330.
DR PDB; 4OR5; X-ray; 2.90 A; A/F=7-332.
DR PDB; 5L1Z; X-ray; 5.90 A; A=1-330.
DR PDB; 6CYT; X-ray; 3.50 A; A=1-330.
DR PDB; 6GZH; X-ray; 3.17 A; A=1-326.
DR PDB; 6W9E; X-ray; 3.10 A; A=1-330.
DR PDB; 6Z45; X-ray; 3.37 A; A=1-330.
DR PDB; 7NWK; X-ray; 2.81 A; A=1-330.
DR PDBsum; 3BLH; -.
DR PDBsum; 3BLQ; -.
DR PDBsum; 3BLR; -.
DR PDBsum; 3LQ5; -.
DR PDBsum; 3MI9; -.
DR PDBsum; 3MIA; -.
DR PDBsum; 3MY1; -.
DR PDBsum; 3TN8; -.
DR PDBsum; 3TNH; -.
DR PDBsum; 3TNI; -.
DR PDBsum; 4BCF; -.
DR PDBsum; 4BCG; -.
DR PDBsum; 4BCH; -.
DR PDBsum; 4BCI; -.
DR PDBsum; 4BCJ; -.
DR PDBsum; 4EC8; -.
DR PDBsum; 4EC9; -.
DR PDBsum; 4IMY; -.
DR PDBsum; 4OGR; -.
DR PDBsum; 4OR5; -.
DR PDBsum; 5L1Z; -.
DR PDBsum; 6CYT; -.
DR PDBsum; 6GZH; -.
DR PDBsum; 6W9E; -.
DR PDBsum; 6Z45; -.
DR PDBsum; 7NWK; -.
DR AlphaFoldDB; P50750; -.
DR SMR; P50750; -.
DR BioGRID; 107459; 628.
DR ComplexPortal; CPX-222; Positive transcription elongation factor B, CDK9-cyclinT1 complex.
DR ComplexPortal; CPX-321; Positive transcription elongation factor B, CDK9-cyclinT2a complex.
DR ComplexPortal; CPX-322; Positive transcription elongation factor B, CDK9-cyclinT2b complex.
DR CORUM; P50750; -.
DR DIP; DIP-29016N; -.
DR ELM; P50750; -.
DR IntAct; P50750; 94.
DR MINT; P50750; -.
DR STRING; 9606.ENSP00000362361; -.
DR BindingDB; P50750; -.
DR ChEMBL; CHEMBL3116; -.
DR DrugBank; DB03496; Alvocidib.
DR DrugBank; DB06195; Seliciclib.
DR DrugBank; DB15442; Trilaciclib.
DR DrugCentral; P50750; -.
DR GuidetoPHARMACOLOGY; 1981; -.
DR GlyGen; P50750; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50750; -.
DR PhosphoSitePlus; P50750; -.
DR SwissPalm; P50750; -.
DR BioMuta; CDK9; -.
DR DMDM; 68067660; -.
DR CPTAC; CPTAC-1602; -.
DR EPD; P50750; -.
DR jPOST; P50750; -.
DR MassIVE; P50750; -.
DR MaxQB; P50750; -.
DR PaxDb; P50750; -.
DR PeptideAtlas; P50750; -.
DR PRIDE; P50750; -.
DR ProteomicsDB; 56263; -. [P50750-1]
DR ProteomicsDB; 56264; -. [P50750-2]
DR Antibodypedia; 1447; 576 antibodies from 41 providers.
DR DNASU; 1025; -.
DR Ensembl; ENST00000373264.5; ENSP00000362361.4; ENSG00000136807.14. [P50750-1]
DR GeneID; 1025; -.
DR KEGG; hsa:1025; -.
DR MANE-Select; ENST00000373264.5; ENSP00000362361.4; NM_001261.4; NP_001252.1.
DR UCSC; uc004bse.3; human. [P50750-1]
DR CTD; 1025; -.
DR DisGeNET; 1025; -.
DR GeneCards; CDK9; -.
DR HGNC; HGNC:1780; CDK9.
DR HPA; ENSG00000136807; Low tissue specificity.
DR MIM; 603251; gene.
DR neXtProt; NX_P50750; -.
DR OpenTargets; ENSG00000136807; -.
DR PharmGKB; PA26316; -.
DR VEuPathDB; HostDB:ENSG00000136807; -.
DR eggNOG; KOG0669; Eukaryota.
DR GeneTree; ENSGT00940000155373; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P50750; -.
DR OMA; YIEEFDF; -.
DR PhylomeDB; P50750; -.
DR TreeFam; TF101039; -.
DR BRENDA; 2.7.11.22; 2681.
DR BRENDA; 2.7.11.23; 2681.
DR PathwayCommons; P50750; -.
DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-HSA-167152; Formation of HIV elongation complex in the absence of HIV Tat.
DR Reactome; R-HSA-167200; Formation of HIV-1 elongation complex containing HIV-1 Tat.
DR Reactome; R-HSA-167238; Pausing and recovery of Tat-mediated HIV elongation.
DR Reactome; R-HSA-167243; Tat-mediated HIV elongation arrest and recovery.
DR Reactome; R-HSA-167246; Tat-mediated elongation of the HIV-1 transcript.
DR Reactome; R-HSA-167287; HIV elongation arrest and recovery.
DR Reactome; R-HSA-167290; Pausing and recovery of HIV elongation.
DR Reactome; R-HSA-176034; Interactions of Tat with host cellular proteins.
DR Reactome; R-HSA-2173796; SMAD2/SMAD3:SMAD4 heterotrimer regulates transcription.
DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-6807505; RNA polymerase II transcribes snRNA genes.
DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; P50750; -.
DR SIGNOR; P50750; -.
DR BioGRID-ORCS; 1025; 834 hits in 1100 CRISPR screens.
DR ChiTaRS; CDK9; human.
DR EvolutionaryTrace; P50750; -.
DR GeneWiki; CDK9; -.
DR GeneWiki; Cyclin-dependent_kinase_9; -.
DR GenomeRNAi; 1025; -.
DR Pharos; P50750; Tchem.
DR PRO; PR:P50750; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P50750; protein.
DR Bgee; ENSG00000136807; Expressed in right uterine tube and 135 other tissues.
DR ExpressionAtlas; P50750; baseline and differential.
DR Genevisible; P50750; HS.
DR GO; GO:0008024; C:cyclin/CDK positive transcription elongation factor complex; IDA:UniProtKB.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0016592; C:mediator complex; IBA:GO_Central.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR GO; GO:0070691; C:P-TEFb complex; IDA:FlyBase.
DR GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR GO; GO:0008023; C:transcription elongation factor complex; IDA:UniProtKB.
DR GO; GO:0097322; F:7SK snRNA binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IEA:Ensembl.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA:UniProtKB.
DR GO; GO:0001223; F:transcription coactivator binding; IPI:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; TAS:ProtInc.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0070816; P:phosphorylation of RNA polymerase II C-terminal domain; IDA:UniProtKB.
DR GO; GO:1903655; P:phosphorylation of RNA polymerase II C-terminal domain serine 2 residues involved in positive regulation of transcription elongation from RNA polymerase II promoter; IDA:ComplexPortal.
DR GO; GO:1903654; P:phosphorylation of RNA polymerase II C-terminal domain serine 5 residues involved in positive regulation of transcription elongation from RNA polymerase II promoter; IDA:ComplexPortal.
DR GO; GO:0043923; P:positive regulation by host of viral transcription; IDA:ComplexPortal.
DR GO; GO:0010613; P:positive regulation of cardiac muscle hypertrophy; IEA:Ensembl.
DR GO; GO:1903839; P:positive regulation of mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0120187; P:positive regulation of protein localization to chromatin; IDA:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0032968; P:positive regulation of transcription elongation from RNA polymerase II promoter; IDA:ComplexPortal.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0006282; P:regulation of DNA repair; IDA:UniProtKB.
DR GO; GO:0031056; P:regulation of histone modification; IDA:UniProtKB.
DR GO; GO:0031440; P:regulation of mRNA 3'-end processing; IMP:UniProtKB.
DR GO; GO:0051147; P:regulation of muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0031297; P:replication fork processing; IDA:UniProtKB.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; TAS:Reactome.
DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:ProtInc.
DR DisProt; DP01309; -.
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 3D-structure; Acetylation; Alternative splicing; ATP-binding; Cytoplasm;
KW DNA damage; DNA repair; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transcription; Transcription regulation; Transferase; Ubl conjugation.
FT CHAIN 1..372
FT /note="Cyclin-dependent kinase 9"
FT /id="PRO_0000085800"
FT DOMAIN 19..315
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 166..191
FT /note="T-loop"
FT REGION 343..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 345..372
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 25..33
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 48
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:18566585"
FT BINDING 104..106
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:18566585"
FT BINDING 167
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:18566585"
FT MOD_RES 44
FT /note="N6-acetyllysine; by EP300/CBP, PCAF/KAT2B and
FT GCN5/KAT2A"
FT /evidence="ECO:0000269|PubMed:17452463,
FT ECO:0000269|PubMed:18250157"
FT MOD_RES 48
FT /note="N6-acetyllysine; by PCAF/KAT2B and GCN5/KAT2A"
FT /evidence="ECO:0000269|PubMed:18250157,
FT ECO:0000269|PubMed:28426094"
FT MOD_RES 175
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:21533037"
FT MOD_RES 186
FT /note="Phosphothreonine; by CaMK1D"
FT /evidence="ECO:0000269|PubMed:15965233,
FT ECO:0000269|PubMed:18483222, ECO:0000269|PubMed:18566585,
FT ECO:0000269|PubMed:18829461, ECO:0000269|PubMed:20535204,
FT ECO:0000269|PubMed:20851342, ECO:0000269|PubMed:21448926,
FT ECO:0000269|PubMed:21779453, ECO:0007744|PubMed:21406692"
FT MOD_RES 347
FT /note="Phosphoserine; by CDK9 and PKA"
FT /evidence="ECO:0000269|PubMed:10958691,
FT ECO:0000269|PubMed:18566585, ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195, ECO:0007744|PubMed:24275569"
FT MOD_RES 350
FT /note="Phosphothreonine; by CDK9"
FT /evidence="ECO:0000269|PubMed:10958691,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES 353
FT /note="Phosphoserine; by CDK9"
FT /evidence="ECO:0000269|PubMed:10958691"
FT MOD_RES 354
FT /note="Phosphothreonine; by CDK9"
FT /evidence="ECO:0000269|PubMed:10958691"
FT MOD_RES 357
FT /note="Phosphoserine; by CDK9"
FT /evidence="ECO:0000269|PubMed:10958691"
FT MOD_RES 362
FT /note="Phosphothreonine; by CDK9"
FT /evidence="ECO:0000269|PubMed:18566585"
FT MOD_RES 363
FT /note="Phosphothreonine; by CDK9"
FT /evidence="ECO:0000269|PubMed:18566585"
FT VAR_SEQ 1
FT /note="M -> MQRDAPPRAPAPAPRLPAPPIGAAASSGGGGGGGSGGGGGGASAAPA
FT PPGLSGTTSPRGPGGGRRAEEAGSAPRGRKWPWRRKWRGRGGAWSAAAAGPGAGAAAAA
FT TGGGGGALEAAM (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_016288"
FT VARIANT 59
FT /note="F -> L (in dbSNP:rs55640715)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_041982"
FT VARIANT 225
FT /note="R -> C (found in patients with global developmental
FT delay and epilepsy with history of choanal atresia; unknown
FT pathological significance; dbSNP:rs767418586)"
FT /evidence="ECO:0000269|PubMed:30237576"
FT /id="VAR_082140"
FT VARIANT 231
FT /note="G -> A"
FT /evidence="ECO:0000269|PubMed:10903437,
FT ECO:0000269|PubMed:7695608"
FT /id="VAR_013456"
FT MUTAGEN 44
FT /note="K->R: Impaired kinase and transcriptional elongation
FT activities, but normal cyclin T1 and HEXIM1 binding."
FT /evidence="ECO:0000269|PubMed:17452463"
FT MUTAGEN 48
FT /note="K->Q: Mimics acetylation; leading to impaired
FT protein kinase activity."
FT /evidence="ECO:0000269|PubMed:28426094"
FT MUTAGEN 48
FT /note="K->R: Decreased acetylation; leading to enhanced
FT protein kinase activity."
FT /evidence="ECO:0000269|PubMed:28426094"
FT MUTAGEN 167
FT /note="D->N: Abrogates kinase activity."
FT /evidence="ECO:0000269|PubMed:10958691,
FT ECO:0000269|PubMed:11145967"
FT MUTAGEN 175
FT /note="S->A: Constitutive kinase activity."
FT /evidence="ECO:0000269|PubMed:21533037"
FT MUTAGEN 175
FT /note="S->D: Mimics phosphorylation, constitutive loss of
FT kinase activity."
FT /evidence="ECO:0000269|PubMed:21533037"
FT MUTAGEN 186
FT /note="T->A: Abrogates autophosphorylation; no effect on
FT kinase activity, but impaired CTD phosphorylation."
FT /evidence="ECO:0000269|PubMed:11145967,
FT ECO:0000269|PubMed:18566585, ECO:0000269|PubMed:21448926"
FT MUTAGEN 186
FT /note="T->D: Mimics autophosphorylation; constitutive
FT kinase activity, independently of calcium signaling."
FT /evidence="ECO:0000269|PubMed:11145967,
FT ECO:0000269|PubMed:18566585, ECO:0000269|PubMed:21448926"
FT MUTAGEN 347..357
FT /note="SQITQQSTNQS->AQIAQQAANQA: Loss of
FT autophosphorylation and impaired interaction with HIV TAT."
FT /evidence="ECO:0000269|PubMed:10958691"
FT MUTAGEN 347..357
FT /note="SQITQQSTNQS->EQIEQQEENQE: Mimics autophosphorylation
FT and promotes interaction with HIV TAT."
FT /evidence="ECO:0000269|PubMed:10958691"
FT CONFLICT 163
FT /note="L -> P (in Ref. 4; AAV38706)"
FT /evidence="ECO:0000305"
FT STRAND 11..13
FT /evidence="ECO:0007829|PDB:6GZH"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 19..24
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:3BLR"
FT STRAND 32..38
FT /evidence="ECO:0007829|PDB:3MI9"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 61..72
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 81..87
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 98..104
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 110..115
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 116..118
FT /evidence="ECO:0007829|PDB:3LQ5"
FT HELIX 123..142
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 155..157
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6GZH"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 168..170
FT /evidence="ECO:0007829|PDB:4OGR"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 192..194
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 197..200
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 209..224
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 234..245
FT /evidence="ECO:0007829|PDB:3MI9"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 256..258
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 263..265
FT /evidence="ECO:0007829|PDB:3MY1"
FT HELIX 275..283
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 286..295
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 300..302
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 306..310
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 313..316
FT /evidence="ECO:0007829|PDB:3MI9"
FT STRAND 317..319
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 325..329
FT /evidence="ECO:0007829|PDB:3MI9"
FT HELIX 335..339
FT /evidence="ECO:0007829|PDB:3MI9"
FT MOD_RES P50750-2:35
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:19369195"
FT MOD_RES P50750-2:54
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:24275569"
SQ SEQUENCE 372 AA; 42778 MW; 69E851CC6F7A0388 CRC64;
MAKQYDSVEC PFCDEVSKYE KLAKIGQGTF GEVFKARHRK TGQKVALKKV LMENEKEGFP
ITALREIKIL QLLKHENVVN LIEICRTKAS PYNRCKGSIY LVFDFCEHDL AGLLSNVLVK
FTLSEIKRVM QMLLNGLYYI HRNKILHRDM KAANVLITRD GVLKLADFGL ARAFSLAKNS
QPNRYTNRVV TLWYRPPELL LGERDYGPPI DLWGAGCIMA EMWTRSPIMQ GNTEQHQLAL
ISQLCGSITP EVWPNVDNYE LYEKLELVKG QKRKVKDRLK AYVRDPYALD LIDKLLVLDP
AQRIDSDDAL NHDFFWSDPM PSDLKGMLST HLTSMFEYLA PPRRKGSQIT QQSTNQSRNP
ATTNQTEFER VF
