ID CDK7_HUMAN Reviewed; 346 AA.
AC P50613; Q9BS60; Q9UE19;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 27-MAR-2024, entry version 237.
DE RecName: Full=Cyclin-dependent kinase 7;
DE EC=2.7.11.22;
DE EC=2.7.11.23 {ECO:0000269|PubMed:9852112};
DE AltName: Full=39 kDa protein kinase;
DE Short=p39 Mo15;
DE AltName: Full=CDK-activating kinase 1;
DE AltName: Full=Cell division protein kinase 7;
DE AltName: Full=Serine/threonine-protein kinase 1;
DE AltName: Full=TFIIH basal transcription factor complex kinase subunit;
GN Name=CDK7; Synonyms=CAK, CAK1, CDKN7, MO15, STK1;
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].
RC TISSUE=Placenta;
RX PubMed=7929589; DOI=10.1083/jcb.127.2.467;
RA Tassan J.-P., Schultz S.J., Bartek J., Nigg E.A.;
RT "Cell cycle analysis of the activity, subcellular localization, and subunit
RT composition of human CAK (CDK-activating kinase).";
RL J. Cell Biol. 127:467-478(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Mammary gland;
RX PubMed=8208544;
RA Levedakou E.N., He M., Baptist E.W., Craven R.J., Cance W.G., Welcsh P.L.,
RA Simmons A., Naylor S.L., Leach R.J., Lewis T.B., Bowcock A., Liu E.T.;
RT "Two novel human serine/threonine kinases with homologies to the cell cycle
RT regulating Xenopus MO15, and NIMA kinases: cloning and characterization of
RT their expression pattern.";
RL Oncogene 9:1977-1988(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7936635;
RA Darbon J.-M., Devault A., Taviaux S., Fesquet D., Martinez A.-M., Galas S.,
RA Cavadore J.-C., Doree M., Blanchard J.-M.;
RT "Cloning, expression and subcellular localization of the human homolog of
RT p40MO15 catalytic subunit of cdk-activating kinase.";
RL Oncogene 9:3127-3138(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Fibroblast;
RX PubMed=8208556;
RA Wu L., Yee A., Liu L., Carbonaro-Hall D., Venkatesan N., Tolo T.,
RA Hall F.L.;
RT "Molecular cloning of the human CAK1 gene encoding a cyclin-dependent
RT kinase-activating kinase.";
RL Oncogene 9:2089-2096(1994).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Lung, and Thymus;
RA Kobelt D., Karn T., Hock B., Holtrich U., Braeuninger A., Wolf G.,
RA Strebhardt K., Ruebsamen-Waigmann H.;
RT "Human and Xenopus MO15 mRNA are highly conserved but show different
RT patterns of expression in adult tissues.";
RL Oncol. Rep. 1:1269-1275(1994).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-163 AND MET-285.
RG NIEHS SNPs program;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Cervix, and Urinary bladder;
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 MUTAGENESIS OF THR-170.
RX PubMed=8069918; DOI=10.1016/0092-8674(94)90535-5;
RA Fisher R.P., Morgan D.O.;
RT "A novel cyclin associates with MO15/CDK7 to form the CDK-activating
RT kinase.";
RL Cell 78:713-724(1994).
RN [9]
RP FUNCTION AS TP53 KINASE.
RX PubMed=9372954; DOI=10.1128/mcb.17.12.7220;
RA Ko L.J., Shieh S.-Y., Chen X., Jayaraman L., Tamai K., Taya Y., Prives C.,
RA Pan Z.-Q.;
RT "p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent manner.";
RL Mol. Cell. Biol. 17:7220-7229(1997).
RN [10]
RP PHOSPHORYLATION AT SER-164 AND THR-170, AND MUTAGENESIS OF SER-164 AND
RP THR-170.
RX PubMed=9832506; DOI=10.1101/gad.12.22.3541;
RA Akoulitchev S., Reinberg D.;
RT "The molecular mechanism of mitotic inhibition of TFIIH is mediated by
RT phosphorylation of CDK7.";
RL Genes Dev. 12:3541-3550(1998).
RN [11]
RP IDENTIFICATION IN THE TFIIH BASAL TRANSCRIPTION FACTOR, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=9852112; DOI=10.1074/jbc.273.51.34444;
RA Kershnar E., Wu S.-Y., Chiang C.-M.;
RT "Immunoaffinity purification and functional characterization of human
RT transcription factor IIH and RNA polymerase II from clonal cell lines that
RT conditionally express epitope-tagged subunits of the multiprotein
RT complexes.";
RL J. Biol. Chem. 273:34444-34453(1998).
RN [12]
RP FUNCTION AS CDK2 KINASE, IDENTIFICATION IN COMPLEX WITH TP53, AND ACTIVITY
RP REGULATION.
RX PubMed=9840937; DOI=10.1038/sj.onc.1202504;
RA Schneider E., Montenarh M., Wagner P.;
RT "Regulation of CAK kinase activity by p53.";
RL Oncogene 17:2733-2741(1998).
RN [13]
RP FUNCTION.
RX PubMed=10024882; DOI=10.1016/s1097-2765(00)80177-x;
RA Tirode F., Busso D., Coin F., Egly J.-M.;
RT "Reconstitution of the transcription factor TFIIH: assignment of functions
RT for the three enzymatic subunits, XPB, XPD, and cdk7.";
RL Mol. Cell 3:87-95(1999).
RN [14]
RP INTERACTION WITH HINTI, MUTAGENESIS OF LYS-41 AND THR-170, AND SUBCELLULAR
RP LOCATION.
RX PubMed=10958787; DOI=10.1074/jbc.c000505200;
RA Korsisaari N., Makela T.P.;
RT "Interactions of Cdk7 and Kin28 with Hint/PKCI-1 and Hnt1 histidine triad
RT proteins.";
RL J. Biol. Chem. 275:34837-34840(2000).
RN [15]
RP INTERACTION WITH PUF60.
RX PubMed=10882074; DOI=10.1016/s1097-2765(00)80428-1;
RA Liu J., He L., Collins I., Ge H., Libutti D., Li J., Egly J.-M., Levens D.;
RT "The FBP interacting repressor targets TFIIH to inhibit activated
RT transcription.";
RL Mol. Cell 5:331-341(2000).
RN [16]
RP PHOSPHORYLATION AT SER-164 AND THR-170 BY CDK2, AND FUNCTION AS CDK2
RP KINASE.
RX PubMed=11113184; DOI=10.1128/mcb.21.1.88-99.2001;
RA Garrett S., Barton W.A., Knights R., Jin P., Morgan D.O., Fisher R.P.;
RT "Reciprocal activation by cyclin-dependent kinases 2 and 7 is directed by
RT substrate specificity determinants outside the T loop.";
RL Mol. Cell. Biol. 21:88-99(2001).
RN [17]
RP INTERACTION WITH PRKCI, AND SUBCELLULAR LOCATION.
RX PubMed=15695176; DOI=10.1016/j.tice.2004.10.004;
RA Bicaku E., Patel R., Acevedo-Duncan M.;
RT "Cyclin-dependent kinase activating kinase/Cdk7 co-localizes with PKC-iota
RT in human glioma cells.";
RL Tissue Cell 37:53-58(2005).
RN [18]
RP FUNCTION AS SPT5/SUPT5H AND CDK KINASE, MUTAGENESIS OF PHE-91, AND
RP IDENTIFICATION IN CAK COMPLEX.
RX PubMed=16327805; DOI=10.1038/nsmb1028;
RA Larochelle S., Batliner J., Gamble M.J., Barboza N.M., Kraybill B.C.,
RA Blethrow J.D., Shokat K.M., Fisher R.P.;
RT "Dichotomous but stringent substrate selection by the dual-function Cdk7
RT complex revealed by chemical genetics.";
RL Nat. Struct. Mol. Biol. 13:55-62(2006).
RN [19]
RP FUNCTION IN CELL CYCLE REGULATION.
RX PubMed=17386261; DOI=10.1016/j.molcel.2007.02.003;
RA Larochelle S., Merrick K.A., Terret M.-E., Wohlbold L., Barboza N.M.,
RA Zhang C., Shokat K.M., Jallepalli P.V., Fisher R.P.;
RT "Requirements for Cdk7 in the assembly of Cdk1/cyclin B and activation of
RT Cdk2 revealed by chemical genetics in human cells.";
RL Mol. Cell 25:839-850(2007).
RN [20]
RP FUNCTION AS CDK2 KINASE, AND INTERACTION WITH CDK2.
RX PubMed=17373709; DOI=10.1002/prot.21370;
RA Lolli G., Johnson L.N.;
RT "Recognition of Cdk2 by Cdk7.";
RL Proteins 67:1048-1059(2007).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-164 AND SER-321, AND
RP IDENTIFICATION BY MASS 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 [23]
RP FUNCTION AS SF1/NR5A1 KINASE, AND INTERACTION WITH SF1/NR5A1.
RX PubMed=17901130; DOI=10.1210/me.2006-0478;
RA Lewis A.E., Rusten M., Hoivik E.A., Vikse E.L., Hansson M.L.,
RA Wallberg A.E., Bakke M.;
RT "Phosphorylation of steroidogenic factor 1 is mediated by cyclin-dependent
RT kinase 7.";
RL Mol. Endocrinol. 22:91-104(2008).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-170, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [25]
RP FUNCTION AS POLR2A CTD KINASE.
RX PubMed=19450536; DOI=10.1016/j.molcel.2009.04.016;
RA Akhtar M.S., Heidemann M., Tietjen J.R., Zhang D.W., Chapman R.D., Eick D.,
RA Ansari A.Z.;
RT "TFIIH kinase places bivalent marks on the carboxy-terminal domain of RNA
RT polymerase II.";
RL Mol. Cell 34:387-393(2009).
RN [26]
RP FUNCTION AS SF1/NR5A1 KINASE.
RX PubMed=19015234; DOI=10.1128/mcb.00295-08;
RA Yang W.-H., Heaton J.H., Brevig H., Mukherjee S., Iniguez-Lluhi J.A.,
RA Hammer G.D.;
RT "SUMOylation inhibits SF-1 activity by reducing CDK7-mediated serine 203
RT phosphorylation.";
RL Mol. Cell. Biol. 29:613-625(2009).
RN [27]
RP FUNCTION AS POLR2A CTD KINASE.
RX PubMed=19667075; DOI=10.1128/mcb.00637-09;
RA Glover-Cutter K., Larochelle S., Erickson B., Zhang C., Shokat K.,
RA Fisher R.P., Bentley D.L.;
RT "TFIIH-associated Cdk7 kinase functions in phosphorylation of C-terminal
RT domain Ser7 residues, promoter-proximal pausing, and termination by RNA
RT polymerase II.";
RL Mol. Cell. Biol. 29:5455-5464(2009).
RN [28]
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 [29]
RP FUNCTION AS POLR2A CTD KINASE.
RX PubMed=19136461; DOI=10.1093/nar/gkn1061;
RA Lolli G.;
RT "Binding to DNA of the RNA-polymerase II C-terminal domain allows
RT discrimination between Cdk7 and Cdk9 phosphorylation.";
RL Nucleic Acids Res. 37:1260-1268(2009).
RN [30]
RP FUNCTION IN DNA-BOUND PEPTIDES TRANSCRIPTION INHIBITION, SUBCELLULAR
RP LOCATION, AND INDUCTION.
RX PubMed=19071173; DOI=10.1016/j.peptides.2008.11.008;
RA Lv X., Wang J., Dong Z., Lv F., Qin Y.;
RT "DNA-Bound peptides control the mRNA transcription through CDK7.";
RL Peptides 30:681-688(2009).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [32]
RP FUNCTION AS CDK1 AND CDK2 KINASE.
RX PubMed=20360007; DOI=10.1074/jbc.m109.096552;
RA Timofeev O., Cizmecioglu O., Settele F., Kempf T., Hoffmann I.;
RT "Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at
RT the G2/M transition.";
RL J. Biol. Chem. 285:16978-16990(2010).
RN [33]
RP ACTIVITY REGULATION.
RX PubMed=19911397; DOI=10.1002/jcb.22400;
RA Rogalinska M., Blonski J.Z., Komina O., Goralski P., Zolnierczyk J.D.,
RA Piekarski H., Robak T., Kilianska Z.M., Wesierska-Gadek J.;
RT "R-roscovitine (Seliciclib) affects CLL cells more strongly than
RT combinations of fludarabine or cladribine with cyclophosphamide: Inhibition
RT of CDK7 sensitizes leukemic cells to caspase-dependent apoptosis.";
RL J. Cell. Biochem. 109:217-235(2010).
RN [34]
RP REVIEW ON CELL CYCLE REGULATION.
RX PubMed=15876871;
RA Lolli G., Johnson L.N.;
RT "CAK-Cyclin-dependent Activating Kinase: a key kinase in cell cycle control
RT and a target for drugs?";
RL Cell Cycle 4:572-577(2005).
RN [35]
RP REVIEW ON INHIBITORS, 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 [36]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170 AND SER-321, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [37]
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 [38]
RP REVIEW ON TRANSCRIPTION REGULATION.
RX PubMed=21592869; DOI=10.1016/j.dnarep.2011.04.021;
RA Egly J.M., Coin F.;
RT "A history of TFIIH: Two decades of molecular biology on a pivotal
RT transcription/repair factor.";
RL DNA Repair 10:714-721(2011).
RN [39]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, 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 [40]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [41]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-164 AND THR-170, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [42]
RP IDENTIFICATION BY MASS 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 [43]
RP X-RAY CRYSTALLOGRAPHY (3.02 ANGSTROMS) IN COMPLEX WITH ATP, ACTIVE SITE,
RP AND PHOSPHORYLATION AT THR-170.
RX PubMed=15530371; DOI=10.1016/j.str.2004.08.013;
RA Lolli G., Lowe E.D., Brown N.R., Johnson L.N.;
RT "The crystal structure of human CDK7 and its protein recognition
RT properties.";
RL Structure 12:2067-2079(2004).
RN [44]
RP VARIANT [LARGE SCALE ANALYSIS] MET-285.
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).
CC -!- FUNCTION: Serine/threonine kinase involved in cell cycle control and in
CC RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases
CC (CDKs) are activated by the binding to a cyclin and mediate the
CC progression through the cell cycle. Each different complex controls a
CC specific transition between 2 subsequent phases in the cell cycle.
CC Required for both activation and complex formation of CDK1/cyclin-B
CC during G2-M transition, and for activation of CDK2/cyclins during G1-S
CC transition (but not complex formation). CDK7 is the catalytic subunit
CC of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H,
CC SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11.
CC CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6
CC by threonine phosphorylation, thus regulating cell cycle progression.
CC CAK complexed to the core-TFIIH basal transcription factor activates
CC RNA polymerase II by serine phosphorylation of the repetitive C-
CC terminal domain (CTD) of its large subunit (POLR2A), allowing its
CC escape from the promoter and elongation of the transcripts
CC (PubMed:9852112). Phosphorylation of POLR2A in complex with DNA
CC promotes transcription initiation by triggering dissociation from DNA.
CC Its expression and activity are constant throughout the cell cycle.
CC Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but
CC is inactivated in turn by p53/TP53; this feedback loop may lead to an
CC arrest of the cell cycle and of the transcription, helping in cell
CC recovery, or to apoptosis. Required for DNA-bound peptides-mediated
CC transcription and cellular growth inhibition.
CC {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:11113184,
CC ECO:0000269|PubMed:16327805, ECO:0000269|PubMed:17373709,
CC ECO:0000269|PubMed:17386261, ECO:0000269|PubMed:17901130,
CC ECO:0000269|PubMed:19015234, ECO:0000269|PubMed:19071173,
CC ECO:0000269|PubMed:19136461, ECO:0000269|PubMed:19450536,
CC ECO:0000269|PubMed:19667075, ECO:0000269|PubMed:20360007,
CC ECO:0000269|PubMed:9372954, ECO:0000269|PubMed:9840937,
CC ECO:0000269|PubMed:9852112}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.22;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.22;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[DNA-directed RNA polymerase] + ATP = ADP + H(+) + phospho-
CC [DNA-directed RNA polymerase]; Xref=Rhea:RHEA:10216, Rhea:RHEA-
CC COMP:11321, Rhea:RHEA-COMP:11322, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43176, ChEBI:CHEBI:68546,
CC ChEBI:CHEBI:456216; EC=2.7.11.23;
CC Evidence={ECO:0000269|PubMed:9852112};
CC -!- ACTIVITY REGULATION: Inactivated by phosphorylation. Repressed by
CC roscovitine (seliciclib, CYC202), R547 (Ro-4584820) and SNS-032 (BMS-
CC 387032). The association of p53/TP53 to the CAK complex in response to
CC DNA damage reduces kinase activity toward CDK2 and RNA polymerase II
CC repetitive C-terminal domain (CTD), thus stopping cell cycle
CC progression. The inactivation by roscovitine promotes caspase-mediated
CC apoptosis in leukemic cells. {ECO:0000269|PubMed:19911397,
CC ECO:0000269|PubMed:9840937}.
CC -!- SUBUNIT: Associates primarily with cyclin-H (CCNH) and MAT1 to form the
CC CAK complex. CAK can further associate with the core-TFIIH to form the
CC TFIIH basal transcription factor; this complex is sensitive to UV
CC light. The CAK complex binds to p53/TP53 in response to DNA damage.
CC Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI. Interacts with HINT1
CC (PubMed:10958787). {ECO:0000269|PubMed:10882074,
CC ECO:0000269|PubMed:10958787, ECO:0000269|PubMed:15530371,
CC ECO:0000269|PubMed:15695176, ECO:0000269|PubMed:16327805,
CC ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17901130,
CC ECO:0000269|PubMed:9840937, ECO:0000269|PubMed:9852112}.
CC -!- INTERACTION:
CC P50613; P24941: CDK2; NbExp=3; IntAct=EBI-1245958, EBI-375096;
CC P50613; P11802: CDK4; NbExp=2; IntAct=EBI-1245958, EBI-295644;
CC P50613; P08238: HSP90AB1; NbExp=2; IntAct=EBI-1245958, EBI-352572;
CC P50613; Q96SB4: SRPK1; NbExp=2; IntAct=EBI-1245958, EBI-539478;
CC P50613; P78362: SRPK2; NbExp=2; IntAct=EBI-1245958, EBI-593303;
CC P50613; O00267: SUPT5H; NbExp=3; IntAct=EBI-1245958, EBI-710464;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10958787,
CC ECO:0000269|PubMed:15695176, ECO:0000269|PubMed:19071173}. Cytoplasm
CC {ECO:0000269|PubMed:15695176}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:19071173}. Note=Colocalizes with PRKCI in the
CC cytoplasm and nucleus (PubMed:15695176). Translocates from the nucleus
CC to cytoplasm and perinuclear region in response to DNA-bound peptides
CC (PubMed:19071173). {ECO:0000269|PubMed:15695176,
CC ECO:0000269|PubMed:19071173}.
CC -!- TISSUE SPECIFICITY: Ubiquitous.
CC -!- INDUCTION: Repressed by DNA-bound peptides.
CC {ECO:0000269|PubMed:19071173}.
CC -!- PTM: Phosphorylation of Ser-164 during mitosis inactivates the enzyme.
CC Phosphorylation of Thr-170 is required for activity. Phosphorylated at
CC Ser-164 and Thr-170 by CDK2. {ECO:0000269|PubMed:11113184,
CC ECO:0000269|PubMed:15530371, ECO:0000269|PubMed:9832506}.
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/cdk7/";
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DR EMBL; X79193; CAA55785.1; -; mRNA.
DR EMBL; L20320; AAA36657.1; -; mRNA.
DR EMBL; X77743; CAA54793.1; -; mRNA.
DR EMBL; X77303; CAA54508.1; -; mRNA.
DR EMBL; Y13120; CAA73587.1; -; mRNA.
DR EMBL; AY130859; AAM77799.1; -; Genomic_DNA.
DR EMBL; BC000834; AAH00834.1; -; mRNA.
DR EMBL; BC005298; AAH05298.1; -; mRNA.
DR CCDS; CCDS3999.1; -.
DR PIR; A54820; A54820.
DR PIR; I37215; I37215.
DR RefSeq; NP_001310998.1; NM_001324069.1.
DR RefSeq; NP_001310999.1; NM_001324070.1.
DR RefSeq; NP_001311000.1; NM_001324071.1.
DR RefSeq; NP_001311006.1; NM_001324077.1.
DR RefSeq; NP_001790.1; NM_001799.3.
DR PDB; 1UA2; X-ray; 3.02 A; A/B/C/D=1-346.
DR PDB; 6O9L; EM; 7.20 A; 8=1-346.
DR PDB; 6XBZ; EM; 2.80 A; J=1-346.
DR PDB; 6XD3; EM; 3.30 A; J=1-346.
DR PDB; 7B5O; EM; 2.50 A; J=1-346.
DR PDB; 7B5Q; EM; 2.50 A; J=1-346.
DR PDB; 7EGB; EM; 3.30 A; 8=1-346.
DR PDB; 7EGC; EM; 3.90 A; 8=1-346.
DR PDB; 7ENA; EM; 4.07 A; 8=1-346.
DR PDB; 7ENC; EM; 4.13 A; 8=1-346.
DR PDB; 7LBM; EM; 4.80 A; e=1-346.
DR PDB; 7NVR; EM; 4.50 A; 8=1-346.
DR PDB; 8BVW; EM; 4.00 A; 8=1-346.
DR PDB; 8BYQ; EM; 4.10 A; 8=1-346.
DR PDB; 8GXQ; EM; 5.04 A; HI=1-346.
DR PDB; 8GXS; EM; 4.16 A; HI=1-346.
DR PDB; 8ORM; EM; 1.90 A; J=1-346.
DR PDB; 8P4Z; X-ray; 2.75 A; A/B=10-311.
DR PDB; 8P6V; EM; 1.90 A; J=1-346.
DR PDB; 8P6Y; EM; 1.90 A; J=1-346.
DR PDBsum; 1UA2; -.
DR PDBsum; 6O9L; -.
DR PDBsum; 6XBZ; -.
DR PDBsum; 6XD3; -.
DR PDBsum; 7B5O; -.
DR PDBsum; 7B5Q; -.
DR PDBsum; 7EGB; -.
DR PDBsum; 7EGC; -.
DR PDBsum; 7ENA; -.
DR PDBsum; 7ENC; -.
DR PDBsum; 7LBM; -.
DR PDBsum; 7NVR; -.
DR PDBsum; 8BVW; -.
DR PDBsum; 8BYQ; -.
DR PDBsum; 8GXQ; -.
DR PDBsum; 8GXS; -.
DR PDBsum; 8ORM; -.
DR PDBsum; 8P4Z; -.
DR PDBsum; 8P6V; -.
DR PDBsum; 8P6Y; -.
DR AlphaFoldDB; P50613; -.
DR EMDB; EMD-12042; -.
DR EMDB; EMD-12610; -.
DR EMDB; EMD-16274; -.
DR EMDB; EMD-16331; -.
DR EMDB; EMD-17129; -.
DR EMDB; EMD-17470; -.
DR EMDB; EMD-17471; -.
DR EMDB; EMD-17472; -.
DR EMDB; EMD-17473; -.
DR EMDB; EMD-17474; -.
DR EMDB; EMD-17475; -.
DR EMDB; EMD-17476; -.
DR EMDB; EMD-17477; -.
DR EMDB; EMD-17478; -.
DR EMDB; EMD-17479; -.
DR EMDB; EMD-17480; -.
DR EMDB; EMD-17481; -.
DR EMDB; EMD-17482; -.
DR EMDB; EMD-17483; -.
DR EMDB; EMD-17484; -.
DR EMDB; EMD-17485; -.
DR EMDB; EMD-17486; -.
DR EMDB; EMD-17487; -.
DR EMDB; EMD-17488; -.
DR EMDB; EMD-17489; -.
DR EMDB; EMD-17490; -.
DR EMDB; EMD-17491; -.
DR EMDB; EMD-17492; -.
DR EMDB; EMD-17493; -.
DR EMDB; EMD-17494; -.
DR EMDB; EMD-17495; -.
DR EMDB; EMD-17496; -.
DR EMDB; EMD-17497; -.
DR EMDB; EMD-17498; -.
DR EMDB; EMD-17499; -.
DR EMDB; EMD-17500; -.
DR EMDB; EMD-17501; -.
DR EMDB; EMD-17502; -.
DR EMDB; EMD-17503; -.
DR EMDB; EMD-17504; -.
DR EMDB; EMD-17505; -.
DR EMDB; EMD-17506; -.
DR EMDB; EMD-17507; -.
DR EMDB; EMD-17508; -.
DR EMDB; EMD-17511; -.
DR EMDB; EMD-22123; -.
DR EMDB; EMD-22131; -.
DR EMDB; EMD-23255; -.
DR EMDB; EMD-31111; -.
DR EMDB; EMD-31112; -.
DR EMDB; EMD-31204; -.
DR EMDB; EMD-31207; -.
DR EMDB; EMD-34359; -.
DR EMDB; EMD-34360; -.
DR SMR; P50613; -.
DR BioGRID; 107457; 511.
DR ComplexPortal; CPX-2395; General transcription factor TFIIH complex.
DR ComplexPortal; CPX-578; Cyclin-dependent protein kinase-activating kinase complex.
DR CORUM; P50613; -.
DR DIP; DIP-5995N; -.
DR IntAct; P50613; 136.
DR MINT; P50613; -.
DR STRING; 9606.ENSP00000256443; -.
DR BindingDB; P50613; -.
DR ChEMBL; CHEMBL3055; -.
DR DrugBank; DB03496; Alvocidib.
DR DrugBank; DB02482; Phosphonothreonine.
DR DrugBank; DB06195; Seliciclib.
DR DrugBank; DB05969; SNS-032.
DR DrugBank; DB15442; Trilaciclib.
DR DrugCentral; P50613; -.
DR GuidetoPHARMACOLOGY; 1979; -.
DR GlyGen; P50613; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P50613; -.
DR PhosphoSitePlus; P50613; -.
DR BioMuta; CDK7; -.
DR DMDM; 1705722; -.
DR CPTAC; CPTAC-3036; -.
DR CPTAC; CPTAC-3037; -.
DR CPTAC; CPTAC-5912; -.
DR EPD; P50613; -.
DR jPOST; P50613; -.
DR MassIVE; P50613; -.
DR MaxQB; P50613; -.
DR PaxDb; 9606-ENSP00000256443; -.
DR PeptideAtlas; P50613; -.
DR ProteomicsDB; 56258; -.
DR Pumba; P50613; -.
DR Antibodypedia; 1446; 931 antibodies from 45 providers.
DR CPTC; P50613; 1 antibody.
DR DNASU; 1022; -.
DR Ensembl; ENST00000256443.8; ENSP00000256443.3; ENSG00000134058.12.
DR Ensembl; ENST00000615305.4; ENSP00000479116.1; ENSG00000277273.5.
DR GeneID; 1022; -.
DR KEGG; hsa:1022; -.
DR MANE-Select; ENST00000256443.8; ENSP00000256443.3; NM_001799.4; NP_001790.1.
DR UCSC; uc003jvs.5; human.
DR AGR; HGNC:1778; -.
DR CTD; 1022; -.
DR DisGeNET; 1022; -.
DR GeneCards; CDK7; -.
DR HGNC; HGNC:1778; CDK7.
DR HPA; ENSG00000134058; Low tissue specificity.
DR MIM; 601955; gene.
DR neXtProt; NX_P50613; -.
DR OpenTargets; ENSG00000134058; -.
DR PharmGKB; PA26314; -.
DR VEuPathDB; HostDB:ENSG00000134058; -.
DR eggNOG; KOG0659; Eukaryota.
DR GeneTree; ENSGT00940000155179; -.
DR InParanoid; P50613; -.
DR OMA; DDNWPGV; -.
DR OrthoDB; 244018at2759; -.
DR PhylomeDB; P50613; -.
DR TreeFam; TF101024; -.
DR BRENDA; 2.7.11.22; 2681.
DR BRENDA; 2.7.11.23; 2681.
DR PathwayCommons; P50613; -.
DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-HSA-113418; Formation of the Early Elongation Complex.
DR Reactome; R-HSA-167152; Formation of HIV elongation complex in the absence of HIV Tat.
DR Reactome; R-HSA-167158; Formation of the HIV-1 Early Elongation Complex.
DR Reactome; R-HSA-167160; RNA Pol II CTD phosphorylation and interaction with CE during HIV infection.
DR Reactome; R-HSA-167161; HIV Transcription Initiation.
DR Reactome; R-HSA-167162; RNA Polymerase II HIV Promoter Escape.
DR Reactome; R-HSA-167172; Transcription of the HIV genome.
DR Reactome; R-HSA-167200; Formation of HIV-1 elongation complex containing HIV-1 Tat.
DR Reactome; R-HSA-167246; Tat-mediated elongation of the HIV-1 transcript.
DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-HSA-6781827; Transcription-Coupled Nucleotide Excision Repair (TC-NER).
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
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-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-HSA-69231; Cyclin D associated events in G1.
DR Reactome; R-HSA-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-HSA-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-HSA-72086; mRNA Capping.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-HSA-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-HSA-73776; RNA Polymerase II Promoter Escape.
DR Reactome; R-HSA-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening.
DR Reactome; R-HSA-73863; RNA Polymerase I Transcription Termination.
DR Reactome; R-HSA-75953; RNA Polymerase II Transcription Initiation.
DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-HSA-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance.
DR Reactome; R-HSA-77075; RNA Pol II CTD phosphorylation and interaction with CE.
DR Reactome; R-HSA-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR SignaLink; P50613; -.
DR SIGNOR; P50613; -.
DR BioGRID-ORCS; 1022; 758 hits in 1195 CRISPR screens.
DR ChiTaRS; CDK7; human.
DR EvolutionaryTrace; P50613; -.
DR GeneWiki; Cyclin-dependent_kinase_7; -.
DR GenomeRNAi; 1022; -.
DR Pharos; P50613; Tchem.
DR PRO; PR:P50613; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; P50613; Protein.
DR Bgee; ENSG00000134058; Expressed in placenta and 102 other cell types or tissues.
DR ExpressionAtlas; P50613; baseline and differential.
DR Genevisible; P50613; HS.
DR GO; GO:0070516; C:CAK-ERCC2 complex; IDA:UniProtKB.
DR GO; GO:0019907; C:cyclin-dependent protein kinase activating kinase holoenzyme complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0000439; C:transcription factor TFIIH core complex; IDA:UniProtKB.
DR GO; GO:0005675; C:transcription factor TFIIH holo complex; IDA:UniProtKB.
DR GO; GO:0070985; C:transcription factor TFIIK complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:UniProtKB.
DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; TAS:Reactome.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; IDA:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0050821; P:protein stabilization; IMP:CAFA.
DR GO; GO:0051726; P:regulation of cell cycle; TAS:UniProtKB.
DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; IDA:ComplexPortal.
DR GO; GO:0042795; P:snRNA transcription by RNA polymerase II; TAS:Reactome.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006367; P:transcription initiation at RNA polymerase II promoter; IDA:ARUK-UCL.
DR CDD; cd07841; STKc_CDK7; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1.
DR IDEAL; IID00716; -.
DR InterPro; IPR037770; CDK7.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24056; CELL DIVISION PROTEIN KINASE; 1.
DR PANTHER; PTHR24056:SF0; CYCLIN-DEPENDENT KINASE 7; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ATP-binding; Cell cycle; Cell division;
KW Cytoplasm; DNA damage; DNA repair; Kinase; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transcription; Transcription regulation; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..346
FT /note="Cyclin-dependent kinase 7"
FT /id="PRO_0000085791"
FT DOMAIN 12..295
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ACT_SITE 137
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027,
FT ECO:0000269|PubMed:15530371"
FT BINDING 18..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:15530371"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:15530371"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976"
FT MOD_RES 164
FT /note="Phosphoserine; by CDK1 and CDK2"
FT /evidence="ECO:0000269|PubMed:11113184,
FT ECO:0000269|PubMed:9832506, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:23186163"
FT MOD_RES 170
FT /note="Phosphothreonine; by CDK2"
FT /evidence="ECO:0000269|PubMed:11113184,
FT ECO:0000269|PubMed:15530371, ECO:0000269|PubMed:9832506,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 321
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18691976,
FT ECO:0007744|PubMed:20068231"
FT VARIANT 163
FT /note="G -> A"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023118"
FT VARIANT 285
FT /note="T -> M (in dbSNP:rs34584424)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.6"
FT /id="VAR_023119"
FT MUTAGEN 41
FT /note="K->A: Total loss of activity."
FT MUTAGEN 41
FT /note="K->M: No effect on interaction with HINT1."
FT /evidence="ECO:0000269|PubMed:10958787"
FT MUTAGEN 91
FT /note="F->G: Enhanced capacity to bind ATP analogs."
FT /evidence="ECO:0000269|PubMed:16327805"
FT MUTAGEN 164
FT /note="S->A: No mitotic repression of transcriptional
FT activity of the reconstituted TFIIH complex."
FT /evidence="ECO:0000269|PubMed:9832506"
FT MUTAGEN 170
FT /note="T->A: Total loss of activity. Total loss of
FT transcriptional activity of the reconstituted TFIIH
FT complex."
FT /evidence="ECO:0000269|PubMed:8069918,
FT ECO:0000269|PubMed:9832506"
FT MUTAGEN 170
FT /note="T->E: No effect on interaction with HINT1."
FT /evidence="ECO:0000269|PubMed:10958787"
FT CONFLICT 130
FT /note="Q -> R (in Ref. 7; AAH05298)"
FT /evidence="ECO:0000305"
FT CONFLICT 249
FT /note="F -> C (in Ref. 5; CAA73587)"
FT /evidence="ECO:0000305"
FT CONFLICT 321
FT /note="S -> A (in Ref. 5; CAA73587)"
FT /evidence="ECO:0000305"
FT STRAND 12..21
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 24..31
FT /evidence="ECO:0007829|PDB:7B5O"
FT TURN 32..35
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 36..43
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 57..66
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 98..103
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 111..130
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:6XBZ"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:6XBZ"
FT HELIX 176..178
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 181..184
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 193..208
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 218..229
FT /evidence="ECO:0007829|PDB:7B5O"
FT TURN 234..236
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1UA2"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 257..260
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 266..275
FT /evidence="ECO:0007829|PDB:7B5O"
FT TURN 280..282
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 286..290
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 293..296
FT /evidence="ECO:0007829|PDB:7B5O"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:7B5O"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:7B5O"
SQ SEQUENCE 346 AA; 39038 MW; 0A94BFA7DD416CEB CRC64;
MALDVKSRAK RYEKLDFLGE GQFATVYKAR DKNTNQIVAI KKIKLGHRSE AKDGINRTAL
REIKLLQELS HPNIIGLLDA FGHKSNISLV FDFMETDLEV IIKDNSLVLT PSHIKAYMLM
TLQGLEYLHQ HWILHRDLKP NNLLLDENGV LKLADFGLAK SFGSPNRAYT HQVVTRWYRA
PELLFGARMY GVGVDMWAVG CILAELLLRV PFLPGDSDLD QLTRIFETLG TPTEEQWPDM
CSLPDYVTFK SFPGIPLHHI FSAAGDDLLD LIQGLFLFNP CARITATQAL KMKYFSNRPG
PTPGCQLPRP NCPVETLKEQ SNPALAIKRK RTEALEQGGL PKKLIF
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