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 11-NOV-2015, entry version 180. DE RecName: Full=Cyclin-dependent kinase 7; DE EC=2.7.11.22; DE EC=2.7.11.23; 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; 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 RT subunit 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., RA Welcsh P.L., Simmons A., Naylor S.L., Leach R.J., Lewis T.B., RA Bowcock A., Liu E.T.; RT "Two novel human serine/threonine kinases with homologies to the cell RT cycle regulating Xenopus MO15, and NIMA kinases: cloning and RT characterization of 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., RA Galas S., Cavadore J.-C., Doree M., Blanchard J.-M.; RT "Cloning, expression and subcellular localization of the human homolog RT of 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 RT project: 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; RA Ko L.J., Shieh S.-Y., Chen X., Jayaraman L., Tamai K., Taya Y., RA Prives C., Pan Z.-Q.; RT "p53 is phosphorylated by CDK7-cyclin H in a p36MAT1-dependent RT 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. 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 RT that 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 RP ENZYME 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 RT functions for the three enzymatic subunits, XPB, XPD, and cdk7."; RL Mol. Cell 3:87-95(1999). RN [14] 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., RA Levens D.; RT "The FBP interacting repressor targets TFIIH to inhibit activated RT transcription."; RL Mol. Cell 5:331-341(2000). RN [15] 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 RT by substrate specificity determinants outside the T loop."; RL Mol. Cell. Biol. 21:88-99(2001). RN [16] 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- RT iota in human glioma cells."; RL Tissue Cell 37:53-58(2005). RN [17] 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 RT Cdk7 complex revealed by chemical genetics."; RL Nat. Struct. Mol. Biol. 13:55-62(2006). RN [18] 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 RT of Cdk2 revealed by chemical genetics in human cells."; RL Mol. Cell 25:839-850(2007). RN [19] 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 [20] 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., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-7; SER-164 AND SER-321, RP AND 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 RT the kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [22] 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- RT dependent kinase 7."; RL Mol. Endocrinol. 22:91-104(2008). RN [23] 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 [24] 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., RA Eick D., Ansari A.Z.; RT "TFIIH kinase places bivalent marks on the carboxy-terminal domain of RT RNA polymerase II."; RL Mol. Cell 34:387-393(2009). RN [25] 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 RT 203 phosphorylation."; RL Mol. Cell. Biol. 29:613-625(2009). RN [26] 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- RT terminal domain Ser7 residues, promoter-proximal pausing, and RT termination by RNA polymerase II."; RL Mol. Cell. Biol. 29:5455-5464(2009). RN [27] 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 [28] 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 [29] 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 [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, AND IDENTIFICATION RP BY 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 [31] 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 RT at the G2/M transition."; RL J. Biol. Chem. 285:16978-16990(2010). RN [32] RP ENZYME 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: RT Inhibition of CDK7 sensitizes leukemic cells to caspase-dependent RT apoptosis."; RL J. Cell. Biochem. 109:217-235(2010). RN [33] 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 RT control and a target for drugs?"; RL Cell Cycle 4:572-577(2005). RN [34] 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 [35] 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., RA Mann M.; RT "Quantitative phosphoproteomics reveals widespread full RT phosphorylation site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [36] 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., RA Buerckstuemmer T., 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 [37] 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 [38] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., RA Blagoev B.; RT "System-wide temporal characterization of the proteome and RT phosphoproteome of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [39] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS RP SPECTROMETRY [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., RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., RA Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N- RT terminal acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [40] 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., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [41] RP X-RAY CRYSTALLOGRAPHY (3.02 ANGSTROMS) IN COMPLEX WITH ATP, ACTIVE RP SITE, 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 [42] 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., RA Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., RA O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., RA Bhamra G., Buck G., Choudhury B., Clements J., Cole J., Dicks E., RA Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., RA Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., RA Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., RA West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., RA Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., RA DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., RA Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., RA Yuen S.T., Leung S.Y., Wooster R., 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 CC and in RNA polymerase II-mediated RNA transcription. Cyclin- CC dependent kinases (CDKs) are activated by the binding to a cyclin CC and mediate the progression through the cell cycle. Each different CC complex controls a specific transition between 2 subsequent phases CC in the cell cycle. Required for both activation and complex CC formation of CDK1/cyclin-B during G2-M transition, and for CC activation of CDK2/cyclins during G1-S transition (but not complex CC formation). CDK7 is the catalytic subunit of the CDK-activating CC kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, CC POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK CC activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 CC by threonine phosphorylation, thus regulating cell cycle CC progression. CAK complexed to the core-TFIIH basal transcription CC factor activates RNA polymerase II by serine phosphorylation of CC the repetitive C-terminal domain (CTD) of its large subunit CC (POLR2A), allowing its escape from the promoter and elongation of CC the transcripts. Phosphorylation of POLR2A in complex with DNA CC promotes transcription initiation by triggering dissociation from CC DNA. Its expression and activity are constant throughout the cell CC cycle. Upon DNA damage, triggers p53/TP53 activation by CC phosphorylation, but is inactivated in turn by p53/TP53; this CC feedback loop may lead to an arrest of the cell cycle and of the CC transcription, helping in cell recovery, or to apoptosis. Required CC for DNA-bound peptides-mediated transcription and cellular growth CC inhibition. {ECO:0000269|PubMed:10024882, CC ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:16327805, CC ECO:0000269|PubMed:17373709, ECO:0000269|PubMed:17386261, CC ECO:0000269|PubMed:17901130, ECO:0000269|PubMed:19015234, CC ECO:0000269|PubMed:19071173, ECO:0000269|PubMed:19136461, CC ECO:0000269|PubMed:19450536, ECO:0000269|PubMed:19667075, CC ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:9372954, CC ECO:0000269|PubMed:9840937}. CC -!- CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein. CC -!- CATALYTIC ACTIVITY: ATP + [DNA-directed RNA polymerase] = ADP + CC [DNA-directed RNA polymerase] phosphate. CC -!- ENZYME REGULATION: Inactivated by phosphorylation. Repressed by CC roscovitine (seliciclib, CYC202), R547 (Ro-4584820) and SNS-032 CC (BMS-387032). The association of p53/TP53 to the CAK complex in CC response to DNA damage reduces kinase activity toward CDK2 and RNA CC polymerase II repetitive C-terminal domain (CTD), thus stopping CC cell cycle progression. The inactivation by roscovitine promotes CC caspase-mediated apoptosis in leukemic cells. CC {ECO:0000269|PubMed:19911397, ECO:0000269|PubMed:9840937}. CC -!- SUBUNIT: Associates primarily with cyclin-H (CCNH) and MAT1 to CC form the CAK complex. CAK can further associate with the core- CC TFIIH to form the TFIIH basal transcription factor; this complex CC is sensitive to UV light. The CAK complex binds to p53/TP53 in CC response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and CC PRKCI. {ECO:0000269|PubMed:10882074, 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 Q01094:E2F1; NbExp=2; IntAct=EBI-1245958, EBI-448924; CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm. Cytoplasm, perinuclear CC region. Note=Colocalizes with PRKCI in the cytoplasm and nucleus. CC Translocates from the nucleus to cytoplasm and perinuclear region CC in response to DNA-bound peptides. 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 CC enzyme. Phosphorylation of Thr-170 is required for activity. CC Phosphorylated at Ser-164 and Thr-170 by CDK2. CC {ECO:0000269|PubMed:11113184, ECO:0000269|PubMed:15530371, CC ECO:0000269|PubMed:9832506}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC CC Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. CC -!- SIMILARITY: Contains 1 protein kinase domain. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/cdk7/"; 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; 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_001790.1; NM_001799.3. DR UniGene; Hs.184298; -. DR PDB; 1LG3; Model; -; A=1-307. DR PDB; 1PA8; Model; -; A=181-346. DR PDB; 1UA2; X-ray; 3.02 A; A/B/C/D=1-346. DR PDB; 2HIC; Model; -; B=13-311. DR PDBsum; 1LG3; -. DR PDBsum; 1PA8; -. DR PDBsum; 1UA2; -. DR PDBsum; 2HIC; -. DR ProteinModelPortal; P50613; -. DR SMR; P50613; 13-311. DR BioGrid; 107457; 82. DR DIP; DIP-5995N; -. DR IntAct; P50613; 23. DR MINT; MINT-3018528; -. DR STRING; 9606.ENSP00000256443; -. DR BindingDB; P50613; -. DR ChEMBL; CHEMBL3055; -. DR GuidetoPHARMACOLOGY; 1979; -. DR PhosphoSite; P50613; -. DR BioMuta; CDK7; -. DR DMDM; 1705722; -. DR MaxQB; P50613; -. DR PaxDb; P50613; -. DR PeptideAtlas; P50613; -. DR PRIDE; P50613; -. DR DNASU; 1022; -. DR Ensembl; ENST00000256443; ENSP00000256443; ENSG00000134058. DR Ensembl; ENST00000615305; ENSP00000479116; ENSG00000277273. DR GeneID; 1022; -. DR KEGG; hsa:1022; -. DR UCSC; uc003jvs.4; human. DR CTD; 1022; -. DR GeneCards; CDK7; -. DR HGNC; HGNC:1778; CDK7. DR HPA; CAB004364; -. DR HPA; HPA007932; -. DR MIM; 601955; gene. DR neXtProt; NX_P50613; -. DR PharmGKB; PA26314; -. DR eggNOG; KOG0659; Eukaryota. DR eggNOG; ENOG410XQDH; LUCA. DR GeneTree; ENSGT00760000119242; -. DR HOGENOM; HOG000233024; -. DR HOVERGEN; HBG014652; -. DR InParanoid; P50613; -. DR KO; K02202; -. DR OMA; VSFKIFP; -. DR PhylomeDB; P50613; -. DR TreeFam; TF101024; -. DR BRENDA; 2.7.11.22; 2681. DR BRENDA; 2.7.11.23; 2681. DR Reactome; R-HSA-110302; Formation of transcription-coupled NER (TC-NER) repair complex. DR Reactome; R-HSA-110304; Dual incision reaction in TC-NER. 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. 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-674695; RNA Polymerase II Pre-transcription Events. 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 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-73777; RNA Polymerase I Chain Elongation. 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-73935; Formation of incision complex in GG-NER. DR Reactome; R-HSA-73941; Dual incision reaction in GG-NER. 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 SignaLink; P50613; -. DR EvolutionaryTrace; P50613; -. DR GeneWiki; Cyclin-dependent_kinase_7; -. DR GenomeRNAi; 1022; -. DR NextBio; 4295; -. DR PRO; PR:P50613; -. DR Proteomes; UP000005640; Chromosome 5. DR Bgee; P50613; -. DR CleanEx; HS_CDK7; -. DR ExpressionAtlas; P50613; baseline and differential. DR Genevisible; P50613; HS. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0005675; C:holo TFIIH complex; IDA:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0050681; F:androgen receptor binding; NAS:UniProtKB. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0008094; F:DNA-dependent ATPase activity; IDA:UniProtKB. DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB. DR GO; GO:0004672; F:protein kinase activity; TAS:ProtInc. DR GO; GO:0008353; F:RNA polymerase II carboxy-terminal domain kinase activity; IDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; NAS:UniProtKB. DR GO; GO:0006370; P:7-methylguanosine mRNA capping; TAS:Reactome. DR GO; GO:0030521; P:androgen receptor signaling pathway; NAS:UniProtKB. DR GO; GO:0007050; P:cell cycle arrest; TAS:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0008283; P:cell proliferation; TAS:ProtInc. DR GO; GO:0006281; P:DNA repair; TAS:Reactome. DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; TAS:Reactome. DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; TAS:Reactome. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0000278; P:mitotic cell cycle; TAS:Reactome. DR GO; GO:0045814; P:negative regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0006289; P:nucleotide-excision repair; TAS:Reactome. DR GO; GO:0000718; P:nucleotide-excision repair, DNA damage removal; TAS:Reactome. DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; NAS:UniProtKB. DR GO; GO:0050434; P:positive regulation of viral transcription; TAS:Reactome. DR GO; GO:0000079; P:regulation of cyclin-dependent protein serine/threonine kinase activity; TAS:ProtInc. DR GO; GO:0040029; P:regulation of gene expression, epigenetic; TAS:Reactome. DR GO; GO:0006363; P:termination of RNA polymerase I transcription; TAS:Reactome. DR GO; GO:0006362; P:transcription elongation from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0006368; P:transcription elongation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006360; P:transcription from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0006366; P:transcription from RNA polymerase II promoter; IDA:UniProtKB. DR GO; GO:0006361; P:transcription initiation from RNA polymerase I promoter; TAS:Reactome. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; TAS:Reactome. DR GO; GO:0016032; P:viral process; TAS:Reactome. DR InterPro; IPR011009; Kinase-like_dom. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR002290; Ser/Thr_dual-sp_kinase. 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; ATP-binding; Cell cycle; Cell division; KW Complete proteome; Cytoplasm; DNA damage; DNA repair; Kinase; KW Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Serine/threonine-protein kinase; Transcription; KW Transcription regulation; Transferase. FT INIT_MET 1 1 Removed. {ECO:0000244|PubMed:22814378}. FT CHAIN 2 346 Cyclin-dependent kinase 7. FT /FTId=PRO_0000085791. FT DOMAIN 12 295 Protein kinase. {ECO:0000255|PROSITE- FT ProRule:PRU00159}. FT NP_BIND 18 26 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159, FT ECO:0000269|PubMed:15530371}. FT ACT_SITE 137 137 Proton acceptor. {ECO:0000255|PROSITE- FT ProRule:PRU00159, ECO:0000255|PROSITE- FT ProRule:PRU10027, FT ECO:0000269|PubMed:15530371}. FT BINDING 41 41 ATP. {ECO:0000255|PROSITE- FT ProRule:PRU00159, FT ECO:0000269|PubMed:15530371}. FT MOD_RES 2 2 N-acetylalanine. FT {ECO:0000244|PubMed:22814378}. FT MOD_RES 7 7 Phosphoserine. FT {ECO:0000244|PubMed:18691976}. FT MOD_RES 164 164 Phosphoserine; by CDK1 and CDK2. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:18691976, FT ECO:0000269|PubMed:11113184, FT ECO:0000269|PubMed:9832506}. FT MOD_RES 170 170 Phosphothreonine; by CDK2. FT {ECO:0000244|PubMed:18669648, FT ECO:0000244|PubMed:19690332, FT ECO:0000244|PubMed:20068231, FT ECO:0000244|PubMed:21406692, FT ECO:0000269|PubMed:11113184, FT ECO:0000269|PubMed:15530371, FT ECO:0000269|PubMed:9832506}. FT MOD_RES 321 321 Phosphoserine. FT {ECO:0000244|PubMed:18691976, FT ECO:0000244|PubMed:20068231}. FT VARIANT 163 163 G -> A. {ECO:0000269|Ref.6}. FT /FTId=VAR_023118. FT VARIANT 285 285 T -> M (in dbSNP:rs34584424). FT {ECO:0000269|PubMed:17344846, FT ECO:0000269|Ref.6}. FT /FTId=VAR_023119. FT MUTAGEN 41 41 K->A: Total loss of activity. FT MUTAGEN 91 91 F->G: Enhanced capacity to bind ATP FT analogs. {ECO:0000269|PubMed:16327805}. FT MUTAGEN 164 164 S->A: No mitotic repression of FT transcriptional activity of the FT reconstituted TFIIH complex. FT {ECO:0000269|PubMed:9832506}. FT MUTAGEN 170 170 T->A: Total loss of activity. Total loss FT of transcriptional activity of the FT reconstituted TFIIH complex. FT {ECO:0000269|PubMed:8069918, FT ECO:0000269|PubMed:9832506}. FT CONFLICT 130 130 Q -> R (in Ref. 7; AAH05298). FT {ECO:0000305}. FT CONFLICT 249 249 F -> C (in Ref. 5; CAA73587). FT {ECO:0000305}. FT CONFLICT 321 321 S -> A (in Ref. 5; CAA73587). FT {ECO:0000305}. FT STRAND 14 21 {ECO:0000244|PDB:1UA2}. FT STRAND 24 30 {ECO:0000244|PDB:1UA2}. FT STRAND 36 42 {ECO:0000244|PDB:1UA2}. FT HELIX 58 68 {ECO:0000244|PDB:1UA2}. FT STRAND 77 81 {ECO:0000244|PDB:1UA2}. FT STRAND 88 92 {ECO:0000244|PDB:1UA2}. FT STRAND 95 97 {ECO:0000244|PDB:1UA2}. FT HELIX 98 102 {ECO:0000244|PDB:1UA2}. FT HELIX 113 130 {ECO:0000244|PDB:1UA2}. FT HELIX 140 142 {ECO:0000244|PDB:1UA2}. FT STRAND 143 145 {ECO:0000244|PDB:1UA2}. FT STRAND 151 153 {ECO:0000244|PDB:1UA2}. FT HELIX 157 159 {ECO:0000244|PDB:1UA2}. FT TURN 161 163 {ECO:0000244|PDB:1UA2}. FT HELIX 181 184 {ECO:0000244|PDB:1UA2}. FT HELIX 192 208 {ECO:0000244|PDB:1UA2}. FT HELIX 218 229 {ECO:0000244|PDB:1UA2}. FT TURN 234 236 {ECO:0000244|PDB:1UA2}. FT STRAND 237 239 {ECO:0000244|PDB:1UA2}. FT HELIX 257 260 {ECO:0000244|PDB:1UA2}. FT HELIX 266 276 {ECO:0000244|PDB:1UA2}. FT TURN 280 282 {ECO:0000244|PDB:1UA2}. FT HELIX 286 290 {ECO:0000244|PDB:1UA2}. FT HELIX 293 295 {ECO:0000244|PDB:1UA2}. FT STRAND 297 299 {ECO:0000244|PDB:1UA2}. FT STRAND 304 307 {ECO:0000244|PDB:1UA2}. 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 //