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 02-SEP-2026, entry version 247. DE RecName: Full=Cyclin-dependent kinase 7; DE EC=2.7.11.22 {ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:9372954, ECO:0000269|PubMed:9840937}; DE EC=2.7.11.23 {ECO:0000269|PubMed:26257281, ECO:0000269|PubMed:28768201, 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; DOI=10.4161/cc.4.4.1607; 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 FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=26257281; DOI=10.1016/j.molcel.2015.06.032; RA Nilson K.A., Guo J., Turek M.E., Brogie J.E., Delaney E., Luse D.S., RA Price D.H.; RT "THZ1 Reveals Roles for Cdk7 in Co-transcriptional Capping and Pausing."; RL Mol. Cell 59:576-587(2015). RN [44] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=28768201; DOI=10.1016/j.celrep.2017.07.021; RA Ebmeier C.C., Erickson B., Allen B.L., Allen M.A., Kim H., Fong N., RA Jacobsen J.R., Liang K., Shilatifard A., Dowell R.D., Old W.M., RA Bentley D.L., Taatjes D.J.; RT "Human TFIIH Kinase CDK7 Regulates Transcription-Associated Chromatin RT Modifications."; RL Cell Rep. 20:1173-1186(2017). RN [45] {ECO:0007744|PDB:1UA2} 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 [46] {ECO:0007744|PDB:9I9I, ECO:0007744|PDB:9I9J, ECO:0007744|PDB:9I9K, ECO:0007744|PDB:9QCV, ECO:0007744|PDB:9QCX, ECO:0007744|PDB:9SKQ} RP STRUCTURE BY ELECTRON MICROSCOPY (2.40 ANGSTROMS) IN COMPLEX WITH ADP AND RP MG(2+), FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBUNIT, AND RP MUTAGENESIS OF ARG-176; SER-217; LEU-219 AND THR-223. RX PubMed=41100585; DOI=10.1126/science.adw0053; RA Cushing V.I., McGeoch A.J.S., Williams S.L., Roumeliotis T.I., Feng J., RA Dan L.M., Choudhary J.S., Davey N.E., Greber B.J.; RT "Structural basis of T-loop-independent recognition and activation of CDKs RT by the CDK-activating kinase."; RL Science 390:911-917(2025). RN [47] 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 (PubMed:9852112, CC PubMed:19136461, PubMed:26257281, PubMed:28768201). As a cyclin- CC dependent kinase, CDK7 is activated by the binding to cyclin-H/CCNH and CC the CDK-activating kinase assembly factor MAT1 (PubMed:41100585). CC Catalytic subunit of the CDK-activating kinase (CAK) complex, a master CC regulator of CDK activity by catalyzing the activating threonine CC phosphorylation of CDKs (PubMed:41100585). CAK activates major CC mediators of cell cycle control, including CDK1, CDK2, CDK4 and CDK6, CC and plays a key role in regulating cell cycle progression CC (PubMed:41100585). CAK complexed to the core-TFIIH basal transcription CC factor activates RNA polymerase II by serine phosphorylation of the CTD CC of POLR2A, allowing its escape from the promoter and elongation of the CC transcripts (PubMed:9852112). Initiates transcription by RNA polymerase CC II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive CC C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting CC dissociation from DNA and initiation (PubMed:19136461, PubMed:26257281, CC PubMed:28768201). Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, CC p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11 (PubMed:9372954, CC PubMed:9840937, PubMed:19136461, PubMed:26257281, PubMed:28768201, CC PubMed:41100585, PubMed:41100585). Its expression and activity are CC constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 CC activation by phosphorylation, but is inactivated in turn by p53/TP53; CC this feedback loop may lead to an arrest of the cell cycle and of the CC transcription, helping in cell recovery, or to apoptosis. Required for CC DNA-bound peptides-mediated transcription and cellular growth CC inhibition. {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:26257281, ECO:0000269|PubMed:28768201, CC ECO:0000269|PubMed:41100585, ECO:0000269|PubMed:9372954, CC ECO:0000269|PubMed:9840937, ECO:0000269|PubMed:9852112}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); 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:20360007, ECO:0000269|PubMed:9372954, CC ECO:0000269|PubMed:9840937}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.22; CC Evidence={ECO:0000269|PubMed:20360007, ECO:0000269|PubMed:41100585, CC ECO:0000269|PubMed:9372954, ECO:0000269|PubMed:9840937}; CC -!- CATALYTIC ACTIVITY: CC Reaction=[DNA-directed RNA polymerase] + ATP = phospho-[DNA-directed CC RNA polymerase] + ADP + H(+); 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:26257281, ECO:0000269|PubMed:28768201, CC ECO:0000269|PubMed:9852112}; CC -!- ACTIVITY REGULATION: Activated by phosphorylation (PubMed:41100585). CC Phosphorylated by CDKs, including CDK1 and CDK2, and reciprocally CC phosphorylating its activating kinase (PubMed:41100585). 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 (PubMed:9840937). The inactivation by roscovitine promotes CC caspase-mediated apoptosis in leukemic cells (PubMed:19911397). CC Specifically inactivated by THZ1 (PubMed:26257281). CC {ECO:0000269|PubMed:19911397, ECO:0000269|PubMed:26257281, CC ECO:0000269|PubMed:41100585, ECO:0000269|PubMed:9840937}. CC -!- SUBUNIT: Component of the CDK-activating kinase (CAK) complex, CC consisting of CDK7, cyclin-H/CCNH and MAT1, which is a master regulator CC of CDK activity (PubMed:41100585). CAK binds to both free CDK2 and CC cyclin-bound CDK2, with a higher affinity for the cyclin-bound form CC (PubMed:41100585). CAK can further associate with the core-TFIIH to CC form the TFIIH basal transcription factor (PubMed:9852112). The CAK CC complex binds to p53/TP53 in response to DNA damage. Interacts with CC 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:41100585, ECO:0000269|PubMed:9840937, CC 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=4; 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 --------------------------------------------------------------------------- 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_001310998.1; NM_001324069.2. DR RefSeq; NP_001310999.1; NM_001324070.2. DR RefSeq; NP_001311000.1; NM_001324071.2. DR RefSeq; NP_001311006.1; NM_001324077.1. DR RefSeq; NP_001790.1; NM_001799.4. 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; 8P6W; EM; 1.90 A; J=1-346. DR PDB; 8P6X; EM; 1.90 A; J=1-346. DR PDB; 8P6Y; EM; 1.90 A; J=1-346. DR PDB; 8P6Z; EM; 2.10 A; J=1-346. DR PDB; 8P70; EM; 2.00 A; J=1-346. DR PDB; 8P71; EM; 2.00 A; J=1-346. DR PDB; 8P72; EM; 1.90 A; J=1-346. DR PDB; 8P73; EM; 2.00 A; J=1-346. DR PDB; 8P74; EM; 2.20 A; J=1-346. DR PDB; 8P75; EM; 2.00 A; J=1-346. DR PDB; 8P76; EM; 2.00 A; J=1-346. DR PDB; 8P77; EM; 1.80 A; J=1-346. DR PDB; 8P78; EM; 1.90 A; J=1-346. DR PDB; 8P79; EM; 1.70 A; J=1-346. DR PDB; 8P7L; EM; 2.10 A; J=1-346. DR PDB; 8PLZ; EM; 1.90 A; J=1-346. DR PDB; 8PYR; X-ray; 2.15 A; A/E=1-346. DR PDB; 8R99; X-ray; 1.81 A; A=1-346. DR PDB; 8R9A; X-ray; 1.71 A; A=1-346. DR PDB; 8R9B; X-ray; 2.21 A; A/B/C/D=1-326. DR PDB; 8R9O; X-ray; 2.22 A; A/B=1-346. DR PDB; 8R9S; X-ray; 2.78 A; A/B=1-346. DR PDB; 8R9U; X-ray; 1.94 A; A/B=1-346. DR PDB; 8S0R; EM; 2.40 A; J=1-346. DR PDB; 8S0T; EM; 2.30 A; J=1-346. DR PDB; 9HIX; EM; 2.60 A; J=1-346. DR PDB; 9HIY; EM; 2.30 A; J=1-346. DR PDB; 9HJ0; EM; 2.60 A; J=1-346. DR PDB; 9I9I; EM; 3.50 A; J=1-346. DR PDB; 9I9J; EM; 3.10 A; J=1-346. DR PDB; 9I9K; EM; 2.40 A; J=1-346. DR PDB; 9QCV; EM; 2.50 A; J=1-346. DR PDB; 9QCX; EM; 2.60 A; J=1-346. DR PDB; 9QJN; EM; 2.40 A; J=1-346. DR PDB; 9SKQ; EM; 3.40 A; J=1-346. 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-17509; -. DR EMDB; EMD-17510; -. DR EMDB; EMD-17511; -. DR EMDB; EMD-17512; -. DR EMDB; EMD-17513; -. DR EMDB; EMD-17514; -. DR EMDB; EMD-17515; -. DR EMDB; EMD-17516; -. DR EMDB; EMD-17517; -. DR EMDB; EMD-17518; -. DR EMDB; EMD-17519; -. DR EMDB; EMD-17520; -. DR EMDB; EMD-17521; -. DR EMDB; EMD-17522; -. DR EMDB; EMD-17523; -. DR EMDB; EMD-17524; -. DR EMDB; EMD-17525; -. DR EMDB; EMD-17526; -. DR EMDB; EMD-17527; -. DR EMDB; EMD-17536; -. DR EMDB; EMD-17754; -. DR EMDB; EMD-19627; -. DR EMDB; EMD-19628; -. 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 EMDB; EMD-52205; -. DR EMDB; EMD-52206; -. DR EMDB; EMD-52207; -. DR EMDB; EMD-52758; -. DR EMDB; EMD-52759; -. DR EMDB; EMD-52760; -. DR EMDB; EMD-52761; -. DR EMDB; EMD-53027; -. DR EMDB; EMD-53028; -. DR EMDB; EMD-53205; -. DR EMDB; EMD-54971; -. DR SMR; P50613; -. DR BioGRID; 107457; 521. 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 FunCoup; P50613; 3585. DR IntAct; P50613; 165. DR MINT; P50613; -. DR NDEx; IQUERY-CP-CDK7; 11 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000256443; -. DR BindingDB; P50613; -. DR ChEMBL; CHEMBL3055; -. DR DrugBank; DB03496; Alvocidib. DR DrugBank; DB21454; Mevociclib. DR DrugBank; DB02482; Phosphonothreonine. DR DrugBank; DB08094; RO-4584820. DR DrugBank; DB16061; Samuraciclib. DR DrugBank; DB06195; Seliciclib. DR DrugBank; DB05969; SNS-032. DR DrugBank; DB15442; Trilaciclib. DR DrugCentral; P50613; -. DR GuidetoPHARMACOLOGY; 1979; -. DR GlyGen; P50613; 2 sites, 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 jPOST; P50613; -. DR MassIVE; P50613; -. DR PaxDb; 9606-ENSP00000256443; -. DR PeptideAtlas; P50613; -. DR ProteomicsDB; 56258; -. DR Pumba; P50613; -. DR ABCD; P50613; 1 sequenced antibody. DR Antibodypedia; 1446; 832 antibodies from 48 providers. DR CPTC; P50613; 1 antibody. DR DNASU; 1022; -. DR Ensembl; ENST00000256443.8; ENSP00000256443.3; ENSG00000134058.13. 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 ClinPGx; PA26314; -. 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 OpenTargets; ENSG00000134058; -. DR VEuPathDB; HostDB:ENSG00000134058; -. DR eggNOG; KOG0659; Eukaryota. DR GeneTree; ENSGT00940000155179; -. DR InParanoid; P50613; -. DR OMA; GIHHCHR; -. DR OrthoDB; 1732493at2759; -. DR PAN-GO; P50613; 7 GO annotations based on evolutionary models. DR PhylomeDB; P50613; -. 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 Agora; ENSG00000134058; -. DR BioGRID-ORCS; 1022; 758 hits in 1195 CRISPR screens. DR CD-CODE; 804901D1; Nuclear speckle. DR CD-CODE; 91857CE7; Nucleolus. 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 GO; GO:0070516; C:CAK-ERCC2 complex; IDA:UniProtKB. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; IDA:ComplexPortal. DR GO; GO:0005737; C:cytoplasm; EXP:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0001650; C:fibrillar center; IDA:HPA. 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: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:InterPro. 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; EXP:UniProtKB. 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:0140836; F:RNA polymerase II CTD heptapeptide repeat S5 kinase activity; IDA:UniProtKB. DR GO; GO:0006289; P:nucleotide-excision repair; NAS:ComplexPortal. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IMP:CAFA. DR GO; GO:0051726; P:regulation of cell cycle; IBA:GO_Central. 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; TAS:Reactome. DR GO; GO:0006367; P:transcription initiation at RNA polymerase II promoter; IDA:UniProtKB. DR CDD; cd07841; STKc_CDK7; 1. DR FunFam; 1.10.510.10:FF:000097; Putative cyclin-dependent kinase 7; 1. DR FunFam; 3.30.200.20:FF:000190; Putative cyclin-dependent kinase 7; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR IDEAL; IID00716; -. DR InterPro; IPR050108; CDK. 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. 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; 8P6W; -. DR PDBsum; 8P6X; -. DR PDBsum; 8P6Y; -. DR PDBsum; 8P6Z; -. DR PDBsum; 8P70; -. DR PDBsum; 8P71; -. DR PDBsum; 8P72; -. DR PDBsum; 8P73; -. DR PDBsum; 8P74; -. DR PDBsum; 8P75; -. DR PDBsum; 8P76; -. DR PDBsum; 8P77; -. DR PDBsum; 8P78; -. DR PDBsum; 8P79; -. DR PDBsum; 8P7L; -. DR PDBsum; 8PLZ; -. DR PDBsum; 8PYR; -. DR PDBsum; 8R99; -. DR PDBsum; 8R9A; -. DR PDBsum; 8R9B; -. DR PDBsum; 8R9O; -. DR PDBsum; 8R9S; -. DR PDBsum; 8R9U; -. DR PDBsum; 8S0R; -. DR PDBsum; 8S0T; -. DR PDBsum; 9HIX; -. DR PDBsum; 9HIY; -. DR PDBsum; 9HJ0; -. DR PDBsum; 9I9I; -. DR PDBsum; 9I9J; -. DR PDBsum; 9I9K; -. DR PDBsum; 9QCV; -. DR PDBsum; 9QCX; -. DR PDBsum; 9QJN; -. DR PDBsum; 9SKQ; -. 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; Proteomics identification; Reference proteome; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW 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 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 19 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 20 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 21 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 22 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9I" FT BINDING 22 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 23 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 24 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 25 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000269|PubMed:15530371" FT BINDING 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="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9K" 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 BINDING 47 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9J" FT BINDING 48 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9J" FT BINDING 92 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9I, ECO:0007744|PDB:9I9K" FT BINDING 94 FT /ligand="ADP" FT /ligand_id="ChEBI:CHEBI:456216" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9I, ECO:0007744|PDB:9I9K" FT BINDING 142 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9J, ECO:0007744|PDB:9I9K, FT ECO:0007744|PDB:9QCV, ECO:0007744|PDB:9SKQ" FT BINDING 155 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000269|PubMed:41100585, FT ECO:0007744|PDB:9I9J, ECO:0007744|PDB:9I9K, FT ECO:0007744|PDB:9QCV, ECO:0007744|PDB:9SKQ" 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 MUTAGEN 176 FT /note="R->A: Impairs phosphorylation of CDK2; when FT associated with A-217 and A-223." FT /evidence="ECO:0000269|PubMed:41100585" FT MUTAGEN 217 FT /note="S->A: Impairs phosphorylation of CDK2; when FT associated with A-176 and A-223." FT /evidence="ECO:0000269|PubMed:41100585" FT MUTAGEN 219 FT /note="L->R: Impairs phosphorylation of CDK2." FT /evidence="ECO:0000269|PubMed:41100585" FT MUTAGEN 223 FT /note="T->A: Impairs phosphorylation of CDK2; when FT associated with A-176 and A-217." FT /evidence="ECO:0000269|PubMed:41100585" 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 TURN 2..4 FT /evidence="ECO:0007829|PDB:8R9B" FT STRAND 5..7 FT /evidence="ECO:0007829|PDB:8R9B" FT STRAND 16..20 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 25..29 FT /evidence="ECO:0007829|PDB:8P79" FT TURN 32..34 FT /evidence="ECO:0007829|PDB:8R9A" FT STRAND 38..41 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 50..53 FT /evidence="ECO:0007829|PDB:8PYR" FT HELIX 57..67 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 77..83 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 86..92 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 95..97 FT /evidence="ECO:0007829|PDB:8P77" FT HELIX 98..103 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 105..107 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 111..130 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:6XBZ" FT HELIX 140..142 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 143..145 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 151..153 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 156..158 FT /evidence="ECO:0007829|PDB:8P77" FT STRAND 160..164 FT /evidence="ECO:0007829|PDB:8R9U" FT HELIX 165..167 FT /evidence="ECO:0007829|PDB:8R9A" FT STRAND 168..170 FT /evidence="ECO:0007829|PDB:8R9A" FT HELIX 176..178 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 181..184 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 188..190 FT /evidence="ECO:0007829|PDB:8PYR" FT HELIX 193..208 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 218..229 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 231..233 FT /evidence="ECO:0007829|PDB:8R9A" FT TURN 234..236 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:1UA2" FT HELIX 240..242 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 246..248 FT /evidence="ECO:0007829|PDB:8P72" FT HELIX 249..251 FT /evidence="ECO:0007829|PDB:8R9A" FT HELIX 254..256 FT /evidence="ECO:0007829|PDB:9HJ0" FT HELIX 257..260 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 261..263 FT /evidence="ECO:0007829|PDB:8P75" FT HELIX 266..275 FT /evidence="ECO:0007829|PDB:8P79" FT TURN 280..282 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 286..291 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 293..296 FT /evidence="ECO:0007829|PDB:8P79" FT STRAND 297..299 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 300..303 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 304..306 FT /evidence="ECO:0007829|PDB:8P79" FT HELIX 308..310 FT /evidence="ECO:0007829|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 //