ID CDK7_RAT Reviewed; 329 AA. AC P51952; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 10-MAY-2005, sequence version 2. DT 08-NOV-2023, entry version 172. DE RecName: Full=Cyclin-dependent kinase 7; DE EC=2.7.11.22; DE EC=2.7.11.23; DE AltName: Full=39 protein kinase; DE Short=P39 Mo15; DE AltName: Full=CDK-activating kinase 1; DE AltName: Full=Cell division protein kinase 7; DE AltName: Full=TFIIH basal transcription factor complex kinase subunit; DE Flags: Fragment; GN Name=Cdk7; Synonyms=Cak, Cak1, Mo15; OS Rattus norvegicus (Rat). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Rattus. OX NCBI_TaxID=10116; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=Sprague-Dawley; TISSUE=Testis; RA Wu L., Hall F.; RL Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases. RN [2] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-162, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22673903; DOI=10.1038/ncomms1871; RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., RA Olsen J.V.; RT "Quantitative maps of protein phosphorylation sites across 14 different rat RT organs and tissues."; RL Nat. Commun. 3:876-876(2012). 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 Phosphorylation of POLR2A in complex with DNA promotes transcription CC initiation by triggering dissociation from DNA. Its expression and CC activity are constant throughout the cell cycle. Upon DNA damage, CC triggers p53/TP53 activation by phosphorylation, but is inactivated in CC turn by p53/TP53; this feedback loop may lead to an arrest of the cell CC cycle and of the transcription, helping in cell recovery, or to CC apoptosis. Required for DNA-bound peptides-mediated transcription and CC cellular growth inhibition (By similarity). {ECO:0000250}. 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 -!- ACTIVITY REGULATION: Phosphorylation at Thr-162 is required for CC enzymatic activity. 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 cell CC cycle progression (By similarity). {ECO:0000250}. 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 (By similarity). CC Interacts with HINT1 (By similarity). {ECO:0000250|UniProtKB:P50613}. CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P50613}. Cytoplasm CC {ECO:0000250|UniProtKB:P50613}. Cytoplasm, perinuclear region CC {ECO:0000250|UniProtKB:P50613}. Note=Colocalizes with PRKCI in the CC cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and CC perinuclear region in response to DNA-bound peptides (By similarity). CC {ECO:0000250|UniProtKB:P50613}. CC -!- PTM: Phosphorylation of Ser-156 during mitosis inactivates the enzyme. CC Phosphorylation of Thr-162 is required for activity. Phosphorylated at CC Ser-156 and Thr-162 by CDK2 (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=CAA58562.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={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; X83579; CAA58562.1; ALT_SEQ; mRNA. DR PIR; S51085; S51085. DR AlphaFoldDB; P51952; -. DR SMR; P51952; -. DR STRING; 10116.ENSRNOP00000025026; -. DR iPTMnet; P51952; -. DR PhosphoSitePlus; P51952; -. DR jPOST; P51952; -. DR PaxDb; 10116-ENSRNOP00000025026; -. DR UCSC; RGD:621124; rat. DR AGR; RGD:621124; -. DR RGD; 621124; Cdk7. DR eggNOG; KOG0659; Eukaryota. DR InParanoid; P51952; -. DR PhylomeDB; P51952; -. DR Reactome; R-RNO-112382; Formation of RNA Pol II elongation complex. DR Reactome; R-RNO-113418; Formation of the Early Elongation Complex. DR Reactome; R-RNO-5696395; Formation of Incision Complex in GG-NER. DR Reactome; R-RNO-674695; RNA Polymerase II Pre-transcription Events. DR Reactome; R-RNO-6781823; Formation of TC-NER Pre-Incision Complex. DR Reactome; R-RNO-6782135; Dual incision in TC-NER. DR Reactome; R-RNO-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER. DR Reactome; R-RNO-6796648; TP53 Regulates Transcription of DNA Repair Genes. DR Reactome; R-RNO-6807505; RNA polymerase II transcribes snRNA genes. DR Reactome; R-RNO-69202; Cyclin E associated events during G1/S transition. DR Reactome; R-RNO-69231; Cyclin D associated events in G1. DR Reactome; R-RNO-69273; Cyclin A/B1/B2 associated events during G2/M transition. DR Reactome; R-RNO-69656; Cyclin A:Cdk2-associated events at S phase entry. DR Reactome; R-RNO-72086; mRNA Capping. DR Reactome; R-RNO-73762; RNA Polymerase I Transcription Initiation. DR Reactome; R-RNO-73772; RNA Polymerase I Promoter Escape. DR Reactome; R-RNO-73776; RNA Polymerase II Promoter Escape. DR Reactome; R-RNO-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening. DR Reactome; R-RNO-73863; RNA Polymerase I Transcription Termination. DR Reactome; R-RNO-75953; RNA Polymerase II Transcription Initiation. DR Reactome; R-RNO-75955; RNA Polymerase II Transcription Elongation. DR Reactome; R-RNO-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance. DR Reactome; R-RNO-77075; RNA Pol II CTD phosphorylation and interaction with CE. DR Reactome; R-RNO-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0070516; C:CAK-ERCC2 complex; ISO:RGD. DR GO; GO:0019907; C:cyclin-dependent protein kinase activating kinase holoenzyme complex; ISO:RGD. DR GO; GO:0000307; C:cyclin-dependent protein kinase holoenzyme complex; TAS:RGD. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0001673; C:male germ cell nucleus; ISO:RGD. DR GO; GO:0005634; C:nucleus; ISO:RGD. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell. DR GO; GO:0000439; C:transcription factor TFIIH core complex; ISO:RGD. DR GO; GO:0005675; C:transcription factor TFIIH holo complex; IDA:RGD. DR GO; GO:0070985; C:transcription factor TFIIK complex; ISO:RGD. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; ISS:UniProtKB. DR GO; GO:0004693; F:cyclin-dependent protein serine/threonine kinase activity; IDA:RGD. DR GO; GO:0016301; F:kinase activity; ISO:RGD. DR GO; GO:0004672; F:protein kinase activity; ISO:RGD. DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA. DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD. DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; ISS:UniProtKB. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0051321; P:meiotic cell cycle; 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; ISO:RGD. DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:RGD. DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:RGD. DR GO; GO:0006367; P:transcription initiation at RNA polymerase II promoter; ISO:RGD. DR CDD; cd07841; STKc_CDK7; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. 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 ATP-binding; Cell cycle; Cell division; Cytoplasm; DNA damage; DNA repair; KW Kinase; Meiosis; Nucleotide-binding; Nucleus; Phosphoprotein; KW Reference proteome; Serine/threonine-protein kinase; Transcription; KW Transcription regulation; Transferase. FT CHAIN <1..>329 FT /note="Cyclin-dependent kinase 7" FT /id="PRO_0000085793" FT DOMAIN 4..287 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT REGION 309..329 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 129 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 10..18 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 33 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOD_RES 156 FT /note="Phosphoserine; by CDK1 and CDK2" FT /evidence="ECO:0000250|UniProtKB:P50613" FT MOD_RES 162 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:22673903" FT MOD_RES 313 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P50613" FT NON_TER 1 FT NON_TER 329 SQ SEQUENCE 329 AA; 37141 MW; B7159FD074881B0F CRC64; ANRNEKLDFL GEGQFATVYK ARDKNTNQIV AIKKIKLGHR SEAKDGINRT ALREIKLLQE LSHPNIIGLL DAFGHKSNIS LVFDFMETDL EVIIKDNSLV LTPSHIKAYM LMTLQGLEYL HQHWILHRDL KPNNLLLDEN GVLKLADFGL AKSFGSPNWA YTHQVVTRWY RAPELLFGAR MYGVGVDMWA VGCILAELLL RVPFLPGDSD LDQLTRIFET LGTPTEEQWP DMCSLPDYVT FKSFPGIPLQ HIFIAAGDDL LELIQGLFLF NPCTRITASQ ALRTKYFSNR PGPTPGCQLP RPNCPVEALK EQSNPAMATK RKRAEALEQ //