CDK7_RAT
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 03-AUG-2022, entry version 166.
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};
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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 UCSC; RGD:621124; rat.
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:0005856; C:cytoskeleton; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0016020; C:membrane; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA: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:0008022; F:protein C-terminus binding; 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:0070816; P:phosphorylation of RNA polymerase II C-terminal domain; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
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 from RNA polymerase II promoter; ISO:RGD.
DR CDD; cd07841; STKc_CDK7; 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:SF375; PTHR24056:SF375; 1.
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 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
