CDK7_MOUSE
ID CDK7_MOUSE Reviewed; 346 AA.
AC Q03147; Q99KK3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 2.
DT 03-AUG-2022, entry version 200.
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;
DE AltName: Full=CR4 protein kinase;
DE Short=CRK4;
DE AltName: Full=Cell division protein kinase 7;
DE AltName: Full=Protein-tyrosine kinase MPK-7;
DE AltName: Full=TFIIH basal transcription factor complex kinase subunit;
GN Name=Cdk7; Synonyms=Cak, Cdkn7, Crk4, Mo15, Mpk-7;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Macrophage;
RX PubMed=7935441; DOI=10.1128/mcb.14.11.7265-7275.1994;
RA Matsuoka M., Kato J.-Y., Fisher R.P., Morgan D.O., Sherr C.J.;
RT "Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated
RT kinase.";
RL Mol. Cell. Biol. 14:7265-7275(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=CBA/J; TISSUE=Bone marrow;
RX PubMed=7959010; DOI=10.1016/0378-1119(94)90169-4;
RA Stepanova L.Y., Ershler M., Belyavsky A.V.;
RT "Sequence of the cDNA encoding murine CRK4 protein kinase.";
RL Gene 149:321-324(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 139-154.
RC STRAIN=C57BL/6J; TISSUE=Embryonic brain;
RX PubMed=1281307;
RA Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A.,
RA Wilkinson D.G., Charnay P.;
RT "An Eph-related receptor protein tyrosine kinase gene segmentally expressed
RT in the developing mouse hindbrain.";
RL Oncogene 7:2499-2506(1992).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 141-176.
RC STRAIN=CBA/J; TISSUE=Bone marrow;
RX PubMed=8444355; DOI=10.1016/0378-1119(93)90411-u;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Novel CDC2-related protein kinases produced in murine hematopoietic stem
RT cells.";
RL Gene 124:305-306(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 141-176.
RC STRAIN=CBA/J; TISSUE=Bone marrow;
RX PubMed=1459009;
RA Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.;
RT "Identification of new protein kinase genes, similar to kinases of the cdc2
RT family and expressed in murine hematopoietic stem cells.";
RL Dokl. Akad. Nauk SSSR 324:893-897(1992).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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.
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-170 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-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 (By similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CMGC Ser/Thr
CC protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
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DR EMBL; U11822; AAA64831.1; -; mRNA.
DR EMBL; X74145; CAA52242.1; -; mRNA.
DR EMBL; BC004605; AAH04605.1; -; mRNA.
DR EMBL; BC068160; AAH68160.1; -; mRNA.
DR EMBL; X57239; CAA40515.1; -; mRNA.
DR EMBL; X65070; CAA46203.1; -; mRNA.
DR CCDS; CCDS36766.1; -.
DR PIR; A56231; A56231.
DR PIR; S30503; S30503.
DR PIR; S34652; S34652.
DR RefSeq; NP_034004.2; NM_009874.3.
DR AlphaFoldDB; Q03147; -.
DR SMR; Q03147; -.
DR BioGRID; 198650; 4.
DR ComplexPortal; CPX-3268; Cyclin-dependent protein kinase-activating kinase complex.
DR IntAct; Q03147; 1.
DR STRING; 10090.ENSMUSP00000088845; -.
DR ChEMBL; CHEMBL2176816; -.
DR iPTMnet; Q03147; -.
DR PhosphoSitePlus; Q03147; -.
DR EPD; Q03147; -.
DR jPOST; Q03147; -.
DR PaxDb; Q03147; -.
DR PeptideAtlas; Q03147; -.
DR PRIDE; Q03147; -.
DR ProteomicsDB; 283772; -.
DR Antibodypedia; 1446; 834 antibodies from 45 providers.
DR DNASU; 12572; -.
DR Ensembl; ENSMUST00000091299; ENSMUSP00000088845; ENSMUSG00000069089.
DR GeneID; 12572; -.
DR KEGG; mmu:12572; -.
DR UCSC; uc007rrk.2; mouse.
DR CTD; 1022; -.
DR MGI; MGI:102956; Cdk7.
DR VEuPathDB; HostDB:ENSMUSG00000069089; -.
DR eggNOG; KOG0659; Eukaryota.
DR GeneTree; ENSGT00940000155179; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; Q03147; -.
DR OMA; GIHHCHR; -.
DR OrthoDB; 1367115at2759; -.
DR PhylomeDB; Q03147; -.
DR TreeFam; TF101024; -.
DR BRENDA; 2.7.11.22; 3474.
DR Reactome; R-MMU-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-MMU-113418; Formation of the Early Elongation Complex.
DR Reactome; R-MMU-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-MMU-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-MMU-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-MMU-6782135; Dual incision in TC-NER.
DR Reactome; R-MMU-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-MMU-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-MMU-6807505; RNA polymerase II transcribes snRNA genes.
DR Reactome; R-MMU-69202; Cyclin E associated events during G1/S transition.
DR Reactome; R-MMU-69231; Cyclin D associated events in G1.
DR Reactome; R-MMU-69273; Cyclin A/B1/B2 associated events during G2/M transition.
DR Reactome; R-MMU-69656; Cyclin A:Cdk2-associated events at S phase entry.
DR Reactome; R-MMU-72086; mRNA Capping.
DR Reactome; R-MMU-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-MMU-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-MMU-73776; RNA Polymerase II Promoter Escape.
DR Reactome; R-MMU-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening.
DR Reactome; R-MMU-73863; RNA Polymerase I Transcription Termination.
DR Reactome; R-MMU-75953; RNA Polymerase II Transcription Initiation.
DR Reactome; R-MMU-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-MMU-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance.
DR Reactome; R-MMU-77075; RNA Pol II CTD phosphorylation and interaction with CE.
DR Reactome; R-MMU-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR BioGRID-ORCS; 12572; 25 hits in 107 CRISPR screens.
DR ChiTaRS; Cdk7; mouse.
DR PRO; PR:Q03147; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q03147; protein.
DR Bgee; ENSMUSG00000069089; Expressed in placenta labyrinth and 246 other tissues.
DR ExpressionAtlas; Q03147; baseline and differential.
DR Genevisible; Q03147; MM.
DR GO; GO:0070516; C:CAK-ERCC2 complex; ISO:MGI.
DR GO; GO:0019907; C:cyclin-dependent protein kinase activating kinase holoenzyme complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005856; C:cytoskeleton; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR GO; GO:0016020; C:membrane; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0000439; C:transcription factor TFIIH core complex; ISO:MGI.
DR GO; GO:0005675; C:transcription factor TFIIH holo complex; ISS:UniProtKB.
DR GO; GO:0070985; C:transcription factor TFIIK complex; ISO:MGI.
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; ISS:MGI.
DR GO; GO:0016301; F:kinase activity; IDA:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IDA:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0008353; F:RNA polymerase II CTD heptapeptide repeat kinase activity; ISS:UniProtKB.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO: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; ISO:MGI.
DR GO; GO:0050821; P:protein stabilization; ISO:MGI.
DR GO; GO:2000045; P:regulation of G1/S transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; ISO:MGI.
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 Acetylation; ATP-binding; Cell cycle; Cell division; Cytoplasm; DNA damage;
KW DNA repair; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transcription;
KW Transcription regulation; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P50613"
FT CHAIN 2..346
FT /note="Cyclin-dependent kinase 7"
FT /id="PRO_0000085792"
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 BINDING 18..26
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 41
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P50613"
FT MOD_RES 7
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P50613"
FT MOD_RES 164
FT /note="Phosphoserine; by CDK1 and CDK2"
FT /evidence="ECO:0000250|UniProtKB:P50613"
FT MOD_RES 170
FT /note="Phosphothreonine; by CDK2"
FT /evidence="ECO:0000250|UniProtKB:P50613"
FT CONFLICT 11..12
FT /note="RY -> HN (in Ref. 2; CAA52242)"
FT /evidence="ECO:0000305"
FT CONFLICT 20
FT /note="E -> R (in Ref. 2; CAA52242)"
FT /evidence="ECO:0000305"
FT CONFLICT 100..136
FT /note="Missing (in Ref. 3; AAH04605)"
FT /evidence="ECO:0000305"
FT CONFLICT 100
FT /note="V -> L (in Ref. 2; CAA52242)"
FT /evidence="ECO:0000305"
FT CONFLICT 104
FT /note="D -> H (in Ref. 2; CAA52242)"
FT /evidence="ECO:0000305"
FT CONFLICT 130..131
FT /note="QH -> HN (in Ref. 2; CAA52242)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 346 AA; 38968 MW; 455FFAB2CFEDEB3E CRC64;
MAVDVKSRAK RYEKLDFLGE GQFATVYKAR DKNTNQIVAI KKIKLGHRSE AKDGINRTAL
REIKLLQELS HPNIIGLLDA FGHKSNISLV FDFMETDLEV IIKDNSLVLT PSHIKAYMLM
TLQGLEYLHQ HWILHRDLKP NNLLLDENGV LKLADFGLAK SFGSPNRAYT HQVVTRWYRA
PELLFGARMY GVGVDMWAVG CILAELLLRV PFLPGDSDLD QLTRIFETLG TPTEEQWPDM
CSLPDYVTFK SFPGVPLQHI FIAAGDDLLE LIQGLFLFNP CTRTTASQAL KTKYFSNRPG
PTPGCQLPRP NCPVEALKEP ANPTVATKRK RAEALEQGIL PKKLIF
