CDK7 - Cyclin-dependent kinase 7 - human protein (Function)
 
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CDK7 »  Cyclin-dependent kinase 7   [ EC 2.7.11.23EC 2.7.11.22 ]
 
Protein also known as:  TFIIH basal transcription factor complex kinase subunit.
Gene name:  CDK7
Entry whose protein(s) existence is based on evidence at protein level
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GENE REF ISO

Function

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Overview 
Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. Cyclin-dependent kinases (CDKs) are activated by the binding to a cyclin and mediate the progression through the cell cycle. Each different complex controls a specific transition between 2 subsequent phases in the cell cycle. Required for both activation and complex formation of CDK1/cyclin-B during G2-M transition, and for activation of CDK2/cyclins during G1-S transition (but not complex formation). CDK7 is the catalytic subunit of the CDK-activating kinase (CAK) complex. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. CAK activates the cyclin-associated kinases CDK1, CDK2, CDK4 and CDK6 by threonine phosphorylation, thus regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the repetitive C-terminal domain (CTD) of its large subunit (POLR2A), allowing its escape from the promoter and elongation of the transcripts. Phosphorylation of POLR2A in complex with DNA promotes transcription initiation by triggering dissociation from DNA. Its expression and activity are constant throughout the cell cycle. Upon DNA damage, triggers p53/TP53 activation by phosphorylation, but is inactivated in turn by p53/TP53; this feedback loop may lead to an arrest of the cell cycle and of the transcription, helping in cell recovery, or to apoptosis. Required for DNA-bound peptides-mediated transcription and cellular growth inhibition.  
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  • CuratedUniProtKB
GO molecular function 
Androgen receptor bindingdefinition[GO:0050681]  
1
  • NASUniProtKB
ATP bindingdefinition[GO:0005524]  
  • IEAUniProtKB KW
Cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0004693]  
  • IEAEC 2 GO
DNA-dependent ATPase activitydefinition[GO:0008094]  
1
  • IDAUniProtKB
Protein bindingdefinition[GO:0005515]  
1
  • IPIIntAct
Protein C-terminus bindingdefinition[GO:0008022]  
1
  • IPIUniProtKB
Protein kinase activitydefinition[GO:0004672]  
1
  • TASPINC
RNA polymerase II carboxy-terminal domain kinase activitydefinition[GO:0008353]  
2
  • IDAUniProtKB
Transcription coactivator activitydefinition[GO:0003713]  
1
  • NASUniProtKB
GO biological process 
Androgen receptor signaling pathwaydefinition[GO:0030521]  
1
  • NASUniProtKB
ATP catabolic processdefinition[GO:0006200]  
1
  • IDAGOC
Cell cycle arrestdefinition[GO:0007050]  
1
  • TASUniProtKB
Cell divisiondefinition[GO:0051301]  
  • IEAUniProtKB KW
Cell proliferationdefinition[GO:0008283]  
1
  • TASPINC
Positive regulation of transcription from RNA polymerase II promoterdefinition[GO:0045944]  
1
  • IDAUniProtKB
Positive regulation of transcription, DNA-templateddefinition[GO:0045893]  
1
  • NASUniProtKB
Protein phosphorylationdefinition[GO:0006468] silver  
  • IEAInterPro 2 GO
Regulation of cyclin-dependent protein serine/threonine kinase activitydefinition[GO:0000079]  
1
  • TASPINC
Transcription from RNA polymerase II promoterdefinition[GO:0006366]  
1
  • IDAUniProtKB
Enzymatic activity 
This protein acts as an enzyme. It is known to catalyze the following reactions
EC 2.7.11.22: ATP + a protein ADP + a phosphoprotein.  
  • CuratedUniProtKB
EC 2.7.11.23: ATP + [DNA-directed RNA polymerase] ADP + [DNA-directed RNA polymerase] phosphate.  
  • CuratedUniProtKB
It is regulated in the following manner
Inactivated by phosphorylation. Repressed by roscovitine (seliciclib, CYC202), R547 (Ro-4584820) and SNS-032 (BMS-387032). The association of p53/TP53 to the CAK complex in response to DNA damage reduces kinase activity toward CDK2 and RNA polymerase II repetitive C-terminal domain (CTD), thus stopping cell cycle progression. The inactivation by roscovitine promotes caspase-mediated apoptosis in leukemic cells.  
2
  • CuratedUniProtKB
 
More information is available from:
Pathways 
According to KEGG, this protein belongs to the following pathways:
Basal transcription factors  hsa03022+1022  
Cell cycle  hsa04110+1022  
Nucleotide excision repair  hsa03420+1022  
According to Reactome, this protein belongs to the following pathways:
Cyclin A/B1 associated events during G2/M transition  REACT_1857  
Cyclin A:Cdk2-associated events at S phase entry  REACT_9029  
Cyclin D associated events in G1  REACT_821  
Dual incision reaction in GG-NER  REACT_311  
Dual incision reaction in TC-NER  REACT_2222  
Formation of HIV elongation complex in the absence of HIV Tat  REACT_22201  
Formation of HIV-1 elongation complex containing HIV-1 Tat  REACT_6346  
Formation of incision complex in GG-NER  REACT_257  
Formation of the Early Elongation Complex  REACT_846  
Formation of the HIV-1 Early Elongation Complex  REACT_6319  
Formation of transcription-coupled NER (TC-NER) repair complex  REACT_1941  
HIV Transcription Initiation  REACT_6332  
mRNA Capping  REACT_1470  
NoRC negatively regulates rRNA expression  REACT_200856  
RNA Pol II CTD phosphorylation and interaction with CE  REACT_6237  
RNA Pol II CTD phosphorylation and interaction with CE  REACT_975  
RNA Polymerase I Chain Elongation  REACT_2204  
RNA Polymerase I Promoter Escape  REACT_1913  
RNA Polymerase I Transcription Initiation  REACT_953  
RNA Polymerase I Transcription Termination  REACT_1074  
RNA Polymerase II HIV Promoter Escape  REACT_6253  
RNA Polymerase II Pre-transcription Events  REACT_22107  
RNA Polymerase II Promoter Escape  REACT_2089  
RNA Polymerase II Transcription Elongation  REACT_833  
RNA Polymerase II Transcription Initiation  REACT_1851  
RNA Polymerase II Transcription Initiation And Promoter Clearance  REACT_834  
RNA Polymerase II Transcription Pre-Initiation And Promoter Opening  REACT_1655  
Tat-mediated elongation of the HIV-1 transcript  REACT_6162  
Transcription of the HIV genome  REACT_6233  
 

Keywords

Biological process 
Cell cycle  definition   [KW-0131]
Cell division  definition   [KW-0132]
DNA damage  definition   [KW-0227]
DNA repair  definition   [KW-0234]
Transcription  definition   [KW-0804]
Transcription regulation  definition   [KW-0805]
Molecular function 
Kinase  definition   [KW-0418]
Serine/threonine-protein kinase  definition   [KW-0723]
Transferase  definition   [KW-0808]
Technical term 
Reference proteome  definition   [KW-1185]
 

Further external links

Other
GeneWiki: Cyclin-dependent_kinase_7
GenomeRNAi: 1022
PRO: PR:P50613
Chemistry
GuidetoPHARMACOLOGY: 1979