Target Information
Target General Infomation | |||||
---|---|---|---|---|---|
Target ID |
T58449
|
||||
Former ID |
TTDC00094
|
||||
Target Name |
Cell division protein kinase 7
|
||||
Gene Name |
CDK7
|
||||
Synonyms |
39 kDa protein kinase; CAK; CAK1; CDK-activating kinase; Cyclin-dependent kinase 7; P39 Mo15; STK1; TFIIH basal transcription factor complex kinase subunit; CDK7
|
||||
Target Type |
Clinical Trial
|
||||
Disease | Advanced solid tumor [ICD9: 140-199; ICD10: C00-C75, C7A, C7B] | ||||
Cancer [ICD9: 140-229; ICD10: C00-C96] | |||||
Solid tumours [ICD9: 140-199, 210-229; ICD10: C00-D48] | |||||
Function |
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.
|
||||
BioChemical Class |
Kinase
|
||||
Target Validation |
T58449
|
||||
UniProt ID | |||||
EC Number |
EC 2.7.11.23
|
||||
Sequence |
MALDVKSRAKRYEKLDFLGEGQFATVYKARDKNTNQIVAIKKIKLGHRSEAKDGINRTAL
REIKLLQELSHPNIIGLLDAFGHKSNISLVFDFMETDLEVIIKDNSLVLTPSHIKAYMLM TLQGLEYLHQHWILHRDLKPNNLLLDENGVLKLADFGLAKSFGSPNRAYTHQVVTRWYRA PELLFGARMYGVGVDMWAVGCILAELLLRVPFLPGDSDLDQLTRIFETLGTPTEEQWPDM CSLPDYVTFKSFPGIPLHHIFSAAGDDLLDLIQGLFLFNPCARITATQALKMKYFSNRPG PTPGCQLPRPNCPVETLKEQSNPALAIKRKRTEALEQGGLPKKLIF |
||||
Drugs and Mode of Action | |||||
Inhibitor | 2,5-dichloro-N-p-tolylthiophene-3-sulfonamide | Drug Info | [551239] | ||
NU6140 | Drug Info | [527749] | |||
PF-228 | Drug Info | [528764] | |||
Phosphonothreonine | Drug Info | [551393] | |||
R-roscovitine | Drug Info | [537564] | |||
R547 | Drug Info | [537564] | |||
RGB-286147 | Drug Info | [529213] | |||
SNS-032 | Drug Info | [537097], [537228] | |||
THZ1 | Drug Info | [532889] | |||
ZK 304709 | Drug Info | [537564] | |||
Pathways | |||||
KEGG Pathway | Basal transcription factors | ||||
Nucleotide excision repair | |||||
Cell cycle | |||||
NetPath Pathway | TCR Signaling Pathway | ||||
RANKL Signaling Pathway | |||||
Pathway Interaction Database | Retinoic acid receptors-mediated signaling | ||||
Reactome | NoRC negatively regulates rRNA expression | ||||
Formation of TC-NER Pre-Incision Complex | |||||
Dual incision in TC-NER | |||||
Gap-filling DNA repair synthesis and ligation in TC-NER | |||||
Cyclin E associated events during G1/S transition | |||||
Cyclin D associated events in G1 | |||||
Cyclin A/B1 associated events during G2/M transition | |||||
Cdk2-associated events at S phase entry | |||||
RNA Polymerase I Transcription Initiation | |||||
WikiPathways | G1 to S cell cycle control | ||||
Eukaryotic Transcription Initiation | |||||
Cardiac Hypertrophic Response | |||||
S Phase | |||||
HIV Life Cycle | |||||
Integrated Breast Cancer Pathway | |||||
Nucleotide Excision Repair | |||||
RNA Polymerase II Transcription | |||||
RNA Polymerase I, RNA Polymerase III, and Mitochondrial Transcription | |||||
mRNA Capping | |||||
Mitotic G2-G2/M phases | |||||
Mitotic G1-G1/S phases | |||||
MicroRNAs in cardiomyocyte hypertrophy | |||||
References | |||||
Ref 524796 | ClinicalTrials.gov (NCT02160730) Treatment of Cushing's Disease With R-roscovitine. U.S. National Institutes of Health. | ||||
Ref 537097 | Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45. Epub 2009 Feb 20. | ||||
Ref 541014 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5670). | ||||
Ref 541047 | (http://www.guidetopharmacology.org/) Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 5707). | ||||
Ref 527749 | Potentiation of paclitaxel-induced apoptosis by the novel cyclin-dependent kinase inhibitor NU6140: a possible role for survivin down-regulation. Mol Cancer Ther. 2005 Sep;4(9):1328-37. | ||||
Ref 528764 | J Biol Chem. 2007 May 18;282(20):14845-52. Epub 2007 Mar 28.Cellular characterization of a novel focal adhesion kinase inhibitor. | ||||
Ref 529213 | Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20523-8. Epub 2007 Dec 11.A systematic interaction map of validated kinase inhibitors with Ser/Thr kinases. | ||||
Ref 532889 | Targeting transcription regulation in cancer with a covalent CDK7 inhibitor. Nature. 2014 Jul 31;511(7511):616-20. | ||||
Ref 537097 | Mechanism of action of SNS-032, a novel cyclin-dependent kinase inhibitor, in chronic lymphocytic leukemia. Blood. 2009 May 7;113(19):4637-45. Epub 2009 Feb 20. | ||||
Ref 537228 | Development of cell-cycle inhibitors for cancer therapy. Curr Oncol. 2009 Mar;16(2):36-43. | ||||
Ref 537564 | Cell cycle kinases as therapeutic targets for cancer. Nat Rev Drug Discov. 2009 Jul;8(7):547-66. |
If You Find Any Error in Data or Bug in Web Service, Please Kindly Report It to Dr. Zhou and Dr. Zhang.