Cyclin-dependent kinase 7
Also known as: CAK, CAK1, CDK7, CDKN7, MO15, STK1
Function
Serine/threonine kinase involved in cell cycle control and in RNA polymerase II-mediated RNA transcription. As a cyclin-dependent kinase, CDK7 is activated by the binding to cyclin-H/CCNH and the CDK-activating kinase assembly factor MAT1. Catalytic subunit of the CDK-activating kinase (CAK) complex, a master regulator of CDK activity by catalyzing the activating threonine phosphorylation of CDKs. CAK activates major mediators of cell cycle control, including CDK1, CDK2, CDK4 and CDK6, and plays a key role in regulating cell cycle progression. CAK complexed to the core-TFIIH basal transcription factor activates RNA polymerase II by serine phosphorylation of the CTD of POLR2A, allowing its escape from the promoter and elongation of the transcripts. Initiates transcription by RNA polymerase II by mediating phosphorylation of POLR2A at 'Ser-5' of the repetitive C-terminal domain (CTD) when POLR2A is in complex with DNA, promoting dissociation from DNA and initiation. Phosphorylates SPT5/SUPT5H, SF1/NR5A1, POLR2A, p53/TP53, CDK1, CDK2, CDK4, CDK6 and CDK11B/CDK11. 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.
Classification
- Family (Pfam)
- PF00069 Pkinase
- InterPro
- CDK, CDK7, Kinase-like_dom_sf, Prot_kinase_dom, Protein_kinase_ATP_BS, Ser/Thr_kinase_AS
- Functional cluster
- Serine/Threonine Protein Kinases
Experimental structures · PDB · 53
- 1UA2 X-ray 3.02A
- 6O9L EM 7.20A
- 6XBZ EM 2.80A
- 6XD3 EM 3.30A
- 7B5O EM 2.50A
- 7B5Q EM 2.50A
- 7EGB EM 3.30A
- 7EGC EM 3.90A
- 7ENA EM 4.07A
- 7ENC EM 4.13A
- 7LBM EM 4.80A
- 7NVR EM 4.50A
- … and 41 more
A predicted model is available from AlphaFold.
Gene Ontology · 27
- GO:0070516 CAK-ERCC2 complex
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0001650 fibrillar center
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0048471 perinuclear region of cytoplasm
- GO:0000439 transcription factor TFIIH core complex
- GO:0005675 transcription factor TFIIH holo complex
- GO:0070985 transcription factor TFIIK complex
- GO:0005524 ATP binding
- GO:0008094 ATP-dependent activity, acting on DNA
- GO:0004693 cyclin-dependent protein serine/threonine kinase activity
- GO:0004672 protein kinase activity
- GO:0106310 protein serine kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0008353 RNA polymerase II CTD heptapeptide repeat kinase activity
- GO:0140836 RNA polymerase II CTD heptapeptide repeat S5 kinase activity
- GO:0051301 cell division
- GO:0006289 nucleotide-excision repair
- GO:0045944 positive regulation of transcription by RNA polymerase II
- GO:0050821 protein stabilization
- GO:0051726 regulation of cell cycle
- GO:2000045 regulation of G1/S transition of mitotic cell cycle
- GO:0042795 snRNA transcription by RNA polymerase II
- GO:0006366 transcription by RNA polymerase II
- GO:0006367 transcription initiation at RNA polymerase II promoter
Drugs targeting this protein · 9
- PHA-793887 inhibitor
- SELICICLIB inhibitor
- ZOTIRACICLIB inhibitor
- BMS-387032 inhibitor
- RGB-286638 inhibitor
- ALVOCIDIB inhibitor
- RONICICLIB inhibitor
- AT-7519 inhibitor
- AZD-5438 inhibitor
Related proteins · sequence + function similarity
- Cyclin-dependent kinase 7 1.00
- Cyclin-dependent kinase 7 0.99
- Cyclin-dependent kinase 7 0.98
- Cyclin-dependent kinase 7 0.96
- Cyclin-dependent kinase D-2 0.95
- Cyclin-dependent kinase 7 0.93
- Cyclin-dependent protein kinase PHO85 0.93
- Negative regulator of the PHO system 0.93
- Serine/threonine-protein kinase pef1 0.92
- Cyclin-dependent kinase 3 0.92
- Negative regulator of the PHO system 0.92
- Cyclin-dependent kinase 20 0.92
Co-cited proteins · studied together in the literature
- Serine/threonine-protein kinase Nek4 1 shared papers
- Steroidogenic factor 1 2 shared papers
- DNA-directed RNA polymerase II subunit RPB1 6 shared papers
- Cyclin-H 4 shared papers
- Cyclin-dependent kinase 2 5 shared papers
- Protein kinase C iota type 1 shared papers
- CDK-activating kinase assembly factor MAT1 3 shared papers
- Cellular tumor antigen p53 2 shared papers
- General transcription factor IIH subunit 1 3 shared papers
- Adenosine 5'-monophosphoramidase HNT1 1 shared papers
- Far upstream element-binding protein 1 1 shared papers
- Cyclin-dependent kinase 11B 2 shared papers
Literature · 45 cited papers
- Structural basis of T-loop-independent recognition and activation of CDKs by the CDK-activating kinase. Science · 2025
- Human TFIIH Kinase CDK7 Regulates Transcription-Associated Chromatin Modifications. Cell Rep. · 2017
- THZ1 Reveals Roles for Cdk7 in Co-transcriptional Capping and Pausing. Mol. Cell · 2015
- An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
- Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
- N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB. Proc. Natl. Acad. Sci. U.S.A. · 2012
- A history of TFIIH: Two decades of molecular biology on a pivotal transcription/repair factor. DNA Repair · 2011
- System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
- Initial characterization of the human central proteome. BMC Syst. Biol. · 2011
- Cdc25 phosphatases are required for timely assembly of CDK1-cyclin B at the G2/M transition. J. Biol. Chem. · 2010
- Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci. Signal. · 2010
- R-roscovitine (Seliciclib) affects CLL cells more strongly than combinations of fludarabine or cladribine with cyclophosphamide: Inhibition of CDK7 sensitizes leukemic cells to caspase-dependent apoptosis. J. Cell. Biochem. · 2010
- … and 33 more in the literature graph