Names & Taxonomy

Uniprot ID:
P50613
Entry Name:
CDK7_HUMAN
Status:
reviewed
Protein Names:
Cyclin-dependent kinase 7 (EC 2.7.11.22) (EC 2.7.11.23) (39 kDa protein kinase) (p39 Mo15) (CDK-activating kinase 1) (Cell division protein kinase 7) (Serine/threonine-protein kinase 1) (TFIIH basal transcription factor complex kinase subunit)
Gene Names:
CDK7 CAK CAK1 CDKN7 MO15 STK1
Gene Names Primary:
CDK7
Organism:
Homo sapiens (Human)

Structure

Length:
346
Sequence:
MALDVKSRAKRYEKLDFLGEGQFATVYKARDKNTNQIVAIKKIKLGHRSEAKDGINRTALREIKLLQELSHPNIIGLLDAFGHKSNISLVFDFMETDLEVIIKDNSLVLTPSHIKAYMLMTLQGLEYLHQHWILHRDLKPNNLLLDENGVLKLADFGLAKSFGSPNRAYTHQVVTRWYRAPELLFGARMYGVGVDMWAVGCILAELLLRVPFLPGDSDLDQLTRIFETLGTPTEEQWPDMCSLPDYVTFKSFPGIPLHHIFSAAGDDLLDLIQGLFLFNPCARITATQALKMKYFSNRPGPTPGCQLPRPNCPVETLKEQSNPALAIKRKRTEALEQGGLPKKLIF
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus. Cytoplasm. Cytoplasm, perinuclear region. Note=Colocalizes with PRKCI in the cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and perinuclear region in response to DNA-bound peptides.

Function

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.
Catalytic Activity:
ATP + a protein = ADP + a phosphoprotein.; ATP + = ADP + phosphate.
Enzyme Regulation:
ENZYME REGULATION: 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.
Active Site:
ACT_SITE 137 137 Proton acceptor.
Gene Ontology Go:
cytoplasm
holo TFIIH complex
mitochondrion
nucleoplasm
nucleus
perinuclear region of cytoplasm
androgen receptor binding
ATP binding
cyclin-dependent protein serine/threonine kinase activity
DNA-dependent ATPase activity
protein C-terminus binding
protein kinase activity
RNA polymerase II carboxy-terminal domain kinase activity
transcription coactivator activity
7-methylguanosine mRNA capping
androgen receptor signaling pathway
cell cycle arrest
cell division
cell proliferation
DNA repair
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
gene expression
global genome nucleotide-excision repair
mitotic cell cycle
negative regulation of gene expression, epigenetic
nucleotide-excision repair
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription, DNA-templated
positive regulation of viral transcription
regulation of cyclin-dependent protein serine/threonine kinase activity
regulation of gene expression, epigenetic
termination of RNA polymerase I transcription
transcription elongation from RNA polymerase I promoter
transcription elongation from RNA polymerase II promoter
transcription from RNA polymerase I promoter
transcription from RNA polymerase II promoter
transcription initiation from RNA polymerase I promoter
transcription initiation from RNA polymerase II promoter
transcription-coupled nucleotide-excision repair
viral process
Gene Ontology Biological Process:
7-methylguanosine mRNA capping
androgen receptor signaling pathway
cell cycle arrest
cell division
cell proliferation
DNA repair
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
gene expression
global genome nucleotide-excision repair
mitotic cell cycle
negative regulation of gene expression, epigenetic
nucleotide-excision repair
positive regulation of transcription, DNA-templated
positive regulation of transcription from RNA polymerase II promoter
positive regulation of viral transcription
regulation of cyclin-dependent protein serine/threonine kinase activity
regulation of gene expression, epigenetic
termination of RNA polymerase I transcription
transcription-coupled nucleotide-excision repair
transcription elongation from RNA polymerase II promoter
transcription elongation from RNA polymerase I promoter
transcription from RNA polymerase II promoter
transcription from RNA polymerase I promoter
transcription initiation from RNA polymerase II promoter
transcription initiation from RNA polymerase I promoter
viral process
Gene Ontology Molecular Function:
androgen receptor binding
ATP binding
cyclin-dependent protein serine/threonine kinase activity
DNA-dependent ATPase activity
protein C-terminus binding
protein kinase activity
RNA polymerase II carboxy-terminal domain kinase activity
transcription coactivator activity
Gene Ontology Cellular Component:
cytoplasm
holo TFIIH complex
mitochondrion
nucleoplasm
nucleus
perinuclear region of cytoplasm
Keywords:
3D-structure
ATP-binding
Acetylation
Cell cycle
Cell division
Complete proteome
Cytoplasm
DNA damage
DNA repair
Kinase
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Serine/threonine-protein kinase
Transcription
Transcription regulation
Transferase
Interacts With:
Q01094

Publication

PubMed ID:
7929589 8208544 7936635 8208556 15489334 8069918 9372954 9832506 9852112 9840937 10024882 10882074 11113184 15695176 16327805 17386261 17373709 18220336 18691976 17901130 18669648 19450536 19015234 19667075 19369195 19136461 19071173 19690332 20360007 19911397 15876871 19238148 20068231 21269460 21592869 21406692 22814378 24275569 15530371 17344846