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MT000114

UniProt Annotations

Entry Information

Gene Name	cyclin-dependent kinase 7
Protein Entry	CDK7_HUMAN
UniProt ID	P50613
Species	Human

Comments

Comment type	Description
Catalytic Activity	ATP + a protein = ADP + a phosphoprotein.
Catalytic Activity	ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
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. {ECO:0000269\|PubMed:19911397, ECO:0000269\|PubMed:9840937}.
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. {ECO:0000269\|PubMed:10024882, ECO:0000269\|PubMed:11113184, ECO:0000269\|PubMed:16327805, ECO:0000269\|PubMed:17373709, ECO:0000269\|PubMed:17386261, ECO:0000269\|PubMed:17901130, ECO:0000269\|PubMed:19015234, ECO:0000269\|PubMed:19071173, ECO:0000269\|PubMed:19136461, ECO:0000269\|PubMed:19450536, ECO:0000269\|PubMed:19667075, ECO:0000269\|PubMed:20360007, ECO:0000269\|PubMed:9372954, ECO:0000269\|PubMed:9840937}.
Induction	Repressed by DNA-bound peptides. {ECO:0000269\|PubMed:19071173}.
Interaction	Q01094:E2F1; NbExp=2; IntAct=EBI-1245958, EBI-448924;
Ptm	Phosphorylation of Ser-164 during mitosis inactivates the enzyme. Phosphorylation of Thr-170 is required for activity. Phosphorylated at Ser-164 and Thr-170 by CDK2. {ECO:0000269\|PubMed:11113184, ECO:0000269\|PubMed:15530371, ECO:0000269\|PubMed:18669648, ECO:0000269\|PubMed:18691976, ECO:0000269\|PubMed:19690332, ECO:0000269\|PubMed:20068231, ECO:0000269\|PubMed:21406692, ECO:0000269\|PubMed:9832506}.
Similarity	Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily. {ECO:0000305}.
Similarity	Contains 1 protein kinase domain. {ECO:0000255\|PROSITE-ProRule:PRU00159}.
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.
Subunit	Associates primarily with cyclin-H (CCNH) and MAT1 to form the CAK complex. CAK can further associate with the core- TFIIH to form the TFIIH basal transcription factor; this complex is sensitive to UV light. The CAK complex binds to p53/TP53 in response to DNA damage. Interacts with CDK2, SF1/NR5A1, PUF60 and PRKCI. {ECO:0000269\|PubMed:10882074, ECO:0000269\|PubMed:15530371, ECO:0000269\|PubMed:15695176, ECO:0000269\|PubMed:16327805, ECO:0000269\|PubMed:17373709, ECO:0000269\|PubMed:17901130, ECO:0000269\|PubMed:9840937, ECO:0000269\|PubMed:9852112}.
Tissue Specificity	Ubiquitous.
Web Resource	Name=NIEHS-SNPs; URL="http://egp.gs.washington.edu/data/cdk7/";