P50613 · CDK7_HUMAN
- ProteinCyclin-dependent kinase 7
- GeneCDK7
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids346 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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 (PubMed:9852112).
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
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 + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity 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.
Features
Showing features for binding site, active site.
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCyclin-dependent kinase 7
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP50613
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 41 | Total loss of activity. | ||||
Sequence: K → A | ||||||
Mutagenesis | 41 | No effect on interaction with HINT1. | ||||
Sequence: K → M | ||||||
Mutagenesis | 91 | Enhanced capacity to bind ATP analogs. | ||||
Sequence: F → G | ||||||
Natural variant | VAR_023118 | 163 | ||||
Sequence: G → A | ||||||
Mutagenesis | 164 | No mitotic repression of transcriptional activity of the reconstituted TFIIH complex. | ||||
Sequence: S → A | ||||||
Mutagenesis | 170 | Total loss of activity. Total loss of transcriptional activity of the reconstituted TFIIH complex. | ||||
Sequence: T → A | ||||||
Mutagenesis | 170 | No effect on interaction with HINT1. | ||||
Sequence: T → E | ||||||
Natural variant | VAR_023119 | 285 | in dbSNP:rs34584424 | |||
Sequence: T → M |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 495 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000085791 | 2-346 | UniProt | Cyclin-dependent kinase 7 | |||
Sequence: ALDVKSRAKRYEKLDFLGEGQFATVYKARDKNTNQIVAIKKIKLGHRSEAKDGINRTALREIKLLQELSHPNIIGLLDAFGHKSNISLVFDFMETDLEVIIKDNSLVLTPSHIKAYMLMTLQGLEYLHQHWILHRDLKPNNLLLDENGVLKLADFGLAKSFGSPNRAYTHQVVTRWYRAPELLFGARMYGVGVDMWAVGCILAELLLRVPFLPGDSDLDQLTRIFETLGTPTEEQWPDMCSLPDYVTFKSFPGIPLHHIFSAAGDDLLDLIQGLFLFNPCARITATQALKMKYFSNRPGPTPGCQLPRPNCPVETLKEQSNPALAIKRKRTEALEQGGLPKKLIF | |||||||
Modified residue | 7 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 96 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 161 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 164 | UniProt | Phosphoserine; by CDK1 and CDK2 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 164 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 169 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 170 | UniProt | Phosphothreonine; by CDK2 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 170 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 175 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 302 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 321 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 321 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Ubiquitous.
Induction
Repressed by DNA-bound peptides.
Gene expression databases
Organism-specific databases
Interaction
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. Interacts with HINT1 (PubMed:10958787).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P50613 | CDK2 P24941 | 3 | EBI-1245958, EBI-375096 | |
BINARY | P50613 | CDK4 P11802 | 2 | EBI-1245958, EBI-295644 | |
BINARY | P50613 | HSP90AB1 P08238 | 4 | EBI-1245958, EBI-352572 | |
BINARY | P50613 | SRPK1 Q96SB4 | 2 | EBI-1245958, EBI-539478 | |
BINARY | P50613 | SRPK2 P78362 | 2 | EBI-1245958, EBI-593303 | |
BINARY | P50613 | SUPT5H O00267 | 3 | EBI-1245958, EBI-710464 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 12-295 | Protein kinase | ||||
Sequence: YEKLDFLGEGQFATVYKARDKNTNQIVAIKKIKLGHRSEAKDGINRTALREIKLLQELSHPNIIGLLDAFGHKSNISLVFDFMETDLEVIIKDNSLVLTPSHIKAYMLMTLQGLEYLHQHWILHRDLKPNNLLLDENGVLKLADFGLAKSFGSPNRAYTHQVVTRWYRAPELLFGARMYGVGVDMWAVGCILAELLLRVPFLPGDSDLDQLTRIFETLGTPTEEQWPDMCSLPDYVTFKSFPGIPLHHIFSAAGDDLLDLIQGLFLFNPCARITATQALKMKYF |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length346
- Mass (Da)39,038
- Last updated1996-10-01 v1
- Checksum0A94BFA7DD416CEB
Computationally mapped potential isoform sequences
There are 9 potential isoforms mapped to this entry
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 130 | in Ref. 7; AAH05298 | ||||
Sequence: Q → R | ||||||
Sequence conflict | 249 | in Ref. 5; CAA73587 | ||||
Sequence: F → C | ||||||
Sequence conflict | 321 | in Ref. 5; CAA73587 | ||||
Sequence: S → A |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
X79193 EMBL· GenBank· DDBJ | CAA55785.1 EMBL· GenBank· DDBJ | mRNA | ||
L20320 EMBL· GenBank· DDBJ | AAA36657.1 EMBL· GenBank· DDBJ | mRNA | ||
X77743 EMBL· GenBank· DDBJ | CAA54793.1 EMBL· GenBank· DDBJ | mRNA | ||
X77303 EMBL· GenBank· DDBJ | CAA54508.1 EMBL· GenBank· DDBJ | mRNA | ||
Y13120 EMBL· GenBank· DDBJ | CAA73587.1 EMBL· GenBank· DDBJ | mRNA | ||
AY130859 EMBL· GenBank· DDBJ | AAM77799.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC000834 EMBL· GenBank· DDBJ | AAH00834.1 EMBL· GenBank· DDBJ | mRNA | ||
BC005298 EMBL· GenBank· DDBJ | AAH05298.1 EMBL· GenBank· DDBJ | mRNA |