UniProtKB - P50613 (CDK7_HUMAN)
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Protein
Cyclin-dependent kinase 7
Gene
CDK7
Organism
Homo sapiens (Human)
Status
Functioni
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.14 Publications
Catalytic activityi
ATP + a protein = ADP + a phosphoprotein.
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.
Enzyme regulationi
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.2 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 41 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
Active sitei | 137 | Proton acceptorPROSITE-ProRule annotation1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 18 – 26 | ATPPROSITE-ProRule annotation1 Publication | 9 |
GO - Molecular functioni
- androgen receptor binding Source: UniProtKB
- ATP binding Source: UniProtKB-KW
- cyclin-dependent protein serine/threonine kinase activity Source: GO_Central
- DNA-dependent ATPase activity Source: UniProtKB
- kinase activity Source: Reactome
- protein C-terminus binding Source: UniProtKB
- protein kinase activity Source: ProtInc
- protein serine/threonine kinase activity Source: Reactome
- RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB
- transcription coactivator activity Source: UniProtKB
GO - Biological processi
- 7-methylguanosine mRNA capping Source: Reactome
- androgen receptor signaling pathway Source: UniProtKB
- cell cycle arrest Source: UniProtKB
- cell division Source: UniProtKB-KW
- cell proliferation Source: ProtInc
- G1/S transition of mitotic cell cycle Source: Reactome
- G2/M transition of mitotic cell cycle Source: Reactome
- nucleotide-excision repair, preincision complex assembly Source: Reactome
- positive regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription by RNA polymerase II Source: UniProtKB
- protein stabilization Source: CAFA
- regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
- snRNA transcription by RNA polymerase II Source: Reactome
- termination of RNA polymerase I transcription Source: Reactome
- transcription by RNA polymerase II Source: UniProtKB
- transcription-coupled nucleotide-excision repair Source: Reactome
- transcription elongation from RNA polymerase II promoter Source: Reactome
- transcription elongation from RNA polymerase I promoter Source: Reactome
- transcription initiation from RNA polymerase II promoter Source: Reactome
- transcription initiation from RNA polymerase I promoter Source: Reactome
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle, Cell division, DNA damage, DNA repair, Transcription, Transcription regulation |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
BRENDAi | 2.7.11.22 2681 2.7.11.23 2681 |
Reactomei | R-HSA-112382 Formation of RNA Pol II elongation complex R-HSA-113418 Formation of the Early Elongation Complex R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat R-HSA-167158 Formation of the HIV-1 Early Elongation Complex R-HSA-167160 RNA Pol II CTD phosphorylation and interaction with CE during HIV infection R-HSA-167161 HIV Transcription Initiation R-HSA-167162 RNA Polymerase II HIV Promoter Escape R-HSA-167172 Transcription of the HIV genome R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript R-HSA-427413 NoRC negatively regulates rRNA expression R-HSA-5696395 Formation of Incision Complex in GG-NER R-HSA-674695 RNA Polymerase II Pre-transcription Events R-HSA-6781823 Formation of TC-NER Pre-Incision Complex R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER) R-HSA-6782135 Dual incision in TC-NER R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes R-HSA-6807505 RNA polymerase II transcribes snRNA genes R-HSA-69202 Cyclin E associated events during G1/S transition R-HSA-69231 Cyclin D associated events in G1 R-HSA-69273 Cyclin A/B1/B2 associated events during G2/M transition R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry R-HSA-72086 mRNA Capping R-HSA-73762 RNA Polymerase I Transcription Initiation R-HSA-73772 RNA Polymerase I Promoter Escape R-HSA-73776 RNA Polymerase II Promoter Escape R-HSA-73777 RNA Polymerase I Chain Elongation R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening R-HSA-73863 RNA Polymerase I Transcription Termination R-HSA-75953 RNA Polymerase II Transcription Initiation R-HSA-75955 RNA Polymerase II Transcription Elongation R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance R-HSA-77075 RNA Pol II CTD phosphorylation and interaction with CE R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs |
SignaLinki | P50613 |
SIGNORi | P50613 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:CDK7 Synonyms:CAK, CAK1, CDKN7, MO15, STK1 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000134058.10 |
HGNCi | HGNC:1778 CDK7 |
MIMi | 601955 gene |
neXtProti | NX_P50613 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 41 | K → A: Total loss of activity. | 1 | |
Mutagenesisi | 91 | F → G: Enhanced capacity to bind ATP analogs. 1 Publication | 1 | |
Mutagenesisi | 164 | S → A: No mitotic repression of transcriptional activity of the reconstituted TFIIH complex. 1 Publication | 1 | |
Mutagenesisi | 170 | T → A: Total loss of activity. Total loss of transcriptional activity of the reconstituted TFIIH complex. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 1022 |
OpenTargetsi | ENSG00000134058 |
PharmGKBi | PA26314 |
Chemistry databases
ChEMBLi | CHEMBL3055 |
DrugBanki | DB03496 Flavopiridol DB02482 Phosphonothreonine |
GuidetoPHARMACOLOGYi | 1979 |
Polymorphism and mutation databases
BioMutai | CDK7 |
DMDMi | 1705722 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000085791 | 2 – 346 | Cyclin-dependent kinase 7Add BLAST | 345 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 7 | PhosphoserineCombined sources | 1 | |
Modified residuei | 164 | Phosphoserine; by CDK1 and CDK2Combined sources2 Publications | 1 | |
Modified residuei | 170 | Phosphothreonine; by CDK2Combined sources3 Publications | 1 | |
Modified residuei | 321 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
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 CDK2.3 Publications
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | P50613 |
MaxQBi | P50613 |
PaxDbi | P50613 |
PeptideAtlasi | P50613 |
PRIDEi | P50613 |
PTM databases
iPTMneti | P50613 |
PhosphoSitePlusi | P50613 |
Expressioni
Tissue specificityi
Ubiquitous.
Inductioni
Repressed by DNA-bound peptides.1 Publication
Gene expression databases
Bgeei | ENSG00000134058 |
CleanExi | HS_CDK7 |
ExpressionAtlasi | P50613 baseline and differential |
Genevisiblei | P50613 HS |
Organism-specific databases
HPAi | CAB004364 HPA007932 |
Interactioni
Subunit structurei
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.8 Publications
Binary interactionsi
GO - Molecular functioni
- androgen receptor binding Source: UniProtKB
- protein C-terminus binding Source: UniProtKB
Protein-protein interaction databases
BioGridi | 10745786 interactors. |
CORUMi | P50613 |
DIPi | DIP-5995N |
IntActi | P50613 30 interactors. |
MINTi | P50613 |
STRINGi | 9606.ENSP00000256443 |
Chemistry databases
BindingDBi | P50613 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more detailsFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Beta strandi | 14 – 21 | Combined sources | 8 | |
Beta strandi | 24 – 30 | Combined sources | 7 | |
Beta strandi | 36 – 42 | Combined sources | 7 | |
Helixi | 58 – 68 | Combined sources | 11 | |
Beta strandi | 77 – 81 | Combined sources | 5 | |
Beta strandi | 88 – 92 | Combined sources | 5 | |
Beta strandi | 95 – 97 | Combined sources | 3 | |
Helixi | 98 – 102 | Combined sources | 5 | |
Helixi | 113 – 130 | Combined sources | 18 | |
Helixi | 140 – 142 | Combined sources | 3 | |
Beta strandi | 143 – 145 | Combined sources | 3 | |
Beta strandi | 151 – 153 | Combined sources | 3 | |
Helixi | 157 – 159 | Combined sources | 3 | |
Turni | 161 – 163 | Combined sources | 3 | |
Helixi | 181 – 184 | Combined sources | 4 | |
Helixi | 192 – 208 | Combined sources | 17 | |
Helixi | 218 – 229 | Combined sources | 12 | |
Turni | 234 – 236 | Combined sources | 3 | |
Beta strandi | 237 – 239 | Combined sources | 3 | |
Helixi | 257 – 260 | Combined sources | 4 | |
Helixi | 266 – 276 | Combined sources | 11 | |
Turni | 280 – 282 | Combined sources | 3 | |
Helixi | 286 – 290 | Combined sources | 5 | |
Helixi | 293 – 295 | Combined sources | 3 | |
Beta strandi | 297 – 299 | Combined sources | 3 | |
Beta strandi | 304 – 307 | Combined sources | 4 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1LG3 | model | - | A | 1-307 | [»] | |
1PA8 | model | - | A | 181-346 | [»] | |
1UA2 | X-ray | 3.02 | A/B/C/D | 1-346 | [»] | |
2HIC | model | - | B | 13-311 | [»] | |
ProteinModelPortali | P50613 | |||||
SMRi | P50613 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P50613 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 12 – 295 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 284 |
Sequence similaritiesi
Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0659 Eukaryota ENOG410XQDH LUCA |
GeneTreei | ENSGT00830000128262 |
HOGENOMi | HOG000233024 |
HOVERGENi | HBG014652 |
InParanoidi | P50613 |
KOi | K02202 |
OMAi | ADIKAWM |
OrthoDBi | EOG091G0CI9 |
PhylomeDBi | P50613 |
TreeFami | TF101024 |
Family and domain databases
InterProi | View protein in InterPro IPR037770 CDK7 IPR011009 Kinase-like_dom_sf IPR000719 Prot_kinase_dom IPR017441 Protein_kinase_ATP_BS IPR008271 Ser/Thr_kinase_AS |
PANTHERi | PTHR24056:SF0 PTHR24056:SF0, 1 hit |
Pfami | View protein in Pfam PF00069 Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220 S_TKc, 1 hit |
SUPFAMi | SSF56112 SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107 PROTEIN_KINASE_ATP, 1 hit PS50011 PROTEIN_KINASE_DOM, 1 hit PS00108 PROTEIN_KINASE_ST, 1 hit |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
P50613-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MALDVKSRAK RYEKLDFLGE GQFATVYKAR DKNTNQIVAI KKIKLGHRSE
60 70 80 90 100
AKDGINRTAL REIKLLQELS HPNIIGLLDA FGHKSNISLV FDFMETDLEV
110 120 130 140 150
IIKDNSLVLT PSHIKAYMLM TLQGLEYLHQ HWILHRDLKP NNLLLDENGV
160 170 180 190 200
LKLADFGLAK SFGSPNRAYT HQVVTRWYRA PELLFGARMY GVGVDMWAVG
210 220 230 240 250
CILAELLLRV PFLPGDSDLD QLTRIFETLG TPTEEQWPDM CSLPDYVTFK
260 270 280 290 300
SFPGIPLHHI FSAAGDDLLD LIQGLFLFNP CARITATQAL KMKYFSNRPG
310 320 330 340
PTPGCQLPRP NCPVETLKEQ SNPALAIKRK RTEALEQGGL PKKLIF
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 130 | Q → R in AAH05298 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 249 | F → C in CAA73587 (Ref. 5) Curated | 1 | |
Sequence conflicti | 321 | S → A in CAA73587 (Ref. 5) Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023118 | 163 | G → A1 Publication | 1 | |
Natural variantiVAR_023119 | 285 | T → M2 PublicationsCorresponds to variant dbSNP:rs34584424Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | X79193 mRNA Translation: CAA55785.1 L20320 mRNA Translation: AAA36657.1 X77743 mRNA Translation: CAA54793.1 X77303 mRNA Translation: CAA54508.1 Y13120 mRNA Translation: CAA73587.1 AY130859 Genomic DNA Translation: AAM77799.1 BC000834 mRNA Translation: AAH00834.1 BC005298 mRNA Translation: AAH05298.1 |
CCDSi | CCDS3999.1 |
PIRi | A54820 I37215 |
RefSeqi | NP_001310998.1, NM_001324069.1 NP_001310999.1, NM_001324070.1 NP_001311000.1, NM_001324071.1 NP_001311006.1, NM_001324077.1 NP_001790.1, NM_001799.3 |
UniGenei | Hs.184298 |
Genome annotation databases
Ensembli | ENST00000256443; ENSP00000256443; ENSG00000134058 ENST00000615305; ENSP00000479116; ENSG00000277273 |
GeneIDi | 1022 |
KEGGi | hsa:1022 |
UCSCi | uc003jvs.5 human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Entry informationi
Entry namei | CDK7_HUMAN | |
Accessioni | P50613Primary (citable) accession number: P50613 Secondary accession number(s): Q9BS60, Q9UE19 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | October 1, 1996 |
Last sequence update: | October 1, 1996 | |
Last modified: | March 28, 2018 | |
This is version 201 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |