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UniProtKB - P50613 (CDK7_HUMAN)

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Protein

Cyclin-dependent kinase 7

Gene

CDK7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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 keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei41ATPPROSITE-ProRule annotation1 Publication1
Active sitei137Proton acceptorPROSITE-ProRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi18 – 26ATPPROSITE-ProRule annotation1 Publication9

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
Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, DNA damage, DNA repair, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.22. 2681.
2.7.11.23. 2681.
ReactomeiR-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 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.
SignaLinkiP50613.
SIGNORiP50613.

Names & Taxonomyi

Protein namesi
Recommended name:
Cyclin-dependent kinase 7 (EC:2.7.11.22, EC:2.7.11.23)
Alternative name(s):
39 kDa protein kinase
Short name:
p39 Mo15
CDK-activating kinase 1
Cell division protein kinase 7
Serine/threonine-protein kinase 1
TFIIH basal transcription factor complex kinase subunit
Gene namesi
Name:CDK7
Synonyms:CAK, CAK1, CDKN7, MO15, STK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:1778. CDK7.

Subcellular locationi

GO - Cellular componenti

  • cyclin-dependent protein kinase activating kinase holoenzyme complex Source: CAFA
  • cytoplasm Source: GO_Central
  • holo TFIIH complex Source: UniProtKB
  • nucleoplasm Source: Reactome
  • nucleus Source: MGI
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • TFIIK complex Source: GO_Central
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi41K → A: Total loss of activity. 1
Mutagenesisi91F → G: Enhanced capacity to bind ATP analogs. 1 Publication1
Mutagenesisi164S → A: No mitotic repression of transcriptional activity of the reconstituted TFIIH complex. 1 Publication1
Mutagenesisi170T → A: Total loss of activity. Total loss of transcriptional activity of the reconstituted TFIIH complex. 2 Publications1

Organism-specific databases

DisGeNETi1022.
OpenTargetsiENSG00000134058.
PharmGKBiPA26314.

Chemistry databases

ChEMBLiCHEMBL3055.
DrugBankiDB03496. Flavopiridol.
DB02482. Phosphonothreonine.
GuidetoPHARMACOLOGYi1979.

Polymorphism and mutation databases

BioMutaiCDK7.
DMDMi1705722.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000857912 – 346Cyclin-dependent kinase 7Add BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei7PhosphoserineCombined sources1
Modified residuei164Phosphoserine; by CDK1 and CDK2Combined sources2 Publications1
Modified residuei170Phosphothreonine; by CDK2Combined sources3 Publications1
Modified residuei321PhosphoserineCombined sources1

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, Phosphoprotein

Proteomic databases

EPDiP50613.
MaxQBiP50613.
PaxDbiP50613.
PeptideAtlasiP50613.
PRIDEiP50613.

PTM databases

iPTMnetiP50613.
PhosphoSitePlusiP50613.

Expressioni

Tissue specificityi

Ubiquitous.

Inductioni

Repressed by DNA-bound peptides.1 Publication

Gene expression databases

BgeeiENSG00000134058.
CleanExiHS_CDK7.
ExpressionAtlasiP50613. baseline and differential.
GenevisibleiP50613. HS.

Organism-specific databases

HPAiCAB004364.
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

WithEntry#Exp.IntActNotes
E2F1Q010942EBI-1245958,EBI-448924

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
Complete GO annotation...

Protein-protein interaction databases

BioGridi107457. 82 interactors.
DIPiDIP-5995N.
IntActiP50613. 23 interactors.
MINTiMINT-3018528.
STRINGi9606.ENSP00000256443.

Chemistry databases

BindingDBiP50613.

Structurei

Secondary structure

1346
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi14 – 21Combined sources8
Beta strandi24 – 30Combined sources7
Beta strandi36 – 42Combined sources7
Helixi58 – 68Combined sources11
Beta strandi77 – 81Combined sources5
Beta strandi88 – 92Combined sources5
Beta strandi95 – 97Combined sources3
Helixi98 – 102Combined sources5
Helixi113 – 130Combined sources18
Helixi140 – 142Combined sources3
Beta strandi143 – 145Combined sources3
Beta strandi151 – 153Combined sources3
Helixi157 – 159Combined sources3
Turni161 – 163Combined sources3
Helixi181 – 184Combined sources4
Helixi192 – 208Combined sources17
Helixi218 – 229Combined sources12
Turni234 – 236Combined sources3
Beta strandi237 – 239Combined sources3
Helixi257 – 260Combined sources4
Helixi266 – 276Combined sources11
Turni280 – 282Combined sources3
Helixi286 – 290Combined sources5
Helixi293 – 295Combined sources3
Beta strandi297 – 299Combined sources3
Beta strandi304 – 307Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1LG3model-A1-307[»]
1PA8model-A181-346[»]
1UA2X-ray3.02A/B/C/D1-346[»]
2HICmodel-B13-311[»]
ProteinModelPortaliP50613.
SMRiP50613.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50613.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini12 – 295Protein kinasePROSITE-ProRule annotationAdd BLAST284

Sequence similaritiesi

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. CDC2/CDKX subfamily.Curated

Phylogenomic databases

eggNOGiKOG0659. Eukaryota.
ENOG410XQDH. LUCA.
GeneTreeiENSGT00830000128262.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiP50613.
KOiK02202.
OMAiADIKAWM.
OrthoDBiEOG091G0CI9.
PhylomeDBiP50613.
TreeFamiTF101024.

Family and domain databases

InterProiView protein in InterPro
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
PfamiView protein in Pfam
PF00069. Pkinase. 1 hit.
SMARTiView protein in SMART
SM00220. S_TKc. 1 hit.
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiView protein in PROSITE
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P50613-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:346
Mass (Da):39,038
Last modified:October 1, 1996 - v1
Checksum:i0A94BFA7DD416CEB
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti130Q → R in AAH05298 (PubMed:15489334).Curated1
Sequence conflicti249F → C in CAA73587 (Ref. 5) Curated1
Sequence conflicti321S → A in CAA73587 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023118163G → A1 Publication1
Natural variantiVAR_023119285T → 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.
CCDSiCCDS3999.1.
PIRiA54820.
I37215.
RefSeqiNP_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.
UniGeneiHs.184298.

Genome annotation databases

EnsembliENST00000256443; ENSP00000256443; ENSG00000134058.
ENST00000615305; ENSP00000479116; ENSG00000277273.
GeneIDi1022.
KEGGihsa:1022.
UCSCiuc003jvs.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiCDK7_HUMAN
AccessioniPrimary (citable) accession number: P50613
Secondary accession number(s): Q9BS60, Q9UE19
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 7, 2017
This is version 195 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families