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Protein

Cyclin-dependent kinase 7

Gene

CDK7

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

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
  • 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 initiation from RNA polymerase II promoter Source: Reactome
  • transcription initiation from RNA polymerase I promoter Source: Reactome

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/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
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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000134058.10
HGNCiHGNC:1778 CDK7
MIMi601955 gene
neXtProtiNX_P50613

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

Show more details

GO - Molecular functioni

  • androgen receptor binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107457, 86 interactors
CORUMiP50613
DIPiDIP-5995N
IntActiP50613, 100 interactors
MINTiP50613
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

Phylogenomic databases

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

Family and domain databases

InterProiView protein in InterPro
IPR037770 CDK7
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PANTHERiPTHR24056:SF0 PTHR24056:SF0, 1 hit
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

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: May 23, 2018
This is version 202 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

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