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Protein

Cyclin-dependent kinase 7

Gene

Cdk7

Organism
Mus musculus (Mouse)
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.

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.
ATP + [DNA-directed RNA polymerase] = ADP + [DNA-directed RNA polymerase] phosphate.

Enzyme regulationi

Phosphorylation at Thr-170 is required for enzymatic activity. 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 (By similarity).By similarity

Sites

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

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi18 – 26ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • cyclin-dependent protein serine/threonine kinase activity Source: MGI
  • DNA-dependent ATPase activity Source: UniProtKB
  • kinase activity Source: MGI
  • protein C-terminus binding Source: MGI
  • protein kinase activity Source: MGI
  • RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, DNA damage, DNA repair, Transcription, Transcription regulation

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.22. 3474.
ReactomeiR-MMU-112382. Formation of RNA Pol II elongation complex.
R-MMU-113418. Formation of the Early Elongation Complex.
R-MMU-5696395. Formation of Incision Complex in GG-NER.
R-MMU-674695. RNA Polymerase II Pre-transcription Events.
R-MMU-6781823. Formation of TC-NER Pre-Incision Complex.
R-MMU-6782135. Dual incision in TC-NER.
R-MMU-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-MMU-6796648. TP53 Regulates Transcription of DNA Repair Genes.
R-MMU-6807505. RNA polymerase II transcribes snRNA genes.
R-MMU-69202. Cyclin E associated events during G1/S transition.
R-MMU-69231. Cyclin D associated events in G1.
R-MMU-69273. Cyclin A/B1 associated events during G2/M transition.
R-MMU-69656. Cyclin A:Cdk2-associated events at S phase entry.
R-MMU-72086. mRNA Capping.
R-MMU-73762. RNA Polymerase I Transcription Initiation.
R-MMU-73772. RNA Polymerase I Promoter Escape.
R-MMU-73776. RNA Polymerase II Promoter Escape.
R-MMU-73777. RNA Polymerase I Chain Elongation.
R-MMU-73779. RNA Polymerase II Transcription Pre-Initiation And Promoter Opening.
R-MMU-73863. RNA Polymerase I Transcription Termination.
R-MMU-75953. RNA Polymerase II Transcription Initiation.
R-MMU-75955. RNA Polymerase II Transcription Elongation.
R-MMU-76042. RNA Polymerase II Transcription Initiation And Promoter Clearance.
R-MMU-77075. RNA Pol II CTD phosphorylation and interaction with CE.

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
CR4 protein kinase
Short name:
CRK4
Cell division protein kinase 7
Protein-tyrosine kinase MPK-7
TFIIH basal transcription factor complex kinase subunit
Gene namesi
Name:Cdk7
Synonyms:Cak, Cdkn7, Crk4, Mo15, Mpk-7
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:102956. Cdk7.

Subcellular locationi

  • Nucleus
  • Cytoplasm By similarity
  • Cytoplasmperinuclear region By similarity

  • Note: Colocalizes with PRKCI in the cytoplasm and nucleus. Translocates from the nucleus to cytoplasm and perinuclear region in response to DNA-bound peptides (By similarity).By similarity

GO - Cellular componenti

  • cytoplasm Source: MGI
  • holo TFIIH complex Source: UniProtKB
  • mitochondrion Source: MGI
  • nucleus Source: MGI
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL2176816.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000857922 – 346Cyclin-dependent kinase 7Add BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei7PhosphoserineBy similarity1
Modified residuei164Phosphoserine; by CDK1 and CDK2By similarity1
Modified residuei170Phosphothreonine; by CDK2By similarity1

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 (By similarity).By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ03147.
PaxDbiQ03147.
PeptideAtlasiQ03147.
PRIDEiQ03147.

PTM databases

iPTMnetiQ03147.
PhosphoSitePlusiQ03147.

Expressioni

Gene expression databases

BgeeiENSMUSG00000069089.
ExpressionAtlasiQ03147. baseline and differential.
GenevisibleiQ03147. MM.

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 (By similarity).By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi198650. 3 interactors.
IntActiQ03147. 2 interactors.
MINTiMINT-4090482.
STRINGi10090.ENSMUSP00000088845.

Structurei

3D structure databases

ProteinModelPortaliQ03147.
SMRiQ03147.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0659. Eukaryota.
ENOG410XQDH. LUCA.
GeneTreeiENSGT00830000128262.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ03147.
KOiK02202.
OMAiDAEWPHL.
OrthoDBiEOG091G0CI9.
PhylomeDBiQ03147.
TreeFamiTF101024.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q03147-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAVDVKSRAK 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
SFPGVPLQHI FIAAGDDLLE LIQGLFLFNP CTRTTASQAL KTKYFSNRPG
310 320 330 340
PTPGCQLPRP NCPVEALKEP ANPTVATKRK RAEALEQGIL PKKLIF
Length:346
Mass (Da):38,968
Last modified:October 1, 1996 - v2
Checksum:i455FFAB2CFEDEB3E
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti11 – 12RY → HN in CAA52242 (PubMed:7959010).Curated2
Sequence conflicti20E → R in CAA52242 (PubMed:7959010).Curated1
Sequence conflicti100 – 136Missing in AAH04605 (PubMed:15489334).CuratedAdd BLAST37
Sequence conflicti100V → L in CAA52242 (PubMed:7959010).Curated1
Sequence conflicti104D → H in CAA52242 (PubMed:7959010).Curated1
Sequence conflicti130 – 131QH → HN in CAA52242 (PubMed:7959010).Curated2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11822 mRNA. Translation: AAA64831.1.
X74145 mRNA. Translation: CAA52242.1.
BC004605 mRNA. Translation: AAH04605.1.
BC068160 mRNA. Translation: AAH68160.1.
X57239 mRNA. Translation: CAA40515.1.
X65070 mRNA. Translation: CAA46203.1.
CCDSiCCDS36766.1.
PIRiA56231.
S30503.
S34652.
RefSeqiNP_034004.2. NM_009874.3.
UniGeneiMm.259718.

Genome annotation databases

EnsembliENSMUST00000091299; ENSMUSP00000088845; ENSMUSG00000069089.
GeneIDi12572.
KEGGimmu:12572.
UCSCiuc007rrk.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U11822 mRNA. Translation: AAA64831.1.
X74145 mRNA. Translation: CAA52242.1.
BC004605 mRNA. Translation: AAH04605.1.
BC068160 mRNA. Translation: AAH68160.1.
X57239 mRNA. Translation: CAA40515.1.
X65070 mRNA. Translation: CAA46203.1.
CCDSiCCDS36766.1.
PIRiA56231.
S30503.
S34652.
RefSeqiNP_034004.2. NM_009874.3.
UniGeneiMm.259718.

3D structure databases

ProteinModelPortaliQ03147.
SMRiQ03147.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi198650. 3 interactors.
IntActiQ03147. 2 interactors.
MINTiMINT-4090482.
STRINGi10090.ENSMUSP00000088845.

Chemistry databases

ChEMBLiCHEMBL2176816.

PTM databases

iPTMnetiQ03147.
PhosphoSitePlusiQ03147.

Proteomic databases

EPDiQ03147.
PaxDbiQ03147.
PeptideAtlasiQ03147.
PRIDEiQ03147.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000091299; ENSMUSP00000088845; ENSMUSG00000069089.
GeneIDi12572.
KEGGimmu:12572.
UCSCiuc007rrk.2. mouse.

Organism-specific databases

CTDi1022.
MGIiMGI:102956. Cdk7.

Phylogenomic databases

eggNOGiKOG0659. Eukaryota.
ENOG410XQDH. LUCA.
GeneTreeiENSGT00830000128262.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ03147.
KOiK02202.
OMAiDAEWPHL.
OrthoDBiEOG091G0CI9.
PhylomeDBiQ03147.
TreeFamiTF101024.

Enzyme and pathway databases

BRENDAi2.7.11.22. 3474.
ReactomeiR-MMU-112382. Formation of RNA Pol II elongation complex.
R-MMU-113418. Formation of the Early Elongation Complex.
R-MMU-5696395. Formation of Incision Complex in GG-NER.
R-MMU-674695. RNA Polymerase II Pre-transcription Events.
R-MMU-6781823. Formation of TC-NER Pre-Incision Complex.
R-MMU-6782135. Dual incision in TC-NER.
R-MMU-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-MMU-6796648. TP53 Regulates Transcription of DNA Repair Genes.
R-MMU-6807505. RNA polymerase II transcribes snRNA genes.
R-MMU-69202. Cyclin E associated events during G1/S transition.
R-MMU-69231. Cyclin D associated events in G1.
R-MMU-69273. Cyclin A/B1 associated events during G2/M transition.
R-MMU-69656. Cyclin A:Cdk2-associated events at S phase entry.
R-MMU-72086. mRNA Capping.
R-MMU-73762. RNA Polymerase I Transcription Initiation.
R-MMU-73772. RNA Polymerase I Promoter Escape.
R-MMU-73776. RNA Polymerase II Promoter Escape.
R-MMU-73777. RNA Polymerase I Chain Elongation.
R-MMU-73779. RNA Polymerase II Transcription Pre-Initiation And Promoter Opening.
R-MMU-73863. RNA Polymerase I Transcription Termination.
R-MMU-75953. RNA Polymerase II Transcription Initiation.
R-MMU-75955. RNA Polymerase II Transcription Elongation.
R-MMU-76042. RNA Polymerase II Transcription Initiation And Promoter Clearance.
R-MMU-77075. RNA Pol II CTD phosphorylation and interaction with CE.

Miscellaneous databases

PROiQ03147.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000069089.
ExpressionAtlasiQ03147. baseline and differential.
GenevisibleiQ03147. MM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCDK7_MOUSE
AccessioniPrimary (citable) accession number: Q03147
Secondary accession number(s): Q99KK3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1996
Last modified: November 2, 2016
This is version 164 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

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.