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Q03147

- CDK7_MOUSE

UniProt

Q03147 - CDK7_MOUSE

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Protein

Cyclin-dependent kinase 7

Gene

Cdk7

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei41 – 411ATPPROSITE-ProRule annotation
Active sitei137 – 1371Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi18 – 269ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. cyclin-dependent protein serine/threonine kinase activity Source: MGI
  3. DNA-dependent ATPase activity Source: UniProtKB
  4. kinase activity Source: MGI
  5. protein kinase activity Source: MGI
  6. RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB

GO - Biological processi

  1. cell cycle Source: UniProtKB-KW
  2. cell division Source: UniProtKB-KW
  3. DNA repair Source: UniProtKB-KW
  4. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
  5. regulation of cell cycle Source: GOC
  6. transcription from RNA polymerase II promoter Source: UniProtKB
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.
ReactomeiREACT_203462. Formation of the Early Elongation Complex.
REACT_206803. Cyclin A/B1 associated events during G2/M transition.
REACT_223647. Cyclin A:Cdk2-associated events at S phase entry.
REACT_223654. Formation of transcription-coupled NER (TC-NER) repair complex.
REACT_224562. Dual incision reaction in TC-NER.
REACT_226490. RNA Polymerase II Transcription Elongation.

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
ProteomesiUP000000589: 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

  1. holo TFIIH complex Source: UniProtKB
  2. mitochondrion Source: Ensembl
  3. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11RemovedBy similarity
Chaini2 – 346345Cyclin-dependent kinase 7PRO_0000085792Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineBy similarity
Modified residuei7 – 71PhosphoserineBy similarity
Modified residuei164 – 1641Phosphoserine; by CDK1 and CDK2By similarity
Modified residuei170 – 1701Phosphothreonine; by CDK2By similarity

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

MaxQBiQ03147.
PaxDbiQ03147.
PRIDEiQ03147.

PTM databases

PhosphoSiteiQ03147.

Expressioni

Gene expression databases

BgeeiQ03147.
ExpressionAtlasiQ03147. baseline and differential.
GenevestigatoriQ03147.

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

Protein-protein interaction databases

BioGridi198650. 3 interactions.
IntActiQ03147. 2 interactions.
MINTiMINT-4090482.

Structurei

3D structure databases

ProteinModelPortaliQ03147.
SMRiQ03147. Positions 13-311.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini12 – 295284Protein kinasePROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000233024.
HOVERGENiHBG014652.
InParanoidiQ03147.
KOiK02202.
OMAiCHRNWIL.
OrthoDBiEOG75J0NH.
PhylomeDBiQ03147.
TreeFamiTF101024.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti11 – 122RY → HN in CAA52242. (PubMed:7959010)Curated
Sequence conflicti20 – 201E → R in CAA52242. (PubMed:7959010)Curated
Sequence conflicti100 – 13637Missing in AAH04605. (PubMed:15489334)CuratedAdd
BLAST
Sequence conflicti100 – 1001V → L in CAA52242. (PubMed:7959010)Curated
Sequence conflicti104 – 1041D → H in CAA52242. (PubMed:7959010)Curated
Sequence conflicti130 – 1312QH → HN in CAA52242. (PubMed:7959010)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS36766.1.
PIRi A56231.
S30503.
S34652.
RefSeqi NP_034004.2. NM_009874.3.
UniGenei Mm.259718.

3D structure databases

ProteinModelPortali Q03147.
SMRi Q03147. Positions 13-311.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 198650. 3 interactions.
IntActi Q03147. 2 interactions.
MINTi MINT-4090482.

Chemistry

ChEMBLi CHEMBL2176816.

PTM databases

PhosphoSitei Q03147.

Proteomic databases

MaxQBi Q03147.
PaxDbi Q03147.
PRIDEi Q03147.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000091299 ; ENSMUSP00000088845 ; ENSMUSG00000069089 .
GeneIDi 12572.
KEGGi mmu:12572.
UCSCi uc007rrk.2. mouse.

Organism-specific databases

CTDi 1022.
MGIi MGI:102956. Cdk7.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000233024.
HOVERGENi HBG014652.
InParanoidi Q03147.
KOi K02202.
OMAi CHRNWIL.
OrthoDBi EOG75J0NH.
PhylomeDBi Q03147.
TreeFami TF101024.

Enzyme and pathway databases

BRENDAi 2.7.11.22. 3474.
Reactomei REACT_203462. Formation of the Early Elongation Complex.
REACT_206803. Cyclin A/B1 associated events during G2/M transition.
REACT_223647. Cyclin A:Cdk2-associated events at S phase entry.
REACT_223654. Formation of transcription-coupled NER (TC-NER) repair complex.
REACT_224562. Dual incision reaction in TC-NER.
REACT_226490. RNA Polymerase II Transcription Elongation.

Miscellaneous databases

NextBioi 281682.
PROi Q03147.
SOURCEi Search...

Gene expression databases

Bgeei Q03147.
ExpressionAtlasi Q03147. baseline and differential.
Genevestigatori Q03147.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Activation of cyclin-dependent kinase 4 (cdk4) by mouse MO15-associated kinase."
    Matsuoka M., Kato J.-Y., Fisher R.P., Morgan D.O., Sherr C.J.
    Mol. Cell. Biol. 14:7265-7275(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Macrophage.
  2. "Sequence of the cDNA encoding murine CRK4 protein kinase."
    Stepanova L.Y., Ershler M., Belyavsky A.V.
    Gene 149:321-324(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: CBA.
    Tissue: Bone marrow.
  3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6.
    Tissue: Brain.
  4. "An Eph-related receptor protein tyrosine kinase gene segmentally expressed in the developing mouse hindbrain."
    Gilardi-Hebenstreit P., Nieto M.A., Frain M., Mattei M.-G., Chestier A., Wilkinson D.G., Charnay P.
    Oncogene 7:2499-2506(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 139-154.
    Strain: C57BL/6.
    Tissue: Embryonic brain.
  5. "Novel CDC2-related protein kinases produced in murine hematopoietic stem cells."
    Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
    Gene 124:305-306(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 141-176.
    Strain: CBA.
    Tissue: Bone marrow.
  6. "Identification of new protein kinase genes, similar to kinases of the cdc2 family and expressed in murine hematopoietic stem cells."
    Ershler M.A., Nagorskaya T.V., Visser J.W.M., Belyavsky A.V.
    Dokl. Akad. Nauk SSSR 324:893-897(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 141-176.
    Strain: CBA.
    Tissue: Bone marrow.

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: October 29, 2014
This is version 144 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

External Data

Dasty 3