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Q03147 (CDK7_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cdk7
Synonyms:Cak, Cdkn7, Crk4, Mo15, Mpk-7
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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-terminus 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 activity

ATP + a protein = ADP + a phosphoprotein.

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

Enzyme regulation

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-terminus domain (CTD), thus stopping cell cycle progression By similarity.

Subunit structure

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.

Subcellular location

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.

Post-translational modification

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.

Sequence similarities

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

Contains 1 protein kinase domain.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 346346Cyclin-dependent kinase 7
PRO_0000085792

Regions

Domain12 – 295284Protein kinase
Nucleotide binding18 – 269ATP By similarity

Sites

Active site1371Proton acceptor By similarity
Binding site411ATP By similarity

Amino acid modifications

Modified residue71Phosphoserine By similarity
Modified residue1641Phosphoserine; by CDK1 and CDK2 By similarity
Modified residue1701Phosphothreonine; by CDK2 By similarity

Experimental info

Sequence conflict11 – 122RY → HN in CAA52242. Ref.2
Sequence conflict201E → R in CAA52242. Ref.2
Sequence conflict100 – 13637Missing in AAH04605. Ref.3
Sequence conflict1001V → L in CAA52242. Ref.2
Sequence conflict1041D → H in CAA52242. Ref.2
Sequence conflict130 – 1312QH → HN in CAA52242. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q03147 [UniParc].

Last modified October 1, 1996. Version 2.
Checksum: 455FFAB2CFEDEB3E

FASTA34638,968
        10         20         30         40         50         60 
MAVDVKSRAK RYEKLDFLGE GQFATVYKAR DKNTNQIVAI KKIKLGHRSE AKDGINRTAL 

        70         80         90        100        110        120 
REIKLLQELS HPNIIGLLDA FGHKSNISLV FDFMETDLEV IIKDNSLVLT PSHIKAYMLM 

       130        140        150        160        170        180 
TLQGLEYLHQ HWILHRDLKP NNLLLDENGV LKLADFGLAK SFGSPNRAYT HQVVTRWYRA 

       190        200        210        220        230        240 
PELLFGARMY GVGVDMWAVG CILAELLLRV PFLPGDSDLD QLTRIFETLG TPTEEQWPDM 

       250        260        270        280        290        300 
CSLPDYVTFK SFPGVPLQHI FIAAGDDLLE LIQGLFLFNP CTRTTASQAL KTKYFSNRPG 

       310        320        330        340 
PTPGCQLPRP NCPVEALKEP ANPTVATKRK RAEALEQGIL PKKLIF 

« Hide

References

« Hide 'large scale' references
[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.
[7]"Solid tumor proteome and phosphoproteome analysis by high resolution mass spectrometry."
Zanivan S., Gnad F., Wickstroem S.A., Geiger T., Macek B., Cox J., Faessler R., Mann M.
J. Proteome Res. 7:5314-5326(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-170, MASS SPECTROMETRY.
Tissue: Melanoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
IPIIPI00129222.
PIRA56231.
S30503.
S34652.
RefSeqNP_034004.2. NM_009874.3.
UniGeneMm.259718.

3D structure databases

ProteinModelPortalQ03147.
SMRQ03147. Positions 13-311.
ModBaseSearch...

Protein-protein interaction databases

IntActQ03147. 1 interaction.

PTM databases

PhosphoSiteQ03147.

Proteomic databases

PaxDbQ03147.
PRIDEQ03147.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000091299; ENSMUSP00000088845; ENSMUSG00000069089.
GeneID12572.
KEGGmmu:12572.

Organism-specific databases

CTD1022.
MGIMGI:102956. Cdk7.

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000233024.
HOVERGENHBG014652.
InParanoidQ03147.
KOK02202.
OMAPRPNCPA.
OrthoDBEOG4KSPK0.

Enzyme and pathway databases

BRENDA2.7.11.22. 3474.

Gene expression databases

ArrayExpressQ03147.
BgeeQ03147.
GenevestigatorQ03147.
GermOnlineENSMUSG00000069089. Mus musculus.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio281682.
SOURCESearch...

Entry information

Entry nameCDK7_MOUSE
AccessionPrimary (citable) accession number: Q03147
Secondary accession number(s): Q99KK3
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1994
Last sequence update: October 1, 1996
Last modified: May 1, 2013
This is version 129 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

SIMILARITY comments

Index of protein domains and families