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Q03147

- CDK7_MOUSE

UniProt

Q03147 - CDK7_MOUSE

Protein

Cyclin-dependent kinase 7

Gene

Cdk7

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
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    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 2 (01 Oct 1996)
      Previous versions | rss
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    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 binding Source: MGI
    6. protein kinase activity Source: MGI
    7. RNA polymerase II carboxy-terminal domain kinase activity Source: UniProtKB

    GO - Biological processi

    1. ATP catabolic process Source: GOC
    2. cell cycle Source: UniProtKB-KW
    3. cell division Source: UniProtKB-KW
    4. DNA repair Source: UniProtKB-KW
    5. positive regulation of transcription from RNA polymerase II promoter Source: Ensembl
    6. regulation of cell cycle Source: GOC
    7. transcription from RNA polymerase II promoter Source: UniProtKB

    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
    4. perinuclear region of cytoplasm Source: UniProtKB-SubCell

    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

    ArrayExpressiQ03147.
    BgeeiQ03147.
    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_dom.
    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

    MAVDVKSRAK RYEKLDFLGE GQFATVYKAR DKNTNQIVAI KKIKLGHRSE    50
    AKDGINRTAL REIKLLQELS HPNIIGLLDA FGHKSNISLV FDFMETDLEV 100
    IIKDNSLVLT PSHIKAYMLM TLQGLEYLHQ HWILHRDLKP NNLLLDENGV 150
    LKLADFGLAK SFGSPNRAYT HQVVTRWYRA PELLFGARMY GVGVDMWAVG 200
    CILAELLLRV PFLPGDSDLD QLTRIFETLG TPTEEQWPDM CSLPDYVTFK 250
    SFPGVPLQHI FIAAGDDLLE LIQGLFLFNP CTRTTASQAL KTKYFSNRPG 300
    PTPGCQLPRP NCPVEALKEP ANPTVATKRK RAEALEQGIL PKKLIF 346
    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

    ArrayExpressi Q03147.
    Bgeei Q03147.
    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_dom.
    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

    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 1, 2014
    This is version 143 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