Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P30285

- CDK4_MOUSE

UniProt

P30285 - CDK4_MOUSE

Protein

Cyclin-dependent kinase 4

Gene

Cdk4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 143 (01 Oct 2014)
      Sequence version 1 (01 Apr 1993)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Ser/Thr-kinase component of cyclin D-CDK4 (DC) complexes that phosphorylate and inhibit members of the retinoblastoma (RB) protein family including RB1 and regulate the cell-cycle during G1/S transition. Phosphorylation of RB1 allows dissociation of the transcription factor E2F from the RB/E2F complexes and the subsequent transcription of E2F target genes which are responsible for the progression through the G1 phase. Hypophosphorylates RB1 in early G1 phase. Cyclin D-CDK4 complexes are major integrators of various mitogenenic and antimitogenic signals. Also phosphorylates SMAD3 in a cell-cycle-dependent manner and represses its transcriptional activity. Component of the ternary complex, cyclin D/CDK4/CDKN1B, required for nuclear translocation and activity of the cyclin D-CDK4 complex By similarity.By similarity

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.1 Publication

    Enzyme regulationi

    Both phosphorylation at Thr-172 and binding of a D-type cyclin are necessary for enzymatic activity. Full activation of the cyclin-D-CDK4 complex appears to require other factors such as recruitment of the substrate via a substrate recruitment motif, and/or formation of the CDKN1B ternary complex. Inhibited by INK4 family members. In resting cells, the non-tyrosine-phosphorylated form of CDKN1B prevents phosphorylation at Thr-172 and inactivation, while, in proliferating cells, tyrosine phosphorylation of CDKN1B allows phosphorylation of Thr-172 of CDK4 and subsequennt activation.

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei35 – 351ATPPROSITE-ProRule annotation
    Active sitei140 – 1401Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi12 – 209ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. cyclin-dependent protein serine/threonine kinase activity Source: MGI
    3. kinase activity Source: MGI
    4. protein binding Source: UniProtKB
    5. protein kinase activity Source: MGI

    GO - Biological processi

    1. cell division Source: UniProtKB-KW
    2. circadian rhythm Source: Ensembl
    3. G1/S transition of mitotic cell cycle Source: Ensembl
    4. negative regulation of cell cycle arrest Source: UniProtKB
    5. organ regeneration Source: Ensembl
    6. positive regulation of apoptotic process Source: Ensembl
    7. positive regulation of cell size Source: Ensembl
    8. positive regulation of fibroblast proliferation Source: Ensembl
    9. positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
    10. positive regulation of translation Source: Ensembl
    11. protein phosphorylation Source: MGI
    12. regulation of cell cycle Source: MGI
    13. regulation of cell proliferation Source: MGI
    14. response to drug Source: Ensembl
    15. response to hyperoxia Source: Ensembl
    16. response to lead ion Source: Ensembl
    17. response to testosterone Source: Ensembl
    18. response to toxic substance Source: Ensembl
    19. signal transduction Source: MGI

    Keywords - Molecular functioni

    Kinase, Serine/threonine-protein kinase, Transferase

    Keywords - Biological processi

    Cell cycle, Cell division

    Keywords - Ligandi

    ATP-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.11.22. 3474.
    ReactomeiREACT_188970. Oxidative Stress Induced Senescence.
    REACT_188971. Oncogene Induced Senescence.
    REACT_198629. Meiotic recombination.
    REACT_206033. Senescence-Associated Secretory Phenotype (SASP).
    REACT_27235. Meiotic Recombination.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 4 (EC:2.7.11.22)
    Alternative name(s):
    CRK3
    Cell division protein kinase 4
    PSK-J3
    Gene namesi
    Name:Cdk4
    Synonyms:Crk3
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 10

    Organism-specific databases

    MGIiMGI:88357. Cdk4.

    Subcellular locationi

    Cytoplasm By similarity. Nucleus By similarity. Membrane By similarity
    Note: Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G1 phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G1 to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus By similarity.By similarity

    GO - Cellular componenti

    1. chromatin Source: Ensembl
    2. cyclin-dependent protein kinase holoenzyme complex Source: MGI
    3. cytosol Source: Ensembl
    4. nuclear membrane Source: Ensembl
    5. nucleolus Source: Ensembl
    6. nucleoplasm Source: Reactome
    7. nucleus Source: MGI
    8. perinuclear region of cytoplasm Source: Ensembl
    9. transcription factor complex Source: MGI

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Keywords - Diseasei

    Proto-oncogene

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11RemovedBy similarity
    Chaini2 – 303302Cyclin-dependent kinase 4PRO_0000085779Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanineBy similarity
    Modified residuei172 – 1721Phosphothreonine; by CAK1 Publication

    Post-translational modificationi

    Phosphorylation at Thr-172 is required for enzymatic activity. Phosphorylated, in vitro, at this site by CCNH-CDK7, but, in vivo, appears to be phosphorylated by a proline-directed kinase. In the cyclin D-CDK4-CDKN1B complex, this phosphorylation and consequent CDK4 enzyme activity, is dependent on the tyrosine phosphorylation state of CDKN1B. Thus, in proliferating cells, CDK4 within the complex is phosphorylated on Thr-172 in the T-loop. In resting cells, phosphorylation on Thr-172 is prevented by the non-tyrosine-phosphorylated form of CDKN1B By similarity.By similarity

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP30285.
    PaxDbiP30285.
    PRIDEiP30285.

    PTM databases

    PhosphoSiteiP30285.

    Expressioni

    Gene expression databases

    ArrayExpressiP30285.
    BgeeiP30285.
    CleanExiMM_CDK4.
    GenevestigatoriP30285.

    Interactioni

    Subunit structurei

    Component of the D-CDK4 complex, composed of CDK4 and some D-type G1 cyclin (CCND1, CCND2 or CCND3). Interacts directly in the complex with CCND1, CCND2 or CCND3. Interacts with ZNF655. Forms a ternary complex, cyclin D-CDK4-CDKN1B, involved in modulating CDK4 enzymatic activity. Interacts directly with CDKN1B (phosphorylated on 'Tyr-88' and 'Tyr-89'); the interaction allows assembly of the cyclin D-CDK4 complex, Thr-172 phosphorylation, nuclear translocation and enhances the cyclin D-CDK4 complex activity. CDK4 activity is either inhibited or enhanced depending on stoichiometry of complex. The non-tyrosine-phosphorylated form of CDKN1B prevents T-loop phosphorylation of CDK4 producing inactive CDK4. Interacts (unphosphorylated form) with CDK2. Also forms ternary complexes with CDKN1A or CDKN2A. Interacts directly with CDKN1A (via its N-terminal); the interaction promotes the assembly of the cyclin D-CDK4 complex, its nuclear translocation and promotes the cyclin D-dependent enzyme activity of CDK4. Interacts with CCND1; the interaction is prevented with the binding of CCND1 to INSM1 during cell cycle progression By similarity. Interacts with SEI1 and CCND1.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCND1P243852EBI-847225,EBI-375001From a different organism.
    Ccnd1P2532213EBI-847225,EBI-847243
    RB1P064002EBI-847225,EBI-491274From a different organism.

    Protein-protein interaction databases

    BioGridi198645. 23 interactions.
    DIPiDIP-194N.
    IntActiP30285. 12 interactions.
    MINTiMINT-4090398.

    Structurei

    3D structure databases

    ProteinModelPortaliP30285.
    SMRiP30285. Positions 5-295.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini6 – 295290Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni50 – 567Required for binding D-type cyclinsBy similarity

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP30285.
    KOiK02089.
    OMAiIDQDLRT.
    OrthoDBiEOG73JKVV.
    PhylomeDBiP30285.
    TreeFamiTF101022.

    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.

    P30285-1 [UniParc]FASTAAdd to Basket

    « Hide

    MAATRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGAAGGGLP    50
    VSTVREVALL RRLEAFEHPN VVRLMDVCAT SRTDRDIKVT LVFEHIDQDL 100
    RTYLDKAPPP GLPVETIKDL MRQFLSGLDF LHANCIVHRD LKPENILVTS 150
    NGTVKLADFG LARIYSYQMA LTPVVVTLWY RAPEVLLQST YATPVDMWSV 200
    GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR EVSLPRGAFA 250
    PRGPRPVQSV VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKEES 300
    DAE 303
    Length:303
    Mass (Da):33,751
    Last modified:April 1, 1993 - v1
    Checksum:iCB4F42A8AA13634A
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L01640 mRNA. Translation: AAA37646.1.
    BC046336 mRNA. Translation: AAH46336.1.
    BC052694 mRNA. Translation: AAH52694.1.
    X57238 mRNA. Translation: CAA40514.1.
    X65069 mRNA. Translation: CAA46202.1.
    CCDSiCCDS24226.1.
    PIRiA44293.
    RefSeqiNP_034000.1. NM_009870.3.
    UniGeneiMm.6839.

    Genome annotation databases

    EnsembliENSMUST00000006911; ENSMUSP00000006911; ENSMUSG00000006728.
    GeneIDi12567.
    KEGGimmu:12567.
    UCSCiuc007hhv.2. mouse.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L01640 mRNA. Translation: AAA37646.1 .
    BC046336 mRNA. Translation: AAH46336.1 .
    BC052694 mRNA. Translation: AAH52694.1 .
    X57238 mRNA. Translation: CAA40514.1 .
    X65069 mRNA. Translation: CAA46202.1 .
    CCDSi CCDS24226.1.
    PIRi A44293.
    RefSeqi NP_034000.1. NM_009870.3.
    UniGenei Mm.6839.

    3D structure databases

    ProteinModelPortali P30285.
    SMRi P30285. Positions 5-295.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 198645. 23 interactions.
    DIPi DIP-194N.
    IntActi P30285. 12 interactions.
    MINTi MINT-4090398.

    Chemistry

    BindingDBi P30285.
    ChEMBLi CHEMBL2134.

    PTM databases

    PhosphoSitei P30285.

    Proteomic databases

    MaxQBi P30285.
    PaxDbi P30285.
    PRIDEi P30285.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000006911 ; ENSMUSP00000006911 ; ENSMUSG00000006728 .
    GeneIDi 12567.
    KEGGi mmu:12567.
    UCSCi uc007hhv.2. mouse.

    Organism-specific databases

    CTDi 1019.
    MGIi MGI:88357. Cdk4.

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P30285.
    KOi K02089.
    OMAi IDQDLRT.
    OrthoDBi EOG73JKVV.
    PhylomeDBi P30285.
    TreeFami TF101022.

    Enzyme and pathway databases

    BRENDAi 2.7.11.22. 3474.
    Reactomei REACT_188970. Oxidative Stress Induced Senescence.
    REACT_188971. Oncogene Induced Senescence.
    REACT_198629. Meiotic recombination.
    REACT_206033. Senescence-Associated Secretory Phenotype (SASP).
    REACT_27235. Meiotic Recombination.

    Miscellaneous databases

    NextBioi 281662.
    PROi P30285.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P30285.
    Bgeei P30285.
    CleanExi MM_CDK4.
    Genevestigatori P30285.

    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. "Identification and properties of an atypical catalytic subunit (p34PSK-J3/cdk4) for mammalian D type G1 cyclins."
      Matsushime H., Ewen M.E., Strom D.K., Kato J.Y., Hanks S.K., Roussel M.F., Sherr C.J.
      Cell 71:323-334(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CATALYTIC ACTIVITY.
    2. "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: Olfactory epithelium.
    3. "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 142-188.
      Strain: C57BL/6.
      Tissue: Embryonic brain.
    4. "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 144-178.
      Strain: CBA.
      Tissue: Bone marrow.
    5. "Regulation of cyclin D-dependent kinase 4 (cdk4) by cdk4-activating kinase."
      Kato J.-Y., Matsuoka M., Strom D.K., Sherr C.J.
      Mol. Cell. Biol. 14:2713-2721(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-172.
    6. Cited for: INTERACTION WITH SEI1.
    7. "Lysine 269 is essential for cyclin D1 ubiquitylation by the SCF(Fbx4/alphaB-crystallin) ligase and subsequent proteasome-dependent degradation."
      Barbash O., Egan E., Pontano L.L., Kosak J., Diehl J.A.
      Oncogene 28:4317-4325(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CCND1.

    Entry informationi

    Entry nameiCDK4_MOUSE
    AccessioniPrimary (citable) accession number: P30285
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: April 1, 1993
    Last modified: October 1, 2014
    This is version 143 of the entry and version 1 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