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P79432

- CDK4_PIG

UniProt

P79432 - CDK4_PIG

Protein

Cyclin-dependent kinase 4

Gene

CDK4

Organism
Sus scrofa (Pig)
Status
Reviewed - Annotation score: 5 out of 5- Protein inferred from homologyi
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    • History
      Entry version 90 (01 Oct 2014)
      Sequence version 1 (01 May 1997)
      Previous versions | rss
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    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.

    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: UniProtKB-EC

    GO - Biological processi

    1. cell division Source: UniProtKB-KW
    2. G1/S transition of mitotic cell cycle Source: Ensembl
    3. negative regulation of cell cycle arrest Source: UniProtKB
    4. positive regulation of fibroblast proliferation Source: Ensembl
    5. positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
    6. regulation of gene expression Source: Ensembl
    7. response to drug Source: Ensembl
    8. signal transduction Source: Ensembl

    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

    ReactomeiREACT_191907. Oncogene Induced Senescence.
    REACT_191909. Senescence-Associated Secretory Phenotype (SASP).
    REACT_193624. Oxidative Stress Induced Senescence.
    REACT_205748. Cyclin D associated events in G1.
    REACT_207430. Meiotic recombination.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 4 (EC:2.7.11.22)
    Alternative name(s):
    Cell division protein kinase 4
    Gene namesi
    Name:CDK4
    OrganismiSus scrofa (Pig)
    Taxonomic identifieri9823 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaSuinaSuidaeSus
    ProteomesiUP000008227: Unplaced

    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: Ensembl
    3. cytosol Source: Ensembl
    4. nuclear membrane Source: Ensembl
    5. nucleolus Source: Ensembl
    6. tight junction Source: Ensembl
    7. transcription factor complex Source: Ensembl

    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_0000085780Add
    BLAST

    Amino acid modifications

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

    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

    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 SEI1 and 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.By similarity

    Protein-protein interaction databases

    STRINGi9823.ENSSSCP00000000473.

    Structurei

    3D structure databases

    ProteinModelPortaliP79432.
    SMRiP79432. Positions 2-299.
    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.
    GeneTreeiENSGT00720000108415.
    HOVERGENiHBG014652.
    KOiK02089.
    OMAiIDQDLRT.
    OrthoDBiEOG73JKVV.
    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.

    P79432-1 [UniParc]FASTAAdd to Basket

    « Hide

    MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGAGGGLP    50
    ISTVREVALL RRLEAFEHPN VVRLMDVCAT ARTDRETKVT LVFEHVDQDL 100
    RTYLDKAPPP GLPVETIKDL MRQFLRGLDF LHANCIVHRD LKPENILVTS 150
    GGTVKLADFG LARIYSYQMA LTPVVVTLWY RAPEVLLQST YATPVDMWSV 200
    GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR DVSLPRGAFS 250
    PRGPRPVQSV VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKAEG 300
    NPE 303
    Length:303
    Mass (Da):33,690
    Last modified:May 1, 1997 - v1
    Checksum:iD77C5630B25EF20B
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U68478 Genomic DNA. Translation: AAB39636.1.
    U68479 Genomic DNA. Translation: AAB39637.1.
    RefSeqiNP_001116569.1. NM_001123097.1.
    UniGeneiSsc.11051.

    Genome annotation databases

    EnsembliENSSSCT00000028348; ENSSSCP00000022407; ENSSSCG00000025092.
    GeneIDi100144492.
    KEGGissc:100144492.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U68478 Genomic DNA. Translation: AAB39636.1 .
    U68479 Genomic DNA. Translation: AAB39637.1 .
    RefSeqi NP_001116569.1. NM_001123097.1.
    UniGenei Ssc.11051.

    3D structure databases

    ProteinModelPortali P79432.
    SMRi P79432. Positions 2-299.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9823.ENSSSCP00000000473.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSSSCT00000028348 ; ENSSSCP00000022407 ; ENSSSCG00000025092 .
    GeneIDi 100144492.
    KEGGi ssc:100144492.

    Organism-specific databases

    CTDi 1019.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00720000108415.
    HOVERGENi HBG014652.
    KOi K02089.
    OMAi IDQDLRT.
    OrthoDBi EOG73JKVV.
    TreeFami TF101022.

    Enzyme and pathway databases

    Reactomei REACT_191907. Oncogene Induced Senescence.
    REACT_191909. Senescence-Associated Secretory Phenotype (SASP).
    REACT_193624. Oxidative Stress Induced Senescence.
    REACT_205748. Cyclin D associated events in G1.
    REACT_207430. Meiotic recombination.

    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. "Sequence and intron/exon organization of porcine CDK4 gene."
      Shibuya H., Renshaw F.G., Bouchard G.F., Nonneman D., Johnson G.S.
      Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].

    Entry informationi

    Entry nameiCDK4_PIG
    AccessioniPrimary (citable) accession number: P79432
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: May 1, 1997
    Last modified: October 1, 2014
    This is version 90 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3