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P11802

- CDK4_HUMAN

UniProt

P11802 - CDK4_HUMAN

Protein

Cyclin-dependent kinase 4

Gene

CDK4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 180 (01 Oct 2014)
      Sequence version 2 (01 Nov 1995)
      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.3 Publications

    Catalytic activityi

    ATP + a protein = ADP + a phosphoprotein.3 Publications

    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.1 Publication

    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 binding Source: UniProtKB
    3. cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
    4. protein binding Source: UniProtKB

    GO - Biological processi

    1. cell division Source: UniProtKB-KW
    2. circadian rhythm Source: Ensembl
    3. G1/S transition of mitotic cell cycle Source: BHF-UCL
    4. mitotic cell cycle Source: Reactome
    5. negative regulation of cell cycle arrest Source: UniProtKB
    6. organ regeneration Source: Ensembl
    7. positive regulation of apoptotic process Source: Ensembl
    8. positive regulation of cell proliferation Source: BHF-UCL
    9. positive regulation of cell size Source: Ensembl
    10. positive regulation of fibroblast proliferation Source: BHF-UCL
    11. positive regulation of G2/M transition of mitotic cell cycle Source: UniProtKB
    12. positive regulation of translation Source: Ensembl
    13. protein phosphorylation Source: BHF-UCL
    14. regulation of gene expression Source: BHF-UCL
    15. response to drug Source: UniProtKB
    16. response to hyperoxia Source: Ensembl
    17. response to lead ion Source: Ensembl
    18. response to testosterone Source: Ensembl
    19. response to toxic substance Source: Ensembl
    20. 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

    BRENDAi2.7.11.22. 2681.
    ReactomeiREACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_27161. Transcriptional regulation of white adipocyte differentiation.
    REACT_27271. Meiotic recombination.
    REACT_4. Ubiquitin-dependent degradation of Cyclin D1.
    REACT_821. Cyclin D associated events in G1.
    SignaLinkiP11802.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cyclin-dependent kinase 4 (EC:2.7.11.22)
    Alternative name(s):
    Cell division protein kinase 4
    PSK-J3
    Gene namesi
    Name:CDK4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:1773. CDK4.

    Subcellular locationi

    Cytoplasm. Nucleus. Membrane
    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.

    GO - Cellular componenti

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

    Keywords - Cellular componenti

    Cytoplasm, Membrane, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Melanoma, cutaneous malignant 3 (CMM3) [MIM:609048]: A malignant neoplasm of melanocytes, arising de novo or from a pre-existing benign nevus, which occurs most often in the skin but also may involve other sites.4 Publications
    Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti24 – 241R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). 2 Publications
    Corresponds to variant rs11547328 [ dbSNP | Ensembl ].
    VAR_006200
    Natural varianti24 – 241R → H in CMM3. 1 Publication
    VAR_006201
    Natural varianti41 – 411N → S in CMM3; sporadic. 1 Publication
    VAR_021152

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi172 – 1721T → A: Weak enzyme activity towards RB1, but no effect on binding of CCDN1 nor CCDN3. 1 Publication
    Mutagenesisi172 – 1721T → E: Retains moderate enzyme activity. 1 Publication
    Mutagenesisi173 – 1731P → S: No effect on in vitro phosphorylation by CDK7. Greatly reduced T-172 phosphorylation and enzyme activity. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi609048. phenotype.
    Orphaneti99970. Dedifferentiated liposarcoma.
    618. Familial melanoma.
    99971. Well-differentiated liposarcoma.
    PharmGKBiPA102.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Initiator methioninei1 – 11Removed1 Publication
    Chaini2 – 303302Cyclin-dependent kinase 4PRO_0000085778Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei2 – 21N-acetylalanine1 Publication
    Modified residuei172 – 1721Phosphothreonine6 Publications

    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.6 Publications

    Keywords - PTMi

    Acetylation, Phosphoprotein

    Proteomic databases

    MaxQBiP11802.
    PaxDbiP11802.
    PRIDEiP11802.

    PTM databases

    PhosphoSiteiP11802.

    Expressioni

    Gene expression databases

    ArrayExpressiP11802.
    BgeeiP11802.
    CleanExiHS_CDK4.
    GenevestigatoriP11802.

    Organism-specific databases

    HPAiCAB015153.

    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.9 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CCND1P2438511EBI-295644,EBI-375001
    CCND3P302818EBI-295644,EBI-375013
    CDC37Q165437EBI-295644,EBI-295634
    CDKN1AP389365EBI-295644,EBI-375077
    CDKN1BP465275EBI-295644,EBI-519280
    CDKN2AP427719EBI-295644,EBI-375053
    CDKN2BP427728EBI-295644,EBI-711280
    CDKN2CP427733EBI-295644,EBI-711290
    HSP90AB1P082383EBI-295644,EBI-352572
    MYCP011062EBI-295644,EBI-447544
    RBL1P287492EBI-295644,EBI-971402
    ZNF655Q8N7203EBI-295644,EBI-625509

    Protein-protein interaction databases

    BioGridi107454. 123 interactions.
    DIPiDIP-875N.
    IntActiP11802. 74 interactions.
    MINTiMINT-1201237.
    STRINGi9606.ENSP00000257904.

    Structurei

    Secondary structure

    1
    303
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi7 – 137
    Beta strandi15 – 173
    Beta strandi20 – 245
    Turni26 – 283
    Beta strandi31 – 4010
    Helixi51 – 6313
    Helixi64 – 663
    Beta strandi74 – 829
    Beta strandi84 – 9411
    Beta strandi97 – 993
    Helixi100 – 1056
    Turni109 – 1113
    Helixi114 – 13320
    Turni143 – 1453
    Beta strandi146 – 1483
    Turni150 – 1523
    Beta strandi154 – 1563
    Helixi162 – 1698
    Helixi172 – 1754
    Turni183 – 1853
    Beta strandi186 – 1894
    Helixi195 – 20814
    Beta strandi209 – 2113
    Helixi219 – 23012
    Turni235 – 2373
    Beta strandi242 – 2443
    Helixi246 – 2483
    Helixi257 – 2604
    Helixi266 – 27510
    Helixi280 – 2823
    Helixi286 – 2905

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1LD2model-A1-303[»]
    2W96X-ray2.30B1-303[»]
    2W99X-ray2.80B1-303[»]
    2W9FX-ray2.85B1-303[»]
    2W9ZX-ray2.45B1-303[»]
    3G33X-ray3.00A/C1-303[»]
    ProteinModelPortaliP11802.
    SMRiP11802. Positions 5-295.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP11802.

    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 cyclins

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi42 – 487Poly-Gly

    Sequence similaritiesi

    Contains 1 protein kinase domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000233024.
    HOVERGENiHBG014652.
    InParanoidiP11802.
    KOiK02089.
    OMAiIDQDLRT.
    OrthoDBiEOG73JKVV.
    PhylomeDBiP11802.
    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]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P11802-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MATSRYEPVA EIGVGAYGTV YKARDPHSGH FVALKSVRVP NGGGGGGGLP    50
    ISTVREVALL RRLEAFEHPN VVRLMDVCAT SRTDREIKVT LVFEHVDQDL 100
    RTYLDKAPPP GLPAETIKDL MRQFLRGLDF LHANCIVHRD LKPENILVTS 150
    GGTVKLADFG LARIYSYQMA LTPVVVTLWY RAPEVLLQST YATPVDMWSV 200
    GCIFAEMFRR KPLFCGNSEA DQLGKIFDLI GLPPEDDWPR DVSLPRGAFP 250
    PRGPRPVQSV VPEMEESGAQ LLLEMLTFNP HKRISAFRAL QHSYLHKDEG 300
    NPE 303
    Length:303
    Mass (Da):33,730
    Last modified:November 1, 1995 - v2
    Checksum:i0916A0C07403A33A
    GO
    Isoform 2 (identifier: P11802-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-120: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:183
    Mass (Da):20,725
    Checksum:i4CD51FFCEAD58E5B
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti117 – 1171I → L in BAG36447. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti24 – 241R → C in CMM3; somatic and familial; generates a dominant oncogene resistant to inhibition by p16(INK4a). 2 Publications
    Corresponds to variant rs11547328 [ dbSNP | Ensembl ].
    VAR_006200
    Natural varianti24 – 241R → H in CMM3. 1 Publication
    VAR_006201
    Natural varianti41 – 411N → S in CMM3; sporadic. 1 Publication
    VAR_021152
    Natural varianti82 – 821R → Q.1 Publication
    Corresponds to variant rs3211612 [ dbSNP | Ensembl ].
    VAR_029153
    Natural varianti122 – 1221R → H.1 Publication
    Corresponds to variant rs34386532 [ dbSNP | Ensembl ].
    VAR_041976

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 120120Missing in isoform 2. 1 PublicationVSP_056487Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M14505 mRNA. Translation: AAA35673.1.
    U81031 Genomic DNA. Translation: AAC39521.2.
    Z48970 mRNA. Translation: CAA88834.1.
    U37022 Genomic DNA. Translation: AAC50506.1.
    AF507942 Genomic DNA. Translation: AAM23014.1.
    AK297901 mRNA. Translation: BAG60221.1.
    AK313701 mRNA. Translation: BAG36447.1.
    CR407668 mRNA. Translation: CAG28596.1.
    CR542247 mRNA. Translation: CAG47043.1.
    AC025165 Genomic DNA. No translation available.
    CH471054 Genomic DNA. Translation: EAW97058.1.
    BC003644 mRNA. Translation: AAH03644.1.
    BC005864 mRNA. Translation: AAH05864.1.
    BC010153 mRNA. Translation: AAH10153.1.
    S67448 Genomic DNA. Translation: AAD13991.1.
    CCDSiCCDS8953.1.
    PIRiI52695.
    S52841.
    RefSeqiNP_000066.1. NM_000075.3.
    UniGeneiHs.95577.

    Genome annotation databases

    EnsembliENST00000257904; ENSP00000257904; ENSG00000135446.
    ENST00000540325; ENSP00000439076; ENSG00000135446.
    GeneIDi1019.
    KEGGihsa:1019.
    UCSCiuc001spv.3. human.

    Polymorphism databases

    DMDMi1168867.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology
    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M14505 mRNA. Translation: AAA35673.1 .
    U81031 Genomic DNA. Translation: AAC39521.2 .
    Z48970 mRNA. Translation: CAA88834.1 .
    U37022 Genomic DNA. Translation: AAC50506.1 .
    AF507942 Genomic DNA. Translation: AAM23014.1 .
    AK297901 mRNA. Translation: BAG60221.1 .
    AK313701 mRNA. Translation: BAG36447.1 .
    CR407668 mRNA. Translation: CAG28596.1 .
    CR542247 mRNA. Translation: CAG47043.1 .
    AC025165 Genomic DNA. No translation available.
    CH471054 Genomic DNA. Translation: EAW97058.1 .
    BC003644 mRNA. Translation: AAH03644.1 .
    BC005864 mRNA. Translation: AAH05864.1 .
    BC010153 mRNA. Translation: AAH10153.1 .
    S67448 Genomic DNA. Translation: AAD13991.1 .
    CCDSi CCDS8953.1.
    PIRi I52695.
    S52841.
    RefSeqi NP_000066.1. NM_000075.3.
    UniGenei Hs.95577.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    1LD2 model - A 1-303 [» ]
    2W96 X-ray 2.30 B 1-303 [» ]
    2W99 X-ray 2.80 B 1-303 [» ]
    2W9F X-ray 2.85 B 1-303 [» ]
    2W9Z X-ray 2.45 B 1-303 [» ]
    3G33 X-ray 3.00 A/C 1-303 [» ]
    ProteinModelPortali P11802.
    SMRi P11802. Positions 5-295.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107454. 123 interactions.
    DIPi DIP-875N.
    IntActi P11802. 74 interactions.
    MINTi MINT-1201237.
    STRINGi 9606.ENSP00000257904.

    Chemistry

    BindingDBi P11802.
    ChEMBLi CHEMBL3038472.
    GuidetoPHARMACOLOGYi 1976.

    PTM databases

    PhosphoSitei P11802.

    Polymorphism databases

    DMDMi 1168867.

    Proteomic databases

    MaxQBi P11802.
    PaxDbi P11802.
    PRIDEi P11802.

    Protocols and materials databases

    DNASUi 1019.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000257904 ; ENSP00000257904 ; ENSG00000135446 .
    ENST00000540325 ; ENSP00000439076 ; ENSG00000135446 .
    GeneIDi 1019.
    KEGGi hsa:1019.
    UCSCi uc001spv.3. human.

    Organism-specific databases

    CTDi 1019.
    GeneCardsi GC12M058142.
    HGNCi HGNC:1773. CDK4.
    HPAi CAB015153.
    MIMi 123829. gene.
    609048. phenotype.
    neXtProti NX_P11802.
    Orphaneti 99970. Dedifferentiated liposarcoma.
    618. Familial melanoma.
    99971. Well-differentiated liposarcoma.
    PharmGKBi PA102.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000233024.
    HOVERGENi HBG014652.
    InParanoidi P11802.
    KOi K02089.
    OMAi IDQDLRT.
    OrthoDBi EOG73JKVV.
    PhylomeDBi P11802.
    TreeFami TF101022.

    Enzyme and pathway databases

    BRENDAi 2.7.11.22. 2681.
    Reactomei REACT_169168. Senescence-Associated Secretory Phenotype (SASP).
    REACT_169325. Oncogene Induced Senescence.
    REACT_169436. Oxidative Stress Induced Senescence.
    REACT_27161. Transcriptional regulation of white adipocyte differentiation.
    REACT_27271. Meiotic recombination.
    REACT_4. Ubiquitin-dependent degradation of Cyclin D1.
    REACT_821. Cyclin D associated events in G1.
    SignaLinki P11802.

    Miscellaneous databases

    ChiTaRSi Cdk4. human.
    EvolutionaryTracei P11802.
    GeneWikii Cyclin-dependent_kinase_4.
    GenomeRNAii 1019.
    NextBioi 35467861.
    PROi P11802.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P11802.
    Bgeei P11802.
    CleanExi HS_CDK4.
    Genevestigatori P11802.

    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. Hanks S.K.
      Submitted (FEB-1987) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Transcript mapping in a 46-kb sequenced region at the core of 12q13.3 amplification in human cancers."
      Elkahloun A.G., Krizman D.B., Wang Z., Hofmann T.A., Roe B.A., Meltzer P.S.
      Genomics 42:295-301(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    3. "A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma."
      Wolfel T., Hauer M., Schneider J., Serrano M., Wolfel C., Klehmann-Hieb E., De Plaen E., Hankeln T., Meyer Zum Bueschenfelde K.-H., Beach D.
      Science 269:1281-1284(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT CMM3 CYS-24, CHARACTERIZATION OF VARIANT CYS-24.
    4. "Germline mutations in the p16INK4a binding domain of CDK4 in familial melanoma."
      Zuo L., Weger J., Yang Q., Goldstein A.M., Tucker M.A., Walker G.J., Hayward N., Dracopoli N.C.
      Nat. Genet. 12:97-99(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT CMM3 CYS-24, CHARACTERIZATION OF VARIANT CYS-24.
    5. NIEHS SNPs program
      Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-82.
    6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Embryo.
    7. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
      Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
      Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    8. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    10. "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] (ISOFORM 1).
      Tissue: Muscle.
    11. "Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family."
      Hanks S.K.
      Proc. Natl. Acad. Sci. U.S.A. 84:388-392(1987) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 88-188 (ISOFORM 1).
    12. "Coamplification of the CDK4 gene with MDM2 and GLI in human sarcomas."
      Khatib Z.A., Matsushime H., Valentine M., Shapiro D.N., Sherr C.J., Look A.T.
      Cancer Res. 53:5535-5541(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-182.
    13. "The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2."
      Kitagawa M., Higashi H., Jung H.K., Suzuki-Takahashi I., Ikeda M., Tamai K., Kato J., Segawa K., Yoshida E., Nishimura S., Taya Y.
      EMBO J. 15:7060-7069(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. Cited for: INTERACTION WITH CDKN1A; CCND1 AND CCND3, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
    15. Cited for: INTERACTION WITH SEI1.
    16. "Cyclin-dependent kinases regulate the antiproliferative function of Smads."
      Matsuura I., Denissova N.G., Wang G., He D., Long J., Liu F.
      Nature 430:226-231(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    17. Cited for: INTERACTION WITH ZNF655.
    18. "Regulated activating Thr172 phosphorylation of cyclin-dependent kinase 4(CDK4): its relationship with cyclins and CDK 'inhibitors'."
      Bockstaele L., Kooken H., Libert F., Paternot S., Dumont J.E., de Launoit Y., Roger P.P., Coulonval K.
      Mol. Cell. Biol. 26:5070-5085(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-172, INTERACTION WITH CCND1; CCND3; CDKN2A AND CDKN1B, MUTAGENESIS OF THR-172.
    19. "Migratory localization of cyclin D2-Cdk4 complex suggests a spatial regulation of the G1-S transition."
      Wang Z., Xie Y., Zhang L., Zhang H., An X., Wang T., Meng A.
      Cell Struct. Funct. 33:171-183(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, FUNCTION, INTERACTION WITH CCND2.
    20. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
    21. "Zinc finger transcription factor INSM1 interrupts cyclin D1 and CDK4 binding and induces cell cycle arrest."
      Zhang T., Liu W.D., Saunee N.A., Breslin M.B., Lan M.S.
      J. Biol. Chem. 284:5574-5581(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CCND1.
    22. "p27Kip1 inhibits cyclin D-cyclin-dependent kinase 4 by two independent modes."
      Ray A., James M.K., Larochelle S., Fisher R.P., Blain S.W.
      Mol. Cell. Biol. 29:986-999(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CDKN1B, PHOSPHORYLATION, CATALYTIC ACTIVITY.
    23. "Differential regulation of cyclin-dependent kinase 4 (CDK4) and CDK6, evidence that CDK4 might not be activated by CDK7, and design of a CDK6 activating mutation."
      Bockstaele L., Bisteau X., Paternot S., Roger P.P.
      Mol. Cell. Biol. 29:4188-4200(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-172, ENZYME REGULATION, MUTAGENESIS OF PRO-173.
    24. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-172, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    25. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    26. Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF THR-172-PHOSPHORYLATED WILD TYPE AND MUTANTS ALA-172; PHE-172 AND ASP-172 IN COMPLEX WITH CCND1, IDENTIFICATION BY MASS SPECTROMETRY, PHOSPHORYLATION AT THR-172, CATALYTIC ACTIVITY.
    27. "The structure of CDK4/cyclin D3 has implications for models of CDK activation."
      Takaki T., Echalier A., Brown N.R., Hunt T., Endicott J.A., Noble M.E.
      Proc. Natl. Acad. Sci. U.S.A. 106:4171-4176(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF NONPHOSPHORYLATED FORM IN COMPLEX WITH CCND3, PHOSPHORYLATION AT THR-172, IDENTIFICATION BY MASS SPECTROMETRY.
    28. "Complete scanning of the CDK4 gene by denaturing gradient gel electrophoresis: a novel missense mutation but low overall frequency of mutations in sporadic metastatic malignant melanoma."
      Guldberg P., Kirkin A.F., Gronbaek K., thor Straten P., Ahrenkiel V., Zeuthen J.
      Int. J. Cancer 72:780-783(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CMM3 SER-41.
    29. "Prevalence of p16 and CDK4 germline mutations in 48 melanoma-prone families in France."
      Soufir N., Avril M.-F., Chompret A., Demenais F., Bombled J., Spatz A., Stoppa-Lyonnet D., Benard J., Bressac-De Paillerets B.
      Hum. Mol. Genet. 7:209-216(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CMM3 HIS-24.
    30. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT [LARGE SCALE ANALYSIS] HIS-122.

    Entry informationi

    Entry nameiCDK4_HUMAN
    AccessioniPrimary (citable) accession number: P11802
    Secondary accession number(s): B2R9A0
    , B4DNF9, O00576, Q6FG61
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1989
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 180 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3