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Index > Protein center > CDK4(Gene name) > Human
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  • CDK4 (Gene name),
  • Cyclin-dependent kinase 4 (Protein name ),  CDK4_HUMAN from NCBI database.
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  • Gene name:
    CDK4;
    Protein name:
    Cyclin-dependent kinase 4;
    Alternative:
    PSK-J3;Cell division protein kinase 4;
    Organism:
    Human (Homo sapiens). 
    General Annotation
    Sub Unit:
    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 phosphosphorylation 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.
    Function:
    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 G(1)/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 G(1) phase. Hypophosphorylates RB1 in early G(1) 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.
    Subcellular Location:
    Cytoplasm Nucleus Membrane Cytoplasmic when non-complexed. Forms a cyclin D-CDK4 complex in the cytoplasm as cells progress through G(1) phase. The complex accumulates on the nuclear membrane and enters the nucleus on transition from G(1) to S phase. Also present in nucleoli and heterochromatin lumps. Colocalizes with RB1 after release into the nucleus.
    Protein Attributes:
    Sequence length:
    303
    Sequence:
    50:
    MATSRYEPVA | EIGVGAYGTV | YKARDPHSGH | FVALKSVRVP | NGGGGGGGLP | 
    100:
    ISTVREVALL | RRLEAFEHPN | VVRLMDVCAT | SRTDREIKVT | LVFEHVDQDL | 
    150:
    RTYLDKAPPP | GLPAETIKDL | MRQFLRGLDF | LHANCIVHRD | LKPENILVTS | 
    200:
    GGTVKLADFG | LARIYSYQMA | LTPVVVTLWY | RAPEVLLQST | YATPVDMWSV | 
    250:
    GCIFAEMFRR | KPLFCGNSEA | DQLGKIFDLI | GLPPEDDWPR | DVSLPRGAFP | 
    300:
    PRGPRPVQSV | VPEMEESGAQ | LLLEMLTFNP | HKRISAFRAL | QHSYLHKDEG | 
    303:
    NPE
    3D Structure:
    N/A
    Predicted Eptitope:
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    EIAab Sequence  Vaild Sequence:
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    Related Databases
    UniGene:
    KEGG:
    SMR:
    String:
    MIM:
    Pfam:
    Uniprot:
     
    FOR
    ELISA Kit for Human Cyclin-dependent kinase 4
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    E1233h
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    ELISA Kit for Human Cyclin-dependent kinase 4
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    E1233b
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    ELISA Kit for Human Cyclin-dependent kinase 4
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    ELISA Kit for Human Cyclin-dependent kinase 4
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    E1233m
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    ELISA Kit for Human Cyclin-dependent kinase 4
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    E1233r
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    96T
    CLIA Kit for Human Cyclin-dependent kinase 4
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    CLIA Kit for Human Cyclin-dependent kinase 4
    Cat.:
    U1233r
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    Packing:
    96T
    CLIA Kit for Human Cyclin-dependent kinase 4
    Cat.:
    U1233p
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    96T
    CLIA Kit for Human Cyclin-dependent kinase 4
    Cat.:
    U1233h
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    CLIA Kit for Human Cyclin-dependent kinase 4
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    Packing:
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    Polyclonal Antibody for Human Cyclin-dependent kinase 4
    Polyclonal Antibody for Human Cyclin-dependent kinase 4
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    P1233Rb-h
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    40ug/0.2ml
    Polyclonal Antibody for Human Cyclin-dependent kinase 4
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    P1233Rb-m
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    Polyclonal Antibody for Human Cyclin-dependent kinase 4
    Cat.:
    P1233Rb-r
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    Packing:
    40ug/0.2ml
    Polyclonal Antibody for Human Cyclin-dependent kinase 4
    Monoclonal Antibody for Human Cyclin-dependent kinase 4
    Monoclonal Antibody for Human Cyclin-dependent kinase 4
    Monoclonal Antibody for Human Cyclin-dependent kinase 4
    Monoclonal Antibody for Human Cyclin-dependent kinase 4
    Monoclonal Antibody for Human Cyclin-dependent kinase 4
    Protein for Human Cyclin-dependent kinase 4
    Protein for Human Cyclin-dependent kinase 4
    Protein for Human Cyclin-dependent kinase 4
    Protein for Human Cyclin-dependent kinase 4
    Protein for Human Cyclin-dependent kinase 4

    R&D Technical Data
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    Precision
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    Recovery
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    Linearity
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    References
    1. 1.
      Hanks S.K.
      Submitted (1987-02) to the EMBL/GenBank/DDBJ databases
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)
    2. 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.
      Genomics42:295-301(1997) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]
    3. 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.
      Science269:1281-1284(1995) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1);VARIANT CMM3 CYS-24;CHARACTERIZATION OF VARIANT CYS-24
    4. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANT CMM3 CYS-24;CHARACTERIZATION OF VARIANT CYS-24
    5. 5.
      NIEHS SNPs program
      Submitted (2002-04) to the EMBL/GenBank/DDBJ databases
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA];VARIANT GLN-82
    6. 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. , more...
      Nat. Genet.36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2)
      tissue: Embryo.
    7. 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 (2004-06) to the EMBL/GenBank/DDBJ databases
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
    8. 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. , more...
      Nature440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]
    9. 9.
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]
    10. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)
      tissue: Muscle.
    11. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 88-188 (ISOFORM 1)
    12. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-182
    13. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: FUNCTION
    14. 14.
      "New functional activities for the p21 family of CDK inhibitors."
      LaBaer J. , Garrett M.D. , Stevenson L.F. , Slingerland J.M. , Sandhu C. , Chou H.S. , Fattaey A. , Harlow E.
      Genes Dev.11:847-862(1997) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: INTERACTION WITH CDKN1A; CCND1 AND CCND3;SUBCELLULAR LOCATION;CATALYTIC ACTIVITY
    15. 15.
      "Regulation of CDK4 activity by a novel CDK4-binding protein, p34(SEI-1)."
      Sugimoto M. , Nakamura T. , Ohtani N. , Hampson L. , Hampson I.N. , Shimamoto A. , Furuichi Y. , Okumura K. , Niwa S. , Taya Y. , Hara E.
      Genes Dev.13:3027-3033(1999) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: INTERACTION WITH SEI1
    16. 16.
      "Cyclin-dependent kinases regulate the antiproliferative function of Smads."
      Matsuura I. , Denissova N.G. , Wang G. , He D. , Long J. , Liu F.
      Nature430:226-231(2004) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: FUNCTION
    17. 17.
      "Characterization of VIK-1: a new Vav-interacting Kruppel-like protein."
      Houlard M. , Romero-Portillo F. , Germani A. , Depaux A. , Regnier-Ricard F. , Gisselbrecht S. , Varin-Blank N.
      Oncogene24:28-38(2005) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: INTERACTION WITH ZNF655
    18. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: PHOSPHORYLATION AT THR-172;INTERACTION WITH CCND1; CCND3; CDKN2A AND CDKN1B;MUTAGENESIS OF THR-172
    19. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: SUBCELLULAR LOCATION;FUNCTION;INTERACTION WITH CCND2
    20. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS];CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS]
    21. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: INTERACTION WITH CCND1
    22. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: INTERACTION WITH CDKN1B;PHOSPHORYLATION;CATALYTIC ACTIVITY
    23. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: PHOSPHORYLATION AT THR-172;ENZYME REGULATION;MUTAGENESIS OF PRO-173
    24. 24.
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-172;IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
    25. 25.
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]
    26. 26.
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) 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. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF NONPHOSPHORYLATED FORM IN COMPLEX WITH CCND3;PHOSPHORYLATION AT THR-172;IDENTIFICATION BY MASS SPECTROMETRY
    28. 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. Cancer72:780-783(1997) [PubMed] [Europe PMC] [Abstract]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: VARIANT CMM3 SER-41
    29. 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]
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: VARIANT CMM3 HIS-24
    30. 30.
      [15/1/25 17:38] Upload to ab completed in less than a minute: 1 file transferred (13.4 Kb/s) Cited for: ERRATUM
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