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    CDK4 cyclin-dependent kinase 4 [ Homo sapiens ]

    Gene ID: 1019, updated on 5-Feb-2012
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    Summary

    Official Symbol
    CDK4provided by HGNC
    Official Full Name
    cyclin-dependent kinase 4provided by HGNC
    Primary source
    HGNC:1773
    See related
    Ensembl:ENSG00000135446; HPRD:00447; MIM:123829; Vega:OTTHUMG00000170382
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    CMM3; PSK-J3
    Summary
    The protein encoded by this gene is a member of the Ser/Thr protein kinase family. This protein is highly similar to the gene products of S. cerevisiae cdc28 and S. pombe cdc2. It is a catalytic subunit of the protein kinase complex that is important for cell cycle G1 phase progression. The activity of this kinase is restricted to the G1-S phase, which is controlled by the regulatory subunits D-type cyclins and CDK inhibitor p16(INK4a). This kinase was shown to be responsible for the phosphorylation of retinoblastoma gene product (Rb). Mutations in this gene as well as in its related proteins including D-type cyclins, p16(INK4a) and Rb were all found to be associated with tumorigenesis of a variety of cancers. Multiple polyadenylation sites of this gene have been reported. [provided by RefSeq, Jul 2008]
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    Genomic context

    Location :
    12q14
    Sequence :
    Chromosome: 12; NC_000012.11 (58142003..58146164, complement)
    See CDK4 in Epigenomics, MapViewer

    Chromosome 12 - NC_000012.11Genomic Context describing neighboring genes Neighboring gene osteosarcoma amplified 9, endoplasmic reticulum lectin Neighboring gene uncharacterized LOC100130776 Neighboring gene ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 Neighboring gene tetraspanin 31 Neighboring gene membrane-associated ring finger (C3HC4) 9 Neighboring gene cytochrome P450, family 27, subfamily B, polypeptide 1

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    Genomic regions, transcripts, and products

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details
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    Bibliography

    Related articles in PubMed

    1. NIRF constitutes a nodal point in the cell cycle network and is a candidate tumor suppressor. Mori T, et al. Cell Cycle, 2011 Oct 1. PMID 21952639.
    2. Mapping a dynamic innate immunity protein interaction network regulating type I interferon production. Li S, et al. Immunity, 2011 Sep 23. PMID 21903422.
    3. A directed protein interaction network for investigating intracellular signal transduction. Vinayagam A, et al. Sci Signal, 2011 Sep 6. PMID 21900206.
    4. The risk factor of gallbladder cancer: hyperplasia of mucous epithelium caused by gallstones associates with p16/CyclinD1/CDK4 pathway. Feng Z, et al. Exp Mol Pathol, 2011 Oct. PMID 21777578.
    5. Incomplete folding upon binding mediates Cdk4/cyclin D complex activation by tyrosine phosphorylation of inhibitor p27 protein. Ou L, et al. J Biol Chem, 2011 Aug 26. PMID 21715330.

    See all (259) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. CDK4-mediated regulation of cell functions via c-Jun phosphorylation and AP-1 activation
      Title: CDK-mediated regulation of cell functions via c-Jun phosphorylation and AP-1 activation.
    2. The expressions of CDK4 and Cyclin D1 increased along with progression of gallbladder mucosa hyperplasia and p16 decreased to the lowest level in gallbladder cancer.
      Title: The risk factor of gallbladder cancer: hyperplasia of mucous epithelium caused by gallstones associates with p16/CyclinD1/CDK4 pathway.
    3. both CDK4 and CDK6 are prognostic markers and bona fide oncogenes in EAC.
      Title: Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma.
    4. Incomplete folding upon binding mediates Cdk4/cyclin D complex activation by tyrosine phosphorylation of inhibitor p27 protein.
      Title: Incomplete folding upon binding mediates Cdk4/cyclin D complex activation by tyrosine phosphorylation of inhibitor p27 protein.
    5. Overexpressed CDK4 is a potential unfavorable prognostic factor and mediates cell cycle progression by regulating the expression of p21 in lung cancer.
      Title: Elevated expression of CDK4 in lung cancer.
    6. Pathogenic mutations in CDKN2A nor exon 2 of CDK4 gene were not identified in uveal melanoma.
      Title: Melanoma candidate genes CDKN2A/p16/INK4A, p14ARF, and CDK4 sequencing in patients with uveal melanoma with relative high-risk for hereditary cancer predisposition.
    7. Targeted inhibition of CDK4 activity may have a role in the treatment of cyclin D-overexpressing breast cancers.
      Title: Cyclin-dependent kinase 4-mediated phosphorylation inhibits Smad3 activity in cyclin D-overexpressing breast cancer cells.
    8. Immunohistochemical expression of MDM2 and CDK4 is specific and provides sensitive markers for the diagnosis of low-grade osteosarcomas.
      Title: MDM2 and CDK4 immunohistochemistry is a valuable tool in the differential diagnosis of low-grade osteosarcomas and other primary fibro-osseous lesions of the bone.
    9. Study elucidates a model to regulate glioma cell cycle progression in which hUCBSC acts to control cyclin D1 induction and in concert its partner kinases, Cdk 4 and Cdk 6 by mediating cell cycle arrest at G(0)-G(1) phase.
      Title: Regulation of glioblastoma progression by cord blood stem cells is mediated by downregulation of cyclin D1.
    10. [over]expression provides evidence of the malignant potential in oral lichen planus
      Title: Overexpression of cdk4 and p16 in oral lichen planus supports the concept of premalignancy.
    Submit: New GeneRIF Correction See all (118)
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    Phenotypes

    Review eQTL and phenotype association data in this region using PheGenI

    Melanoma, cutaneous malignant, 3

    Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.

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    HIV-1 protein interactions

    Protein Gene Interaction Pubs
    Tat tat When expressed in astrocytes, neurons, and non-glial 293T cells, HIV-1 Tat interacts with a number of cell cycle-related proteins including cyclin A, cyclin B, cyclin D3, Cdk2, Cdk4, Cdk1/Cdc2, cdc6, p27, p53, p63, hdlg, and PCNA PubMed
    tat Cell cycle progression through G1 phase, and in particular the activity of the G1-specific CDK4, is required for HIV-1 Tat transactivation of the HIV-1 LTR promoter PubMed

    Go to the HIV-1, Human Protein Interaction Database

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    Interactions

    Products Interactant Other Gene Complex Source Pubs Description
    NC_000012.9 NP_002458.1 MYC    BIND  PubMed MYC (c-Myc) interacts with CDK4 promoter. 
    NP_000066.1 NP_009227.1 BRCA1    BIND  PubMed BRCA1 associates with CDK4 
    NP_000066.1 NP_444284.1 CCND1    BIND  PubMed CCND1 (cyclin D1) interacts with CDK4. 
    NP_000066.1 NP_444284.1 CCND1    BIND  PubMed CDK4 interacts with Cyclin D1. This interaction was modelled on a demonstrated interaction between human CDK4 and Cyclin D1 from an unspecified species. 
    NP_000066.1 NP_001750.1 CCND2    BIND  PubMed CCND2 interacts with CDK4 
    NP_000066.1 NP_000380.1 CDKN1A    BIND  PubMed Cdk4 interacts with p21. 
    NP_000066.1 AAR05391.1 CDKN2A    BIND  PubMed p16 interacts with cdk4. 
    NP_000066.1 NP_000068.1 CDKN2A    BIND  PubMed p16 interacts with cdk4. This interaction was modeled on a demonstrated interaction between human p16 and cdk4 from an unspecified species. 
    NP_000066.1 NP_000068.1 CDKN2A    BIND  PubMed p16 interacts with CDK4. This interaction was modeled on a demonstrated interaction between human p16 and CDK4 from an unspecified species. 
    NP_000066.1 NP_000068.1 CDKN2A    BIND  PubMed CDKN2A interacts with CDK4 
    NP_000066.1 CDKN2C    BIND  PubMed An unspecified isoform of p18 interacts with cdk4. This interaction was modeled on a demonstrated interaction between human p18 and cdk4 from an unspecified species. 
    NP_000066.1 NP_000312.1 RB1    BIND  PubMed CDK4 phosphorylates Rb carboxy-terminus. This interaction was modelled on a demonstrated interaction between human Rb and mouse CDK4. 
    NP_000066.1 NP_005892.1 SMAD2    BIND  PubMed CDK4 phosphorylates Smad2. This interaction was modelled on a demonstrated interaction between Smad2 from an unspecified species and mouse CDK4. 
    NP_000066.1 NP_005893.1 SMAD3    BIND  PubMed CDK4 phosphorylates Smad3 on Thr8, Thr179, Ser204, Ser208 and Ser213. This interaction was modelled on a demonstrated interaction between Smad3 from an unspecified species and mouse CDK4. 
    NP_000066.1 NP_057864.1 tax    BIND  PubMed Tax interacts with CDK4. 
    P11802 P46379 BAG6    HPRD  PubMed  
    P11802 O15392 BIRC5    HPRD  PubMed  
    P11802 O00238 BMPR1B    HPRD  PubMed  
    P11802 P38398 BRCA1    HPRD  PubMed  
    P11802 P04632 CAPNS1    HPRD  PubMed  
    P11802 P24385 CCND1    HPRD  PubMed  
    P11802 P30279 CCND2    HPRD  PubMed  
    P11802 P30281 CCND3    HPRD  PubMed  
    P11802 Q16543 CDC37    HPRD  PubMed  
    P11802 O75419 CDC45    HPRD  PubMed  
    P11802 O00311 CDC7    HPRD  PubMed  
    P11802 P38936 CDKN1A    HPRD  PubMed  
    P11802 P46527 CDKN1B    HPRD  PubMed  
    P11802 P49918 CDKN1C    HPRD  PubMed  
    P11802 Q8N726 CDKN2A    HPRD  PubMed  
    P11802 P42772 CDKN2B    HPRD  PubMed  
    P11802 P42773 CDKN2C    HPRD  PubMed  
    P11802 P55273 CDKN2D    HPRD  PubMed  
    P11802 P49715 CEBPA    HPRD  PubMed  
    P11802 Q9UIV1 CNOT7    HPRD  PubMed  
    P11802 P40305 IFI27    HPRD  PubMed  
    P11802 P49736 MCM2    HPRD  PubMed  
    P11802 P15172 MYOD1    HPRD  PubMed  
    P11802 Q15596 NCOA2    HPRD  PubMed  
    P11802 Q9UGY1 NOL12    HPRD  PubMed  
    P11802 Q9UBD5 ORC3    HPRD  PubMed  
    P11802 P30154 PPP2R1B    HPRD  PubMed  
    P11802 P10644 PRKAR1A    HPRD  PubMed  
    P11802 O75832 PSMD10    HPRD  PubMed  
    P11802 P06454 PTMA    HPRD  PubMed  
    P11802 P06400 RB1    HPRD  PubMed  
    P11802 P28749 RBL1    HPRD  PubMed  
    P11802 P35251 RFC1    HPRD  PubMed  
    P11802 P35249 RFC4    HPRD  PubMed  
    P11802 Q9UHV2 SERTAD1    HPRD  PubMed  
    P11802 Q15047 SETDB1    HPRD  PubMed  
    P11802 Q15796 SMAD2    HPRD  PubMed  
    P11802 P84022 SMAD3    HPRD  PubMed  
    P11802 P36897 TGFBR1    HPRD  PubMed  
    P11802 Q9NP79 VTA1    HPRD  PubMed  
    P11802 Q8N720 ZNF655    HPRD  PubMed  
    BioGRID:107454 BioGRID:121429 ACTR3B    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:106807 ANXA7    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:106830 APLP1    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:111861 ARID4A    BioGRID  PubMed Biochemical Activity 
    BioGRID:107454 BioGRID:106994 ATP5B    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:113647 BAG6    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:106829 BIRC5    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:107140 BRCA1    BioGRID  PubMed Biochemical Activity; Reconstituted Complex 
    BioGRID:107454 BioGRID:107276 CAPNS1    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:107067 CCND1    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex 
    BioGRID:107454 BioGRID:107334 CCND2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:107336 CCND3    BioGRID  PubMed Affinity Capture-Western; Two-hybrid 
    BioGRID:107454 BioGRID:116312 CDC37    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Co-fractionation; Reconstituted Complex; Two-hybrid 
    BioGRID:107454 BioGRID:107460 CDKN1A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:107461 CDKN1B    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:107454 BioGRID:107463 CDKN2A    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Protein-peptide; Reconstituted Complex; Two-hybrid 
    BioGRID:107454 BioGRID:107464 CDKN2B    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:107465 CDKN2C    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western; Reconstituted Complex; Two-hybrid 
    BioGRID:107454 BioGRID:107466 CDKN2D    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:123555 CDT1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:107479 CEBPA    BioGRID  PubMed Affinity Capture-Western; Co-fractionation; Reconstituted Complex 
    BioGRID:107454 BioGRID:118938 CNOT7    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:115143 DAZAP2    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:118809 DBNL    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:117107 DDAH2    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:119102 GEMIN4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:116640 HMGXB3    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:35923 HSP82    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:109544 HSPA8    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:33650 IME2    BioGRID  PubMed Phenotypic Suppression 
    BioGRID:107454 BioGRID:109621 IRF8    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:119646 LUC7L2    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:110245 LYN    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:110737 MYOD1    BioGRID  PubMed Reconstituted Complex; Two-hybrid 
    BioGRID:107454 BioGRID:115761 NCOA2    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107454 BioGRID:111142 PCNA    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:111332 PKM2    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:111510 PPP2R1A    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:111511 PPP2R1B    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:107454 BioGRID:115688 PRMT5    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:111797 QARS    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:111860 RB1    BioGRID  PubMed Biochemical Activity 
    BioGRID:107454 BioGRID:111913 RFC1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:121145 RPRM    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:107308 RUNX2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:941018 SAP25    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:118987 SERTAD1    BioGRID  PubMed Reconstituted Complex 
    BioGRID:107454 BioGRID:115202 SETDB1    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:113871 SMC1A    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:114574 SMC3    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:112506 SNCA    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:112550 SP1    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:112938 TK1    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:117968 TRMT2A    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:122034 TSPYL2    BioGRID  PubMed Biochemical Activity 
    BioGRID:107454 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:119239 UBXN1    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:107454 BioGRID:125434 UHRF2    BioGRID  PubMed Far Western 
    BioGRID:107454 BioGRID:119595 VTA1    BioGRID  PubMed Two-hybrid 
    BioGRID:107454 BioGRID:122532 WDR77    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:107454 BioGRID:113498 ZBTB16    BioGRID  PubMed Two-hybrid 
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    General gene information

    Markers

    Genotypes

    Homology

    Pathways from BioSystems

    • ATF-2 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      ATF-2 transcription factor network, organism-specific biosystem
      ATF-2 transcription factor network
    • B Cell Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      B Cell Receptor Signaling Pathway, organism-specific biosystemThe B cell receptor includes membrane ?? heavy chain molecules bound to a light chain and an Ig alpha (CD79A)/Ig beta (CD79B) heterodimer. Activation of the B cell receptor involves phosphorylation o...
    • Bladder cancer, organism-specific biosystem (from KEGG)
      Bladder cancer, organism-specific biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • Bladder cancer, conserved biosystem (from KEGG)
      Bladder cancer, conserved biosystemThe urothelium covers the luminal surface of almost the entire urinary tract, extending from the renal pelvis, through the ureter and bladder, to the proximal urethra. The majority of urothelial carc...
    • Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem (from Pathway Interaction Database)
      Calcineurin-regulated NFAT-dependent transcription in lymphocytes, organism-specific biosystem
      Calcineurin-regulated NFAT-dependent transcription in lymphocytes
    • Cell Cycle, organism-specific biosystem (from REACTOME)
      Cell Cycle, organism-specific biosystem
      Cell Cycle
    • Cell Cycle, Mitotic, organism-specific biosystem (from REACTOME)
      Cell Cycle, Mitotic, organism-specific biosystemThe replication of the genome and the subsequent segregation of chromosomes into daughter cells are controlled by a series of events collectively known as the cell cycle. DNA replication is carried o...
    • Cell cycle, organism-specific biosystem (from WikiPathways)
      Cell cycle, organism-specific biosystem(From http://en.wikipedia.org/wiki/Cell_cycle) The cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle in...
    • Cell cycle, organism-specific biosystem (from KEGG)
      Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Cell cycle, conserved biosystem (from KEGG)
      Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
    • Chronic myeloid leukemia, organism-specific biosystem (from KEGG)
      Chronic myeloid leukemia, organism-specific biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
    • Chronic myeloid leukemia, conserved biosystem (from KEGG)
      Chronic myeloid leukemia, conserved biosystemChronic myelogenous leukemia (CML) originates in a pluripotent hematopoetic stem cell of the bone marrow and is characterized by greatly increased numbers of granulocytes in the blood. Myeloid and ot...
    • Cyclin D associated events in G1, organism-specific biosystem (from REACTOME)
      Cyclin D associated events in G1, organism-specific biosystemThree D-type cyclins are essential for progression from G1 to S-phase. These D cyclins bind to and activate both CDK4 and CDK6. The formation of all possible complexes between the D-type cyclins and...
    • Developmental Biology, organism-specific biosystem (from REACTOME)
      Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
    • FOXM1 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      FOXM1 transcription factor network, organism-specific biosystem
      FOXM1 transcription factor network
    • G1 Phase, organism-specific biosystem (from REACTOME)
      G1 Phase, organism-specific biosystemEarly cell cycle progression in G1 is under the control of the D-type cyclins together with Cdk4 and Cdk6. An important target for these CDKs is the Retinoblastoma (Rb) protein, which when phosphoryl...
    • G1 to S cell cycle control, organism-specific biosystem (from WikiPathways)
      G1 to S cell cycle control, organism-specific biosystemIn the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding C...
    • Glioma, organism-specific biosystem (from KEGG)
      Glioma, organism-specific biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • Glioma, conserved biosystem (from KEGG)
      Glioma, conserved biosystemGliomas are the most common of the primary brain tumors and account for more than 40% of all central nervous system neoplasms. Gliomas include tumours that are composed predominantly of astrocytes (a...
    • HTLV-I infection, organism-specific biosystem (from KEGG)
      HTLV-I infection, organism-specific biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • HTLV-I infection, conserved biosystem (from KEGG)
      HTLV-I infection, conserved biosystemHuman T-lymphotropic virus type 1 (HTLV-1) is a pathogenic retrovirus that is associated with adult T-cell leukemia/lymphoma (ATL). It is also strongly implicated in non-neoplastic chronic inflammato...
    • IL-7 Signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-7 Signaling Pathway, organism-specific biosystemInterleukin-7 belongs to a family of cytokines, which includes IL-2, IL-4, IL-9, IL-15 and IL-21. It signals through a receptor complex consisting of IL-7 receptor alpha chain (IL7RA) and a common ga...
    • Measles, organism-specific biosystem (from KEGG)
      Measles, organism-specific biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Measles, conserved biosystem (from KEGG)
      Measles, conserved biosystemMeasles virus (MV) is highly contagious virus that leads infant death worldwide. Humans are the unique natural reservoir for this virus. It causes severe immunosuppression favouring secondary bacteri...
    • Meiosis, organism-specific biosystem (from REACTOME)
      Meiosis, organism-specific biosystemDuring meiosis the replicated chromosomes of a single diploid cell are segregated into 4 haploid daughter cells by two successive divisions, meiosis I and meiosis II. In meiosis I, the distinguishing...
    • Meiotic Recombination, organism-specific biosystem (from REACTOME)
      Meiotic Recombination, organism-specific biosystemMeiotic recombination exchanges segments of duplex DNA between chromosomal homologs, generating genetic diversity (reviewed in Handel and Schimenti 2010, Inagaki et al. 2010, Cohen et al. 2006). Ther...
    • Melanoma, organism-specific biosystem (from KEGG)
      Melanoma, organism-specific biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • Melanoma, conserved biosystem (from KEGG)
      Melanoma, conserved biosystemMelanoma is a form of skin cancer that has a poor prognosis and which is on the rise in Western populations. Melanoma arises from the malignant transformation of pigment-producing cells, melanocytes...
    • Mitotic G1-G1/S phases, organism-specific biosystem (from REACTOME)
      Mitotic G1-G1/S phases, organism-specific biosystem
      Mitotic G1-G1/S phases
    • Non-small cell lung cancer, organism-specific biosystem (from KEGG)
      Non-small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
    • Non-small cell lung cancer, conserved biosystem (from KEGG)
      Non-small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
    • Ovarian Infertility Genes, organism-specific biosystem (from WikiPathways)
      Ovarian Infertility Genes, organism-specific biosystemOvarian ???bottleneck??? genes associated with infertility. A valuable approach to the study of infertility is the comparison of mutations of individual human and mouse genes associated with infertil...
    • Pancreatic cancer, organism-specific biosystem (from KEGG)
      Pancreatic cancer, organism-specific biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Pancreatic cancer, conserved biosystem (from KEGG)
      Pancreatic cancer, conserved biosystemInfiltrating ductal adenocarcinoma is the most common malignancy of the pancreas. When most investigators use the term 'pancreatic cancer' they are referring to pancreatic ductal adenocarcinoma (PDA)...
    • Pathways in cancer, organism-specific biosystem (from KEGG)
      Pathways in cancer, organism-specific biosystem
      Pathways in cancer
    • Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem (from Pathway Interaction Database)
      Regulation of nuclear SMAD2/3 signaling, organism-specific biosystem
      Regulation of nuclear SMAD2/3 signaling
    • S Phase, organism-specific biosystem (from REACTOME)
      S Phase, organism-specific biosystemDNA synthesis occurs in the S phase, or the synthesis phase, of the cell cycle. The cell duplicates its hereditary material, and two copies of the chromosome are formed. As DNA replication continu...
    • Small cell lung cancer, organism-specific biosystem (from KEGG)
      Small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
    • Small cell lung cancer, conserved biosystem (from KEGG)
      Small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
    • T cell receptor signaling pathway, organism-specific biosystem (from KEGG)
      T cell receptor signaling pathway, organism-specific biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • T cell receptor signaling pathway, conserved biosystem (from KEGG)
      T cell receptor signaling pathway, conserved biosystemActivation of T lymphocytes is a key event for an efficient response of the immune system. It requires the involvement of the T-cell receptor (TCR) as well as costimulatory molecules such as CD28. En...
    • TGF-beta Receptor Signaling Pathway, organism-specific biosystem (from WikiPathways)
      TGF-beta Receptor Signaling Pathway, organism-specific biosystem"The TGF beta receptors TGFBR1 and TGFBR2 belong to a subfamily of membrane-bound serine/threonine kinases which are designated as Type I or II based on their structural and functional properties. Th...
    • Tight junction, organism-specific biosystem (from KEGG)
      Tight junction, organism-specific biosystemEpithelial tight junctions (TJs) are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic 'plaque' consisting of ma...
    • Tight junction, conserved biosystem (from KEGG)
      Tight junction, conserved biosystemEpithelial tight junctions (TJs) are composed of at least three types of transmembrane protein -occludin, claudin and junctional adhesion molecules (JAMs)- and a cytoplasmic 'plaque' consisting of ma...
    • Transcriptional Regulation of White Adipocyte Differentiation, organism-specific biosystem (from REACTOME)
      Transcriptional Regulation of White Adipocyte Differentiation, organism-specific biosystemAdipogenesis is the process of cell differentiation by which preadipocytes become adipocytes. During this process the preadipocytes cease to proliferate, begin to accumulate lipid droplets and develo...
    • Ubiquitin-dependent degradation of Cyclin D, organism-specific biosystem (from REACTOME)
      Ubiquitin-dependent degradation of Cyclin D, organism-specific biosystemCyclin D turnover is regulated by ubiquitination and proteasomal degradation which are positively regulated by cyclin D phosphorylation on threonine-286 (Diehl et al., 1997).
    • Ubiquitin-dependent degradation of Cyclin D1, organism-specific biosystem (from REACTOME)
      Ubiquitin-dependent degradation of Cyclin D1, organism-specific biosystemAfter the Cyclin D serves the role of mediating reactions by Cdk4 and Cdk6, it is shuttled to the cytoplasm and degraded in a ubiquitin-dependent manner. Whether Cdk4 and Cdk6 are truly redundant is...
    • Validated targets of C-MYC transcriptional activation, organism-specific biosystem (from Pathway Interaction Database)
      Validated targets of C-MYC transcriptional activation, organism-specific biosystem
      Validated targets of C-MYC transcriptional activation
    • p53 signaling pathway, organism-specific biosystem (from KEGG)
      p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
    • p53 signaling pathway, conserved biosystem (from KEGG)
      p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...

    Clone Names

    • MGC14458

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    ATP binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    cyclin-dependent protein kinase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    protein kinase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    G1 phase of mitotic cell cycle TAS
    Traceable Author Statement
    more info
    		  
    G1/S transition of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    S phase of mitotic cell cycle TAS
    Traceable Author Statement
    more info
    		  
    cell cycle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cell division IEA
    Inferred from Electronic Annotation
    more info
    		  
    mitotic cell cycle TAS
    Traceable Author Statement
    more info
    		  
    positive regulation of cell proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    positive regulation of fibroblast proliferation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    regulation of cell cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    response to drug IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    signal transduction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    chromatin IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cyclin-dependent protein kinase holoenzyme complex IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  
    cytosol IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytosol TAS
    Traceable Author Statement
    more info
    		  
    membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    nuclear membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleolus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    transcription factor complex IEA
    Inferred from Electronic Annotation
    more info
    		  
    Help top of page

    General protein information

    Preferred Names
    cyclin-dependent kinase 4
    Names
    cyclin-dependent kinase 4
    cell division protein kinase 4
    NP_000066.1
    Help top of page

    NCBI Reference Sequences (RefSeq)

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007484.1 RefSeqGene

      Range
      4935..9655
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000075.3 → NP_000066.1  cyclin-dependent kinase 4

      Status: REVIEWED

      Source sequence(s)
      AC025165, BC003644, BI832658, BQ773564
      Consensus CDS
      CCDS8953.1
      UniProtKB/Swiss-Prot
      P11802
      Related
      ENSP00000257904, OTTHUMP00000243624, ENST00000257904, OTTHUMT00000408790
      Conserved Domains (2) summary
      cd07863
      Location:5 – 295
      Blast Score: 1402
      STKc_CDK4; Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4
      smart00220
      Location:6 – 295
      Blast Score: 698
      S_TKc; Serine/Threonine protein kinases, catalytic domain

    RefSeqs of Annotated Genomes: Build 37.3

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh37.p5 Primary Assembly

    Genomic

    1. NC_000012.11 Reference GRCh37.p5 Primary Assembly

      Range
      58142003..58146164, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000144.1 Alternate HuRef

      Range
      55178843..55183004, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

     

    1. NM_052984.1: Suppressed sequence

      Description
      NM_052984.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.
    Help top of page

    Related Sequences

    Nucleotide Protein
    Heading Accession and Version
    genomic AC025165.27 (141844..146299) None
    genomic AF507942.1 AAM23014.1
    genomic CH471054.1 EAW97058.1
      EAW97059.1
      EAW97060.1
      EAW97061.1
      EAW97062.1
    genomic S67448.1 AAD13991.1
    genomic U37022.1 AAC50506.1
    genomic U81031.2 AAC39521.2
    mRNA AK297901.1 BAG60221.1
    mRNA AK310724.1 None
    mRNA AK313701.1 BAG36447.1
    mRNA BC003644.2 AAH03644.1
    mRNA BC005864.2 AAH05864.1
    mRNA BC010153.2 AAH10153.1
    mRNA BC015669.2 AAH15669.1
    mRNA BI832658.1 None
    mRNA BQ773564.1 None
    mRNA CR407668.1 CAG28596.1
    mRNA CR542247.1 CAG47043.1
    mRNA M14505.1 AAA35673.1
    mRNA U79269.1 AAB50213.1
    mRNA Z48970.1 CAA88834.1
    other-genetic DQ893137.2 ABM84063.1
    other-genetic DQ896420.2 ABM87419.1
    Protein Accession Links
    GenePept Link UniProtKB Link
    P11802.2 GenPept UniProtKB/Swiss-Prot:P11802
    Q6LC83 GenPept UniProtKB/TrEMBL:Q6LC83
    Q96BE9 GenPept UniProtKB/TrEMBL:Q96BE9
    Help top of page

    Additional Links

    Additional Links

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
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