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    CDK4 cyclin dependent kinase 4 [ Homo sapiens (human) ]

    Gene ID: 1019, updated on 19-Jun-2024

    Summary

    Official Symbol
    CDK4provided by HGNC
    Official Full Name
    cyclin dependent kinase 4provided by HGNC
    Primary source
    HGNC:HGNC:1773
    See related
    Ensembl:ENSG00000135446 MIM:123829; AllianceGenome:HGNC:1773
    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]
    Expression
    Ubiquitous expression in ovary (RPKM 36.9), endometrium (RPKM 35.9) and 25 other tissues See more
    Orthologs
    NEW
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    Try the new Transcript table

    Genomic context

    See CDK4 in Genome Data Viewer
    Location:
    12q14.1
    Exon count:
    8
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (57747727..57752310, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (57716081..57720660, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (58141510..58146093, complement)

    Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr12:58087544-58088118 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6550 Neighboring gene OS9 endoplasmic reticulum lectin Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:58120605-58121240 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:58121241-58121874 Neighboring gene AGAP2 antisense RNA 1 Neighboring gene ArfGAP with GTPase domain, ankyrin repeat and PH domain 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr12:58127413-58128612 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:58131678-58131897 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6551 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6552 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6553 Neighboring gene tetraspanin 31 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4588 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:58145719-58146452 Neighboring gene microRNA 6759 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4591 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4593 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 4592 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6554 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6555 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6556 Neighboring gene membrane associated ring-CH-type finger 9 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:58158104-58158882 Neighboring gene cytochrome P450 family 27 subfamily B member 1

    Genomic regions, transcripts, and products

    Expression

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

    Description Tests
    Melanoma, cutaneous malignant, susceptibility to, 3
    MedGen: C1836892 OMIM: 609048 GeneReviews: Not available
    Compare labs

    Copy number response

    Description
    Copy number response
    Haploinsufficency

    No evidence available (Last evaluated 2020-09-02)

    ClinGen Genome Curation Page
    Triplosensitivity

    No evidence available (Last evaluated 2020-09-02)

    ClinGen Genome Curation Page

    EBI GWAS Catalog

    Description
    Genetics of rheumatoid arthritis contributes to biology and drug discovery.
    EBI GWAS Catalog
    Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci.
    EBI GWAS Catalog

    HIV-1 interactions

    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 Interaction Database

    Pathways from PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • MGC14458

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables ATP binding IEA
    Inferred from Electronic Annotation
    more info
     
    enables cyclin binding IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables cyclin binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables cyclin-dependent protein serine/threonine kinase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    enables cyclin-dependent protein serine/threonine kinase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    enables cyclin-dependent protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
     
    enables cyclin-dependent protein serine/threonine kinase regulator activity TAS
    Traceable Author Statement
    more info
     
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    enables protein serine kinase activity IEA
    Inferred from Electronic Annotation
    more info
     
    Process Evidence Code Pubs
    involved_in G1/S transition of mitotic cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in G1/S transition of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in G1/S transition of mitotic cell cycle IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in G1/S transition of mitotic cell cycle NAS
    Non-traceable Author Statement
    more info
    PubMed 
    involved_in cell division IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to interleukin-4 IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to ionomycin IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to lipopolysaccharide IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in cellular response to phorbol 13-acetate 12-myristate IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in positive regulation of G2/M transition of mitotic cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in positive regulation of cell population proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in positive regulation of fibroblast proliferation IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in protein phosphorylation IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in protein phosphorylation IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of G2/M transition of mitotic cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of cell cycle IDA
    Inferred from Direct Assay
    more info
    PubMed 
    involved_in regulation of gene expression IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    involved_in regulation of gene expression IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    involved_in regulation of transcription initiation by RNA polymerase II TAS
    Traceable Author Statement
    more info
     
    involved_in regulation of type B pancreatic cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    involved_in response to xenobiotic stimulus IEP
    Inferred from Expression Pattern
    more info
    PubMed 
    involved_in signal transduction IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    Component Evidence Code Pubs
    located_in bicellular tight junction IEA
    Inferred from Electronic Annotation
    more info
     
    part_of chromatin IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of cyclin D1-CDK4 complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of cyclin D2-CDK4 complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of cyclin D3-CDK4 complex IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    part_of cyclin-dependent protein kinase holoenzyme complex IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    part_of cyclin-dependent protein kinase holoenzyme complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in cytosol IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in cytosol TAS
    Traceable Author Statement
    more info
     
    located_in nuclear membrane IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleolus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
     
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    PubMed 
    part_of transcription regulator complex IEA
    Inferred from Electronic Annotation
    more info
     

    General protein information

    Preferred Names
    cyclin-dependent kinase 4
    Names
    cell division protein kinase 4
    NP_000066.1

    NCBI Reference Sequences (RefSeq)

    NEW Try the new Transcript table

    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_007484.2 RefSeqGene

      Range
      4935..9655
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_490

    mRNA and Protein(s)

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

      See identical proteins and their annotated locations for NP_000066.1

      Status: REVIEWED

      Source sequence(s)
      AC025165, BC003644, BI832658, BQ773564
      Consensus CDS
      CCDS8953.1
      UniProtKB/Swiss-Prot
      B2R9A0, B4DNF9, O00576, P11802, Q6FG61
      Related
      ENSP00000257904.5, ENST00000257904.11
      Conserved Domains (1) summary
      cl21453
      Location:5295
      PKc_like; Protein Kinases, catalytic domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000012.12 Reference GRCh38.p14 Primary Assembly

      Range
      57747727..57752310 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060936.1 Alternate T2T-CHM13v2.0

      Range
      57716081..57720660 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.