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

Gene ID: 1019, updated on 16-Apr-2024

Summary

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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
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Genomic context

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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

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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

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Related articles in PubMed

  1. Mitochondrial creatine kinase 1 regulates the cell cycle in non-small cell lung cancer via activation of cyclin-dependent kinase 4. Yang M, et al. Respir Res, 2023 Apr 15. PMID 37061730, Free PMC Article
  2. Computational screening and structural analysis of Gly201Arg and Gly201Asp missense mutations in human cyclin-dependent kinase 4 protein. Thirumal Kumar D, et al. Adv Protein Chem Struct Biol, 2023. PMID 37061341
  3. Expression patterns and therapeutic implications of CDK4 across multiple carcinomas: a molecular docking and MD simulation study. Qayoom H, et al. Med Oncol, 2022 Jul 23. PMID 35870089
  4. Cyclin-Dependent Kinase 4 is expected to be a therapeutic target for hepatocellular carcinoma metastasis using integrated bioinformatic analysis. Zhang JN, et al. Bioengineered, 2021 Dec. PMID 34784846, Free PMC Article
  5. Basic Pan-Cancer Analysis of the Carcinogenic Effects of Cyclin-Dependent Kinase 4 (CDK4) in Human Surface Tumors. Wu J, et al. J Healthc Eng, 2021. PMID 34422248, Free PMC Article

See all (677) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.
    Title: Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.
  2. Deregulation of the p19/CDK4/CDK6 axis in Jak2[V617F] megakaryocytes accelerates the development of myelofibrosis.
    Title: Deregulation of the p19/CDK4/CDK6 axis in Jak2(V617F) megakaryocytes accelerates the development of myelofibrosis.
  3. N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4.
    Title: N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4.
  4. Beyond cell cycle regulation: The pleiotropic function of CDK4 in cancer.
    Title: Beyond cell cycle regulation: The pleiotropic function of CDK4 in cancer.
  5. Cyclin D-CDK4 Disulfide Bond Attenuates Pulmonary Vascular Cell Proliferation.
    Title: Cyclin D-CDK4 Disulfide Bond Attenuates Pulmonary Vascular Cell Proliferation.
  6. DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway.
    Title: DNA damage induced by CDK4 and CDK6 blockade triggers anti-tumor immune responses through cGAS-STING pathway.
  7. FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.
    Title: FOXM1, MEK, and CDK4/6: New Targets for Malignant Peripheral Nerve Sheath Tumor Therapy.
  8. METTL3-modified lncRNA-MALAT1 regulates the molecular axis of miR-124-3p/CDK4 involved in Ewing's sarcoma.
    Title: METTL3-modified lncRNA-MALAT1 regulates the molecular axis of miR-124-3p/CDK4 involved in Ewing's sarcoma.
  9. Astragaloside IV promotes keratinocyte proliferation and migration through upregulating lncRNA H19 recruited ILF3 to enhance the stability of CDK4 mRNA.
    Title: Astragaloside IV promotes keratinocyte proliferation and migration through upregulating lncRNA H19 recruited ILF3 to enhance the stability of CDK4 mRNA.
  10. A Japanese case of familial malignant melanoma with germline CDK4 variant incidentally diagnosed by cancer genome profiling.
    Title: A Japanese case of familial malignant melanoma with germline CDK4 variant incidentally diagnosed by cancer genome profiling.
Submit: New GeneRIF Correction See all GeneRIFs (361)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

HIV-1 interactions

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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

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

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 organic substance IBA
Inferred from Biological aspect of Ancestor
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

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

NCBI Reference Sequences (RefSeq)

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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_000075.4 → NP_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:5 → 295
    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.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P11802.2 GenPept UniProtKB/Swiss-Prot:P11802

Gene LinkOut

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

Chemical Information
Molecular Biology Databases
Research Materials
Tools
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