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

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: mouse all
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Genomic context

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_000012.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

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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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.
Title: Combined SET7/9 and CDK4 inhibition act synergistically against osteosarcoma.
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.
N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4.
Title: N6-methyladenosine-induced METTL1 promotes tumor proliferation via CDK4.
Beyond cell cycle regulation: The pleiotropic function of CDK4 in cancer.
Title: Beyond cell cycle regulation: The pleiotropic function of CDK4 in cancer.
Cyclin D-CDK4 Disulfide Bond Attenuates Pulmonary Vascular Cell Proliferation.
Title: Cyclin D-CDK4 Disulfide Bond Attenuates Pulmonary Vascular Cell Proliferation.
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.
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.
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.
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.
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	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 EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies in celiac disease and rheumatoid arthritis identifies fourteen non-HLA shared loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

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

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D12S1972 (e-PCR)
- UniSTS:40227

D15S1477 (e-PCR)
- UniSTS:474482

PMC25103P2 (e-PCR)
- UniSTS:272282

GDB:384863 (e-PCR)
- UniSTS:157112

STS-M14505 (e-PCR)
- UniSTS:1480

GDB:593068 (e-PCR)
- UniSTS:157933

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

EC 2.7.11.22

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

NG_007484.2 RefSeqGene

Range

4935..9655

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_490

mRNA and Protein(s)

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

NC_000012.12 Reference GRCh38.p14 Primary Assembly

Range

57747727..57752310 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060936.1 Alternate T2T-CHM13v2.0

Range

57716081..57720660 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_052984.1: Suppressed sequence

Description

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