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CDK2 cyclin dependent kinase 2 [ Homo sapiens (human) ]

Gene ID: 1017, updated on 18-Nov-2024

Summary

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Official Symbol
CDK2provided by HGNC
Official Full Name
cyclin dependent kinase 2provided by HGNC
Primary source
HGNC:HGNC:1771
See related
Ensembl:ENSG00000123374 MIM:116953; AllianceGenome:HGNC:1771
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
CDKN2; p33(CDK2)
Summary
This gene encodes a member of a family of serine/threonine protein kinases that participate in cell cycle regulation. The encoded protein is the catalytic subunit of the cyclin-dependent protein kinase complex, which regulates progression through the cell cycle. Activity of this protein is especially critical during the G1 to S phase transition. This protein associates with and regulated by other subunits of the complex including cyclin A or E, CDK inhibitor p21Cip1 (CDKN1A), and p27Kip1 (CDKN1B). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
Expression
Ubiquitous expression in placenta (RPKM 29.3), bone marrow (RPKM 14.9) and 24 other tissues See more
Orthologs
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Genomic context

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See CDK2 in Genome Data Viewer
Location:
12q13.2
Exon count:
8
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 12 NC_000012.12 (55966830..55972789)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 12 NC_060936.1 (55933893..55939852)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 12 NC_000012.11 (56360614..56366573)

Chromosome 12 - NC_000012.12Genomic Context describing neighboring genes Neighboring gene PYM homolog 1, exon junction complex associated factor Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:56320788-56321368 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr12:56321369-56321949 Neighboring gene diacylglycerol kinase alpha Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56333724-56334224 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56334225-56334725 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56350689-56351190 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr12:56354315-56354815 Neighboring gene premelanosome protein Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6464 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 6465 Neighboring gene RAB13, member RAS oncogene family pseudogene Neighboring gene RAB5B, member RAS oncogene family Neighboring gene H3K27ac hESC enhancer GRCh37_chr12:56390834-56391334 Neighboring gene ReSE screen-validated silencer GRCh37_chr12:56394413-56394603 Neighboring gene Sharpr-MPRA regulatory region 2650 Neighboring gene sulfite oxidase

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 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. Biochemical and cellular effects of roscovitine, a potent and selective inhibitor of the cyclin-dependent kinases cdc2, cdk2 and cdk5. Meijer L, et al. Eur J Biochem, 1997 Jan 15. PMID 9030781
  2. Role of cyclin-dependent kinase inhibitors in the growth arrest at senescence in human prostate epithelial and uroepithelial cells. Schwarze SR, et al. Oncogene, 2001 Dec 13. PMID 11781834
  3. Cdk2 strengthens the intra-S checkpoint and counteracts cell cycle exit induced by DNA damage. Bačević K, et al. Sci Rep, 2017 Oct 18. PMID 29044141, Free PMC Article
  4. PolyC-binding proteins enhance expression of the CDK2 cell cycle regulatory protein via alternative splicing. Ji X, et al. Nucleic Acids Res, 2018 Feb 28. PMID 29253178, Free PMC Article
  5. Bioinformatics analysis of the CDK2 functions in neuroblastoma. Bo L, et al. Mol Med Rep, 2018 Mar. PMID 29328425

See all (914) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.
    Title: NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2.
  2. CDK2-activated TRIM32 phosphorylation and nuclear translocation promotes radioresistance in triple-negative breast cancer.
    Title: CDK2-activated TRIM32 phosphorylation and nuclear translocation promotes radioresistance in triple-negative breast cancer.
  3. Hsa_circ_0005320 affects cell proliferation and the cell cycle via the IGF2BP3/CDK2 axis in bladder cancer.
    Title: Hsa_circ_0005320 affects cell proliferation and the cell cycle via the IGF2BP3/CDK2 axis in bladder cancer.
  4. Exploring the mechanism of C473D mutation on CDC25B causing weak binding affinity with CDK2/CyclinA by molecular dynamics study.
    Title: Exploring the mechanism of C473D mutation on CDC25B causing weak binding affinity with CDK2/CyclinA by molecular dynamics study.
  5. KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations.
    Title: KDM4C-mediated senescence defense is a targetable vulnerability in gastric cancer harboring TP53 mutations.
  6. N6-methyladenosine reader YTHDF2 promotes multiple myeloma cell proliferation through EGR1/p21[cip1/waf1]/CDK2-Cyclin E1 axis-mediated cell cycle transition.
    Title: N6-methyladenosine reader YTHDF2 promotes multiple myeloma cell proliferation through EGR1/p21(cip1/waf1)/CDK2-Cyclin E1 axis-mediated cell cycle transition.
  7. SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.
    Title: SARS-CoV-2 hijacks cellular kinase CDK2 to promote viral RNA synthesis.
  8. Role of Genetic Variations in CDK2, CCNE1 and p27(KIP1) in Prostate Cancer.
    Title: Role of Genetic Variations in CDK2, CCNE1 and p27(KIP1) in Prostate Cancer.
  9. Overexpression of IncRNA TPT1-AS1 Suppresses Hepatocellular Carcinoma Cell Proliferation by Downregulating CDK2.
    Title: Overexpression of IncRNA TPT1-AS1 Suppresses Hepatocellular Carcinoma Cell Proliferation by Downregulating CDK2.
  10. A comprehensive bioinformatic analysis of cyclin-dependent kinase 2 (CDK2) in glioma.
    Title: A comprehensive bioinformatic analysis of cyclin-dependent kinase 2 (CDK2) in glioma.
Submit: New GeneRIF Correction See all GeneRIFs (362)

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

EBI GWAS Catalog

Description
A novel susceptibility locus for type 1 diabetes on Chr12q13 identified by a genome-wide association study.
EBI GWAS Catalog
Association analyses identify three susceptibility Loci for vitiligo in the Chinese Han population.
EBI GWAS Catalog
Genetics of rheumatoid arthritis contributes to biology and drug discovery.
EBI GWAS Catalog
Genome-wide association study identifies three new susceptibility loci for adult asthma in the Japanese population.
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)

HIV-1 interactions

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Protein interactions

Protein Gene Interaction Pubs
Tat tat CDK2 regulates HIV-1 Tat-mediated transcription by phosphorylation of CDK9 at position Ser90 and decreases 7SK RNA levels PubMed
tat Iron chelators 311 and ICL670 decrease cellular activity of CDK2 and reduce HIV-1 Tat phosphorylation by CDK2 PubMed
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 Amino acid residues serine 16 and 46 of HIV-1 Tat are phosphorylated by CDK2; mutation of these two residues reduces HIV-1 transcription in cells PubMed
tat HIV-1 Tat 41/44 peptide TAALS from the core domain of Tat inhibits Tat-mediated HIV-1 gene expression and replication by binding the Cdk2/Cyclin E complex and inhibiting the phosphorylation of serine 5 of RNAPII PubMed
tat Cdk2 phosphorylates HIV-1 Tat PubMed
tat Tat-mediated phosphorylation of RNA Polymerase C-terminal domain involves dynamic interactions of Cdk2 with Tat amino acids 15-24 and 36-49 and requires cysteine 22 in the activation domain of Tat and amino acids 42-72 of Tat PubMed
tat Cdk2 activity is enhanced by HIV-1 Tat expression in Jurkat T cells and is associated with Tat-induced apoptosis PubMed
tat HIV-1 Tat induces Cyclin E-associated cdk activity in lymphocytes, indicating Tat drives cells to the late G1 phase of the cell cycle PubMed
tat HIV-1 Tat induces a G1 arrest in cells of glial origin, leading to a downregulation of cyclin E-Cdk2 kinase activity and phosphorylation of Rb 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

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 IDA
Inferred from Direct Assay
more info
 PubMed 
enables cyclin binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables cyclin-dependent protein kinase activity IDA
Inferred from Direct Assay
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
  
contributes_to histone kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables magnesium ion binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein domain specific binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein serine kinase activity IEA
Inferred from Electronic Annotation
more info
  
enables protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine/threonine kinase activity IGI
Inferred from Genetic Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in DNA repair IEA
Inferred from Electronic Annotation
more info
  
involved_in DNA replication TAS
Traceable Author Statement
more info
 PubMed 
involved_in DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
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 NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in G2/M transition of mitotic cell cycle NAS
Non-traceable Author Statement
more info
 PubMed 
involved_in Ras protein signal transduction IEP
Inferred from Expression Pattern
more info
 PubMed 
involved_in cell division IEA
Inferred from Electronic Annotation
more info
  
involved_in cellular response to nitric oxide TAS
Traceable Author Statement
more info
 PubMed 
involved_in cellular senescence TAS
Traceable Author Statement
more info
  
involved_in centriole replication IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in centrosome duplication TAS
Traceable Author Statement
more info
 PubMed 
involved_in chromatin remodeling IEA
Inferred from Electronic Annotation
more info
  
involved_in meiotic cell cycle TAS
Traceable Author Statement
more info
 PubMed 
involved_in mitotic G1 DNA damage checkpoint signaling TAS
Traceable Author Statement
more info
 PubMed 
involved_in negative regulation of transcription by RNA polymerase II IEA
Inferred from Electronic Annotation
more info
  
involved_in peptidyl-serine phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of DNA replication TAS
Traceable Author Statement
more info
  
involved_in positive regulation of DNA-templated DNA replication initiation IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of DNA-templated transcription IEA
Inferred from Electronic Annotation
more info
  
involved_in positive regulation of cell population proliferation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in positive regulation of heterochromatin formation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in post-translational protein modification IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in potassium ion transport IEA
Inferred from Electronic Annotation
more info
  
involved_in protein phosphorylation IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in protein phosphorylation IMP
Inferred from Mutant Phenotype
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 anaphase-promoting complex-dependent catabolic process TAS
Traceable Author Statement
more info
  
involved_in regulation of gene expression IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of mitotic cell cycle TAS
Traceable Author Statement
more info
  
involved_in signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in telomere maintenance in response to DNA damage IDA
Inferred from Direct Assay
more info
 PubMed 
Component Evidence Code Pubs
located_in Cajal body IDA
Inferred from Direct Assay
more info
 PubMed 
located_in X chromosome IEA
Inferred from Electronic Annotation
more info
  
located_in Y chromosome IEA
Inferred from Electronic Annotation
more info
  
located_in centrosome IDA
Inferred from Direct Assay
more info
  
located_in centrosome TAS
Traceable Author Statement
more info
 PubMed 
located_in chromosome, telomeric region IEA
Inferred from Electronic Annotation
more info
  
located_in condensed chromosome IEA
Inferred from Electronic Annotation
more info
  
part_of cyclin A1-CDK2 complex NAS
Non-traceable Author Statement
more info
 PubMed 
part_of cyclin A2-CDK2 complex IDA
Inferred from Direct Assay
more info
 PubMed 
part_of cyclin A2-CDK2 complex IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of cyclin E1-CDK2 complex IPI
Inferred from Physical Interaction
more info
 PubMed 
part_of cyclin E2-CDK2 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 cytoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
located_in cytosol TAS
Traceable Author Statement
more info
  
located_in endosome IDA
Inferred from Direct Assay
more info
 PubMed 
located_in male germ cell nucleus IEA
Inferred from Electronic Annotation
more info
  
located_in nuclear envelope IEA
Inferred from Electronic Annotation
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
 PubMed 
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 2
Names
cdc2-related protein kinase
cell division protein kinase 2
p33 protein kinase
NP_001277159.1
NP_001789.2
NP_439892.2
XP_011536034.1
XP_054226706.1

NCBI Reference Sequences (RefSeq)

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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_034014.1 RefSeqGene

    Range
    5062..11021
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001290230.2 → NP_001277159.1  cyclin-dependent kinase 2 isoform 3

    See identical proteins and their annotated locations for NP_001277159.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks two alternate in-frame exons, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AA789250, AK293246, BC003065, DA814453
    Consensus CDS
    CCDS76567.1
    UniProtKB/TrEMBL
    B4DDL9, E7ESI2
    Related
    ENSP00000393605.2, ENST00000440311.6
    Conserved Domains (1) summary
    cl21453
    Location:3 → 226
    PKc_like; Protein Kinases, catalytic domain

  2. NM_001798.5 → NP_001789.2  cyclin-dependent kinase 2 isoform 1

    See identical proteins and their annotated locations for NP_001789.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AA789250, AK291941, BC003065, DA814453
    Consensus CDS
    CCDS8898.1
    UniProtKB/Swiss-Prot
    A8K7C6, O75100, P24941
    Related
    ENSP00000266970.4, ENST00000266970.9
    Conserved Domains (1) summary
    cd07860
    Location:3 → 286
    STKc_CDK2_3; Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3

  3. NM_052827.4 → NP_439892.2  cyclin-dependent kinase 2 isoform 2

    See identical proteins and their annotated locations for NP_439892.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2, also known as CDK2deltaT) lacks an alternate in-frame exon, compared to variant 1. The encoded isoform (2, also known as d-HSCDK2) is shorter than isoform 1.
    Source sequence(s)
    AA789250, AB012305, BC003065, DA814453
    Consensus CDS
    CCDS8899.1
    UniProtKB/TrEMBL
    B4DDL9
    Related
    ENSP00000243067.4, ENST00000354056.4
    Conserved Domains (1) summary
    cl21453
    Location:3 → 252
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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
    55966830..55972789
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011537732.2 → XP_011536034.1  cyclin-dependent kinase 2 isoform X1

    See identical proteins and their annotated locations for XP_011536034.1

    UniProtKB/TrEMBL
    G3V5T9
    Related
    ENSP00000452514.1, ENST00000553376.5
    Conserved Domains (1) summary
    cd07860
    Location:3 → 334
    STKc_CDK2_3; Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase 2 and 3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060936.1 Alternate T2T-CHM13v2.0

    Range
    55933893..55939852
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054370731.1 → XP_054226706.1  cyclin-dependent kinase 2 isoform X1

    UniProtKB/TrEMBL
    G3V5T9
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P24941.2 GenPept UniProtKB/Swiss-Prot:P24941

Gene LinkOut

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