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CHEK2 checkpoint kinase 2 [ Homo sapiens (human) ]

Gene ID: 11200, updated on 22-Nov-2014
Official Symbol
CHEK2provided by HGNC
Official Full Name
checkpoint kinase 2provided by HGNC
Primary source
HGNC:HGNC:16627
Locus tag
RP11-436C9.1
See related
Ensembl:ENSG00000183765; HPRD:05084; MIM:604373; Vega:OTTHUMG00000151023
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
CDS1; CHK2; LFS2; RAD53; hCds1; HuCds1; PP1425
Summary
In response to DNA damage and replication blocks, cell cycle progression is halted through the control of critical cell cycle regulators. The protein encoded by this gene is a cell cycle checkpoint regulator and putative tumor suppressor. It contains a forkhead-associated protein interaction domain essential for activation in response to DNA damage and is rapidly phosphorylated in response to replication blocks and DNA damage. When activated, the encoded protein is known to inhibit CDC25C phosphatase, preventing entry into mitosis, and has been shown to stabilize the tumor suppressor protein p53, leading to cell cycle arrest in G1. In addition, this protein interacts with and phosphorylates BRCA1, allowing BRCA1 to restore survival after DNA damage. Mutations in this gene have been linked with Li-Fraumeni syndrome, a highly penetrant familial cancer phenotype usually associated with inherited mutations in TP53. Also, mutations in this gene are thought to confer a predisposition to sarcomas, breast cancer, and brain tumors. This nuclear protein is a member of the CDS1 subfamily of serine/threonine protein kinases. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]
See CHEK2 in Epigenomics, MapViewer
Location:
22q12.1
Exon count:
20
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 22 NC_000022.11 (28687743..28741834, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (29083731..29137822, complement)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene tetratricopeptide repeat domain 28 Neighboring gene uncharacterized LOC101929594 Neighboring gene microRNA 5739 Neighboring gene coiled-coil domain containing 117 Neighboring gene HscB mitochondrial iron-sulfur cluster co-chaperone

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Associated conditions

Description Tests
Familial cancer of breast Compare labs
Li-Fraumeni syndrome 2
MedGen: C1836482 OMIM: 609265 GeneReviews: Not available
Compare labs
Malignant tumor of prostate
MedGen: C0376358 OMIM: 176807 GeneReviews: Not available
Compare labs
Osteosarcoma
MedGen: C0029463 OMIM: 259500 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
A genome-wide association study of optic disc parameters.
NHGRI GWA Catalog
A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma.
NHGRI GWA Catalog
Genetic variants associated with breast size also influence breast cancer risk.
NHGRI GWA Catalog
Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.
NHGRI GWA Catalog
Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
NHGRI GWA Catalog

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp160, precursor env PML, TopBP1, NBS1 or ATM-induced activation of phosphorylation of Chk2 participates in the DNA damage-elicited pro-apoptotic cascade that leads to the demise of Env-elicited syncytia PubMed
Vpr vpr Vpr-dependent induction and Vif-mediated attenuation of NKG2D ligands are required for Chk2 phosphorylation in HIV infection PubMed
vpr HIV-1 Vpr induces expression of gamma-H2AX and phosphorylation of Chk2 PubMed

Go to the HIV-1, Human Interaction Database

  • Cell Cycle, organism-specific biosystem (from REACTOME)
    Cell Cycle, organism-specific biosystem
    Cell Cycle
  • Cell Cycle Checkpoints, organism-specific biosystem (from REACTOME)
    Cell Cycle Checkpoints, organism-specific biosystemA hallmark of the human cell cycle in normal somatic cells is its precision. This remarkable fidelity is achieved by a number of signal transduction pathways, known as checkpoints, which monitor cell...
  • Cell cycle, organism-specific biosystem (from WikiPathways)
    Cell cycle, organism-specific biosystemThe 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 involves processes crucial to the survival of a c...
  • 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...
  • DNA damage response, organism-specific biosystem (from WikiPathways)
    DNA damage response, organism-specific biosystemThis is the first pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and ATR) which are connected to the sources of DNA damage (in blue). The two ...
  • FOXM1 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
    FOXM1 transcription factor network, organism-specific biosystem
    FOXM1 transcription factor network
  • G1/S DNA Damage Checkpoints, organism-specific biosystem (from REACTOME)
    G1/S DNA Damage Checkpoints, 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 ...
  • G2/M Checkpoints, organism-specific biosystem (from REACTOME)
    G2/M Checkpoints, organism-specific biosystemG2/M checkpoints include the checks for damaged DNA, unreplicated DNA, and checks that ensure that the genome is replicated once and only once per cell cycle. If cells pass these checkpoints, they f...
  • G2/M DNA damage checkpoint, organism-specific biosystem (from REACTOME)
    G2/M DNA damage checkpoint, organism-specific biosystemThroughout the cell cycle, the genome is constantly monitored for damage, resulting either from errors of replication, by-products of metabolism or through extrinsic sources such as ultra-violet or i...
  • 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...
  • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
  • Integrated Cancer pathway, organism-specific biosystem (from WikiPathways)
    Integrated Cancer pathway, organism-specific biosystem
    Integrated Cancer pathway
  • Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
  • PLK3 signaling events, organism-specific biosystem (from Pathway Interaction Database)
    PLK3 signaling events, organism-specific biosystem
    PLK3 signaling events
  • Prostate Cancer, organism-specific biosystem (from WikiPathways)
    Prostate Cancer, organism-specific biosystem
    Prostate Cancer
  • Ubiquitin Mediated Degradation of Phosphorylated Cdc25A, organism-specific biosystem (from REACTOME)
    Ubiquitin Mediated Degradation of Phosphorylated Cdc25A, organism-specific biosystemcdc25A protein is degraded by the ubiquitin-proteasome machinery in both terminally differentiating and cycling cells (Bernardi et al. 2000).
  • p53 pathway, organism-specific biosystem (from Pathway Interaction Database)
    p53 pathway, organism-specific biosystem
    p53 pathway
  • 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...
  • p53-Independent DNA Damage Response, organism-specific biosystem (from REACTOME)
    p53-Independent DNA Damage Response, organism-specific biosystemIn response to DNA damage due to exposure to ultraviolet light or to ionizing radiation, Cdc25A is phosphorylated by Chk1 or Chk2. The phosphorylation of Cdc25A at ser-123, in response to DNA damage...
  • p53-Independent G1/S DNA damage checkpoint, organism-specific biosystem (from REACTOME)
    p53-Independent G1/S DNA damage checkpoint, organism-specific biosystemThe G1 arrest induced by DNA damage has been ascribed to the transcription factor and tumor suppressor protein p53. To be effective within minutes after DNA damage, induction of the G1 block should ...
Products Interactant Other Gene Complex Source Pubs Description

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
protein kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein serine/threonine kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Process Evidence Code Pubs
DNA damage checkpoint TAS
Traceable Author Statement
more info
PubMed 
DNA damage induced protein phosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
G2/M transition of mitotic cell cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to DNA damage stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to DNA damage stimulus TAS
Traceable Author Statement
more info
PubMed 
double-strand break repair IMP
Inferred from Mutant Phenotype
more info
PubMed 
intrinsic apoptotic signaling pathway in response to DNA damage IDA
Inferred from Direct Assay
more info
PubMed 
intrinsic apoptotic signaling pathway in response to DNA damage IMP
Inferred from Mutant Phenotype
more info
PubMed 
positive regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
protein autophosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
protein stabilization IDA
Inferred from Direct Assay
more info
PubMed 
regulation of protein catabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of transcription, DNA-templated IDA
Inferred from Direct Assay
more info
PubMed 
replicative senescence NAS
Non-traceable Author Statement
more info
PubMed 
response to gamma radiation IEA
Inferred from Electronic Annotation
more info
 
signal transduction in response to DNA damage IDA
Inferred from Direct Assay
more info
PubMed 
signal transduction involved in intra-S DNA damage checkpoint IMP
Inferred from Mutant Phenotype
more info
PubMed 
spindle assembly involved in mitosis IMP
Inferred from Mutant Phenotype
more info
PubMed 
transcription, DNA-templated IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
PML body IDA
Inferred from Direct Assay
more info
PubMed 
colocalizes_with chromosome, telomeric region IDA
Inferred from Direct Assay
more info
PubMed 
nucleoplasm TAS
Traceable Author Statement
more info
 
Preferred Names
serine/threonine-protein kinase Chk2
Names
serine/threonine-protein kinase Chk2
cds1 homolog
CHK2 checkpoint homolog
checkpoint-like protein CHK2
NP_001005735.1
NP_001244316.1
NP_009125.1
NP_665861.1

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_008150.1 

    Range
    5001..59092
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001005735.1NP_001005735.1  serine/threonine-protein kinase Chk2 isoform c

    See proteins identical to NP_001005735.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) contains an alternate in-frame exon compared to variant 1. The resulting isoform (c) has the same N- and C-termini but is longer compared to isoform a.
    Source sequence(s)
    AW778747, AY551297, BM838597
    Consensus CDS
    CCDS33629.1
    UniProtKB/Swiss-Prot
    O96017
    Related
    ENSP00000372023, OTTHUMP00000198970, ENST00000382580, OTTHUMT00000321016
    Conserved Domains (4) summary
    smart00220
    Location:263529
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1716
    Location:113242
    COG1716; FOG: FHA domain [Signal transduction mechanisms]
    cd00060
    Location:156244
    FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...
    cl09925
    Location:261554
    PKc_like; Protein Kinases, catalytic domain
  2. NM_001257387.1NP_001244316.1  serine/threonine-protein kinase Chk2 isoform d

    See proteins identical to NP_001244316.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4) contains an alternate exon compared to variant 1, that causes a frameshift. The resulting isoform (d) is shorter at the N-terminus compared to isoform a.
    Source sequence(s)
    AF217975
    UniProtKB/Swiss-Prot
    O96017
    Conserved Domains (2) summary
    smart00220
    Location:3265
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cl09925
    Location:3290
    PKc_like; Protein Kinases, catalytic domain
  3. NM_007194.3NP_009125.1  serine/threonine-protein kinase Chk2 isoform a

    See proteins identical to NP_009125.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the predominant transcript and encodes isoform a.
    Source sequence(s)
    AF096279, AW778747, BM838597
    Consensus CDS
    CCDS13843.1
    UniProtKB/Swiss-Prot
    O96017
    Related
    ENSP00000329178, OTTHUMP00000198969, ENST00000328354, OTTHUMT00000321015
    Conserved Domains (4) summary
    smart00220
    Location:220486
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1716
    Location:116199
    COG1716; FOG: FHA domain [Signal transduction mechanisms]
    cd00060
    Location:93201
    FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...
    cl09925
    Location:218511
    PKc_like; Protein Kinases, catalytic domain
  4. NM_145862.2NP_665861.1  serine/threonine-protein kinase Chk2 isoform b

    See proteins identical to NP_665861.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 1. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform a.
    Source sequence(s)
    AW778747, AY551299, BM838597
    Consensus CDS
    CCDS13844.1
    UniProtKB/Swiss-Prot
    O96017
    Related
    ENSP00000329012, ENST00000348295
    Conserved Domains (4) summary
    smart00220
    Location:220457
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1716
    Location:116199
    COG1716; FOG: FHA domain [Signal transduction mechanisms]
    cd00060
    Location:93201
    FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...
    cl09925
    Location:218482
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Alternate HuRef

Genomic

  1. AC_000154.1 

    Range
    12048435..12103008
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000022.11 

    Range
    28687743..28741834
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_006724114.1XP_006724177.1  

    Conserved Domains (2) summary
    smart00220
    Location:68326
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cl09925
    Location:69325
    PKc_like; Protein Kinases, catalytic domain
  2. XM_006724116.1XP_006724179.1  

    Conserved Domains (2) summary
    smart00220
    Location:38297
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cl09925
    Location:38296
    PKc_like; Protein Kinases, catalytic domain
  3. XM_006724115.1XP_006724178.1  

    Conserved Domains (4) summary
    cd00180
    Location:226337
    PKc; Catalytic domain of Protein Kinases
    smart00220
    Location:220337
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1716
    Location:116199
    COG1716; FOG: FHA domain [Signal transduction mechanisms]
    cd00060
    Location:93201
    FHA; Forkhead associated domain (FHA); found in eukaryotic and prokaryotic proteins. Putative nuclear signalling domain. FHA domains may bind phosphothreonine, phosphoserine and sometimes phosphotyrosine. In eukaryotes, many FHA domain-containing proteins ...

RNA

  1. XR_244350.1 RNA Sequence

Alternate CHM1_1.1

Genomic

  1. NC_018933.2 

    Range
    29042794..29096883
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)