CHEK2 checkpoint kinase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CHEK2provided by HGNC
Official Full Name: checkpoint kinase 2provided by HGNC
Primary source: HGNC:HGNC:16627
See related: Ensembl:ENSG00000183765 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]
Expression: Ubiquitous expression in bone marrow (RPKM 3.3), lymph node (RPKM 3.1) and 24 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 22q12.1

Exon count:: 22

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	22	NC_000022.11 (28687743..28741866, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (29083731..29137822, complement)

Chromosome 22 - NC_000022.11 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 Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Truncating variants in PALB2, ATM and CHEK2 , but not XRCC2 were associated with increased breast cancer risk.
Title: Rare, protein-truncating variants in ATM, CHEK2 and PALB2, but not XRCC2, are associated with increased breast cancer risks.
our results identify a novel link between XRRA1 and the ATM/CHK1/2 pathway and suggest that XRRA1 is involved in a DNA damage response that drives radio- and chemoresistance by regulating the ATM/CHK1/2 pathway.
Title: XRRA1 Targets ATM/CHK1/2-Mediated DNA Repair in Colorectal Cancer.
BRCA2 and CHEK2 play an important role in the genetic susceptibility to urinary tract cancers.
Title: Rare variants in BRCA2 and CHEK2 are associated with the risk of urinary tract cancers.
Checkpoint kinase 2 (Chk2) inhibition suppressed C-terminal acetylation of p53 and delayed the induction of p53-target genes under heat stress (HS). Chk2 inhibition failed to inhibit apoptosis induced by HS, indicating that Chk2 was dispensable for p53-dependent apoptosis under HS. Chk2 inhibition abrogated G2/M arrest and promoted cell death induced by HS in cells with p53 defects.
Title: Checkpoint kinase 2 is dispensable for regulation of the p53 response but is required for G2/M arrest and cell survival in cells with p53 defects under heat stress.
The inhibition CHK2 expression reduced detachment-induced apoptosis but did not influence the ability of cells to migrate and invade, which illustrates that CHK2 could inhibit tumor progression and metastatic potential by enhancing anoikis.
Title: CHK2 Promotes Anoikis and is Associated with the Progression of Papillary Thyroid Cancer.
These data suggest that the CHEK2 c.1100delC mutation is associated with an increased risk for MBC in the Finnish population.
Title: CHEK2 c.1100delC mutation is associated with an increased risk for male breast cancer in Finnish patient population.
Data suggest that mediator complex subunit 1 (Med1/TRAP220) is a target for checkpoint kinase 2 (Chk2)-mediated phosphorylation and may play a role in cellular DNA damage responses by mediating proper induction of gene transcription upon DNA damage.
Title: Checkpoint-dependent phosphorylation of Med1/TRAP220 in response to DNA damage.
this report conceives a novel strategy of Twist1 suppression through Chk2 induction, which prevents metastatic dissemination and promotes premature senescence in p53-defective invasive cancer cells.
Title: Inhibition of Twist1-mediated invasion by Chk2 promotes premature senescence in p53-defective cancer cells.
we have provided evidence in this study that hepatocarcinogenesis with lagging chromosomes elicits the expression of DNA damage response protein Chk2. Thus, the overexpression of Chk2 and its mislocalisation within structures of the mitotic spindle contribute to sustain cell division and chromosomes missegregation.
Title: CHK2 overexpression and mislocalisation within mitotic structures enhances chromosomal instability and hepatocellular carcinoma progression.
PI3K kinase activity is necessary for maintaining 4E-BP1 stability. Our results also suggest 4E-BP1 a novel biological role of regulating cell cycle G2 checkpoint in responding to IR stress in association with controlling CHK2 phosphorylation
Title: Stabilization of 4E-BP1 by PI3K kinase and its involvement in CHK2 phosphorylation in the cellular response to radiation.

Submit: New GeneRIF Correction See all GeneRIFs (377)

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
Familial cancer of breast MedGen: C0346153 OMIM: 114480 GeneReviews: BRCA1- and BRCA2-Associated Hereditary Breast and Ovarian Cancer	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 NHGRI GWA CatalogPubMed
A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genetic variants associated with breast size also influence breast cancer risk. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Large-scale genotyping identifies 41 new loci associated with breast cancer risk. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer. NHGRI GWA Catalog NHGRI GWA 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
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

Pathways from BioSystems

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ATM Signaling Network in Development and Disease, organism-specific biosystem (from WikiPathways)
ATM Signaling Network in Development and Disease, organism-specific biosystemThis pathway is modeled after Figure 4 in the article "The ATM signaling network in development and disease" (See Bibliography). When DNA is damaged, DDR begins to work on recuperating the damage th...
ATM Signaling Pathway, organism-specific biosystem (from WikiPathways)
ATM Signaling Pathway, organism-specific biosystemAtaxia-telangiectasia (A-T) is a highly pleiotropic, autosomal recessive disease that leads to multisystem defects and has an intricate cellular phenotype, all linked to the functional inactivation o...
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 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 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 ...
DNA Double Strand Break Response, organism-specific biosystem (from REACTOME)
DNA Double Strand Break Response, organism-specific biosystemDNA double strand break (DSB) response involves sensing of DNA DSBs by the MRN complex which triggers ATM activation. ATM phosphorylates a number of proteins involved in DNA damage checkpoint signali...
DNA Double-Strand Break Repair, organism-specific biosystem (from REACTOME)
DNA Double-Strand Break Repair, organism-specific biosystemNumerous types of DNA damage can occur within a cell due to the endogenous production of oxygen free radicals, normal alkylation reactions, or exposure to exogenous radiations and chemicals. Double-s...
DNA Repair, organism-specific biosystem (from REACTOME)
DNA Repair, organism-specific biosystemDNA repair is a phenomenal multi-enzyme, multi-pathway system required to ensure the integrity of the cellular genome. Living organisms are constantly exposed to harmful metabolic by-products, enviro...
DNA damage-induced cell cycle checkpoints, organism-specific biosystem (from KEGG)
DNA damage-induced cell cycle checkpoints, organism-specific biosystemFunctional set; Cellular processes; Cell signaling
DNA damage-induced cell cycle checkpoints, conserved biosystem (from KEGG)
DNA damage-induced cell cycle checkpoints, conserved biosystemFunctional set; Cellular processes; Cell signaling
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...
Gene Expression, organism-specific biosystem (from REACTOME)
Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
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
Pathways Affected in Adenoid Cystic Carcinoma, organism-specific biosystem (from WikiPathways)
Pathways Affected in Adenoid Cystic Carcinoma, organism-specific biosystemProtein pathways altered by mutations in adenoid cystic carcinoma. Pathways include epigentic modification, DNA damage checkpoint signals, MYB/MYC signalling pathway, FGF/IGF/PI3K signalling, and not...
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks, organism-specific biosystem (from REACTOME)
Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks, organism-specific biosystemActivated ATM phosphorylates a number of proteins involved in the DNA damage checkpoint and DNA repair (Thompson and Schild 2002, Ciccia and Elledge 2010), thereby triggering and coordinating accumul...
Regulation of TP53 Activity, organism-specific biosystem (from REACTOME)
Regulation of TP53 Activity, organism-specific biosystemProtein stability and transcriptional activity of TP53 (p53) tumor suppressor are regulated by post-translational modifications that include ubiquitination, phosphorylation, acetylation, methylation,...
Regulation of TP53 Activity through Methylation, organism-specific biosystem (from REACTOME)
Regulation of TP53 Activity through Methylation, organism-specific biosystemTP53 (p53) undergoes methylation on several lysine and arginine residues, which modulates its transcriptional activity.PRMT5, recruited to TP53 as part of the ATM-activated complex that includes TTC5...
Regulation of TP53 Activity through Phosphorylation, organism-specific biosystem (from REACTOME)
Regulation of TP53 Activity through Phosphorylation, organism-specific biosystemPhosphorylation of TP53 (p53) at the N-terminal serine residues S15 and S20 plays a critical role in protein stabilization as phosphorylation at these sites interferes with binding of the ubiquitin l...
Regulation of TP53 Degradation, organism-specific biosystem (from REACTOME)
Regulation of TP53 Degradation, organism-specific biosystemIn unstressed cells, TP53 (p53) has a short half-life as it undergoes rapid ubiquitination and proteasome-mediated degradation. The E3 ubiquitin ligase MDM2, which is a transcriptional target of TP53...
Regulation of TP53 Expression and Degradation, organism-specific biosystem (from REACTOME)
Regulation of TP53 Expression and Degradation, organism-specific biosystemTP53 (p53) tumor suppressor protein is a transcription factor that functions as a homotetramer (Jeffrey et al. 1995). The protein levels of TP53 are low in unstressed cells due to MDM2-mediated ubiqu...
Stabilization of p53, organism-specific biosystem (from REACTOME)
Stabilization of p53, organism-specific biosystemLater studies pin-pointed that a single serine (Ser-15) was phosphorylated by ATM and phosphorylation of Ser-15 was rapidly-induced in IR-treated cells and this response was ATM-dependent (Canman et ...
Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...
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).
miRNA Regulation of DNA Damage Response, organism-specific biosystem (from WikiPathways)
miRNA Regulation of DNA Damage Response, organism-specific biosystemThis is the first out of two pathways which deals with the DNA damage response. It is comprised of two central gene products (ATM and ATR) influenced by different sources of DNA damage (in blue). The...
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-Dependent G1 DNA Damage Response, organism-specific biosystem (from REACTOME)
p53-Dependent G1 DNA Damage Response, organism-specific biosystemMost of the damage-induced modifications of p53 are dependent on the ATM kinase. The first link between ATM and p53 was predicted based on the earlier studies that showed that AT cells exhibit a redu...
p53-Dependent G1/S DNA damage checkpoint, organism-specific biosystem (from REACTOME)
p53-Dependent G1/S DNA damage checkpoint, organism-specific biosystemThe arrest at G1/S checkpoint is mediated by the action of a widely known tumor suppressor protein, p53. Loss of p53 functions, as a result of mutations in cancer prevent the G1/S checkpoint (Kuerbi...
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 ...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D22S275 (e-PCR)
- UniSTS:87591

PMC111029P1 (e-PCR)
- UniSTS:270202

PMC111029P10 (e-PCR)
- UniSTS:270203

PMC111029P12 (e-PCR)
- UniSTS:270205

PMC111029P13 (e-PCR)
- UniSTS:270206

PMC111029P14 (e-PCR)
- UniSTS:270207

PMC111029P2 (e-PCR)
- UniSTS:270208

PMC111029P3 (e-PCR)
- UniSTS:270209

PMC111029P4 (e-PCR)
- UniSTS:270210

PMC111029P5 (e-PCR)
- UniSTS:270211

PMC111029P6 (e-PCR)
- UniSTS:270212

PMC111029P7 (e-PCR)
- UniSTS:270213

PMC111029P8 (e-PCR)
- UniSTS:270214

PMC111029P9 (e-PCR)
- UniSTS:270215

PMC149355P2 (e-PCR)
- UniSTS:271033

Homology

Homologs of the CHEK2 gene: The CHEK2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, and frog.
Orthologs from Annotation Pipeline: 227 organisms have orthologs with human gene CHEK2
The Hierarchical Catalog of Orthologs

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
kinase activity	TAS Traceable Author Statement more info
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	IBA Inferred from Biological aspect of Ancestor 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
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest	TAS Traceable Author Statement more info
DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator	IEA Inferred from Electronic Annotation more info
G2/M transition of mitotic cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
cell division	IEA Inferred from Electronic Annotation more info
cellular protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
cellular response to DNA damage stimulus	IDA Inferred from Direct Assay 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
cellular response to bisphenol A	IEA Inferred from Electronic Annotation more info
cellular response to gamma radiation	IEA Inferred from Electronic Annotation more info
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
intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator	IEA Inferred from Electronic Annotation more info
mitotic DNA damage checkpoint	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitotic spindle assembly	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of DNA damage checkpoint	IEA Inferred from Electronic Annotation more info
negative regulation of cell cycle arrest	IEA Inferred from Electronic Annotation more info
positive regulation of anoikis	IEA Inferred from Electronic Annotation more info
positive regulation of protein phosphorylation	IEA Inferred from Electronic Annotation more info
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 apoptotic process	IBA Inferred from Biological aspect of Ancestor more info	PubMed
regulation of protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of signal transduction by p53 class mediator	TAS Traceable Author Statement more info
regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
replicative cell aging	IMP Inferred from Mutant Phenotype more info	PubMed
replicative senescence	NAS Non-traceable Author Statement more info	PubMed
response to glycoside	IEA Inferred from Electronic Annotation more info
signal transduction in response to DNA damage	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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
transcription, DNA-templated	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
Golgi apparatus	IDA Inferred from Direct Assay more info
PML body	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with chromosome, telomeric region	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase Chk2

Names: CHK2 checkpoint homolog; cds1 homolog; checkpoint-like protein CHK2

NP_001005735.1

EC 2.7.11.1

NP_001244316.1

EC 2.7.11.1

NP_001336885.1

EC 2.7.11.1

NP_009125.1

EC 2.7.11.1

NP_665861.1

EC 2.7.11.1

XP_006724177.2

EC 2.7.11.1

XP_006724179.2

EC 2.7.11.1

XP_011528141.1

EC 2.7.11.1

XP_011528142.1

EC 2.7.11.1

XP_011528143.1

EC 2.7.11.1

XP_011528144.1

EC 2.7.11.1

XP_011528146.1

EC 2.7.11.1

XP_011528147.1

EC 2.7.11.1

XP_016884049.1

EC 2.7.11.1

XP_016884050.1

EC 2.7.11.1

XP_024307916.1

EC 2.7.11.1

XP_024307917.1

EC 2.7.11.1

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

NG_008150.2 RefSeqGene

Range

5047..59124

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

See identical proteins and their annotated locations for 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

ENSP00000372023.2, OTTHUMP00000198970, ENST00000382580.6, OTTHUMT00000321016

Conserved Domains (3) summary

smart00220
Location:263 → 529

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd00060
Location:156 → 244

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 ...

cd14084
Location:256 → 529

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
NM_001257387.1 → NP_001244316.1 serine/threonine-protein kinase Chk2 isoform d

See identical proteins and their annotated locations for 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:3 → 265

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14084
Location:1 → 265

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
NM_001349956.1 → NP_001336885.1 serine/threonine-protein kinase Chk2 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an exon, and contains an alternate in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2) [is shorter/has a distinct C-terminus], compared to isoform a. The resulting isoform (e) has the same N- and C-termini but is shorter compared to isoform a.

Source sequence(s)

AF096279, AK290754, AW778747, BX393617

Conserved Domains (1) summary

cd14084
Location:162 → 419

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
NM_007194.4 → NP_009125.1 serine/threonine-protein kinase Chk2 isoform a

See identical proteins and their annotated locations for 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

ENSP00000329178.6, OTTHUMP00000198969, ENST00000328354.10

Conserved Domains (3) summary

smart00220
Location:220 → 486

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd00060
Location:93 → 201

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 ...

cd14084
Location:213 → 486

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
NM_145862.2 → NP_665861.1 serine/threonine-protein kinase Chk2 isoform b

See identical proteins and their annotated locations for 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

ENSP00000329012.5, ENST00000348295.7

Conserved Domains (4) summary

smart00220
Location:220 → 457

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1716
Location:116 → 199

FHA; Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]

cd00060
Location:93 → 201

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 ...

cl21453
Location:213 → 457

PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

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

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000022.11 Reference GRCh38.p12 Primary Assembly

Range

28687743..28741866 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011529845.2 → XP_011528147.1 serine/threonine-protein kinase Chk2 isoform X11

See identical proteins and their annotated locations for XP_011528147.1

UniProtKB/Swiss-Prot

O96017

Conserved Domains (2) summary

smart00220
Location:3 → 265

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14084
Location:1 → 265

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
XM_011529841.1 → XP_011528143.1 serine/threonine-protein kinase Chk2 isoform X6

Conserved Domains (2) summary

smart00220
Location:205 → 462

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14084
Location:205 → 462

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
XM_011529840.3 → XP_011528142.1 serine/threonine-protein kinase Chk2 isoform X3

Conserved Domains (4) summary

smart00220
Location:273 → 510

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1716
Location:123 → 252

FHA; Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]

cd00060
Location:166 → 254

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 ...

cl21453
Location:266 → 510

PKc_like; Protein Kinases, catalytic domain
XM_017028560.1 → XP_016884049.1 serine/threonine-protein kinase Chk2 isoform X2
XM_011529839.2 → XP_011528141.1 serine/threonine-protein kinase Chk2 isoform X1

Conserved Domains (3) summary

smart00220
Location:273 → 539

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd00060
Location:166 → 254

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 ...

cd14084
Location:266 → 539

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
XM_011529842.2 → XP_011528144.1 serine/threonine-protein kinase Chk2 isoform X7

Conserved Domains (2) summary

smart00220
Location:172 → 429

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14084
Location:172 → 429

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
XM_024452149.1 → XP_024307917.1 serine/threonine-protein kinase Chk2 isoform X5

Conserved Domains (2) summary

cd00060
Location:103 → 211

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 ...

cl21453
Location:223 → 467

PKc_like; Protein Kinases, catalytic domain
XM_024452148.1 → XP_024307916.1 serine/threonine-protein kinase Chk2 isoform X4

Conserved Domains (2) summary

cd00060
Location:103 → 211

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 ...

cd14084
Location:223 → 496

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
XM_017028561.2 → XP_016884050.1 serine/threonine-protein kinase Chk2 isoform X11

UniProtKB/Swiss-Prot

O96017

Related

ENSP00000416721.1, OTTHUMP00000199064, ENST00000434810.5

Conserved Domains (2) summary

smart00220
Location:3 → 265

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14084
Location:1 → 265

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
XM_006724114.3 → XP_006724177.2 serine/threonine-protein kinase Chk2 isoform X9
XM_006724116.2 → XP_006724179.2 serine/threonine-protein kinase Chk2 isoform X10

Conserved Domains (2) summary

smart00220
Location:46 → 305

S_TKc; Serine/Threonine protein kinases, catalytic domain

cd14084
Location:39 → 305

STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
XM_011529844.2 → XP_011528146.1 serine/threonine-protein kinase Chk2 isoform X8

Conserved Domains (4) summary

smart00220
Location:273 → 390

S_TKc; Serine/Threonine protein kinases, catalytic domain

COG1716
Location:123 → 252

FHA; Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]

cd00060
Location:166 → 254

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 ...

cl21453
Location:266 → 390

PKc_like; Protein Kinases, catalytic domain