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CHEK2 checkpoint kinase 2 [ Homo sapiens (human) ]

Gene ID: 11200, updated on 29-Nov-2020

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
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

Genomic context

See CHEK2 in Genome Data Viewer
Location:
22q12.1
Exon count:
22
Annotation release Status Assembly Chr Location
109.20201120 current GRCh38.p13 (GCF_000001405.39) 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_000022.11Genomic Context describing neighboring genes Neighboring gene tetratricopeptide repeat domain 28 Neighboring gene Sharpr-MPRA regulatory region 11195 Neighboring gene RNA, 7SL, cytoplasmic 162, pseudogene Neighboring gene coiled-coil domain containing 117 Neighboring gene HscB mitochondrial iron-sulfur cluster cochaperone

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
A genome-wide association study of optic disc parameters.
GeneReviews: Not available
A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma.
GeneReviews: Not available
Familial cancer of breast not available
Genetic variants associated with breast size also influence breast cancer risk.
GeneReviews: Not available
Genome-wide association analyses of esophageal squamous cell carcinoma in Chinese identify multiple susceptibility loci and gene-environment interactions.
GeneReviews: Not available
Genome-wide association study identifies multiple susceptibility loci for pancreatic cancer.
GeneReviews: Not available
Joint analysis of three genome-wide association studies of esophageal squamous cell carcinoma in Chinese populations.
GeneReviews: Not available
Large-scale genotyping identifies 41 new loci associated with breast cancer risk.
GeneReviews: Not available
Li-Fraumeni syndrome 2
MedGen: C1836482 OMIM: 609265 GeneReviews: Not available
not available
Malignant tumor of prostate
MedGen: C0376358 OMIM: 176807 GeneReviews: Not available
not available
Meta-analysis of genome-wide association studies identifies novel loci that influence cupping and the glaucomatous process.
GeneReviews: Not available
Osteosarcoma
MedGen: C0029463 OMIM: 259500 GeneReviews: Not available
not available
Rare variants of large effect in BRCA2 and CHEK2 affect risk of lung cancer.
GeneReviews: Not available

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2020-01-08)

ClinGen Genome Curation Page
Haploinsufficency

Sufficient evidence for dosage pathogenicity (Last evaluated (2020-01-08)

ClinGen Genome Curation PagePubMed

HIV-1 interactions

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 PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

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 
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 kinase activity IEA
Inferred from Electronic Annotation
more info
 
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 
protein threonine kinase activity IEA
Inferred from Electronic Annotation
more info
 
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
 
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 drug 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 
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
 
peptidyl-serine phosphorylation 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 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 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 
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

Preferred Names
serine/threonine-protein kinase Chk2
Names
CHK2 checkpoint homolog
cds1 homolog
checkpoint-like protein CHK2
NP_001005735.1
NP_001244316.1
NP_001336885.1
NP_009125.1
NP_665861.1
XP_006724177.2
XP_006724179.2
XP_011528141.1
XP_011528142.1
XP_011528143.1
XP_011528144.1
XP_011528146.1
XP_011528147.1
XP_016884049.1
XP_016884050.1
XP_024307916.1
XP_024307917.1

NCBI Reference Sequences (RefSeq)

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_008150.2 RefSeqGene

    Range
    5047..59124
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001005735.2NP_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, ENST00000382580.6
    Conserved Domains (3) summary
    smart00220
    Location:263529
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    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 ...
    cd14084
    Location:256529
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  2. NM_001257387.2NP_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:3265
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14084
    Location:1265
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  3. NM_001349956.2NP_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:162419
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  4. NM_007194.4NP_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
    ENSP00000385747.1, ENST00000404276.6
    Conserved Domains (3) summary
    smart00220
    Location:220486
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    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 ...
    cd14084
    Location:213486
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  5. NM_145862.2NP_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:220457
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1716
    Location:116199
    FHA; Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [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 ...
    cl21453
    Location:213457
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20201120

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

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p13 Primary Assembly

    Range
    28687743..28741866 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011529845.2XP_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:3265
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14084
    Location:1265
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  2. XM_011529841.1XP_011528143.1  serine/threonine-protein kinase Chk2 isoform X6

    Conserved Domains (2) summary
    smart00220
    Location:205462
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14084
    Location:205462
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  3. XM_011529840.3XP_011528142.1  serine/threonine-protein kinase Chk2 isoform X3

    Conserved Domains (4) summary
    smart00220
    Location:273510
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1716
    Location:123252
    FHA; Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]
    cd00060
    Location:166254
    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:266510
    PKc_like; Protein Kinases, catalytic domain
  4. XM_017028560.1XP_016884049.1  serine/threonine-protein kinase Chk2 isoform X2

  5. XM_011529839.2XP_011528141.1  serine/threonine-protein kinase Chk2 isoform X1

    Conserved Domains (3) summary
    smart00220
    Location:273539
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd00060
    Location:166254
    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:266539
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  6. XM_011529842.2XP_011528144.1  serine/threonine-protein kinase Chk2 isoform X7

    Conserved Domains (2) summary
    smart00220
    Location:172429
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14084
    Location:172429
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  7. XM_024452149.1XP_024307917.1  serine/threonine-protein kinase Chk2 isoform X5

    Conserved Domains (2) summary
    cd00060
    Location:103211
    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:223467
    PKc_like; Protein Kinases, catalytic domain
  8. XM_024452148.1XP_024307916.1  serine/threonine-protein kinase Chk2 isoform X4

    Conserved Domains (2) summary
    cd00060
    Location:103211
    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:223496
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  9. XM_017028561.2XP_016884050.1  serine/threonine-protein kinase Chk2 isoform X11

    UniProtKB/Swiss-Prot
    O96017
    Related
    ENSP00000496928.1, ENST00000649563.1
    Conserved Domains (2) summary
    smart00220
    Location:3265
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14084
    Location:1265
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  10. XM_006724114.3XP_006724177.2  serine/threonine-protein kinase Chk2 isoform X9

    Related
    ENST00000648295.1
  11. XM_006724116.2XP_006724179.2  serine/threonine-protein kinase Chk2 isoform X10

    Conserved Domains (2) summary
    smart00220
    Location:46305
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    cd14084
    Location:39305
    STKc_Chk2; Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2
  12. XM_011529844.2XP_011528146.1  serine/threonine-protein kinase Chk2 isoform X8

    Conserved Domains (4) summary
    smart00220
    Location:273390
    S_TKc; Serine/Threonine protein kinases, catalytic domain
    COG1716
    Location:123252
    FHA; Forkhead associated (FHA) domain, binds pSer, pThr, pTyr [Signal transduction mechanisms]
    cd00060
    Location:166254
    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:266390
    PKc_like; Protein Kinases, catalytic domain

RNA

  1. XR_937805.2 RNA Sequence

    Related
    ENST00000433728.5
  2. XR_937806.2 RNA Sequence

  3. XR_937807.2 RNA Sequence

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