CHEK2
Serine/threonine-protein kinase Chk2
Also known as: bA444G7, CDS1, CHK2, CHK2_HUMAN, HuCds1, PP1425, RAD53
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- O96017
- Gene
- CHEK2
- Ensembl
- ENSG00000183765
- Chromosome
- 22
- Canonical length
- 543 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins
- Subcellular location
- Nucleoplasm,Golgi apparatus
- Quaternary structure
- Homodimer
OverviewNCBI Gene
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]
Canonical amino-acid sequenceUniProt
543 residues, UniProt reviewed canonical sequence.
>O96017|CHEK2
1 MSRESDVEAQ QSHGSSACSQ PHGSVTQSQG SSSQSQGISS SSTSTMPNSS QSSHSSSGTL
61 SSLETVSTQE LYSIPEDQEP EDQEPEEPTP APWARLWALQ DGFANLECVN DNYWFGRDKS
121 CEYCFDEPLL KRTDKYRTYS KKHFRIFREV GPKNSYIAYI EDHSGNGTFV NTELVGKGKR
181 RPLNNNSEIA LSLSRNKVFV FFDLTVDDQS VYPKALRDEY IMSKTLGSGA CGEVKLAFER
241 KTCKKVAIKI ISKRKFAIGS AREADPALNV ETEIEILKKL NHPCIIKIKN FFDAEDYYIV
301 LELMEGGELF DKVVGNKRLK EATCKLYFYQ MLLAVQYLHE NGIIHRDLKP ENVLLSSQEE
361 DCLIKITDFG HSKILGETSL MRTLCGTPTY LAPEVLVSVG TAGYNRAVDC WSLGVILFIC
421 LSGYPPFSEH RTQVSLKDQI TSGKYNFIPE VWAEVSEKAL DLVKKLLVVD PKARFTTEEA
481 LRHPWLQDED MKRKFQDLLS EENESTALPQ VLAQPSTSRK RPREGEAEGA ETTKRPAVCA
541 AVLLocalizationUniProt · AlphaFold · HPA
Whether an antibody against CHEK2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Intracellular
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.38
- Highest tissue expression
- 15 nTPM
Expression across tissuesHPA
Tissue
- bone marrow: 15 nTPM
- lymph node: 11 nTPM
- tonsil: 11 nTPM
- rectum: 10 nTPM
- thymus: 8.9 nTPM
- ovary: 8.5 nTPM
Single-cell type
- decidual stromal cells: 68 nCPM
- megakaryocyte progenitors: 47 nCPM
- monocyte progenitors: 42 nCPM
- erythrocyte progenitors: 40 nCPM
- epicardial cells: 36 nCPM
- undifferentiated spermatogonia: 34 nCPM
Immune cell
- memory B-cell: 12 nTPM
- basophil: 10 nTPM
- intermediate monocyte: 8.3 nTPM
- myeloid DC: 8.2 nTPM
- naive B-cell: 8.1 nTPM
- plasmacytoid DC: 6.2 nTPM
Brain region
- white matter: 2.8 nTPM
- choroid plexus: 2.6 nTPM
- hypothalamus: 2.6 nTPM
- pons: 2.6 nTPM
- thalamus: 2.6 nTPM
- medulla oblongata: 2.4 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about CHEK2.
Disease | AllUniProt
Conditions CHEK2 is implicated in, by any mechanism.
- Tumor predisposition syndrome 4 (TPDS4) MIM:609265
- Prostate cancer (PC) MIM:176807
- Osteogenic sarcoma (OSRC) MIM:259500
- Breast cancer (BC) MIM:114480
Disease | GeneticClinVar
1,081 pathogenic / likely-pathogenic of 4,609 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- Familial cancer of breast
- Hereditary cancer-predisposing syndrome
- CHEK2-related cancer predisposition
- Hereditary breast ovarian cancer syndrome
- Bone osteosarcoma
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 1.53
- gnomAD pLI
- 0
- gnomAD missense Z
- -0.45
- DepMap mean gene effect
- 0.17
- DepMap dependency class
- none
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 6% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- cell division
- cellular response to bisphenol A
- cellular response to gamma radiation
- cellular response to stress
- cellular response to xenobiotic stimulus
- DNA damage checkpoint signaling
- DNA damage response
- DNA damage response, signal transduction by p53 class mediator
- double-strand break repair
- G2/M transition of mitotic cell cycle
- intrinsic apoptotic signaling pathway in response to DNA damage
- intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
- mitotic DNA damage checkpoint signaling
- mitotic intra-S DNA damage checkpoint signaling
- mitotic spindle assembly
- negative regulation of DNA damage checkpoint
- positive regulation of anoikis
- positive regulation of DNA-templated transcription
- protein autophosphorylation
- protein catabolic process
- protein phosphorylation
- protein stabilization
- regulation of autophagosome assembly
- regulation of DNA-templated transcription
- regulation of protein catabolic process
- regulation of signal transduction by p53 class mediator
- replicative senescence
- response to glycoside
- signal transduction in response to DNA damage
- thymocyte apoptotic process
Molecular functions
- ATP binding
- identical protein binding
- metal ion binding
- protein homodimerization activity
- protein kinase binding
- protein serine kinase activity
- protein serine/threonine kinase activity
- ubiquitin protein ligase binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of CHEK2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads CHEK2 as an antibody target. Whether an autoantibody or antibody against CHEK2 could matter depends on whether native CHEK2 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
CHEK2 is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.
Annotation status
The present source text does not explicitly label CHEK2 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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