Skip Header

Contribute Send feedback
Read comments (?) or add your own

O96017 (CHK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase Chk2
EC=2.7.11.1
Alternative name(s):
CHK2 checkpoint homolog
Cds1 homolog
Short name=Hucds1
Short name=hCds1
Checkpoint kinase 2
Gene names
Name:CHEK2
Synonyms:CDS1, CHK2, RAD53
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length543 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X-R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. Ref.1 Ref.2 Ref.3 Ref.14 Ref.17 Ref.20 Ref.22 Ref.23 Ref.24 Ref.27 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.37

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme regulation

Activated through phosphorylation at Thr-68 by ATM in response to DNA double-strand breaks. Activation is modulated by several mediators including MDC1 and TP53BP1. Induces homodimerization with exchange of the T-loop/activation segment between protomers and transphosphorylation of the protomers. The autophosphorylated kinase dimer is fully active. Negatively regulated by PPM1D through dephosphorylation of Thr-68. Ref.26

Subunit structure

Homodimer. Homodimerization is part of the activation process but the dimer may dissociate following activation. Interacts with PML. Interacts with TP53. Interacts with RB1; phosphorylates RB1. Interacts with BRCA1. Interacts (phosphorylated at Thr-68) with MDC1; requires ATM-mediated phosphorylation of CHEK2. Interacts with TP53BP1; modulates CHEK2 phosphorylation at Thr-68 in response to ionizing radiation. Interacts with CDC25A; phosphorylates CDC25A and mediates its degradation in response to ionizing radiation. Interacts with CUL1; mediates CHEK2 ubiquitination and regulation. Ref.14 Ref.17 Ref.19 Ref.21 Ref.22 Ref.24 Ref.34 Ref.42

Subcellular location

Isoform 2: Nucleus Ref.4 Ref.20 Ref.22. Note: Isoform 10 is present throughout the cell. Ref.4 Ref.20 Ref.22

Isoform 4: Nucleus Ref.4 Ref.20 Ref.22.

Isoform 7: Nucleus Ref.4 Ref.20 Ref.22.

Isoform 9: Nucleus Ref.4 Ref.20 Ref.22.

Isoform 12: Nucleus Ref.4 Ref.20 Ref.22.

Nucleus › PML body. Nucleus › nucleoplasm. Note: Recruited into PML bodies together with TP53. Ref.4 Ref.20 Ref.22

Tissue specificity

High expression is found in testis, spleen, colon and peripheral blood leukocytes. Low expression is found in other tissues.

Post-translational modification

Phosphorylated. Phosphorylated at Ser-73 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-68 by ATM and the G2/M transition checkpoint. Phosphorylation at Thr-68 induces homodimerization. Autophosphorylates at Thr-383 and Thr-387 in the T-loop/activation segment upon dimerization to become fully active and phosphorylate its substrates like for instance CDC25C. DNA damage-induced autophosphorylation at Ser-379 induces CUL1-mediated ubiquitination and regulates the pro-apoptotic function. Phosphorylation at Ser-456 also regulates ubiquitination. Phosphorylated by PLK4. Ref.15 Ref.16 Ref.19 Ref.26 Ref.28 Ref.29 Ref.31 Ref.34 Ref.36 Ref.42

Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination. Ref.31 Ref.34 Ref.40

Involvement in disease

Li-Fraumeni syndrome 2 (LFS2) [MIM:609265]: A highly penetrant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.46

Prostate cancer (PC) [MIM:176807]: A malignancy originating in tissues of the prostate. Most prostate cancers are adenocarcinomas that develop in the acini of the prostatic ducts. Other rare histopathologic types of prostate cancer that occur in approximately 5% of patients include small cell carcinoma, mucinous carcinoma, prostatic ductal carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell carcinoma and neuroendocrine carcinoma.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry.

Osteogenic sarcoma (OSRC) [MIM:259500]: A sarcoma originating in bone-forming cells, affecting the ends of long bones.
Note: The gene represented in this entry may be involved in disease pathogenesis.

Breast cancer (BC) [MIM:114480]: A common malignancy originating from breast epithelial tissue. Breast neoplasms can be distinguished by their histologic pattern. Invasive ductal carcinoma is by far the most common type. Breast cancer is etiologically and genetically heterogeneous. Important genetic factors have been indicated by familial occurrence and bilateral involvement. Mutations at more than one locus can be involved in different families or even in the same case.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry (Ref.18). Ref.18 Ref.39

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. CHK2 subfamily.

Contains 1 FHA domain.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processApoptosis
Cell cycle
Cell division
DNA damage
DNA repair
Mitosis
Transcription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Li-Fraumeni syndrome
Tumor suppressor
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA damage induced protein phosphorylation

Inferred from mutant phenotype Ref.17. Source: UniProtKB

G2/M transition of mitotic cell cycle

Inferred from mutant phenotype Ref.29. Source: UniProtKB

cell division

Inferred from electronic annotation. Source: UniProtKB-KW

cellular protein catabolic process

Inferred from mutant phenotype Ref.17. Source: UniProtKB

double-strand break repair

Inferred from mutant phenotype Ref.35. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to DNA damage

Inferred from direct assay Ref.20. Source: UniProtKB

positive regulation of transcription, DNA-dependent

Inferred from direct assay Ref.32. Source: UniProtKB

protein autophosphorylation

Inferred from direct assay Ref.42Ref.34. Source: UniProtKB

regulation of protein catabolic process

Inferred from mutant phenotype Ref.32. Source: UniProtKB

replicative senescence

Non-traceable author statement PubMed 15149599. Source: BHF-UCL

response to gamma radiation

Inferred from electronic annotation. Source: Compara

signal transduction involved in intra-S DNA damage checkpoint

Inferred from mutant phenotype Ref.17. Source: UniProtKB

spindle assembly involved in mitosis

Inferred from mutant phenotype Ref.37. Source: UniProtKB

transcription, DNA-dependent

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentPML body

Inferred from direct assay Ref.20. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein homodimerization activity

Inferred from direct assay Ref.42. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay Ref.42. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 13 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O96017-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O96017-2)

Also known as: ins2;

The sequence of this isoform differs from the canonical sequence as follows:
     198-224: VFVFFDLTVDDQSVYPKALRDEYIMSK → EKILKIYSLSRFSKIRRGAVAHVFNPS
     228-234: SGACGEV → GRGWQIT
     235-543: Missing.
Note: Lacks enzymatic activity.
Isoform 3 (identifier: O96017-3)

Also known as: del2-12;

The sequence of this isoform differs from the canonical sequence as follows:
     107-487: Missing.
Isoform 4 (identifier: O96017-4)

Also known as: del2-3;

The sequence of this isoform differs from the canonical sequence as follows:
     107-197: Missing.
Note: Lacks enzymatic activity.
Isoform 5 (identifier: O96017-5)

Also known as: del4;

The sequence of this isoform differs from the canonical sequence as follows:
     199-203: FVFFD → VPVER
     204-543: Missing.
Isoform 6 (identifier: O96017-6)

Also known as: sub3;

The sequence of this isoform differs from the canonical sequence as follows:
     150-165: VGPKNSYIAYIEDHSG → ENLSCPYRIWFNFCLF
     166-543: Missing.
Isoform 7 (identifier: O96017-7)

Also known as: del9-12;

The sequence of this isoform differs from the canonical sequence as follows:
     337-339: YLH → MKT
     340-543: Missing.
Note: Lacks enzymatic activity.
Isoform 8 (identifier: O96017-8)

Also known as: del7;

The sequence of this isoform differs from the canonical sequence as follows:
     283-289: PCIIKIK → DGRGRAV
     290-543: Missing.
Isoform 9 (identifier: O96017-9)

Also known as: insx;

The sequence of this isoform differs from the canonical sequence as follows:
     107-107: E → ETESGHVTQSDLELLLSSDPPASASQSAGIRGVRHHPRPVCSLK
Note: Retains low level of catalytic activity.
Isoform 10 (identifier: O96017-10)

Also known as: iso2;

The sequence of this isoform differs from the canonical sequence as follows:
     131-147: KRTDKYRTYSKKHFRIF → EFRSYSFYLP
     148-543: Missing.
Note: Lacks enzymatic activity.
Isoform 11 (identifier: O96017-11)

Also known as: iso1;

The sequence of this isoform differs from the canonical sequence as follows:
     75-392: Missing.
Isoform 12 (identifier: O96017-12)

Also known as: del9;

The sequence of this isoform differs from the canonical sequence as follows:
     337-365: Missing.
Note: Lacks enzymatic activity.
Isoform 13 (identifier: O96017-13)

The sequence of this isoform differs from the canonical sequence as follows:
     1-221: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 543543Serine/threonine-protein kinase Chk2
PRO_0000085858

Regions

Domain113 – 17563FHA
Domain220 – 486267Protein kinase
Nucleotide binding227 – 2348ATP
Nucleotide binding302 – 3087ATP
Nucleotide binding351 – 3522ATP
Region368 – 39427T-loop/activation segment

Sites

Active site3471Proton acceptor
Binding site2491ATP
Binding site3681ATP

Amino acid modifications

Modified residue621Phosphoserine; by PLK3 Ref.29
Modified residue681Phosphothreonine; by ATM and MLTK Ref.26 Ref.28 Ref.29
Modified residue731Phosphoserine; by PLK3 Ref.29
Modified residue3791Phosphoserine; by autocatalysis Ref.34
Modified residue3831Phosphothreonine; by autocatalysis Ref.16
Modified residue3871Phosphothreonine; by autocatalysis Ref.16
Modified residue4561Phosphoserine Ref.31

Natural variations

Alternative sequence1 – 221221Missing in isoform 13.
VSP_045148
Alternative sequence75 – 392318Missing in isoform 11.
VSP_014556
Alternative sequence107 – 487381Missing in isoform 3.
VSP_014559
Alternative sequence107 – 19791Missing in isoform 4.
VSP_014558
Alternative sequence1071E → ETESGHVTQSDLELLLSSDP PASASQSAGIRGVRHHPRPV CSLK in isoform 9.
VSP_014557
Alternative sequence131 – 14717KRTDK…HFRIF → EFRSYSFYLP in isoform 10.
VSP_014560
Alternative sequence148 – 543396Missing in isoform 10.
VSP_014561
Alternative sequence150 – 16516VGPKN…EDHSG → ENLSCPYRIWFNFCLF in isoform 6.
VSP_014562
Alternative sequence166 – 543378Missing in isoform 6.
VSP_014563
Alternative sequence198 – 22427VFVFF…YIMSK → EKILKIYSLSRFSKIRRGAV AHVFNPS in isoform 2.
VSP_014564
Alternative sequence199 – 2035FVFFD → VPVER in isoform 5.
VSP_014565
Alternative sequence204 – 543340Missing in isoform 5.
VSP_014566
Alternative sequence228 – 2347SGACGEV → GRGWQIT in isoform 2.
VSP_014567
Alternative sequence235 – 543309Missing in isoform 2.
VSP_014568
Alternative sequence283 – 2897PCIIKIK → DGRGRAV in isoform 8.
VSP_014569
Alternative sequence290 – 543254Missing in isoform 8.
VSP_014570
Alternative sequence337 – 36529Missing in isoform 12.
VSP_014571
Alternative sequence337 – 3393YLH → MKT in isoform 7.
VSP_014572
Alternative sequence340 – 543204Missing in isoform 7.
VSP_014573
Natural variant171A → S in an osteogenic sarcoma sample; somatic mutation; might influence susceptibility to breast cancer; does not cause protein abrogation in familial colorectal cancer. Ref.49
VAR_019101
Natural variant591T → K in multiple cancers. Ref.47
VAR_026630
Natural variant641E → K in prostate cancer; somatic mutation. Ref.50
VAR_019107
Natural variant851P → L in an osteogenic sarcoma sample; neutral allele among Ashkenazi Jewish women. Ref.10 Ref.49 Ref.58
Corresponds to variant rs17883862 [ dbSNP | Ensembl ].
VAR_019102
Natural variant1171R → G. Ref.48 Ref.51 Ref.60
Corresponds to variant rs28909982 [ dbSNP | Ensembl ].
VAR_022461
Natural variant1371R → Q Might influence susceptibility to breast cancer; does not cause protein abrogation in familial colorectal cancer. Ref.48 Ref.60
VAR_022462
Natural variant1451R → P in prostate cancer; somatic mutation. Ref.50
VAR_019108
Natural variant1451R → W in colon cancer and LFS2; does not cause protein abrogation in familial colorectal cancer; loss of the ability to interact with and phosphorylate CDC25A and to promote CDC25A degradation in response to ionizing radiation. Ref.17 Ref.44 Ref.46 Ref.51 Ref.54 Ref.60
VAR_008554
Natural variant1571I → T Might influence susceptibility to different types of cancer; does not cause protein abrogation in familial colorectal cancer; loss of the ability to interact with and phosphorylate CDC25A and to promote CDC25A degradation in response to ionizing radiation. Ref.10 Ref.17 Ref.44 Ref.45 Ref.50 Ref.51 Ref.52 Ref.53 Ref.54 Ref.55 Ref.56 Ref.57 Ref.59 Ref.60
Corresponds to variant rs17879961 [ dbSNP | Ensembl ].
VAR_008555
Natural variant1671G → R in prostate cancer; somatic mutation. Ref.50
VAR_019109
Natural variant1801R → C in prostate cancer; somatic mutation. Ref.39 Ref.50
Corresponds to variant rs77130927 [ dbSNP | Ensembl ].
VAR_019103
Natural variant1801R → H in prostate cancer; somatic mutation. Ref.48 Ref.50 Ref.60
Corresponds to variant rs137853009 [ dbSNP | Ensembl ].
VAR_019110
Natural variant1811R → C in prostate cancer; somatic mutation. Ref.50
Corresponds to variant rs137853010 [ dbSNP | Ensembl ].
VAR_019104
Natural variant1811R → H in prostate cancer; somatic mutation. Ref.50
Corresponds to variant rs121908701 [ dbSNP | Ensembl ].
VAR_019105
Natural variant2391E → K in prostate cancer; germline mutation. Ref.50
VAR_019106
Natural variant2511I → F in prostate cancer; germline mutation. Ref.50
VAR_019111
Natural variant3181R → H in prostate cancer; somatic mutation. Ref.50
Corresponds to variant rs143611747 [ dbSNP | Ensembl ].
VAR_019112
Natural variant3231T → P in prostate cancer; somatic mutation. Ref.50
VAR_019113
Natural variant3271Y → C in prostate cancer; somatic mutation. Ref.50
VAR_019114
Natural variant3471D → N.
Corresponds to variant rs28909980 [ dbSNP | Ensembl ].
VAR_029154
Natural variant3711H → Y Confers a moderate risk of breast cancer; partially reduces kinase activity. Ref.39
VAR_066012
Natural variant4061R → H.
Corresponds to variant rs299671 [ dbSNP | Ensembl ].
VAR_024572
Natural variant4281S → F May increase breast cancer risk. Ref.58
Corresponds to variant rs137853011 [ dbSNP | Ensembl ].
VAR_022463
Natural variant4361L → M. Ref.10
Corresponds to variant rs17882922 [ dbSNP | Ensembl ].
VAR_021117
Natural variant4461N → K. Ref.10
Corresponds to variant rs17880867 [ dbSNP | Ensembl ].
VAR_021118
Natural variant4471F → I. Ref.10
Corresponds to variant rs17881473 [ dbSNP | Ensembl ].
VAR_021119
Natural variant4481I → S. Ref.10
Corresponds to variant rs17886163 [ dbSNP | Ensembl ].
VAR_021120
Natural variant4761T → K in prostate cancer; somatic mutation. Ref.50
VAR_019115
Natural variant5001S → C.
Corresponds to variant rs28909981 [ dbSNP | Ensembl ].
VAR_029155
Natural variant5011E → K. Ref.10
Corresponds to variant rs17883172 [ dbSNP | Ensembl ].
VAR_021121
Natural variant5121L → V. Ref.10
Corresponds to variant rs17882942 [ dbSNP | Ensembl ].
VAR_021122

Experimental info

Mutagenesis681T → A: Loss of activation and phosphorylation. Ref.19 Ref.26
Mutagenesis731S → A: Impaired activation, phosphorylation by ATM and G2/M transition checkpoint. Ref.29
Mutagenesis3471D → A: Loss of kinase activity and of the ability to phosphorylate CDC25A. Ref.1 Ref.17
Mutagenesis3681D → N: Loss of autophosphorylation activity. Ref.26
Mutagenesis3791S → A: Abrogates autophosphorylation at Ser-379 and prevents ubiquitination. Ref.34
Mutagenesis3831T → A: Loss of phosphorylation in response to ionizing radiation. Ref.16
Mutagenesis3871T → A: Loss of phosphorylation in response to ionizing radiation. Ref.16
Mutagenesis4561S → A: Increased ubiquitination and degradation by the proteasome. Ref.31

Secondary structure

1 .................................................................................. 543
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 28890ACF3C1F3408

FASTA54360,915
        10         20         30         40         50         60 
MSRESDVEAQ QSHGSSACSQ PHGSVTQSQG SSSQSQGISS SSTSTMPNSS QSSHSSSGTL 

        70         80         90        100        110        120 
SSLETVSTQE LYSIPEDQEP EDQEPEEPTP APWARLWALQ DGFANLECVN DNYWFGRDKS 

       130        140        150        160        170        180 
CEYCFDEPLL KRTDKYRTYS KKHFRIFREV GPKNSYIAYI EDHSGNGTFV NTELVGKGKR 

       190        200        210        220        230        240 
RPLNNNSEIA LSLSRNKVFV FFDLTVDDQS VYPKALRDEY IMSKTLGSGA CGEVKLAFER 

       250        260        270        280        290        300 
KTCKKVAIKI ISKRKFAIGS AREADPALNV ETEIEILKKL NHPCIIKIKN FFDAEDYYIV 

       310        320        330        340        350        360 
LELMEGGELF DKVVGNKRLK EATCKLYFYQ MLLAVQYLHE NGIIHRDLKP ENVLLSSQEE 

       370        380        390        400        410        420 
DCLIKITDFG HSKILGETSL MRTLCGTPTY LAPEVLVSVG TAGYNRAVDC WSLGVILFIC 

       430        440        450        460        470        480 
LSGYPPFSEH RTQVSLKDQI TSGKYNFIPE VWAEVSEKAL DLVKKLLVVD PKARFTTEEA 

       490        500        510        520        530        540 
LRHPWLQDED MKRKFQDLLS EENESTALPQ VLAQPSTSRK RPREGEAEGA ETTKRPAVCA 


AVL

« Hide

Isoform 2 (ins2) [UniParc].

Checksum: 46766F331DD13DA8
Show »

FASTA23426,084
Isoform 3 (del2-12) [UniParc].

Checksum: D3BF7E0BC0DB0EC1
Show »

FASTA16217,370
Isoform 4 (del2-3) [UniParc].

Checksum: 96F7C353E4F3C85B
Show »

FASTA45250,203
Isoform 5 (del4) [UniParc].

Checksum: 9D1ED8844633607E
Show »

FASTA20322,594
Isoform 6 (sub3) [UniParc].

Checksum: 795CC81539178CF0
Show »

FASTA16518,706
Isoform 7 (del9-12) [UniParc].

Checksum: CAE0E58DF0308393
Show »

FASTA33938,125
Isoform 8 (del7) [UniParc].

Checksum: 630D0AF3AE5114E6
Show »

FASTA28932,142
Isoform 9 (insx) [UniParc].

Checksum: 55BDE42C9A0F98A7
Show »

FASTA58665,419
Isoform 10 (iso2) [UniParc].

Checksum: 54BBB0152B5668D5
Show »

FASTA14015,420
Isoform 11 (iso1) [UniParc].

Checksum: 57F0155780C96BA2
Show »

FASTA22524,396
Isoform 12 (del9) [UniParc].

Checksum: 8B99B81830B8092F
Show »

FASTA51457,526
Isoform 13 [UniParc].

Checksum: D31257F4B9652438
Show »

FASTA32236,157

References

« Hide 'large scale' references
[1]"Linkage of ATM to cell cycle regulation by the Chk2 protein kinase."
Matsuoka S., Huang M., Elledge S.J.
Science 282:1893-1897(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN PHOSPHORYLATION OF CDC25C, MUTAGENESIS OF ASP-347.
[2]"A human homologue of the checkpoint kinase Cds1 directly inhibits Cdc25 phosphatase."
Blasina A., van de Weyer I., Laus M.C., Luyten W.H.M.L., Parker A.E., McGowan C.H.
Curr. Biol. 9:1-10(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN MITOSIS.
[3]"A human Cds1-related kinase that functions downstream of ATM protein in the cellular response to DNA damage."
Brown A.L., Lee C.-H., Schwarz J.K., Mitiku N., Piwnica-Worms H., Chung J.H.
Proc. Natl. Acad. Sci. U.S.A. 96:3745-3750(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION IN PHOSPHORYLATION OF CDC25C.
[4]"Alternative splicing and mutation status of CHEK2 in stage III breast cancer."
Staalesen V., Falck J., Geisler S., Bartkova J., Boerresen-Dale A.-L., Lukas J., Lillehaug J.R., Bartek J., Lonning P.E.
Oncogene 23:8535-8544(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3; 4; 5; 6; 7; 8; 9; 10; 11 AND 12), SUBCELLULAR LOCATION.
Tissue: Mammary gland.
[5]"A genome annotation-driven approach to cloning the human ORFeome."
Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I.
Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 9).
[6]"Chk2/HuCds1 cell cycle checkpoint protein kinase from human colon carcinoma HT29 cells: regulation by autophosphorylation and DNA-dependent protein kinase and inhibition by cell cycle regulatory drugs."
Shao R.-G., Zhang H., Yu Q., Pommier Y.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Colon carcinoma.
[7]"An alternative spliced Chk2."
Ogawa A., Okabe-Nakamura A.
Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 12).
Tissue: T-cell.
[8]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[9]"Large-scale cDNA transfection screening for genes related to cancer development and progression."
Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X. expand/collapse author list , Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.
Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 13).
[10]NIEHS SNPs program
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-85; THR-157; MET-436; LYS-446; ILE-447; SER-448; LYS-501 AND VAL-512.
[11]"The DNA sequence of human chromosome 22."
Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. expand/collapse author list , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H.
Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[12]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[13]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Muscle.
[14]"hCds1-mediated phosphorylation of BRCA1 regulates the DNA damage response."
Lee J.S., Collins K.M., Brown A.L., Lee C.H., Chung J.H.
Nature 404:201-204(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BRCA1, INTERACTION WITH BRCA1.
[15]"Ataxia telangiectasia-mutated phosphorylates Chk2 in vivo and in vitro."
Matsuoka S., Rotman G., Ogawa A., Shiloh Y., Tamai K., Elledge S.J.
Proc. Natl. Acad. Sci. U.S.A. 97:10389-10394(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY ATM AT THR-68.
[16]"The hCds1 (Chk2)-FHA domain is essential for a chain of phosphorylation events on hCds1 that is induced by ionizing radiation."
Lee C.H., Chung J.H.
J. Biol. Chem. 276:30537-30541(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: AUTOPHOSPHORYLATION AT THR-383 AND THR-387, MUTAGENESIS OF THR-383 AND THR-387.
[17]"The ATM-Chk2-Cdc25A checkpoint pathway guards against radioresistant DNA synthesis."
Falck J., Mailand N., Syljuaasen R.G., Bartek J., Lukas J.
Nature 410:842-847(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INTRA S-PHASE CHECKPOINT, FUNCTION IN PHOSPHORYLATION OF CDC25A, INTERACTION WITH CDC25A, MUTAGENESIS OF ASP-347, CHARACTERIZATION OF VARIANT COLON CANCER TRP-145, CHARACTERIZATION OF VARIANT THR-157.
[18]"A CHEK2 genetic variant contributing to a substantial fraction of familial breast cancer."
Vahteristo P., Bartkova J., Eerola H., Syrjakoski K., Ojala S., Kilpivaara O., Tamminen A., Kononen J., Aittomaki K., Heikkila P., Holli K., Blomqvist C., Bartek J., Kallioniemi O.P., Nevanlinna H.
Am. J. Hum. Genet. 71:432-438(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO BC.
[19]"Phosphorylation of threonine 68 promotes oligomerization and autophosphorylation of the Chk2 protein kinase via the forkhead-associated domain."
Ahn J.Y., Li X., Davis H.L., Canman C.E.
J. Biol. Chem. 277:19389-19395(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: HOMODIMERIZATION, AUTOPHOSPHORYLATION, MUTAGENESIS OF THR-68.
[20]"PML-dependent apoptosis after DNA damage is regulated by the checkpoint kinase hCds1/Chk2."
Yang S., Kuo C., Bisi J.E., Kim M.K.
Nat. Cell Biol. 4:865-870(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS, FUNCTION IN PHOSPHORYLATION OF PML, SUBCELLULAR LOCATION.
[21]"53BP1, a mediator of the DNA damage checkpoint."
Wang B., Matsuoka S., Carpenter P.B., Elledge S.J.
Science 298:1435-1438(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH TP53BP1.
[22]"The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation."
Louria-Hayon I., Grossman T., Sionov R.V., Alsheich O., Pandolfi P.P., Haupt Y.
J. Biol. Chem. 278:33134-33141(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH PML AND TP53, SUBCELLULAR LOCATION.
[23]"Chk2 activates E2F-1 in response to DNA damage."
Stevens C., Smith L., La Thangue N.B.
Nat. Cell Biol. 5:401-409(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TRANSCRIPTION REGULATION, FUNCTION IN APOPTOSIS, FUNCTION IN PHOSPHORYLATION OF E2F1.
[24]"MDC1 is coupled to activated CHK2 in mammalian DNA damage response pathways."
Lou Z., Minter-Dykhouse K., Wu X., Chen J.
Nature 421:957-961(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA DAMAGE RESPONSE, INTERACTION WITH MDC1.
[25]"The Chk2 protein kinase."
Ahn J., Urist M., Prives C.
DNA Repair 3:1039-1047(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON PHOSPHORYLATION OF TP53 AND OTHER SUBSTRATES.
[26]"The stress kinase MRK contributes to regulation of DNA damage checkpoints through a p38gamma-independent pathway."
Tosti E., Waldbaum L., Warshaw G., Gross E.A., Ruggieri R.
J. Biol. Chem. 279:47652-47660(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION AT THR-68 BY MLTK, MUTAGENESIS OF THR-68 AND ASP-368.
[27]"ATM and Chk2-dependent phosphorylation of MDMX contribute to p53 activation after DNA damage."
Chen L., Gilkes D.M., Pan Y., Lane W.S., Chen J.
EMBO J. 24:3411-3422(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN TP53 ACTIVATION, FUNCTION IN PHOSPHORYLATION OF MDM4.
[28]"Regulation of the antioncogenic Chk2 kinase by the oncogenic Wip1 phosphatase."
Fujimoto H., Onishi N., Kato N., Takekawa M., Xu X.Z., Kosugi A., Kondo T., Imamura M., Oishi I., Yoda A., Minami Y.
Cell Death Differ. 13:1170-1180(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT THR-68, DEPHOSPHORYLATION AT THR-68 BY PPM1D.
[29]"Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3) mediates its full activation by ATM and a downstream checkpoint in response to DNA damage."
Bahassi el M., Myer D.L., McKenney R.J., Hennigan R.F., Stambrook P.J.
Mutat. Res. 596:166-176(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-62; THR-68 AND SER-73, MUTAGENESIS OF SER-73.
[30]"Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB and E2F-1 after DNA damage."
Inoue Y., Kitagawa M., Taya Y.
EMBO J. 26:2083-2093(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF RB1.
[31]"Stability of checkpoint kinase 2 is regulated via phosphorylation at serine 456."
Kass E.M., Ahn J., Tanaka T., Freed-Pastor W.A., Keezer S., Prives C.
J. Biol. Chem. 282:30311-30321(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS, PHOSPHORYLATION AT SER-456, UBIQUITINATION, MUTAGENESIS OF SER-456.
[32]"Chk2 mediates stabilization of the FoxM1 transcription factor to stimulate expression of DNA repair genes."
Tan Y., Raychaudhuri P., Costa R.H.
Mol. Cell. Biol. 27:1007-1016(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN DNA REPAIR, FUNCTION IN PHOSPHORYLATION OF FOXM1.
[33]"Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-induced phosphorylation."
Lee M.Y., Kim H.J., Kim M.A., Jee H.J., Kim A.J., Bae Y.S., Park J.I., Chung J.H., Yun J.
Cell Cycle 7:2705-2709(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF NEK6.
[34]"Regulation of Chk2 ubiquitination and signaling through autophosphorylation of serine 379."
Lovly C.M., Yan L., Ryan C.E., Takada S., Piwnica-Worms H.
Mol. Cell. Biol. 28:5874-5885(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN APOPTOSIS, AUTOPHOSPHORYLATION AT SER-379, MUTAGENESIS OF SER-379, UBIQUITINATION, INTERACTION WITH CUL1.
[35]"The checkpoint kinases Chk1 and Chk2 regulate the functional associations between hBRCA2 and Rad51 in response to DNA damage."
Bahassi E.M., Ovesen J.L., Riesenberg A.L., Bernstein W.Z., Hasty P.E., Stambrook P.J.
Oncogene 27:3977-3985(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN RAD51-MEDIATED DNA REPAIR, FUNCTION IN PHOSPHORYLATION OF BRCA2.
[36]"Polo-like kinase 4 phosphorylates Chk2."
Petrinac S., Ganuelas M.L., Bonni S., Nantais J., Hudson J.W.
Cell Cycle 8:327-329(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PLK4.
[37]"The CHK2-BRCA1 tumour suppressor pathway ensures chromosomal stability in human somatic cells."
Stolz A., Ertych N., Kienitz A., Vogel C., Schneider V., Fritz B., Jacob R., Dittmar G., Weichert W., Petersen I., Bastians H.
Nat. Cell Biol. 12:492-499(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BRCA1, FUNCTION IN CHROMOSOMAL STABILITY.
[38]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[39]"A recurrent CHEK2 p.H371Y mutation is associated with breast cancer risk in Chinese women."
Liu Y., Liao J., Xu Y., Chen W., Liu D., Ouyang T., Li J., Wang T., Fan Z., Fan T., Lin B., Xu X., Xie Y.
Hum. Mutat. 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN SUSCEPTIBILITY TO BC, VARIANTS CYS-180 AND TYR-371, CHARACTERIZATION OF VARIANT TYR-371.
[40]"The E3 ligase RNF8 regulates KU80 removal and NHEJ repair."
Feng L., Chen J.
Nat. Struct. Mol. Biol. 19:201-206(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION BY RNF8.
[41]"Structural and functional versatility of the FHA domain in DNA-damage signaling by the tumor suppressor kinase Chk2."
Li J., Williams B.L., Haire L.F., Goldberg M., Wilker E., Durocher D., Yaffe M.B., Jackson S.P., Smerdon S.J.
Mol. Cell 9:1045-1054(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 64-212.
[42]"Trans-activation of the DNA-damage signalling protein kinase Chk2 by T-loop exchange."
Oliver A.W., Paul A., Boxall K.J., Barrie S.E., Aherne G.W., Garrett M.D., Mittnacht S., Pearl L.H.
EMBO J. 25:3179-3190(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 210-531 IN COMPLEX WITH ADP AND INHIBITOR, HOMODIMERIZATION, AUTOPHOSPHORYLATION.
[43]"Structure and activation mechanism of the CHK2 DNA damage checkpoint kinase."
Cai Z., Chehab N.H., Pavletich N.P.
Mol. Cell 35:818-829(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 84-502 OF HOMODIMER.
[44]"Heterozygous germ line hCHK2 mutations in Li-Fraumeni syndrome."
Bell D.W., Varley J.M., Szydlo T.E., Kang D.H., Wahrer D.C.R., Shannon K.E., Lubratovich M., Versalis S.J., Isselbacher K.J., Fraumeni J.F. Jr., Birch J.M., Li F.P., Garber J.E., Haber D.A.
Science 286:2528-2531(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157, VARIANT COLON CANCER TRP-145.
[45]"Mutation analysis of the CHK2 gene in families with hereditary breast cancer."
Allinen M., Huusko P., Maentyniemi S., Launonen V., Winqvist R.
Br. J. Cancer 85:209-212(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157.
[46]"Destabilization of CHK2 by a missense mutation associated with Li-Fraumeni Syndrome."
Lee S.B., Kim S.H., Bell D.W., Wahrer D.C.R., Schiripo T.A., Jorczak M.M., Sgroi D.C., Garber J.E., Li F.P., Nichols K.E., Varley J.M., Godwin A.K., Shannon K.M., Harlow E., Haber D.A.
Cancer Res. 61:8062-8067(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT LFS2 TRP-145.
[47]"Mutation analysis of the CHK2 gene in breast carcinoma and other cancers."
Ingvarsson S., Sigbjornsdottir B.I., Huiping C., Hafsteinsdottir S.H., Ragnarsson G., Barkardottir R.B., Arason A., Egilsson V., Bergthorsson J.T.
Breast Cancer Res. 4:R4-R4(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT MULTIPLE CANCERS LYS-59.
[48]"CHEK2 variants in susceptibility to breast cancer and evidence of retention of the wild type allele in tumours."
Sodha N., Bullock S., Taylor R., Mitchell G., Guertl-Lackner B., Williams R.D., Bevan S., Bishop K., McGuire S., Houlston R.S., Eeles R.A.
Br. J. Cancer 87:1445-1448(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-117; GLN-137 AND HIS-180.
[49]"Mutations of the CHK2 gene are found in some osteosarcomas, but are rare in breast, lung, and ovarian tumors."
Miller C.W., Ikezoe T., Krug U., Hofmann W.K., Tavor S., Vegesna V., Tsukasaki K., Takeuchi S., Koeffler H.P.
Genes Chromosomes Cancer 33:17-21(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS OSTEOSARCOMA SER-17 AND LEU-85.
[50]"Mutations in CHEK2 associated with prostate cancer risk."
Dong X., Wang L., Taniguchi K., Wang X., Cunningham J.M., McDonnell S.K., Qian C., Marks A.F., Slager S.L., Peterson B.J., Smith D.I., Cheville J.C., Blute M.L., Jacobsen S.J., Schaid D.J., Tindall D.J., Thibodeau S.N., Liu W.
Am. J. Hum. Genet. 72:270-280(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS PROSTATE CANCER LYS-64; PRO-145; ARG-167; CYS-180; HIS-180; CYS-181; HIS-181; LYS-239; PHE-251; HIS-318; PRO-323; CYS-327 AND LYS-476, VARIANT THR-157.
[51]"Variants in CHEK2 other than 1100delC do not make a major contribution to breast cancer susceptibility."
Schutte M., Seal S., Barfoot R., Meijers-Heijboer H., Wasielewski M., Evans D.G., Eccles D., Meijers C., Lohman F., Klijn J., van den Ouweland A., Brady A., Cole T., Collins A., Cox H., Donaldson A., Eeles R., Evans G. expand/collapse author list , Gregory H., Gray J., Houlston R., Lalloo F., Lucassen A., Mackay J., Mitchell G., Morrison P., Murday V., Narod S., Patterson J., Peretz T., Phelan C.M., Rogers M., Schofield A., Tonin P., Weber B., Weber W., Futreal P.A., Nathanson K.L., Weber B.L., Easton D.F., Stratton M.R., Rahman N.
Am. J. Hum. Genet. 72:1023-1028(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-117; TRP-145 AND THR-157.
[52]"CHEK2 variants associate with hereditary prostate cancer."
Seppaelae E.H., Ikonen T., Mononen N., Autio V., Roekman A., Matikainen M.P., Tammela T.L.J., Schleutker J.
Br. J. Cancer 89:1966-1970(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157.
[53]"CHEK2 is a multiorgan cancer susceptibility gene."
Cybulski C., Gorski B., Huzarski T., Masojc B., Mierzejewski M., Debniak T., Teodorczyk U., Byrski T., Gronwald J., Matyjasik J., Zlowocka E., Lenner M., Grabowska E., Nej K., Castaneda J., Medrek K., Szymanska A., Szymanska J. expand/collapse author list , Kurzawski G., Suchy J., Oszurek O., Witek A., Narod S.A., Lubinski J.
Am. J. Hum. Genet. 75:1131-1135(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157.
[54]"Frequency of CHEK2 mutations in a population based, case-control study of breast cancer in young women."
Friedrichsen D.M., Malone K.E., Doody D.R., Daling J.R., Ostrander E.A.
Breast Cancer Res. 6:R629-R635(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS TRP-145 AND THR-157.
[55]"A novel founder CHEK2 mutation is associated with increased prostate cancer risk."
Cybulski C., Huzarski T., Gorski B., Masojc B., Mierzejewski M., Debniak T., Gliniewicz B., Matyjasik J., Zlowocka E., Kurzawski G., Sikorski A., Posmyk M., Szwiec M., Czajka R., Narod S.A., Lubinski J.
Cancer Res. 64:2677-2679(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157.
[56]"Limited relevance of the CHEK2 gene in hereditary breast cancer."
Dufault M.R., Betz B., Wappenschmidt B., Hofmann W., Bandick K., Golla A., Pietschmann A., Nestle-Kraemling C., Rhiem K., Huettner C., von Lindern C., Dall P., Kiechle M., Untch M., Jonat W., Meindl A., Scherneck S., Niederacher D., Schmutzler R.K., Arnold N.
Int. J. Cancer 110:320-325(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157.
[57]"CHEK2 variant I157T may be associated with increased breast cancer risk."
Kilpivaara O., Vahteristo P., Falck J., Syrjaekoski K., Eerola H., Easton D., Bartkova J., Lukas J., Heikkilae P., Aittomaeki K., Holli K., Blomqvist C., Kallioniemi O.-P., Bartek J., Nevanlinna H.
Int. J. Cancer 111:543-547(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157.
[58]"Functional and genomic approaches reveal an ancient CHEK2 allele associated with breast cancer in the Ashkenazi Jewish population."
Shaag A., Walsh T., Renbaum P., Kirchhoff T., Nafa K., Shiovitz S., Mandell J.B., Welcsh P., Lee M.K., Ellis N., Offit K., Levy-Lahad E., King M.-C.
Hum. Mol. Genet. 14:555-563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS LEU-85 AND PHE-428.
[59]"Association of two mutations in the CHEK2 gene with breast cancer."
Bogdanova N., Enbetaen-Dubrowinskaja N., Feshchenko S., Lazjuk G.I., Rogov Y.I., Dammann O., Bremer M., Karstens J.H., Sohn C., Doerk T.
Int. J. Cancer 116:263-266(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT THR-157.
[60]"Homozygosity for a CHEK2*1100delC mutation identified in familial colorectal cancer does not lead to a severe clinical phenotype."
van Puijenbroek M., van Asperen C.J., van Mil A., Devilee P., van Wezel T., Morreau H.
J. Pathol. 206:198-204(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-117; GLN-137; TRP-145; THR-157 AND HIS-180.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ		AF086904 mRNA. Translation: AAC83693.1.
AJ131197 mRNA. Translation: CAA10319.1.
AF096279 mRNA. Translation: AAD11784.1.
AY551295 mRNA. Translation: AAS58456.1.
AY551296 mRNA. Translation: AAS58457.1.
AY551297 mRNA. Translation: AAS58458.1.
AY551298 mRNA. Translation: AAS58459.1.
AY551299 mRNA. Translation: AAS58460.1.
AY551300 mRNA. Translation: AAS58461.1.
AY551301 mRNA. Translation: AAS58462.1.
AY551302 mRNA. Translation: AAS58463.1.
AY551303 mRNA. Translation: AAS58464.1.
AY551304 mRNA. Translation: AAS58465.1.
AY551305 mRNA. Translation: AAS58466.1.
CR456418 mRNA. Translation: CAG30304.1.
AF174135 mRNA. Translation: AAD48504.1.
AB040105 mRNA. Translation: BAB17231.1.
AK290754 mRNA. Translation: BAF83443.1.
AF217975 mRNA. Translation: AAG17218.1.
AY800241 Genomic DNA. Translation: AAV41895.1.
AL121825, AL117330 Genomic DNA. Translation: CAH73823.1.
AL117330, AL121825 Genomic DNA. Translation: CAH73875.1.
AL121825, AL117330 Genomic DNA. Translation: CAX11957.1.
AL121825, AL117330 Genomic DNA. Translation: CAX11958.1.
AL121825, AL117330 Genomic DNA. Translation: CAX11959.1.
AL117330, AL121825 Genomic DNA. Translation: CAX14026.1.
AL117330, AL121825 Genomic DNA. Translation: CAX14027.1.
AL117330, AL121825 Genomic DNA. Translation: CAX14028.1.
CH471095 Genomic DNA. Translation: EAW59755.1.
BC004207 mRNA. Translation: AAH04207.1.
IPIIPI00014072.
IPI00030746.
IPI00423146.
IPI00423149.
IPI00423156.
IPI00423157.
IPI00607619.
IPI00607680.
IPI00607709.
IPI00607739.
IPI00607753.
IPI00607851.
RefSeqNP_001005735.1. NM_001005735.1.
NP_001244316.1. NM_001257387.1.
NP_009125.1. NM_007194.3.
NP_665861.1. NM_145862.2.
UniGeneHs.291363.
Hs.505297.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1GXCX-ray2.70A/D/G/J64-212[»]
2CN5X-ray2.25A210-531[»]
2CN8X-ray2.70A210-531[»]
2W0JX-ray2.05A210-531[»]
2W7XX-ray2.07A210-531[»]
2WTCX-ray3.00A210-531[»]
2WTDX-ray2.75A210-531[»]
2WTIX-ray2.50A210-531[»]
2WTJX-ray2.10A210-531[»]
2XBJX-ray2.30A210-531[»]
2XK9X-ray2.35A210-531[»]
2XM8X-ray3.40A210-531[»]
2XM9X-ray2.50A210-531[»]
2YCFX-ray1.77A210-530[»]
2YCQX-ray2.05A210-531[»]
2YCRX-ray2.20A210-531[»]
2YCSX-ray2.35A210-531[»]
2YIQX-ray1.89A210-531[»]
2YIRX-ray2.10A210-531[»]
2YITX-ray2.20A210-531[»]
3I6UX-ray3.00A/B84-502[»]
3I6WX-ray3.25A/B/C/D/E/F/G/H70-512[»]
3VA4X-ray1.54C63-73[»]
4A9RX-ray2.85A210-531[»]
4A9SX-ray2.66A210-531[»]
4A9TX-ray2.70A210-531[»]
4A9UX-ray2.48A210-531[»]
ProteinModelPortalO96017.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-24270N.
IntActO96017. 17 interactions.
MINTMINT-124588.

PTM databases

PhosphoSiteO96017.

Proteomic databases

PaxDbO96017.
PRIDEO96017.

Protocols and materials databases

DNASU11200.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000328354; ENSP00000329178; ENSG00000183765.
ENST00000348295; ENSP00000329012; ENSG00000183765.
ENST00000382566; ENSP00000372007; ENSG00000183765.
ENST00000382578; ENSP00000372021; ENSG00000183765.
ENST00000382580; ENSP00000372023; ENSG00000183765.
ENST00000402731; ENSP00000384835; ENSG00000183765.
ENST00000403642; ENSP00000384919; ENSG00000183765.
ENST00000404276; ENSP00000385747; ENSG00000183765.
ENST00000405598; ENSP00000386087; ENSG00000183765.
ENST00000417588; ENSP00000412901; ENSG00000183765.
ENST00000433728; ENSP00000404400; ENSG00000183765.
ENST00000448511; ENSP00000404567; ENSG00000183765.
ENST00000544772; ENSP00000442458; ENSG00000183765.
GeneID11200.
KEGGhsa:11200.
UCSCuc003ads.1. human.
uc003adt.1. human.
uc003adv.1. human.
uc010gvh.1. human.

Organism-specific databases

CTD11200.
GeneCardsGC22M029083.
HGNCHGNC:16627. CHEK2.
HPACAB002030.
HPA001878.
MIM114480. phenotype.
176807. phenotype.
259500. phenotype.
604373. gene+phenotype.
609265. phenotype.
neXtProtNX_O96017.
Orphanet1331. Familial prostate cancer.
145. Hereditary breast and ovarian cancer syndrome.
524. Li-Fraumeni syndrome.
668. Osteosarcoma.
PharmGKBPA404.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108055.
KOK06641.
OMAKFAIGSE.
OrthoDBEOG4M0F1R.
PhylomeDBO96017.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
Pathway_Interaction_DBfoxm1pathway. FOXM1 transcription factor network.
ReactomeREACT_115566. Cell Cycle.

Gene expression databases

ArrayExpressO96017.
BgeeO96017.
GenevestigatorO96017.
GermOnlineENSG00000183765. Homo sapiens.

Family and domain databases

Gene3D2.60.200.20. 1 hit.
InterProIPR000253. FHA_dom.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_cat_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR008984. SMAD_FHA_domain.
[Graphical view]
PfamPF00498. FHA. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00240. FHA. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. Kinase_like. 1 hit.
SSF49879. SMAD_FHA. 1 hit.
PROSITEPS50006. FHA_DOMAIN. 1 hit.
PS00107. PROTEIN_KINASE_ATP. False negative.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

BindingDBO96017.
ChEMBLCHEMBL2527.
EvolutionaryTraceO96017.
GenomeRNAi11200.
NextBio42629.
SOURCESearch...

Entry information

Entry nameCHK2_HUMAN
AccessionPrimary (citable) accession number: O96017
Secondary accession number(s): A8K3Y9 expand/collapse secondary AC list , B7ZBF3, B7ZBF4, B7ZBF5, Q6QA03, Q6QA04, Q6QA05, Q6QA06, Q6QA07, Q6QA08, Q6QA10, Q6QA11, Q6QA12, Q6QA13, Q9HBS5, Q9HCQ8, Q9UGF0, Q9UGF1
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: May 1, 2013
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

Human chromosome 22

Human chromosome 22: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·Documents