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Protein

Serine/threonine-protein kinase Chk2

Gene

CHEK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978).By similarity19 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Activity regulationi

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-68.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei249ATP1
Active sitei347Proton acceptor1
Binding sitei368ATP1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi227 – 234ATP8
Nucleotide bindingi302 – 308ATP7
Nucleotide bindingi351 – 352ATP2

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis, Cell cycle, Cell division, DNA damage, DNA repair, Mitosis, Transcription, Transcription regulation
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-6804760 Regulation of TP53 Activity through Methylation
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-69541 Stabilization of p53
R-HSA-69601 Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
SignaLinkiO96017
SIGNORiO96017

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:CHEK2
Synonyms:CDS1, CHK2, RAD53
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000183765.20
HGNCiHGNC:16627 CHEK2
MIMi604373 gene+phenotype
neXtProtiNX_O96017

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Li-Fraumeni syndrome 2 (LFS2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:609265
Prostate cancer (PC)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:176807
Osteogenic sarcoma (OSRC)
The gene represented in this entry may be involved in disease pathogenesis.
Disease descriptionA sarcoma originating in bone-forming cells, affecting the ends of long bones.
See also OMIM:259500
Breast cancer (BC)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.1 Publication
Disease descriptionA 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.
See also OMIM:114480
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_073020390Y → C in BC; does not phosphorylate p53/TP53. 1 PublicationCorresponds to variant dbSNP:rs200928781EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi68T → A: Loss of activation and phosphorylation. 2 Publications1
Mutagenesisi73S → A: Impaired activation, phosphorylation by ATM and G2/M transition checkpoint. 1 Publication1
Mutagenesisi347D → A: Loss of kinase activity and of the ability to phosphorylate CDC25A. 2 Publications1
Mutagenesisi368D → N: Loss of autophosphorylation activity. 1 Publication1
Mutagenesisi379S → A: Abrogates autophosphorylation at Ser-379 and prevents ubiquitination. 1 Publication1
Mutagenesisi383T → A: Loss of phosphorylation in response to ionizing radiation. 1 Publication1
Mutagenesisi387T → A: Loss of phosphorylation in response to ionizing radiation. 1 Publication1
Mutagenesisi456S → A: Increased ubiquitination and degradation by the proteasome. 1 Publication1

Keywords - Diseasei

Disease mutation, Li-Fraumeni syndrome, Tumor suppressor

Organism-specific databases

DisGeNETi11200
MalaCardsiCHEK2
MIMi114480 phenotype
176807 phenotype
259500 phenotype
604373 gene+phenotype
609265 phenotype
OpenTargetsiENSG00000183765
Orphaneti1331 Familial prostate cancer
145 Hereditary breast and ovarian cancer syndrome
524 Li-Fraumeni syndrome
668 Osteosarcoma
PharmGKBiPA404

Chemistry databases

ChEMBLiCHEMBL2527
DrugBankiDB05149 XL844
GuidetoPHARMACOLOGYi1988

Polymorphism and mutation databases

BioMutaiCHEK2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858581 – 543Serine/threonine-protein kinase Chk2Add BLAST543

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei62Phosphoserine; by PLK31 Publication1
Modified residuei68Phosphothreonine; by ATM and MAP3K204 Publications1
Modified residuei73Phosphoserine; by PLK31 Publication1
Modified residuei379Phosphoserine; by autocatalysis1 Publication1
Modified residuei383Phosphothreonine; by autocatalysis1 Publication1
Modified residuei387Phosphothreonine; by autocatalysis1 Publication1
Modified residuei456Phosphoserine1 Publication1

Post-translational modificationi

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 PLK4.8 Publications
Ubiquitinated. CUL1-mediated ubiquitination regulates the pro-apoptotic function. Ubiquitination may also regulate protein stability. Ubiquitinated by RNF8 via 'Lys-48'-linked ubiquitination.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO96017
MaxQBiO96017
PeptideAtlasiO96017
PRIDEiO96017
ProteomicsDBi51198
51199 [O96017-10]
51200 [O96017-11]
51201 [O96017-12]
51202 [O96017-2]
51203 [O96017-3]
51204 [O96017-4]
51205 [O96017-5]
51206 [O96017-6]
51207 [O96017-7]
51208 [O96017-8]
51209 [O96017-9]

PTM databases

iPTMnetiO96017
PhosphoSitePlusiO96017

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000183765 Expressed in 121 organ(s), highest expression level in tibial nerve
ExpressionAtlasiO96017 baseline and differential
GenevisibleiO96017 HS

Organism-specific databases

HPAiCAB002030
HPA001878

Interactioni

Subunit structurei

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. Interacts with CDKN2AIP. Interacts (via protein kinase domain) with CCAR2 (via N-terminus). Interacts with SIRT1.9 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi116369, 116 interactors
CORUMiO96017
DIPiDIP-24270N
ELMiO96017
IntActiO96017, 109 interactors
MINTiO96017

Chemistry databases

BindingDBiO96017

Structurei

Secondary structure

1543
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliO96017
SMRiO96017
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO96017

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini113 – 175FHAPROSITE-ProRule annotationAdd BLAST63
Domaini220 – 486Protein kinasePROSITE-ProRule annotationAdd BLAST267

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni368 – 394T-loop/activation segmentAdd BLAST27

Sequence similaritiesi

Phylogenomic databases

GeneTreeiENSGT00800000124190
HOGENOMiHOG000233016
HOVERGENiHBG108055
InParanoidiO96017
KOiK06641
OMAiSRAVDCW
OrthoDBiEOG091G0DVW
PhylomeDBiO96017
TreeFamiTF101082

Family and domain databases

CDDicd00060 FHA, 1 hit
InterProiView protein in InterPro
IPR000253 FHA_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR008984 SMAD_FHA_dom_sf
PfamiView protein in Pfam
PF00498 FHA, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00240 FHA, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50006 FHA_DOMAIN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (13+)i

Sequence statusi: Complete.

This entry describes 13 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 13 described isoforms and 11 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: O96017-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MSRESDVEAQ QSHGSSACSQ PHGSVTQSQG SSSQSQGISS SSTSTMPNSS
60 70 80 90 100
QSSHSSSGTL SSLETVSTQE LYSIPEDQEP EDQEPEEPTP APWARLWALQ
110 120 130 140 150
DGFANLECVN DNYWFGRDKS CEYCFDEPLL KRTDKYRTYS KKHFRIFREV
160 170 180 190 200
GPKNSYIAYI EDHSGNGTFV NTELVGKGKR RPLNNNSEIA LSLSRNKVFV
210 220 230 240 250
FFDLTVDDQS VYPKALRDEY IMSKTLGSGA CGEVKLAFER KTCKKVAIKI
260 270 280 290 300
ISKRKFAIGS AREADPALNV ETEIEILKKL NHPCIIKIKN FFDAEDYYIV
310 320 330 340 350
LELMEGGELF DKVVGNKRLK EATCKLYFYQ MLLAVQYLHE NGIIHRDLKP
360 370 380 390 400
ENVLLSSQEE DCLIKITDFG HSKILGETSL MRTLCGTPTY LAPEVLVSVG
410 420 430 440 450
TAGYNRAVDC WSLGVILFIC LSGYPPFSEH RTQVSLKDQI TSGKYNFIPE
460 470 480 490 500
VWAEVSEKAL DLVKKLLVVD PKARFTTEEA LRHPWLQDED MKRKFQDLLS
510 520 530 540
EENESTALPQ VLAQPSTSRK RPREGEAEGA ETTKRPAVCA AVL
Length:543
Mass (Da):60,915
Last modified:May 1, 1999 - v1
Checksum:i28890ACF3C1F3408
GO
Isoform 2 (identifier: O96017-2) [UniParc]FASTAAdd to basket
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.
Show »
Length:234
Mass (Da):26,084
Checksum:i46766F331DD13DA8
GO
Isoform 3 (identifier: O96017-3) [UniParc]FASTAAdd to basket
Also known as: del2-12

The sequence of this isoform differs from the canonical sequence as follows:
     107-487: Missing.

Show »
Length:162
Mass (Da):17,370
Checksum:iD3BF7E0BC0DB0EC1
GO
Isoform 4 (identifier: O96017-4) [UniParc]FASTAAdd to basket
Also known as: del2-3

The sequence of this isoform differs from the canonical sequence as follows:
     107-197: Missing.

Note: Lacks enzymatic activity.
Show »
Length:452
Mass (Da):50,203
Checksum:i96F7C353E4F3C85B
GO
Isoform 5 (identifier: O96017-5) [UniParc]FASTAAdd to basket
Also known as: del4

The sequence of this isoform differs from the canonical sequence as follows:
     199-203: FVFFD → VPVER
     204-543: Missing.

Show »
Length:203
Mass (Da):22,594
Checksum:i9D1ED8844633607E
GO
Isoform 6 (identifier: O96017-6) [UniParc]FASTAAdd to basket
Also known as: sub3

The sequence of this isoform differs from the canonical sequence as follows:
     150-165: VGPKNSYIAYIEDHSG → ENLSCPYRIWFNFCLF
     166-543: Missing.

Show »
Length:165
Mass (Da):18,706
Checksum:i795CC81539178CF0
GO
Isoform 7 (identifier: O96017-7) [UniParc]FASTAAdd to basket
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.
Show »
Length:339
Mass (Da):38,125
Checksum:iCAE0E58DF0308393
GO
Isoform 8 (identifier: O96017-8) [UniParc]FASTAAdd to basket
Also known as: del7

The sequence of this isoform differs from the canonical sequence as follows:
     283-289: PCIIKIK → DGRGRAV
     290-543: Missing.

Show »
Length:289
Mass (Da):32,142
Checksum:i630D0AF3AE5114E6
GO
Isoform 9 (identifier: O96017-9) [UniParc]FASTAAdd to basket
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.
Show »
Length:586
Mass (Da):65,419
Checksum:i55BDE42C9A0F98A7
GO
Isoform 10 (identifier: O96017-10) [UniParc]FASTAAdd to basket
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.
Show »
Length:140
Mass (Da):15,420
Checksum:i54BBB0152B5668D5
GO
Isoform 11 (identifier: O96017-11) [UniParc]FASTAAdd to basket
Also known as: iso1

The sequence of this isoform differs from the canonical sequence as follows:
     75-392: Missing.

Show »
Length:225
Mass (Da):24,396
Checksum:i57F0155780C96BA2
GO
Isoform 12 (identifier: O96017-12) [UniParc]FASTAAdd to basket
Also known as: del9

The sequence of this isoform differs from the canonical sequence as follows:
     337-365: Missing.

Note: Lacks enzymatic activity.
Show »
Length:514
Mass (Da):57,526
Checksum:i8B99B81830B8092F
GO
Isoform 13 (identifier: O96017-13) [UniParc]FASTAAdd to basket

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

Show »
Length:322
Mass (Da):36,157
Checksum:iD31257F4B9652438
GO

Computationally mapped potential isoform sequencesi

There are 11 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B7ZBF6B7ZBF6_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
298Annotation score:
B7ZBF7B7ZBF7_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
295Annotation score:
C9JFD7C9JFD7_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
207Annotation score:
B7ZBF8B7ZBF8_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
172Annotation score:
B7ZBF2B7ZBF2_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
121Annotation score:
H0Y820H0Y820_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
276Annotation score:
H0Y4V6H0Y4V6_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
144Annotation score:
A0A087X102A0A087X102_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
137Annotation score:
H7C0V7H7C0V7_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
57Annotation score:
F8WCV2F8WCV2_HUMAN
Serine/threonine-protein kinase Chk...
CHEK2
161Annotation score:
There is more potential isoformShow all

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01910117A → S in an osteogenic sarcoma sample; somatic mutation; might influence susceptibility to breast cancer; does not cause protein abrogation in familial colorectal cancer. 1 PublicationCorresponds to variant dbSNP:rs137853008EnsemblClinVar.1
Natural variantiVAR_02663059T → K in multiple cancers. 1 PublicationCorresponds to variant dbSNP:rs149991239EnsemblClinVar.1
Natural variantiVAR_01910764E → K in prostate cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs141568342EnsemblClinVar.1
Natural variantiVAR_01910285P → L in an osteogenic sarcoma sample; neutral allele among Ashkenazi Jewish women. 3 PublicationsCorresponds to variant dbSNP:rs17883862EnsemblClinVar.1
Natural variantiVAR_022461117R → G3 PublicationsCorresponds to variant dbSNP:rs28909982EnsemblClinVar.1
Natural variantiVAR_022462137R → Q Might influence susceptibility to breast cancer; does not cause protein abrogation in familial colorectal cancer. 2 PublicationsCorresponds to variant dbSNP:rs368570187EnsemblClinVar.1
Natural variantiVAR_019108145R → P in prostate cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587781667Ensembl.1
Natural variantiVAR_008554145R → 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. 6 PublicationsCorresponds to variant dbSNP:rs137853007EnsemblClinVar.1
Natural variantiVAR_008555157I → 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. 14 PublicationsCorresponds to variant dbSNP:rs17879961EnsemblClinVar.1
Natural variantiVAR_019109167G → R in prostate cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs72552322EnsemblClinVar.1
Natural variantiVAR_019103180R → C in prostate cancer; somatic mutation. 2 PublicationsCorresponds to variant dbSNP:rs77130927EnsemblClinVar.1
Natural variantiVAR_019110180R → H in prostate cancer; somatic mutation. 3 PublicationsCorresponds to variant dbSNP:rs137853009EnsemblClinVar.1
Natural variantiVAR_019104181R → C in prostate cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs137853010EnsemblClinVar.1
Natural variantiVAR_019105181R → H in prostate cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs121908701EnsemblClinVar.1
Natural variantiVAR_019106239E → K in prostate cancer; germline mutation. 1 PublicationCorresponds to variant dbSNP:rs121908702EnsemblClinVar.1
Natural variantiVAR_019111251I → F in prostate cancer; germline mutation. 1 PublicationCorresponds to variant dbSNP:rs587780189EnsemblClinVar.1
Natural variantiVAR_019112318R → H in prostate cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs143611747EnsemblClinVar.1
Natural variantiVAR_019113323T → P in prostate cancer; somatic mutation. 1 Publication1
Natural variantiVAR_019114327Y → C in prostate cancer; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587780194EnsemblClinVar.1
Natural variantiVAR_029154347D → N. Corresponds to variant dbSNP:rs28909980EnsemblClinVar.1
Natural variantiVAR_066012371H → Y Confers a moderate risk of breast cancer; partially reduces kinase activity. 1 PublicationCorresponds to variant dbSNP:rs531398630EnsemblClinVar.1
Natural variantiVAR_073020390Y → C in BC; does not phosphorylate p53/TP53. 1 PublicationCorresponds to variant dbSNP:rs200928781EnsemblClinVar.1
Natural variantiVAR_024572406R → H. Corresponds to variant dbSNP:rs200649225EnsemblClinVar.1
Natural variantiVAR_022463428S → F May increase breast cancer risk. 1 PublicationCorresponds to variant dbSNP:rs137853011EnsemblClinVar.1
Natural variantiVAR_021117436L → M1 PublicationCorresponds to variant dbSNP:rs17882922Ensembl.1
Natural variantiVAR_021118446N → K1 PublicationCorresponds to variant dbSNP:rs17880867Ensembl.1
Natural variantiVAR_021119447F → I1 PublicationCorresponds to variant dbSNP:rs17881473Ensembl.1
Natural variantiVAR_021120448I → S1 PublicationCorresponds to variant dbSNP:rs17886163EnsemblClinVar.1
Natural variantiVAR_019115476T → K in prostate cancer; somatic mutation. 1 Publication1
Natural variantiVAR_029155500S → C. Corresponds to variant dbSNP:rs28909981Ensembl.1
Natural variantiVAR_021121501E → K1 PublicationCorresponds to variant dbSNP:rs17883172EnsemblClinVar.1
Natural variantiVAR_021122512L → V1 PublicationCorresponds to variant dbSNP:rs17882942EnsemblClinVar.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0451481 – 221Missing in isoform 13. 1 PublicationAdd BLAST221
Alternative sequenceiVSP_01455675 – 392Missing in isoform 11. 1 PublicationAdd BLAST318
Alternative sequenceiVSP_014559107 – 487Missing in isoform 3. 1 PublicationAdd BLAST381
Alternative sequenceiVSP_014558107 – 197Missing in isoform 4. 1 PublicationAdd BLAST91
Alternative sequenceiVSP_014557107E → ETESGHVTQSDLELLLSSDP PASASQSAGIRGVRHHPRPV CSLK in isoform 9. 2 Publications1
Alternative sequenceiVSP_014560131 – 147KRTDK…HFRIF → EFRSYSFYLP in isoform 10. 1 PublicationAdd BLAST17
Alternative sequenceiVSP_014561148 – 543Missing in isoform 10. 1 PublicationAdd BLAST396
Alternative sequenceiVSP_014562150 – 165VGPKN…EDHSG → ENLSCPYRIWFNFCLF in isoform 6. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_014563166 – 543Missing in isoform 6. 1 PublicationAdd BLAST378
Alternative sequenceiVSP_014564198 – 224VFVFF…YIMSK → EKILKIYSLSRFSKIRRGAV AHVFNPS in isoform 2. 2 PublicationsAdd BLAST27
Alternative sequenceiVSP_014565199 – 203FVFFD → VPVER in isoform 5. 1 Publication5
Alternative sequenceiVSP_014566204 – 543Missing in isoform 5. 1 PublicationAdd BLAST340
Alternative sequenceiVSP_014567228 – 234SGACGEV → GRGWQIT in isoform 2. 2 Publications7
Alternative sequenceiVSP_014568235 – 543Missing in isoform 2. 2 PublicationsAdd BLAST309
Alternative sequenceiVSP_014569283 – 289PCIIKIK → DGRGRAV in isoform 8. 1 Publication7
Alternative sequenceiVSP_014570290 – 543Missing in isoform 8. 1 PublicationAdd BLAST254
Alternative sequenceiVSP_014571337 – 365Missing in isoform 12. 2 PublicationsAdd BLAST29
Alternative sequenceiVSP_014572337 – 339YLH → MKT in isoform 7. 1 Publication3
Alternative sequenceiVSP_014573340 – 543Missing in isoform 7. 1 PublicationAdd BLAST204

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AL117330 Genomic DNA No translation available.
AL121825 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW59755.1
BC004207 mRNA Translation: AAH04207.1
CCDSiCCDS13843.1 [O96017-1]
CCDS13844.1 [O96017-12]
CCDS33629.1 [O96017-9]
RefSeqiNP_001005735.1, NM_001005735.1 [O96017-9]
NP_001244316.1, NM_001257387.1 [O96017-13]
NP_009125.1, NM_007194.3 [O96017-1]
NP_665861.1, NM_145862.2 [O96017-12]
XP_011528147.1, XM_011529845.2 [O96017-13]
XP_016884050.1, XM_017028561.1 [O96017-13]
UniGeneiHs.291363
Hs.505297

Genome annotation databases

EnsembliENST00000328354; ENSP00000329178; ENSG00000183765 [O96017-1]
ENST00000348295; ENSP00000329012; ENSG00000183765 [O96017-12]
ENST00000382580; ENSP00000372023; ENSG00000183765 [O96017-9]
ENST00000402731; ENSP00000384835; ENSG00000183765 [O96017-12]
ENST00000403642; ENSP00000384919; ENSG00000183765 [O96017-4]
ENST00000404276; ENSP00000385747; ENSG00000183765 [O96017-1]
ENST00000405598; ENSP00000386087; ENSG00000183765 [O96017-1]
ENST00000417588; ENSP00000412901; ENSG00000183765 [O96017-5]
ENST00000433728; ENSP00000404400; ENSG00000183765 [O96017-8]
ENST00000448511; ENSP00000404567; ENSG00000183765 [O96017-6]
GeneIDi11200
KEGGihsa:11200
UCSCiuc003adt.2 human [O96017-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology
NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AL117330 Genomic DNA No translation available.
AL121825 Genomic DNA No translation available.
CH471095 Genomic DNA Translation: EAW59755.1
BC004207 mRNA Translation: AAH04207.1
CCDSiCCDS13843.1 [O96017-1]
CCDS13844.1 [O96017-12]
CCDS33629.1 [O96017-9]
RefSeqiNP_001005735.1, NM_001005735.1 [O96017-9]
NP_001244316.1, NM_001257387.1 [O96017-13]
NP_009125.1, NM_007194.3 [O96017-1]
NP_665861.1, NM_145862.2 [O96017-12]
XP_011528147.1, XM_011529845.2 [O96017-13]
XP_016884050.1, XM_017028561.1 [O96017-13]
UniGeneiHs.291363
Hs.505297

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4BDAX-ray2.60A210-531[»]
4BDBX-ray2.50A210-531[»]
4BDCX-ray3.00A210-531[»]
4BDDX-ray2.67A210-531[»]
4BDEX-ray2.55A210-531[»]
4BDFX-ray2.70A210-531[»]
4BDGX-ray2.84A210-531[»]
4BDHX-ray2.70A210-531[»]
4BDIX-ray2.32A210-531[»]
4BDJX-ray3.01A210-531[»]
4BDKX-ray3.30A210-531[»]
ProteinModelPortaliO96017
SMRiO96017
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116369, 116 interactors
CORUMiO96017
DIPiDIP-24270N
ELMiO96017
IntActiO96017, 109 interactors
MINTiO96017

Chemistry databases

BindingDBiO96017
ChEMBLiCHEMBL2527
DrugBankiDB05149 XL844
GuidetoPHARMACOLOGYi1988

PTM databases

iPTMnetiO96017
PhosphoSitePlusiO96017

Polymorphism and mutation databases

BioMutaiCHEK2

Proteomic databases

EPDiO96017
MaxQBiO96017
PeptideAtlasiO96017
PRIDEiO96017
ProteomicsDBi51198
51199 [O96017-10]
51200 [O96017-11]
51201 [O96017-12]
51202 [O96017-2]
51203 [O96017-3]
51204 [O96017-4]
51205 [O96017-5]
51206 [O96017-6]
51207 [O96017-7]
51208 [O96017-8]
51209 [O96017-9]

Protocols and materials databases

DNASUi11200
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000328354; ENSP00000329178; ENSG00000183765 [O96017-1]
ENST00000348295; ENSP00000329012; ENSG00000183765 [O96017-12]
ENST00000382580; ENSP00000372023; ENSG00000183765 [O96017-9]
ENST00000402731; ENSP00000384835; ENSG00000183765 [O96017-12]
ENST00000403642; ENSP00000384919; ENSG00000183765 [O96017-4]
ENST00000404276; ENSP00000385747; ENSG00000183765 [O96017-1]
ENST00000405598; ENSP00000386087; ENSG00000183765 [O96017-1]
ENST00000417588; ENSP00000412901; ENSG00000183765 [O96017-5]
ENST00000433728; ENSP00000404400; ENSG00000183765 [O96017-8]
ENST00000448511; ENSP00000404567; ENSG00000183765 [O96017-6]
GeneIDi11200
KEGGihsa:11200
UCSCiuc003adt.2 human [O96017-1]

Organism-specific databases

CTDi11200
DisGeNETi11200
EuPathDBiHostDB:ENSG00000183765.20
GeneCardsiCHEK2
HGNCiHGNC:16627 CHEK2
HPAiCAB002030
HPA001878
MalaCardsiCHEK2
MIMi114480 phenotype
176807 phenotype
259500 phenotype
604373 gene+phenotype
609265 phenotype
neXtProtiNX_O96017
OpenTargetsiENSG00000183765
Orphaneti1331 Familial prostate cancer
145 Hereditary breast and ovarian cancer syndrome
524 Li-Fraumeni syndrome
668 Osteosarcoma
PharmGKBiPA404
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00800000124190
HOGENOMiHOG000233016
HOVERGENiHBG108055
InParanoidiO96017
KOiK06641
OMAiSRAVDCW
OrthoDBiEOG091G0DVW
PhylomeDBiO96017
TreeFamiTF101082

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-5693565 Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-6804756 Regulation of TP53 Activity through Phosphorylation
R-HSA-6804757 Regulation of TP53 Degradation
R-HSA-6804760 Regulation of TP53 Activity through Methylation
R-HSA-69473 G2/M DNA damage checkpoint
R-HSA-69541 Stabilization of p53
R-HSA-69601 Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
R-HSA-75035 Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex
SignaLinkiO96017
SIGNORiO96017

Miscellaneous databases

EvolutionaryTraceiO96017
GeneWikiiCHEK2
GenomeRNAii11200
PROiPR:O96017
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000183765 Expressed in 121 organ(s), highest expression level in tibial nerve
ExpressionAtlasiO96017 baseline and differential
GenevisibleiO96017 HS

Family and domain databases

CDDicd00060 FHA, 1 hit
InterProiView protein in InterPro
IPR000253 FHA_dom
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR008271 Ser/Thr_kinase_AS
IPR008984 SMAD_FHA_dom_sf
PfamiView protein in Pfam
PF00498 FHA, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00240 FHA, 1 hit
SM00220 S_TKc, 1 hit
SUPFAMiSSF49879 SSF49879, 1 hit
SSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS50006 FHA_DOMAIN, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCHK2_HUMAN
AccessioniPrimary (citable) accession number: O96017
Secondary accession number(s): A8K3Y9
, B7ZBF3, B7ZBF4, B7ZBF5, Q6QA03, Q6QA04, Q6QA05, Q6QA06, Q6QA07, Q6QA08, Q6QA10, Q6QA11, Q6QA12, Q6QA13, Q9HBS5, Q9HCQ8, Q9UGF0, Q9UGF1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1999
Last modified: November 7, 2018
This is version 214 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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