O96017 · CHK2_HUMAN
- ProteinSerine/threonine-protein kinase Chk2
- GeneCHEK2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids543 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Under oxidative stress, promotes ATG7 ubiquitination by phosphorylating the E3 ubiquitin ligase TRIM32 at 'Ser-55' leading to positive regulation of the autophagosme assembly (PubMed:37943659).
Catalytic activity
- L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H+
Cofactor
Activity regulation
Features
Showing features for binding site, active site.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Binding site | 227-234 | ATP (UniProtKB | ChEBI) | |||
Binding site | 249 | ATP (UniProtKB | ChEBI) | |||
Binding site | 302-308 | ATP (UniProtKB | ChEBI) | |||
Active site | 347 | Proton acceptor | |||
Binding site | 351-352 | ATP (UniProtKB | ChEBI) | |||
Binding site | 368 | ATP (UniProtKB | ChEBI) | |||
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase Chk2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionO96017
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Isoform 2
Isoform 4
Isoform 7
Isoform 9
Isoform 12
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Tumor predisposition syndrome 4 (TPDS4)
- Note
- DescriptionA disorder characterized by an increased risk for developing various types of benign and/or malignant neoplasms that arise at an accelerated rate and in different organs.
- See alsoMIM:609265
Natural variants in TPDS4
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_008554 | 145 | R>W | in TPDS4; loss of the ability to interact with and phosphorylate CDC25A and to promote CDC25A degradation in response to ionizing radiation; dbSNP:rs137853007 |
Prostate cancer (PC)
- Note
- 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 alsoMIM:176807
Osteogenic sarcoma (OSRC)
- Note
- DescriptionA sarcoma originating in bone-forming cells, affecting the ends of long bones.
- See alsoMIM:259500
Breast cancer (BC)
- Note
- 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 alsoMIM:114480
Natural variants in BC
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_022461 | 117 | R>G | in BC; dbSNP:rs28909982 | |
VAR_073020 | 390 | Y>C | in BC; does not phosphorylate p53/TP53; dbSNP:rs200928781 |
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Natural variant | VAR_019101 | 17 | found in an osteogenic sarcoma sample; somatic mutation; might influence susceptibility to breast cancer; dbSNP:rs137853008 | ||
Natural variant | VAR_026630 | 59 | in multiple cancers; dbSNP:rs149991239 | ||
Natural variant | VAR_019107 | 64 | in prostate cancer; somatic mutation; dbSNP:rs141568342 | ||
Mutagenesis | 68 | Loss of activation and phosphorylation. | |||
Mutagenesis | 73 | Impaired activation, phosphorylation by ATM and G2/M transition checkpoint. | |||
Natural variant | VAR_019102 | 85 | found in an osteogenic sarcoma sample; somatic mutation; dbSNP:rs17883862 | ||
Natural variant | VAR_022461 | 117 | in BC; dbSNP:rs28909982 | ||
Natural variant | VAR_022462 | 137 | might influence susceptibility to breast cancer; dbSNP:rs368570187 | ||
Natural variant | VAR_019108 | 145 | in prostate cancer; somatic mutation; dbSNP:rs587781667 | ||
Natural variant | VAR_008554 | 145 | in TPDS4; loss of the ability to interact with and phosphorylate CDC25A and to promote CDC25A degradation in response to ionizing radiation; dbSNP:rs137853007 | ||
Natural variant | VAR_008555 | 157 | might influence susceptibility to different types of cancer; loss of the ability to interact with and phosphorylate CDC25A and to promote CDC25A degradation in response to ionizing radiation; dbSNP:rs17879961 | ||
Natural variant | VAR_019109 | 167 | in prostate cancer; somatic mutation; dbSNP:rs72552322 | ||
Natural variant | VAR_019103 | 180 | in prostate cancer; somatic mutation; dbSNP:rs77130927 | ||
Natural variant | VAR_019110 | 180 | in prostate cancer; somatic mutation; dbSNP:rs137853009 | ||
Natural variant | VAR_019104 | 181 | in prostate cancer; somatic mutation; dbSNP:rs137853010 | ||
Natural variant | VAR_019105 | 181 | in prostate cancer; somatic mutation; dbSNP:rs121908701 | ||
Natural variant | VAR_019106 | 239 | in prostate cancer; germline mutation; dbSNP:rs121908702 | ||
Natural variant | VAR_019111 | 251 | in prostate cancer; uncertain significance; dbSNP:rs587780189 | ||
Natural variant | VAR_019112 | 318 | in prostate cancer; uncertain significance; somatic mutation; dbSNP:rs143611747 | ||
Natural variant | VAR_019113 | 323 | in prostate cancer; somatic mutation; dbSNP:rs750984976 | ||
Natural variant | VAR_019114 | 327 | in prostate cancer; uncertain significance; somatic mutation; dbSNP:rs587780194 | ||
Natural variant | VAR_029154 | 347 | in dbSNP:rs28909980 | ||
Mutagenesis | 347 | Loss of kinase activity and of the ability to phosphorylate CDC25A. | |||
Mutagenesis | 368 | Loss of autophosphorylation activity. | |||
Natural variant | VAR_066012 | 371 | confers a moderate risk of breast cancer; partially reduces kinase activity; dbSNP:rs531398630 | ||
Mutagenesis | 379 | Abrogates autophosphorylation at Ser-379 and prevents ubiquitination. | |||
Mutagenesis | 383 | Loss of phosphorylation in response to ionizing radiation. | |||
Mutagenesis | 387 | Loss of phosphorylation in response to ionizing radiation. | |||
Natural variant | VAR_073020 | 390 | in BC; does not phosphorylate p53/TP53; dbSNP:rs200928781 | ||
Natural variant | VAR_024572 | 406 | in dbSNP:rs200649225 | ||
Natural variant | VAR_022463 | 428 | may increase breast cancer risk; dbSNP:rs137853011 | ||
Natural variant | VAR_021117 | 436 | in dbSNP:rs17882922 | ||
Natural variant | VAR_021118 | 446 | in dbSNP:rs17880867 | ||
Natural variant | VAR_021119 | 447 | in dbSNP:rs17881473 | ||
Natural variant | VAR_021120 | 448 | in dbSNP:rs17886163 | ||
Mutagenesis | 456 | Increased ubiquitination and degradation by the proteasome. | |||
Natural variant | VAR_019115 | 476 | in prostate cancer; somatic mutation | ||
Natural variant | VAR_029155 | 500 | in dbSNP:rs28909981 | ||
Natural variant | VAR_021121 | 501 | in dbSNP:rs17883172 | ||
Natural variant | VAR_021122 | 512 | in dbSNP:rs17882942 | ||
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 2,897 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | ||
---|---|---|---|---|---|---|
Chain | PRO_0000085858 | 1-543 | UniProt | Serine/threonine-protein kinase Chk2 | ||
Modified residue | 62 | UniProt | Phosphoserine; by PLK3 | |||
Modified residue | 68 | UniProt | Phosphothreonine; by ATM and MAP3K20 | |||
Modified residue | 73 | UniProt | Phosphoserine; by PLK3 | |||
Modified residue (large scale data) | 120 | PRIDE | Phosphoserine | |||
Modified residue (large scale data) | 225 | PRIDE | Phosphothreonine | |||
Modified residue (large scale data) | 260 | PRIDE | Phosphoserine | |||
Modified residue (large scale data) | 378 | PRIDE | Phosphothreonine | |||
Modified residue | 379 | UniProt | Phosphoserine; by autocatalysis | |||
Modified residue (large scale data) | 379 | PRIDE | Phosphoserine | |||
Modified residue | 383 | UniProt | Phosphothreonine; by autocatalysis | |||
Modified residue (large scale data) | 383 | PRIDE | Phosphothreonine | |||
Modified residue | 387 | UniProt | Phosphothreonine; by autocatalysis | |||
Modified residue (large scale data) | 389 | PRIDE | Phosphothreonine | |||
Modified residue | 456 | UniProt | Phosphoserine | |||
Post-translational modification
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Gene expression databases
Organism-specific databases
Interaction
Subunit
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Region | 1-66 | Disordered | |||
Compositional bias | 7-66 | Polar residues | |||
Domain | 113-175 | FHA | |||
Domain | 220-486 | Protein kinase | |||
Region | 368-394 | T-loop/activation segment | |||
Region | 506-538 | Disordered | |||
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 13 isoforms produced by Alternative splicing.
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.
- Name1
- NoteLacks enzymatic activity.
- Length543
- Mass (Da)60,915
- Last updated1999-05-01 v1
- MD5 ChecksumD4BFE45A8F3D01CBF5EAC244D893BA1A
O96017-2
- Name2
- Synonymsins2
- NoteLacks enzymatic activity.
O96017-3
- Name3
- Synonymsdel2-12
- Differences from canonical
- 107-487: Missing
O96017-4
- Name4
- Synonymsdel2-3
- NoteLacks enzymatic activity.
- Differences from canonical
- 107-197: Missing
O96017-5
- Name5
- Synonymsdel4
O96017-6
- Name6
- Synonymssub3
O96017-7
- Name7
- Synonymsdel9-12
- NoteLacks enzymatic activity.
O96017-8
- Name8
- Synonymsdel7
O96017-9
- Name9
- Synonymsinsx
- NoteRetains low level of catalytic activity.
- Differences from canonical
- 107-107: E → ETESGHVTQSDLELLLSSDPPASASQSAGIRGVRHHPRPVCSLK
O96017-10
- Name10
- Synonymsiso2
- NoteLacks enzymatic activity.
O96017-11
- Name11
- Synonymsiso1
- Differences from canonical
- 75-392: Missing
O96017-12
- Name12
- Synonymsdel9
- NoteLacks enzymatic activity.
- Differences from canonical
- 337-365: Missing
O96017-13
- Name13
- Differences from canonical
- 1-221: Missing
Computationally mapped potential isoform sequences
There are 13 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A7P0MUT5 | A0A7P0MUT5_HUMAN | CHEK2 | 476 | ||
F8WCV2 | F8WCV2_HUMAN | CHEK2 | 161 | ||
B7ZBF2 | B7ZBF2_HUMAN | CHEK2 | 121 | ||
B7ZBF7 | B7ZBF7_HUMAN | CHEK2 | 295 | ||
B7ZBF8 | B7ZBF8_HUMAN | CHEK2 | 162 | ||
C9JFD7 | C9JFD7_HUMAN | CHEK2 | 207 | ||
H0Y820 | H0Y820_HUMAN | CHEK2 | 276 | ||
H0Y4V6 | H0Y4V6_HUMAN | CHEK2 | 144 | ||
A0AA34QVK6 | A0AA34QVK6_HUMAN | CHEK2 | 337 | ||
H7BZ30 | H7BZ30_HUMAN | CHEK2 | 167 | ||
H7C0V7 | H7C0V7_HUMAN | CHEK2 | 57 | ||
A0A3B3ITA7 | A0A3B3ITA7_HUMAN | CHEK2 | 176 | ||
A0A087X102 | A0A087X102_HUMAN | CHEK2 | 323 |
Features
Showing features for alternative sequence, compositional bias.
Type | ID | Position(s) | Description | ||
---|---|---|---|---|---|
Alternative sequence | VSP_045148 | 1-221 | in isoform 13 | ||
Compositional bias | 7-66 | Polar residues | |||
Alternative sequence | VSP_014556 | 75-392 | in isoform 11 | ||
Alternative sequence | VSP_014557 | 107 | in isoform 9 | ||
Alternative sequence | VSP_014558 | 107-197 | in isoform 4 | ||
Alternative sequence | VSP_014559 | 107-487 | in isoform 3 | ||
Alternative sequence | VSP_014560 | 131-147 | in isoform 10 | ||
Alternative sequence | VSP_014561 | 148-543 | in isoform 10 | ||
Alternative sequence | VSP_014562 | 150-165 | in isoform 6 | ||
Alternative sequence | VSP_014563 | 166-543 | in isoform 6 | ||
Alternative sequence | VSP_014564 | 198-224 | in isoform 2 | ||
Alternative sequence | VSP_014565 | 199-203 | in isoform 5 | ||
Alternative sequence | VSP_014566 | 204-543 | in isoform 5 | ||
Alternative sequence | VSP_014567 | 228-234 | in isoform 2 | ||
Alternative sequence | VSP_014568 | 235-543 | in isoform 2 | ||
Alternative sequence | VSP_014569 | 283-289 | in isoform 8 | ||
Alternative sequence | VSP_014570 | 290-543 | in isoform 8 | ||
Alternative sequence | VSP_014572 | 337-339 | in isoform 7 | ||
Alternative sequence | VSP_014571 | 337-365 | in isoform 12 | ||
Alternative sequence | VSP_014573 | 340-543 | in isoform 7 | ||
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF086904 EMBL· GenBank· DDBJ | AAC83693.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ131197 EMBL· GenBank· DDBJ | CAA10319.1 EMBL· GenBank· DDBJ | mRNA | ||
AF096279 EMBL· GenBank· DDBJ | AAD11784.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551295 EMBL· GenBank· DDBJ | AAS58456.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551296 EMBL· GenBank· DDBJ | AAS58457.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551297 EMBL· GenBank· DDBJ | AAS58458.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551298 EMBL· GenBank· DDBJ | AAS58459.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551299 EMBL· GenBank· DDBJ | AAS58460.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551300 EMBL· GenBank· DDBJ | AAS58461.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551301 EMBL· GenBank· DDBJ | AAS58462.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551302 EMBL· GenBank· DDBJ | AAS58463.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551303 EMBL· GenBank· DDBJ | AAS58464.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551304 EMBL· GenBank· DDBJ | AAS58465.1 EMBL· GenBank· DDBJ | mRNA | ||
AY551305 EMBL· GenBank· DDBJ | AAS58466.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456418 EMBL· GenBank· DDBJ | CAG30304.1 EMBL· GenBank· DDBJ | mRNA | ||
AF174135 EMBL· GenBank· DDBJ | AAD48504.1 EMBL· GenBank· DDBJ | mRNA | ||
AB040105 EMBL· GenBank· DDBJ | BAB17231.1 EMBL· GenBank· DDBJ | mRNA | ||
AK290754 EMBL· GenBank· DDBJ | BAF83443.1 EMBL· GenBank· DDBJ | mRNA | ||
AF217975 EMBL· GenBank· DDBJ | AAG17218.1 EMBL· GenBank· DDBJ | mRNA | ||
AY800241 EMBL· GenBank· DDBJ | AAV41895.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AL117330 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AL121825 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471095 EMBL· GenBank· DDBJ | EAW59755.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC004207 EMBL· GenBank· DDBJ | AAH04207.1 EMBL· GenBank· DDBJ | mRNA |