Q6DE87 · CHK1_XENLA
- ProteinSerine/threonine-protein kinase Chk1
- Genechek1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids474 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. Recognizes the substrate consensus sequence [R-X-X-S/T]. Phosphorylates wee1 at 'Ser-549' and cdc25c at 'Ser-287', which creates binding sites for 14-3-3 proteins which activate wee1 and inhibit cdc25c. Phosphorylates cdc25a at 'Ser-504' which prevents the interaction of cdc25a with CDK2-cyclin E1, CDC2-cyclin A1 and CDC2-cyclin B1. This inhibitory effect does not require 14-3-3 protein binding. Activation of wee1 and inhibition of CDC25 results in increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and consequent inhibition of cell cycle progression. May promote DNA repair, regulate chromatin assembly and the transcription of genes that regulate cell-cycle progression. May also play a role in replication fork maintenance.
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Activity regulation
Activated through phosphorylation by atr or atm in response to DNA damage or inhibition of DNA replication.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | centrosome | |
Cellular Component | chromatin | |
Cellular Component | condensed nuclear chromosome | |
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | histone H3T11 kinase activity | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | chromatin remodeling | |
Biological Process | DNA damage checkpoint signaling | |
Biological Process | DNA damage response | |
Biological Process | mitotic G2 DNA damage checkpoint signaling | |
Biological Process | negative regulation of gene expression, epigenetic | |
Biological Process | negative regulation of mitotic nuclear division | |
Biological Process | peptidyl-threonine phosphorylation | |
Biological Process | protein phosphorylation | |
Biological Process | regulation of double-strand break repair via homologous recombination | |
Biological Process | regulation of mitotic centrosome separation | |
Biological Process | signal transduction in response to DNA damage |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase Chk1
- EC number
- Alternative names
Gene names
Organism names
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Anura > Pipoidea > Pipidae > Xenopodinae > Xenopus > Xenopus
Accessions
- Primary accessionQ6DE87
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 54 | Abolishes interaction with CLSPN. Abrogates phosphorylation at S-344 and kinase activation during checkpoint signaling. | ||||
Sequence: K → A | ||||||
Mutagenesis | 129 | Abolishes interaction with CLSPN, abrogates phosphorylation at S-344 and abolishes kinase activity. | ||||
Sequence: R → A | ||||||
Mutagenesis | 135 | Abolishes kinase activity; no effect on interaction with CLSPN. | ||||
Sequence: N → A | ||||||
Mutagenesis | 148 | Abolishes kinase activity. | ||||
Sequence: D → A | ||||||
Mutagenesis | 153 | Abolishes interaction with CLSPN. Abrogates phosphorylation at S-344 and kinase activation during checkpoint signaling. | ||||
Sequence: T → A | ||||||
Mutagenesis | 162 | Abolishes interaction with CLSPN and kinase activation during checkpoint signaling. No effect on phosphorylation at S-344. | ||||
Sequence: R → A | ||||||
Mutagenesis | 314 | Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-344; A-356 and A-365. | ||||
Sequence: T → A | ||||||
Mutagenesis | 314 | Impairs autoinhibition by the AIR domain; when associated with D-344; D-356 and D-365. | ||||
Sequence: T → D | ||||||
Mutagenesis | 314 | Impairs autoinhibition by the AIR domain; when associated with E-344; E-356 and E-365. | ||||
Sequence: T → E | ||||||
Mutagenesis | 344 | Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-314; A-356 and A-365. | ||||
Sequence: S → A | ||||||
Mutagenesis | 344 | Impairs autoinhibition by the AIR domain; when associated with D-314; D-356 and D-365. | ||||
Sequence: S → D | ||||||
Mutagenesis | 344 | Impairs autoinhibition by the AIR domain; when associated with E-314; E-356 and E-365. | ||||
Sequence: S → E | ||||||
Mutagenesis | 356 | Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-314; A-344 and A-365. | ||||
Sequence: S → A | ||||||
Mutagenesis | 356 | Impairs autoinhibition by the AIR domain; when associated with D-314; D-344 and D-365. | ||||
Sequence: S → D | ||||||
Mutagenesis | 356 | Impairs autoinhibition by the AIR domain; when associated with E-314; E-344 and E-365. | ||||
Sequence: S → E | ||||||
Mutagenesis | 365 | Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-314; A-344 and A-356. | ||||
Sequence: S → A | ||||||
Mutagenesis | 365 | Impairs autoinhibition by the AIR domain; when associated with D-314; D-344 and D-356. | ||||
Sequence: S → D | ||||||
Mutagenesis | 365 | Impairs autoinhibition by the AIR domain; when associated with E-314; E-344 and E-356. | ||||
Sequence: S → E | ||||||
Mutagenesis | 374-375 | Impairs autoinhibition and abrogates nuclear localization. | ||||
Sequence: KR → AA | ||||||
Mutagenesis | 374-380 | Induces hyperphosphorylation and enhances kinase activity. | ||||
Sequence: Missing | ||||||
Mutagenesis | 377 | Induces hyperphosphorylation and enhances kinase activity and cell cycle arrest. Abolishes interaction with CLSPN. | ||||
Sequence: T → A | ||||||
Mutagenesis | 377 | Enhances kinase activity. | ||||
Sequence: T → E | ||||||
Mutagenesis | 451-452 | Enhances kinase activity. | ||||
Sequence: KR → AA | ||||||
Mutagenesis | 456-458 | Enhances kinase activity and abrogates nuclear localization. | ||||
Sequence: KIK → AAA |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000085852 | 1-474 | Serine/threonine-protein kinase Chk1 | |||
Sequence: MAVPFVEDWDLVQTLGEGAYGEVQLAVNRKTEEAVAVKIVDMTRAADCPENIKKEICINRMLSHTNIVRFYGHRREGNIQYLFLEYCRGGELFDRIEPDVGMPEQDAQKFFQQLIAGVEYLHSIGITHRDIKPENLLLDERDQLKISDFGLATVFRHNGKERLLNKMCGTLPYVAPELIKSRAFHADPVDVWSCGIVLTAMLAGELPWDQPNEVCQEYCDWKEKNHYLTPWKKISATPLALLCKMLTENPQSRITIPDIKKDRWFTEIIKKGLKRSRVISGGSSDSSVLCKQIRSDIDISHFSHSEEKTALSSTQPEPRTALATWDSNSSYIDNLVQGKGISFSQPACPDNMLLNSQLIGTPGSSQNVWQRLVKRMTRFFTKVNAESSYSNLMDTCEKMGYVLKKSCANEVTLSTTDRRNNKLIFKVNLVEMEDRILLDFRLSKGDGLEFKRHFLKIKKKMDAVVAVQKVLPDT | ||||||
Modified residue | 314 | Phosphothreonine; by ATR | ||||
Sequence: T | ||||||
Modified residue | 344 | Phosphoserine; by ATR | ||||
Sequence: S | ||||||
Modified residue | 356 | Phosphoserine; by ATR | ||||
Sequence: S | ||||||
Modified residue | 365 | Phosphoserine; by ATR | ||||
Sequence: S |
Post-translational modification
Phosphorylated by atm in response to ionizing irradiation (By similarity).
Phosphorylated by atr at Thr-314, Ser-344, Ser-356 and Ser-365 in response to various stimuli that cause checkpoint activation, such as hydrogen peroxide-induced oxidative stress (PubMed:23754435).
Phosphorylation impairs binding of the C-terminal autoinhibitory region (AIR) to the kinase domain and thereby enhances kinase activity
Phosphorylated by atr at Thr-314, Ser-344, Ser-356 and Ser-365 in response to various stimuli that cause checkpoint activation, such as hydrogen peroxide-induced oxidative stress (PubMed:23754435).
Phosphorylation impairs binding of the C-terminal autoinhibitory region (AIR) to the kinase domain and thereby enhances kinase activity
Keywords
- PTM
PTM databases
Expression
Developmental stage
Expressed throughout development. Transiently activated by ATR-mediated phosphorylation from the midblastula transition (MBT) to the initial gastrula stage. Developmentally regulated activation of the DNA replication checkpoint may occur as the nucleo-cytoplasmic ratio increases and maternal replication factors are depleted. Elongation of the embryonic cell cycle may allow time for the transcription of genes that initiate the switch from maternal to zygotic control of embryogenesis.
Gene expression databases
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-265 | Interaction with CLSPN | ||||
Sequence: MAVPFVEDWDLVQTLGEGAYGEVQLAVNRKTEEAVAVKIVDMTRAADCPENIKKEICINRMLSHTNIVRFYGHRREGNIQYLFLEYCRGGELFDRIEPDVGMPEQDAQKFFQQLIAGVEYLHSIGITHRDIKPENLLLDERDQLKISDFGLATVFRHNGKERLLNKMCGTLPYVAPELIKSRAFHADPVDVWSCGIVLTAMLAGELPWDQPNEVCQEYCDWKEKNHYLTPWKKISATPLALLCKMLTENPQSRITIPDIKKDRWF | ||||||
Domain | 9-265 | Protein kinase | ||||
Sequence: WDLVQTLGEGAYGEVQLAVNRKTEEAVAVKIVDMTRAADCPENIKKEICINRMLSHTNIVRFYGHRREGNIQYLFLEYCRGGELFDRIEPDVGMPEQDAQKFFQQLIAGVEYLHSIGITHRDIKPENLLLDERDQLKISDFGLATVFRHNGKERLLNKMCGTLPYVAPELIKSRAFHADPVDVWSCGIVLTAMLAGELPWDQPNEVCQEYCDWKEKNHYLTPWKKISATPLALLCKMLTENPQSRITIPDIKKDRWF | ||||||
Region | 360-474 | Autoinhibitory region | ||||
Sequence: GTPGSSQNVWQRLVKRMTRFFTKVNAESSYSNLMDTCEKMGYVLKKSCANEVTLSTTDRRNNKLIFKVNLVEMEDRILLDFRLSKGDGLEFKRHFLKIKKKMDAVVAVQKVLPDT | ||||||
Region | 367-474 | Required for nuclear localization | ||||
Sequence: NVWQRLVKRMTRFFTKVNAESSYSNLMDTCEKMGYVLKKSCANEVTLSTTDRRNNKLIFKVNLVEMEDRILLDFRLSKGDGLEFKRHFLKIKKKMDAVVAVQKVLPDT |
Domain
The autoinhibitory region (AIR) binds to the kinase domain and inhibits its activity.
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length474
- Mass (Da)53,975
- Last updated2005-09-27 v2
- ChecksumB6D09B14838F1C0A
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 165 | in Ref. 1; AAC64262 and 2; BAA34058 | ||||
Sequence: N → S | ||||||
Sequence conflict | 230-231 | in Ref. 2; BAA34058 | ||||
Sequence: Missing | ||||||
Sequence conflict | 232 | in Ref. 3; AAF00098 | ||||
Sequence: K → E | ||||||
Sequence conflict | 238 | in Ref. 2; BAA34058 | ||||
Sequence: P → L | ||||||
Sequence conflict | 243 | in Ref. 1; AAC64262 and 2; BAA34058 | ||||
Sequence: C → G | ||||||
Sequence conflict | 307 | in Ref. 3; AAF00098 and 4; AAH77249 | ||||
Sequence: Missing | ||||||
Sequence conflict | 331-333 | in Ref. 1; AAC64262 and 2; BAA34058 | ||||
Sequence: YID → DIN | ||||||
Sequence conflict | 472-473 | in Ref. 1; AAC64262 and 2; BAA34058 | ||||
Sequence: PD → SA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF053120 EMBL· GenBank· DDBJ | AAC64262.1 EMBL· GenBank· DDBJ | mRNA | ||
AB019218 EMBL· GenBank· DDBJ | BAA34058.1 EMBL· GenBank· DDBJ | mRNA | ||
AF117816 EMBL· GenBank· DDBJ | AAF00098.1 EMBL· GenBank· DDBJ | mRNA | ||
BC077249 EMBL· GenBank· DDBJ | AAH77249.1 EMBL· GenBank· DDBJ | mRNA |