Q6DE87 · CHK1_XENLA

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

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.

TypeIDPosition(s)Description
Binding site15-23ATP (UniProtKB | ChEBI)
Binding site38ATP (UniProtKB | ChEBI)
Active site130Proton acceptor

GO annotations

AspectTerm
Cellular Componentcentrosome
Cellular Componentchromatin
Cellular Componentcondensed nuclear chromosome
Cellular Componentcytoplasm
Cellular Componentnucleus
Molecular FunctionATP binding
Molecular Functionhistone H3T11 kinase activity
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Biological Processchromatin remodeling
Biological ProcessDNA damage checkpoint signaling
Biological ProcessDNA damage response
Biological Processmitotic G2 DNA damage checkpoint signaling
Biological Processnegative regulation of gene expression, epigenetic
Biological Processnegative regulation of mitotic nuclear division
Biological Processpeptidyl-threonine phosphorylation
Biological Processprotein phosphorylation
Biological Processregulation of double-strand break repair via homologous recombination
Biological Processregulation of mitotic centrosome separation
Biological Processsignal transduction in response to DNA damage

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Serine/threonine-protein kinase Chk1
  • EC number
  • Alternative names
    • CHK1 checkpoint homolog
    • Checkpoint kinase-1 (xChk1)

Gene names

    • Name
      chek1
    • Synonyms
      chk1

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Amphibia > Batrachia > Anura > Pipoidea > Pipidae > Xenopodinae > Xenopus > Xenopus

Accessions

  • Primary accession
    Q6DE87
  • Secondary accessions
    • Q78CK1
    • Q78DQ2
    • Q9YI18

Proteomes

Organism-specific databases

Phenotypes & Variants

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis54Abolishes interaction with CLSPN. Abrogates phosphorylation at S-344 and kinase activation during checkpoint signaling.
Mutagenesis129Abolishes interaction with CLSPN, abrogates phosphorylation at S-344 and abolishes kinase activity.
Mutagenesis135Abolishes kinase activity; no effect on interaction with CLSPN.
Mutagenesis148Abolishes kinase activity.
Mutagenesis153Abolishes interaction with CLSPN. Abrogates phosphorylation at S-344 and kinase activation during checkpoint signaling.
Mutagenesis162Abolishes interaction with CLSPN and kinase activation during checkpoint signaling. No effect on phosphorylation at S-344.
Mutagenesis314Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-344; A-356 and A-365.
Mutagenesis314Impairs autoinhibition by the AIR domain; when associated with D-344; D-356 and D-365.
Mutagenesis314Impairs autoinhibition by the AIR domain; when associated with E-344; E-356 and E-365.
Mutagenesis344Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-314; A-356 and A-365.
Mutagenesis344Impairs autoinhibition by the AIR domain; when associated with D-314; D-356 and D-365.
Mutagenesis344Impairs autoinhibition by the AIR domain; when associated with E-314; E-356 and E-365.
Mutagenesis356Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-314; A-344 and A-365.
Mutagenesis356Impairs autoinhibition by the AIR domain; when associated with D-314; D-344 and D-365.
Mutagenesis356Impairs autoinhibition by the AIR domain; when associated with E-314; E-344 and E-365.
Mutagenesis365Abrogates phosphorylation and activation during checkpoint signaling; when associated with A-314; A-344 and A-356.
Mutagenesis365Impairs autoinhibition by the AIR domain; when associated with D-314; D-344 and D-356.
Mutagenesis365Impairs autoinhibition by the AIR domain; when associated with E-314; E-344 and E-356.
Mutagenesis374-375Impairs autoinhibition and abrogates nuclear localization.
Mutagenesis374-380Induces hyperphosphorylation and enhances kinase activity.
Mutagenesis377Induces hyperphosphorylation and enhances kinase activity and cell cycle arrest. Abolishes interaction with CLSPN.
Mutagenesis377Enhances kinase activity.
Mutagenesis451-452Enhances kinase activity.
Mutagenesis456-458Enhances kinase activity and abrogates nuclear localization.

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000858521-474Serine/threonine-protein kinase Chk1
Modified residue314Phosphothreonine; by ATR
Modified residue344Phosphoserine; by ATR
Modified residue356Phosphoserine; by ATR
Modified residue365Phosphoserine; by ATR

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

Keywords

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

    • 398191Expressed in ovary and 18 other cell types or tissues

Interaction

Subunit

Interacts with and phosphorylates clspn, an adapter protein that regulates the ATR-dependent phosphorylation of chek1. Interacts with apex2.L (PubMed:23754435).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, domain.

TypeIDPosition(s)Description
Region1-265Interaction with CLSPN
Domain9-265Protein kinase
Region360-474Autoinhibitory region
Region367-474Required for nuclear localization

Domain

The autoinhibitory region (AIR) binds to the kinase domain and inhibits its activity.

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    474
  • Mass (Da)
    53,975
  • Last updated
    2005-09-27 v2
  • Checksum
    B6D09B14838F1C0A
MAVPFVEDWDLVQTLGEGAYGEVQLAVNRKTEEAVAVKIVDMTRAADCPENIKKEICINRMLSHTNIVRFYGHRREGNIQYLFLEYCRGGELFDRIEPDVGMPEQDAQKFFQQLIAGVEYLHSIGITHRDIKPENLLLDERDQLKISDFGLATVFRHNGKERLLNKMCGTLPYVAPELIKSRAFHADPVDVWSCGIVLTAMLAGELPWDQPNEVCQEYCDWKEKNHYLTPWKKISATPLALLCKMLTENPQSRITIPDIKKDRWFTEIIKKGLKRSRVISGGSSDSSVLCKQIRSDIDISHFSHSEEKTALSSTQPEPRTALATWDSNSSYIDNLVQGKGISFSQPACPDNMLLNSQLIGTPGSSQNVWQRLVKRMTRFFTKVNAESSYSNLMDTCEKMGYVLKKSCANEVTLSTTDRRNNKLIFKVNLVEMEDRILLDFRLSKGDGLEFKRHFLKIKKKMDAVVAVQKVLPDT

Features

Showing features for sequence conflict.

TypeIDPosition(s)Description
Sequence conflict165in Ref. 1; AAC64262 and 2; BAA34058
Sequence conflict230-231in Ref. 2; BAA34058
Sequence conflict232in Ref. 3; AAF00098
Sequence conflict238in Ref. 2; BAA34058
Sequence conflict243in Ref. 1; AAC64262 and 2; BAA34058
Sequence conflict307in Ref. 3; AAF00098 and 4; AAH77249
Sequence conflict331-333in Ref. 1; AAC64262 and 2; BAA34058
Sequence conflict472-473in Ref. 1; AAC64262 and 2; BAA34058

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
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

Genome annotation databases

Similar Proteins

Disclaimer

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