UniProtKB - Q91ZN7 (CHK1_RAT)
Serine/threonine-protein kinase Chk1
Chek1
Functioni
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]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination. Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA (By similarity).
May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity).
May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest. Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (By similarity).
Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (By similarity).
By similarityCatalytic activityi
Activity regulationi
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 38 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 130 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 15 – 23 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB-KW
- histone kinase activity (H3-T11 specific) Source: UniProtKB
- protein domain specific binding Source: RGD
- protein kinase activity Source: RGD
- protein serine/threonine/tyrosine kinase activity Source: RHEA
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: RHEA
GO - Biological processi
- apoptotic process Source: RGD
- apoptotic process involved in development Source: RGD
- cellular response to caffeine Source: RGD
- cellular response to DNA damage stimulus Source: UniProtKB
- cellular response to mechanical stimulus Source: RGD
- cellular response to organic substance Source: RGD
- DNA damage checkpoint signaling Source: UniProtKB
- DNA damage induced protein phosphorylation Source: RGD
- DNA repair Source: RGD
- epigenetic maintenance of chromatin in transcription-competent conformation Source: UniProtKB
- G2/M transition of mitotic cell cycle Source: RGD
- inner cell mass cell proliferation Source: RGD
- intracellular signal transduction Source: GO_Central
- mitotic G2/M transition checkpoint Source: UniProtKB
- mitotic G2 DNA damage checkpoint signaling Source: RGD
- negative regulation of DNA biosynthetic process Source: RGD
- negative regulation of G2/M transition of mitotic cell cycle Source: RGD
- negative regulation of mitotic nuclear division Source: UniProtKB
- nucleus organization Source: RGD
- peptidyl-threonine phosphorylation Source: UniProtKB
- positive regulation of cell cycle Source: RGD
- protein phosphorylation Source: RGD
- regulation of cell population proliferation Source: RGD
- regulation of double-strand break repair via homologous recombination Source: UniProtKB
- regulation of gene expression Source: RGD
- regulation of histone H3-K9 acetylation Source: UniProtKB
- regulation of mitotic centrosome separation Source: UniProtKB
- regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Cell cycle, DNA damage, DNA repair |
Ligand | ATP-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-RNO-1433557, Signaling by SCF-KIT R-RNO-176187, Activation of ATR in response to replication stress R-RNO-5693607, Processing of DNA double-strand break ends R-RNO-5693616, Presynaptic phase of homologous DNA pairing and strand exchange R-RNO-6804756, Regulation of TP53 Activity through Phosphorylation R-RNO-69473, G2/M DNA damage checkpoint R-RNO-69601, Ubiquitin Mediated Degradation of Phosphorylated Cdc25A R-RNO-8953750, Transcriptional Regulation by E2F6 |
SABIO-RKi | Q91ZN7 |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase Chk1 (EC:2.7.11.1By similarity)Alternative name(s): CHK1 checkpoint homolog Checkpoint kinase-1 |
Gene namesi | Name:Chek1 Synonyms:Chk1 |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 620545, Chek1 |
Subcellular locationi
Cytoskeleton
- centrosome By similarity
Cytoplasm and Cytosol
- Cytoplasm By similarity
Nucleus
- Nucleus By similarity
Other locations
- Chromosome By similarity
Note: Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B. Proteolytic cleavage at the C-terminus by SPRTN promotes removal from chromatin.By similarity
Cytoskeleton
- centrosome Source: UniProtKB
Nucleus
- condensed nuclear chromosome Source: UniProtKB
- nucleoplasm Source: Ensembl
- nucleus Source: UniProtKB
Other locations
- chromatin Source: UniProtKB
- chromosome, telomeric region Source: Ensembl
- cytoplasm Source: RGD
- protein-containing complex Source: RGD
- replication fork Source: RGD
Keywords - Cellular componenti
Chromosome, Cytoplasm, Cytoskeleton, NucleusPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000085850 | 1 – 476 | Serine/threonine-protein kinase Chk1Add BLAST | 476 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Cross-linki | 132 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 280 | Phosphoserine; by PKB/AKT1By similarity | 1 | |
Modified residuei | 286 | PhosphoserineBy similarity | 1 | |
Modified residuei | 296 | PhosphoserineBy similarity | 1 | |
Modified residuei | 301 | PhosphoserineBy similarity | 1 | |
Modified residuei | 317 | Phosphoserine; by ATM and ATRBy similarity | 1 | |
Modified residuei | 345 | Phosphoserine; by ATM and ATRBy similarity | 1 | |
Cross-linki | 436 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity | ||
Modified residuei | 463 | PhosphoserineBy similarity | 1 | |
Modified residuei | 467 | PhosphoserineBy similarity | 1 | |
Modified residuei | 468 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
Isopeptide bond, Phosphoprotein, Ubl conjugationProteomic databases
PaxDbi | Q91ZN7 |
PTM databases
PhosphoSitePlusi | Q91ZN7 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSRNOG00000031896, Expressed in liver and 20 other tissues |
ExpressionAtlasi | Q91ZN7, baseline and differential |
Genevisiblei | Q91ZN7, RN |
Interactioni
Subunit structurei
Interacts (phosphorylated by ATR) with RAD51.
Interacts with and phosphorylates CLSPN, an adapter protein that regulates the ATR-dependent phosphorylation of CHEK1.
Interacts with BRCA1.
Interacts with and phosphorylates CDC25A, CDC25B and CDC25C.
Interacts with FBXO6, which regulates CHEK1.
Interacts with PPM1D, which regulates CHEK1 through dephosphorylation.
Interacts with TIMELESS; DNA damage-dependent.
Interacts with FEM1B; activates CHEK1 in response to stress.
Interacts with TLK1.
Interacts with XPO1 and YWHAZ.
Interacts with CDK5RAP3; antagonizes CHEK1.
By similarityGO - Molecular functioni
- protein domain specific binding Source: RGD
Protein-protein interaction databases
BioGRIDi | 250797, 2 interactors |
STRINGi | 10116.ENSRNOP00000011226 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 9 – 265 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 257 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 265 | Interaction with CLSPNBy similarityAdd BLAST | 265 | |
Regioni | 267 – 329 | DisorderedSequence analysisAdd BLAST | 63 | |
Regioni | 391 – 476 | Autoinhibitory regionBy similarityAdd BLAST | 86 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 280 – 329 | Polar residuesSequence analysisAdd BLAST | 50 |
Domaini
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG0590, Eukaryota |
GeneTreei | ENSGT00940000156655 |
HOGENOMi | CLU_000288_59_8_1 |
InParanoidi | Q91ZN7 |
OrthoDBi | 698464at2759 |
PhylomeDBi | Q91ZN7 |
TreeFami | TF351441 |
Family and domain databases
CDDi | cd14069, STKc_Chk1, 1 hit |
InterProi | View protein in InterPro IPR034670, Chk1_catalytic_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative promoter usage. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAVPFVEDWD LVQTLGEGAY GEVQLAVNRI TEEAVAVKIV DMKRAIDCPE
60 70 80 90 100
NIKKEICINK MLNHENVVKF YGHRREGNIQ YLFLEYCSGG ELFDRIEPDI
110 120 130 140 150
GMPEQDAQRF FHQLMAGVVY LHGIGITHRD IKPENLLLDE RDNLKISDFG
160 170 180 190 200
LATVFRHNNR ERLLNKMCGT LPYVAPELLK RKEFHAEPVD VWSCGIVLTA
210 220 230 240 250
MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA LLHKILVENP
260 270 280 290 300
SARITIPDIK KDRWYNKPLN RGAKRPRATS GGMSESSSGF SKHIHSNLDF
310 320 330 340 350
SPINSGSSEE NVKFSSSQPE PRTGLSLWDT GPSNVDKLVQ GISFSQPTCP
360 370 380 390 400
DHMLVNSQLL GTPGSSQNPW QRLVKRMTRF FTKLDADKSY QCLKETFEKL
410 420 430 440 450
GYQWKKSCMN QVTVSTMDRR NNKLIFKINL VEMDEKILVD FRLSKGDGLE
460 470
FKRHFLKIKG KLSDIVSSQK VWFPVT
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketB4F7C9 | B4F7C9_RAT | Dolichyl-diphosphooligosaccharide--... | Stt3a Chek1 | 705 | Annotation score: | ||
A0A0G2JWH5 | A0A0G2JWH5_RAT | Dolichyl-diphosphooligosaccharide--... | Stt3a Chek1 | 773 | Annotation score: |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_015770 | 1 – 282 | Missing in isoform 2. 1 PublicationAdd BLAST | 282 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF414135 mRNA Translation: AAK98619.1 AF414136 mRNA Translation: AAK98620.1 AF443592 mRNA Translation: AAL37894.1 |
RefSeqi | NP_536325.1, NM_080400.1 [Q91ZN7-1] XP_008764264.1, XM_008766042.2 [Q91ZN7-1] XP_008764265.1, XM_008766043.1 [Q91ZN7-1] |
Genome annotation databases
Ensembli | ENSRNOT00000011226; ENSRNOP00000011226; ENSRNOG00000031896 [Q91ZN7-1] ENSRNOT00000090161; ENSRNOP00000070708; ENSRNOG00000031896 [Q91ZN7-2] |
GeneIDi | 140583 |
KEGGi | rno:140583 |
UCSCi | RGD:620545, rat [Q91ZN7-1] |
Keywords - Coding sequence diversityi
Alternative promoter usageSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF414135 mRNA Translation: AAK98619.1 AF414136 mRNA Translation: AAK98620.1 AF443592 mRNA Translation: AAL37894.1 |
RefSeqi | NP_536325.1, NM_080400.1 [Q91ZN7-1] XP_008764264.1, XM_008766042.2 [Q91ZN7-1] XP_008764265.1, XM_008766043.1 [Q91ZN7-1] |
3D structure databases
SMRi | Q91ZN7 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 250797, 2 interactors |
STRINGi | 10116.ENSRNOP00000011226 |
PTM databases
PhosphoSitePlusi | Q91ZN7 |
Proteomic databases
PaxDbi | Q91ZN7 |
Genome annotation databases
Ensembli | ENSRNOT00000011226; ENSRNOP00000011226; ENSRNOG00000031896 [Q91ZN7-1] ENSRNOT00000090161; ENSRNOP00000070708; ENSRNOG00000031896 [Q91ZN7-2] |
GeneIDi | 140583 |
KEGGi | rno:140583 |
UCSCi | RGD:620545, rat [Q91ZN7-1] |
Organism-specific databases
CTDi | 1111 |
RGDi | 620545, Chek1 |
Phylogenomic databases
eggNOGi | KOG0590, Eukaryota |
GeneTreei | ENSGT00940000156655 |
HOGENOMi | CLU_000288_59_8_1 |
InParanoidi | Q91ZN7 |
OrthoDBi | 698464at2759 |
PhylomeDBi | Q91ZN7 |
TreeFami | TF351441 |
Enzyme and pathway databases
Reactomei | R-RNO-1433557, Signaling by SCF-KIT R-RNO-176187, Activation of ATR in response to replication stress R-RNO-5693607, Processing of DNA double-strand break ends R-RNO-5693616, Presynaptic phase of homologous DNA pairing and strand exchange R-RNO-6804756, Regulation of TP53 Activity through Phosphorylation R-RNO-69473, G2/M DNA damage checkpoint R-RNO-69601, Ubiquitin Mediated Degradation of Phosphorylated Cdc25A R-RNO-8953750, Transcriptional Regulation by E2F6 |
SABIO-RKi | Q91ZN7 |
Miscellaneous databases
PROi | PR:Q91ZN7 |
Gene expression databases
Bgeei | ENSRNOG00000031896, Expressed in liver and 20 other tissues |
ExpressionAtlasi | Q91ZN7, baseline and differential |
Genevisiblei | Q91ZN7, RN |
Family and domain databases
CDDi | cd14069, STKc_Chk1, 1 hit |
InterProi | View protein in InterPro IPR034670, Chk1_catalytic_dom IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | CHK1_RAT | |
Accessioni | Q91ZN7Primary (citable) accession number: Q91ZN7 Secondary accession number(s): Q91ZN6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | September 27, 2005 |
Last sequence update: | December 1, 2001 | |
Last modified: | February 23, 2022 | |
This is version 153 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families