Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Serine/threonine-protein kinase Chk1

Gene

Chek1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

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. This inhibits their activity through proteasomal degradation, nucleo-cytoplasmic shuttling and inhibition by proteins of the 13-3-3 family. 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, 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. 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. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Activity regulationi

Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication. Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei38ATPPROSITE-ProRule annotation1
Active sitei130Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi15 – 23ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, DNA damage, DNA repair
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

SABIO-RKiQ91ZN7

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase Chk1 (EC:2.7.11.1)
Alternative name(s):
CHK1 checkpoint homolog
Checkpoint kinase-1
Gene namesi
Name:Chek1
Synonyms:Chk1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi620545 Chek1

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

Cytoplasm, Cytoskeleton, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000858501 – 476Serine/threonine-protein kinase Chk1Add BLAST476

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei280Phosphoserine; by PKB/AKT1By similarity1
Modified residuei286PhosphoserineBy similarity1
Modified residuei296PhosphoserineBy similarity1
Modified residuei301PhosphoserineBy similarity1
Modified residuei317Phosphoserine; by ATM and ATRBy similarity1
Modified residuei345Phosphoserine; by ATM and ATRBy similarity1
Cross-linki436Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei463PhosphoserineBy similarity1
Modified residuei467PhosphoserineBy similarity1
Modified residuei468PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication. Phosphorylated by ATM in response to ionizing irradiation. ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity. Phosphorylation at Ser-345 induces a change in the conformation of the protein, activates the kinase activity and is a prerequisite for interaction with FBXO6 and subsequent ubiquitination at Lys-436. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention. Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell cycle arrest. Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination. Also phosphorylated at undefined residues during mitotic arrest, resulting in decreased activity (By similarity).By similarity
Ubiquitinated. Mono or diubiquitination promotes nuclear exclusion. The activated form (phosphorylated on Ser-345) is polyubiquitinated at Lys-436 by some SCF-type E3 ubiquitin ligase complex containing FBXO6 promoting its degradation. Ubiquitination and degradation are required to terminate the checkpoint and ensure that activated CHEK1 does not accumulate as cells progress through S phase, when replication forks encounter transient impediments during normal DNA replication (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ91ZN7
PRIDEiQ91ZN7

PTM databases

iPTMnetiQ91ZN7
PhosphoSitePlusiQ91ZN7

Expressioni

Tissue specificityi

Isoform 1 is expressed in brain, heart, liver, lung, skeletal muscle, spleen and testis. Isoform 2 is expressed only in liver.1 Publication

Gene expression databases

BgeeiENSRNOG00000031896 Expressed in 9 organ(s), highest expression level in liver
ExpressionAtlasiQ91ZN7 baseline and differential
GenevisibleiQ91ZN7 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 similarity

Protein-protein interaction databases

BioGridi250797, 1 interactor
STRINGi10116.ENSRNOP00000011226

Structurei

3D structure databases

ProteinModelPortaliQ91ZN7
SMRiQ91ZN7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini9 – 265Protein kinasePROSITE-ProRule annotationAdd BLAST257

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 265Interaction with CLSPNBy similarityAdd BLAST265
Regioni391 – 476Autoinhibitory regionBy similarityAdd BLAST86

Domaini

The autoinhibitory region (AIR) inhibits the activity of the kinase domain.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG0590 Eukaryota
ENOG410XQ0D LUCA
GeneTreeiENSGT00390000015238
HOGENOMiHOG000216658
HOVERGENiHBG002590
InParanoidiQ91ZN7
KOiK02216
PhylomeDBiQ91ZN7
TreeFamiTF351441

Family and domain databases

CDDicd14069 STKc_Chk1, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q91ZN7-1) [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
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
Length:476
Mass (Da):54,428
Last modified:December 1, 2001 - v1
Checksum:i5635614A3E5B4657
GO
Isoform 2 (identifier: Q91ZN7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-282: Missing.

Show »
Length:194
Mass (Da):22,102
Checksum:i1E1B1CA8B0C4D7AC
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B4F7C9B4F7C9_RAT
Serine/threonine-protein kinase Chk...
Stt3a Chek1
705Annotation score:
A0A0G2JWH5A0A0G2JWH5_RAT
Serine/threonine-protein kinase Chk...
Stt3a Chek1
773Annotation score:

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0157701 – 282Missing in isoform 2. 1 PublicationAdd BLAST282

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
RefSeqiNP_536325.1, NM_080400.1 [Q91ZN7-1]
XP_008764264.1, XM_008766042.2 [Q91ZN7-1]
XP_008764265.1, XM_008766043.1 [Q91ZN7-1]
UniGeneiRn.33267

Genome annotation databases

EnsembliENSRNOT00000011226; ENSRNOP00000011226; ENSRNOG00000031896 [Q91ZN7-1]
ENSRNOT00000090161; ENSRNOP00000070708; ENSRNOG00000031896 [Q91ZN7-2]
GeneIDi140583
KEGGirno:140583
UCSCiRGD:620545 rat [Q91ZN7-1]

Keywords - Coding sequence diversityi

Alternative promoter usage

Similar 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
RefSeqiNP_536325.1, NM_080400.1 [Q91ZN7-1]
XP_008764264.1, XM_008766042.2 [Q91ZN7-1]
XP_008764265.1, XM_008766043.1 [Q91ZN7-1]
UniGeneiRn.33267

3D structure databases

ProteinModelPortaliQ91ZN7
SMRiQ91ZN7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi250797, 1 interactor
STRINGi10116.ENSRNOP00000011226

PTM databases

iPTMnetiQ91ZN7
PhosphoSitePlusiQ91ZN7

Proteomic databases

PaxDbiQ91ZN7
PRIDEiQ91ZN7

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000011226; ENSRNOP00000011226; ENSRNOG00000031896 [Q91ZN7-1]
ENSRNOT00000090161; ENSRNOP00000070708; ENSRNOG00000031896 [Q91ZN7-2]
GeneIDi140583
KEGGirno:140583
UCSCiRGD:620545 rat [Q91ZN7-1]

Organism-specific databases

CTDi1111
RGDi620545 Chek1

Phylogenomic databases

eggNOGiKOG0590 Eukaryota
ENOG410XQ0D LUCA
GeneTreeiENSGT00390000015238
HOGENOMiHOG000216658
HOVERGENiHBG002590
InParanoidiQ91ZN7
KOiK02216
PhylomeDBiQ91ZN7
TreeFamiTF351441

Enzyme and pathway databases

SABIO-RKiQ91ZN7

Miscellaneous databases

PROiPR:Q91ZN7

Gene expression databases

BgeeiENSRNOG00000031896 Expressed in 9 organ(s), highest expression level in liver
ExpressionAtlasiQ91ZN7 baseline and differential
GenevisibleiQ91ZN7 RN

Family and domain databases

CDDicd14069 STKc_Chk1, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCHK1_RAT
AccessioniPrimary (citable) accession number: Q91ZN7
Secondary accession number(s): Q91ZN6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 27, 2005
Last sequence update: December 1, 2001
Last modified: September 12, 2018
This is version 138 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again