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Protein

Serine/threonine-protein kinase Chk1

Gene

Chek1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

Enzyme 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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei38 – 381ATPPROSITE-ProRule annotation
Active sitei130 – 1301Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi15 – 239ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, DNA damage, DNA repair

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

SABIO-RKQ91ZN7.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 8

Organism-specific databases

RGDi620545. Chek1.

Subcellular locationi

  • Nucleus By similarity
  • Cytoplasm By similarity
  • Cytoplasmcytoskeletonmicrotubule organizing centercentrosome 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 (By similarity).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 476476Serine/threonine-protein kinase Chk1PRO_0000085850Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei280 – 2801Phosphoserine; by PKB/AKT1By similarity
Modified residuei286 – 2861PhosphoserineBy similarity
Modified residuei296 – 2961PhosphoserineBy similarity
Modified residuei301 – 3011PhosphoserineBy similarity
Modified residuei317 – 3171Phosphoserine; by ATM and ATRBy similarity
Modified residuei345 – 3451Phosphoserine; by ATM and ATRBy similarity
Cross-linki436 – 436Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
Modified residuei463 – 4631PhosphoserineBy similarity
Modified residuei467 – 4671PhosphoserineBy similarity
Modified residuei468 – 4681PhosphoserineBy similarity

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.
PhosphoSiteiQ91ZN7.

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

BgeeiENSRNOG00000008181.
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

STRINGi10116.ENSRNOP00000011226.

Structurei

3D structure databases

ProteinModelPortaliQ91ZN7.
SMRiQ91ZN7. Positions 3-273.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini9 – 265257Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 265265Interaction with CLSPNBy similarityAdd
BLAST
Regioni391 – 47686Autoinhibitory regionBy similarityAdd
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0590. Eukaryota.
ENOG410XQ0D. LUCA.
GeneTreeiENSGT00390000015238.
HOGENOMiHOG000216658.
HOVERGENiHBG002590.
InParanoidiQ91ZN7.
KOiK02216.
PhylomeDBiQ91ZN7.
TreeFamiTF351441.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 282282Missing in isoform 2. 1 PublicationVSP_015770Add
BLAST

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_008766042.1. [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

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_008766042.1. [Q91ZN7-1]
XP_008764265.1. XM_008766043.1. [Q91ZN7-1]
UniGeneiRn.33267.

3D structure databases

ProteinModelPortaliQ91ZN7.
SMRiQ91ZN7. Positions 3-273.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000011226.

PTM databases

iPTMnetiQ91ZN7.
PhosphoSiteiQ91ZN7.

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-RKQ91ZN7.

Miscellaneous databases

PROiQ91ZN7.

Gene expression databases

BgeeiENSRNOG00000008181.
ExpressionAtlasiQ91ZN7. baseline and differential.
GenevisibleiQ91ZN7. RN.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCHK1_RAT
AccessioniPrimary (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: September 7, 2016
This is version 126 of the entry and version 1 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.