CHK1_MOUSE
ID CHK1_MOUSE Reviewed; 476 AA.
AC O35280; O54925; Q8CI40; Q9D0N2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2005, sequence version 2.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Serine/threonine-protein kinase Chk1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:18243098};
DE AltName: Full=CHK1 checkpoint homolog;
DE AltName: Full=Checkpoint kinase-1;
GN Name=Chek1; Synonyms=Chk1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX PubMed=9278511; DOI=10.1126/science.277.5331.1497;
RA Sanchez Y., Wong C., Thoma R.S., Richman R., Wu Z., Piwnica-Worms H.,
RA Elledge S.J.;
RT "Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA
RT damage to Cdk regulation through Cdc25.";
RL Science 277:1497-1501(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 204-450 (ISOFORMS 1/2), SUBCELLULAR LOCATION,
RP AND DEVELOPMENTAL STAGE.
RX PubMed=9382850; DOI=10.1016/s0960-9822(06)00417-9;
RA Flaggs G., Plug A.W., Dunks K.M., Mundt K.E., Ford J.C., Quiggle M.R.E.,
RA Taylor E.M., Westphal C.H., Ashley T., Hoekstra M.F., Carr A.M.;
RT "Atm-dependent interactions of a mammalian chk1 homolog with meiotic
RT chromosomes.";
RL Curr. Biol. 7:977-986(1997).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10859163;
RA Takai H., Tominaga K., Motoyama N., Minamishima Y.A., Nagahama H.,
RA Tsukiyama T., Ikeda K., Nakayama K., Nakanishi M., Nakayama K.;
RT "Aberrant cell cycle checkpoint function and early embryonic death in
RT Chk1(-/-) mice.";
RL Genes Dev. 14:1439-1447(2000).
RN [6]
RP FUNCTION IN G2/M DNA DAMAGE CHECKPOINT.
RX PubMed=10859164;
RA Liu Q., Guntuku S., Cui X.-S., Matsuoka S., Cortez D., Tamai K., Luo G.,
RA Carattini-Rivera S., DeMayo F., Bradley A., Donehower L.A., Elledge S.J.;
RT "Chk1 is an essential kinase that is regulated by Atr and required for the
RT G(2)/M DNA damage checkpoint.";
RL Genes Dev. 14:1448-1459(2000).
RN [7]
RP FUNCTION.
RX PubMed=15261141; DOI=10.1016/j.ccr.2004.06.015;
RA Lam M.H., Liu Q., Elledge S.J., Rosen J.M.;
RT "Chk1 is haploinsufficient for multiple functions critical to tumor
RT suppression.";
RL Cancer Cell 6:45-59(2004).
RN [8]
RP SUBCELLULAR LOCATION, UBIQUITINATION, PHOSPHORYLATION AT SER-280 AND
RP SER-345, AND MUTAGENESIS OF SER-280.
RX PubMed=15710331; DOI=10.1016/j.ccr.2005.01.009;
RA Puc J., Keniry M., Li H.S., Pandita T.K., Choudhury A.D., Memeo L.,
RA Mansukhani M., Murty V.V.V.S., Gaciong Z., Meek S.E.M., Piwnica-Worms H.,
RA Hibshoosh H., Parsons R.;
RT "Lack of PTEN sequesters CHK1 and initiates genetic instability.";
RL Cancer Cell 7:193-204(2005).
RN [9]
RP PHOSPHORYLATION AT SER-317.
RX PubMed=17376776; DOI=10.1074/jbc.c700019200;
RA Yong W., Bao S., Chen H., Li D., Sanchez E.R., Shou W.;
RT "Mice lacking protein phosphatase 5 are defective in ataxia telangiectasia
RT mutated (ATM)-mediated cell cycle arrest.";
RL J. Biol. Chem. 282:14690-14694(2007).
RN [10]
RP FUNCTION IN EPIGENETIC REGULATION OF TRANSCRIPTION, CATALYTIC ACTIVITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=18243098; DOI=10.1016/j.cell.2007.12.013;
RA Shimada M., Niida H., Zineldeen D.H., Tagami H., Tanaka M., Saito H.,
RA Nakanishi M.;
RT "Chk1 is a histone H3 threonine 11 kinase that regulates DNA damage-induced
RT transcriptional repression.";
RL Cell 132:221-232(2008).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-463, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP INTERACTION WITH TIMELESS.
RX PubMed=23418588; DOI=10.1371/journal.pone.0056623;
RA Engelen E., Janssens R.C., Yagita K., Smits V.A., van der Horst G.T.,
RA Tamanini F.;
RT "Mammalian TIMELESS is involved in period determination and DNA damage-
RT dependent phase advancing of the circadian clock.";
RL PLoS ONE 8:E56623-E56623(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase which is required for
CC checkpoint-mediated cell cycle arrest and activation of DNA repair in
CC response to the presence of DNA damage or unreplicated DNA
CC (PubMed:10859163, PubMed:10859164, PubMed:15261141). May also
CC negatively regulate cell cycle progression during unperturbed cell
CC cycles (PubMed:10859163, PubMed:10859164, PubMed:15261141). This
CC regulation is achieved by a number of mechanisms that together help to
CC preserve the integrity of the genome (PubMed:10859163, PubMed:10859164,
CC PubMed:15261141). Recognizes the substrate consensus sequence [R-X-X-
CC S/T] (PubMed:10859163, PubMed:10859164, PubMed:15261141). Binds to and
CC phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at
CC 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216'
CC creates binding sites for 14-3-3 proteins which inhibit CDC25A and
CC CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178',
CC 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Phosphorylation
CC of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation
CC at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for
CC polyubiquitination and degradation of CDCD25A. Inhibition of CDC25
CC leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin
CC complexes and blocks cell cycle progression. Also phosphorylates NEK6.
CC Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the
CC release of RAD51 from BRCA2 and enhances the association of RAD51 with
CC chromatin, thereby promoting DNA repair by homologous recombination.
CC Phosphorylates multiple sites within the C-terminus of TP53, which
CC promotes activation of TP53 by acetylation and promotes cell cycle
CC arrest and suppression of cellular proliferation. Also promotes repair
CC of DNA cross-links through phosphorylation of FANCE. Binds to and
CC phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent
CC phosphorylation of the chromatin assembly factor ASF1A. This may
CC enhance chromatin assembly both in the presence or absence of DNA
CC damage. May also play a role in replication fork maintenance through
CC regulation of PCNA (By similarity). May regulate the transcription of
CC genes that regulate cell-cycle progression through the phosphorylation
CC of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads
CC to epigenetic inhibition of a subset of genes (PubMed:18243098). May
CC also phosphorylate RB1 to promote its interaction with the E2F family
CC of transcription factors and subsequent cell cycle arrest.
CC Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (By
CC similarity). Reduces replication stress and activates the G2/M
CC checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and
CC promoting the serine/threonine-protein phosphatase 2A-mediated
CC dephosphorylation and stabilization of WEE1 levels and activity (By
CC similarity). {ECO:0000250|UniProtKB:O14757,
CC ECO:0000269|PubMed:10859163, ECO:0000269|PubMed:10859164,
CC ECO:0000269|PubMed:15261141, ECO:0000269|PubMed:18243098}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000269|PubMed:18243098};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000269|PubMed:18243098};
CC -!- ACTIVITY REGULATION: Activated through phosphorylation predominantly by
CC ATR but also by ATM in response to DNA damage or inhibition of DNA
CC replication. Activation is modulated by several mediators including
CC CLSPN, BRCA1 and FEM1B. Proteolytic cleavage at the C-terminus by SPRTN
CC during normal DNA replication activates the protein kinase activity.
CC {ECO:0000250|UniProtKB:O14757}.
CC -!- SUBUNIT: Interacts (phosphorylated by ATR) with RAD51 (By similarity).
CC Interacts with and phosphorylates CLSPN, an adapter protein that
CC regulates the ATR-dependent phosphorylation of CHEK1 (By similarity).
CC Interacts with BRCA1 (By similarity). Interacts with and phosphorylates
CC CDC25A, CDC25B and CDC25C (By similarity). Interacts with FBXO6, which
CC regulates CHEK1 (By similarity). Interacts with PPM1D, which regulates
CC CHEK1 through dephosphorylation (By similarity). Interacts with
CC TIMELESS; DNA damage-dependent (PubMed:23418588). Interacts with FEM1B;
CC activates CHEK1 in response to stress (By similarity). Interacts with
CC TLK1 (By similarity). Interacts with XPO1 and YWHAZ (By similarity).
CC Interacts with CDK5RAP3; antagonizes CHEK1 (By similarity).
CC {ECO:0000250|UniProtKB:O14757, ECO:0000269|PubMed:23418588}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15710331,
CC ECO:0000269|PubMed:9382850}. Chromosome {ECO:0000269|PubMed:18243098,
CC ECO:0000269|PubMed:9382850}. Cytoplasm {ECO:0000250|UniProtKB:O14757}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000250|UniProtKB:O14757}. Note=Nuclear export is mediated at
CC least in part by XPO1/CRM1. Also localizes to the centrosome
CC specifically during interphase, where it may protect centrosomal CDC2
CC kinase from inappropriate activation by cytoplasmic CDC25B. Proteolytic
CC cleavage at the C-terminus by SPRTN promotes removal from chromatin.
CC {ECO:0000250|UniProtKB:O14757}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O35280-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O35280-2; Sequence=VSP_015791, VSP_015792;
CC -!- TISSUE SPECIFICITY: Found in all adult tissues tested. Elevated
CC expression in testis, lung and spleen. 15.5 day old embryos show
CC ubiquitous expression with strong expression in brain, liver, kidney,
CC pancreas, intestine, thymus and lung. {ECO:0000269|PubMed:9278511}.
CC -!- DEVELOPMENTAL STAGE: In the testis, present in cells undergoing meiosis
CC I. Not detected in peripheral cells in seminiferous tubules that are
CC undergoing pre-meiotic DNA synthesis or in late condensing or mature
CC sperm. {ECO:0000269|PubMed:9382850}.
CC -!- DOMAIN: The autoinhibitory region (AIR) inhibits the activity of the
CC kinase domain. {ECO:0000250|UniProtKB:O14757}.
CC -!- PTM: Phosphorylated by ATR in a RAD17-dependent manner in response to
CC ultraviolet irradiation and inhibition of DNA replication.
CC Phosphorylated by ATM in response to ionizing irradiation. ATM and ATR
CC can both phosphorylate Ser-317 and Ser-345 and this results in enhanced
CC kinase activity. Phosphorylation at Ser-345 induces a change in the
CC conformation of the protein, activates the kinase activity and is a
CC prerequisite for interaction with FBXO6 and subsequent ubiquitination
CC at Lys-436. Phosphorylation at Ser-345 also increases binding to 14-3-3
CC proteins and promotes nuclear retention. Conversely, dephosphorylation
CC at Ser-345 by PPM1D may contribute to exit from checkpoint mediated
CC cell cycle arrest. Phosphorylation at Ser-280 by AKT1/PKB, may promote
CC mono and/or diubiquitination. Also phosphorylated at undefined residues
CC during mitotic arrest, resulting in decreased activity.
CC {ECO:0000269|PubMed:15710331, ECO:0000269|PubMed:17376776}.
CC -!- PTM: Ubiquitinated (PubMed:15710331). Mono or diubiquitination promotes
CC nuclear exclusion (PubMed:15710331). The activated form (phosphorylated
CC on Ser-345) is polyubiquitinated at Lys-436 by some SCF-type E3
CC ubiquitin ligase complex containing FBXO6 promoting its degradation (By
CC similarity). Ubiquitination and degradation are required to terminate
CC the checkpoint and ensure that activated CHEK1 does not accumulate as
CC cells progress through S phase, when replication forks encounter
CC transient impediments during normal DNA replication. 'Lys-63'-mediated
CC ubiquitination by TRAF4 at Lys-132 activates cell cycle arrest and
CC activation of DNA repair (By similarity).
CC {ECO:0000250|UniProtKB:O14757, ECO:0000269|PubMed:15710331}.
CC -!- PTM: Proteolytically cleaved at the C-terminus by SPRTN during normal
CC DNA replication, thereby promoting CHEK1 removal from chromatin and
CC activating the protein kinase activity. {ECO:0000250|UniProtKB:O14757}.
CC -!- DISRUPTION PHENOTYPE: Mice die of apoptosis at the blastocyst stage.
CC {ECO:0000269|PubMed:10859163}.
CC -!- MISCELLANEOUS: Haploinsufficient for the suppression of genomic
CC instability and tumor progression.
CC -!- MISCELLANEOUS: [Isoform 2]: 3 initiator methionines can be considered.
CC If this isoform were to start at the first ATG, it would produce a 28
CC amino acid-long peptide, sharing the first 22 amino acids with the
CC canonical sequence (isoform 1) and differing in the last 6 residues
CC (VQLAVN -> ARHRDA). An initiation at this site could target the mRNA to
CC nonsense-mediated mRNA decay and, in this case, the peptide would be
CC produced at very low levels. The second possible translation initiation
CC site would lead to the synthesis of the sequence shown in this entry as
CC isoform 2. However, the Kozak sequence for this site is not optimal.
CC Finally the third potential initiator methionine corresponds to
CC position 167 in isoform 1 and would lead to the synthesis of a 310
CC amino acid-long protein identical to isoform 1 residues 167 through
CC 476. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. NIM1 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH37613.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF016583; AAC53334.1; -; mRNA.
DR EMBL; AK011258; BAB27500.1; -; mRNA.
DR EMBL; AK033179; BAC28185.1; -; mRNA.
DR EMBL; AK045336; BAC32315.1; -; mRNA.
DR EMBL; BC037613; AAH37613.1; ALT_INIT; mRNA.
DR EMBL; AF032875; AAB88853.1; -; mRNA.
DR CCDS; CCDS22972.1; -. [O35280-1]
DR RefSeq; NP_031717.2; NM_007691.5. [O35280-1]
DR AlphaFoldDB; O35280; -.
DR SMR; O35280; -.
DR BioGRID; 198694; 17.
DR IntAct; O35280; 8.
DR MINT; O35280; -.
DR STRING; 10090.ENSMUSP00000134388; -.
DR iPTMnet; O35280; -.
DR PhosphoSitePlus; O35280; -.
DR EPD; O35280; -.
DR jPOST; O35280; -.
DR MaxQB; O35280; -.
DR PaxDb; O35280; -.
DR PeptideAtlas; O35280; -.
DR PRIDE; O35280; -.
DR ProteomicsDB; 281554; -. [O35280-1]
DR ProteomicsDB; 281555; -. [O35280-2]
DR Antibodypedia; 3671; 1892 antibodies from 48 providers.
DR DNASU; 12649; -.
DR Ensembl; ENSMUST00000034625; ENSMUSP00000034625; ENSMUSG00000032113. [O35280-1]
DR Ensembl; ENSMUST00000172702; ENSMUSP00000134388; ENSMUSG00000032113. [O35280-1]
DR GeneID; 12649; -.
DR KEGG; mmu:12649; -.
DR UCSC; uc009otv.1; mouse. [O35280-1]
DR UCSC; uc009otx.2; mouse. [O35280-2]
DR CTD; 1111; -.
DR MGI; MGI:1202065; Chek1.
DR VEuPathDB; HostDB:ENSMUSG00000032113; -.
DR eggNOG; KOG0590; Eukaryota.
DR GeneTree; ENSGT00940000159682; -.
DR InParanoid; O35280; -.
DR OMA; KRSQGHV; -.
DR OrthoDB; 698464at2759; -.
DR PhylomeDB; O35280; -.
DR TreeFam; TF351441; -.
DR BRENDA; 2.7.11.1; 3474.
DR Reactome; R-MMU-1433557; Signaling by SCF-KIT.
DR Reactome; R-MMU-176187; Activation of ATR in response to replication stress.
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR Reactome; R-MMU-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
DR Reactome; R-MMU-8953750; Transcriptional Regulation by E2F6.
DR BioGRID-ORCS; 12649; 31 hits in 114 CRISPR screens.
DR PRO; PR:O35280; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; O35280; protein.
DR Bgee; ENSMUSG00000032113; Expressed in secondary oocyte and 168 other tissues.
DR ExpressionAtlas; O35280; baseline and differential.
DR Genevisible; O35280; MM.
DR GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0000781; C:chromosome, telomeric region; ISO:MGI.
DR GO; GO:0000794; C:condensed nuclear chromosome; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0005657; C:replication fork; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0035402; F:histone kinase activity (H3-T11 specific); IDA:UniProtKB.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0004672; F:protein kinase activity; IMP:MGI.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:1902742; P:apoptotic process involved in development; IMP:MGI.
DR GO; GO:0071313; P:cellular response to caffeine; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:MGI.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:MGI.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IDA:MGI.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; IMP:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:MGI.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IMP:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; ISS:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; ISS:UniProtKB.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; ISO:MGI.
DR GO; GO:0010972; P:negative regulation of G2/M transition of mitotic cell cycle; ISO:MGI.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; ISS:UniProtKB.
DR GO; GO:0006997; P:nucleus organization; IMP:MGI.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; ISS:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IDA:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IGI:MGI.
DR GO; GO:2000615; P:regulation of histone H3-K9 acetylation; IDA:UniProtKB.
DR GO; GO:0046602; P:regulation of mitotic centrosome separation; ISS:UniProtKB.
DR GO; GO:0010767; P:regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage; IMP:UniProtKB.
DR CDD; cd14069; STKc_Chk1; 1.
DR InterPro; IPR034670; Chk1_catalytic_dom.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Cell cycle; Chromosome; Cytoplasm;
KW Cytoskeleton; DNA damage; DNA repair; Isopeptide bond; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Ubl conjugation.
FT CHAIN 1..476
FT /note="Serine/threonine-protein kinase Chk1"
FT /id="PRO_0000085849"
FT DOMAIN 9..265
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..265
FT /note="Interaction with CLSPN"
FT /evidence="ECO:0000250"
FT REGION 267..331
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..476
FT /note="Autoinhibitory region"
FT /evidence="ECO:0000250"
FT COMPBIAS 280..330
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 130
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 15..23
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 38
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 280
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:15710331"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT MOD_RES 317
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:17376776"
FT MOD_RES 345
FT /note="Phosphoserine; by ATR"
FT /evidence="ECO:0000269|PubMed:15710331"
FT MOD_RES 463
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT CROSSLNK 132
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT CROSSLNK 436
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O14757"
FT VAR_SEQ 1..94
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015791"
FT VAR_SEQ 95..97
FT /note="RIE -> MEK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_015792"
FT MUTAGEN 280
FT /note="S->A: Enhances cell cycle arrest."
FT /evidence="ECO:0000269|PubMed:15710331"
FT MUTAGEN 280
FT /note="S->E: Promotes mono and/or diubiquitination and
FT nuclear exclusion. Reduces phosphorylation at S-345."
FT /evidence="ECO:0000269|PubMed:15710331"
FT CONFLICT 33
FT /note="E -> Q (in Ref. 1; AAC53334)"
FT /evidence="ECO:0000305"
FT CONFLICT 50
FT /note="E -> Q (in Ref. 1; AAC53334)"
FT /evidence="ECO:0000305"
FT CONFLICT 219..223
FT /note="SDWKE -> LIVKK (in Ref. 4; AAB88853)"
FT /evidence="ECO:0000305"
FT CONFLICT 252
FT /note="A -> S (in Ref. 4; AAB88853)"
FT /evidence="ECO:0000305"
FT CONFLICT 365
FT /note="S -> F (in Ref. 1; AAC53334)"
FT /evidence="ECO:0000305"
FT CONFLICT 449..450
FT /note="LE -> YN (in Ref. 4; AAB88853)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 476 AA; 54381 MW; 0642D238EB3C5BE3 CRC64;
MAVPFVEDWD LVQTLGEGAY GEVQLAVNRI TEEAVAVKIV DMKRAIDCPE NIKKEICINK
MLSHENVVKF YGHRREGHIQ YLFLEYCSGG ELFDRIEPDI GMPEQDAQRF FHQLMAGVVY
LHGIGITHRD IKPENLLLDE RDNLKISDFG LATVFRHNNR ERLLNKMCGT LPYVAPELLK
RKEFHAEPVD VWSCGIVLTA MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA
LLHKILVETP SARITIPDIK KDRWYNKPLN RGAKRPRATS GGMSESSSGF SKHIHSNLDF
SPVNNGSSEE TVKFSSSQPE PRTGLSLWDT GPSNVDKLVQ GISFSQPTCP EHMLVNSQLL
GTPGSSQNPW QRLVKRMTRF FTKLDADKSY QCLKETFEKL GYQWKKSCMN QVTVSTTDRR
NNKLIFKINL VEMDEKILVD FRLSKGDGLE FKRHFLKIKG KLSDVVSSQK VWFPVT
