CHK1_HUMAN
ID CHK1_HUMAN Reviewed; 476 AA.
AC O14757; A8K934; B4DDD0; B4DSK3; B5BTY6; F5H7S4; H2BI51;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 2.
DT 03-AUG-2022, entry version 238.
DE RecName: Full=Serine/threonine-protein kinase Chk1;
DE EC=2.7.11.1 {ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:9278511};
DE AltName: Full=CHK1 checkpoint homolog;
DE AltName: Full=Cell cycle checkpoint kinase;
DE AltName: Full=Checkpoint kinase-1;
GN Name=CHEK1; Synonyms=CHK1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION IN PHOSPHORYLATION OF
RP CDC25A; CDC25B AND CDC25C, CATALYTIC ACTIVITY, INTERACTION WITH CDC25A;
RP CDC25B AND CDC25C, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF
RP ASP-130, AND VARIANT VAL-471.
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND VARIANT VAL-471.
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 [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-471.
RX PubMed=10717241; DOI=10.3892/ijo.16.4.731;
RA Semba S., Ouyang H., Han S.-Y., Kato Y., Horii A.;
RT "Analysis of the candidate target genes for mutation in microsatellite
RT instability-positive cancers of the colorectum, stomach, and endometrium.";
RL Int. J. Oncol. 16:731-737(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), AND
RP ALTERNATIVE SPLICING.
RC TISSUE=Fetal thymus;
RX PubMed=22184239; DOI=10.1073/pnas.1104767109;
RA Pabla N., Bhatt K., Dong Z.;
RT "Checkpoint kinase 1 (Chk1)-short is a splice variant and endogenous
RT inhibitor of Chk1 that regulates cell cycle and DNA damage checkpoints.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:197-202(2012).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3), AND VARIANT
RP VAL-471.
RC TISSUE=Brain, and Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-156 AND VAL-471.
RG NIEHS SNPs program;
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-471.
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-471.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-471.
RC TISSUE=Bone marrow, and Muscle;
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 [11]
RP FUNCTION IN PHOSPHORYLATION OF TP53, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP ASP-130.
RX PubMed=10673501;
RA Shieh S.-Y., Ahn J., Tamai K., Taya Y., Prives C.;
RT "The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2)
RT phosphorylate p53 at multiple DNA damage-inducible sites.";
RL Genes Dev. 14:289-300(2000).
RN [12]
RP ERRATUM OF PUBMED:10673501.
RA Shieh S.-Y., Ahn J., Tamai K., Taya Y., Prives C.;
RL Genes Dev. 14:750-750(2000).
RN [13]
RP PHOSPHORYLATION AT SER-345 BY ATR.
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 [14]
RP FUNCTION IN DNA REPLICATION, PHOSPHORYLATION BY ATR, AND MUTAGENESIS OF
RP ASP-130.
RX PubMed=11535615; DOI=10.1083/jcb.200104099;
RA Feijoo C., Hall-Jackson C., Wu R., Jenkins D., Leitch J., Gilbert D.M.,
RA Smythe C.;
RT "Activation of mammalian Chk1 during DNA replication arrest: a role for
RT Chk1 in the intra-S phase checkpoint monitoring replication origin
RT firing.";
RL J. Cell Biol. 154:913-923(2001).
RN [15]
RP PHOSPHORYLATION AT SER-317 AND SER-345, AND MUTAGENESIS OF ASP-130;
RP SER-317; SER-345; SER-357; SER-366 AND SER-468.
RX PubMed=11390642; DOI=10.1128/mcb.21.13.4129-4139.2001;
RA Zhao H., Piwnica-Worms H.;
RT "ATR-mediated checkpoint pathways regulate phosphorylation and activation
RT of human Chk1.";
RL Mol. Cell. Biol. 21:4129-4139(2001).
RN [16]
RP SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF ASP-130.
RX PubMed=11821419; DOI=10.1074/jbc.m111705200;
RA O'Neill T., Giarratani L., Chen P., Iyer L., Lee C.-H., Bobiak M.,
RA Kanai F., Zhou B.-B., Chung J.H., Rathbun G.A.;
RT "Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the
RT oriented peptide library approach.";
RL J. Biol. Chem. 277:16102-16115(2002).
RN [17]
RP ERRATUM OF PUBMED:11821419.
RA O'Neill T., Giarratani L., Chen P., Iyer L., Lee C.-H., Bobiak M.,
RA Kanai F., Zhou B.-B., Chung J.H., Rathbun G.A.;
RL J. Biol. Chem. 277:35776-35777(2002).
RN [18]
RP FUNCTION IN DNA DAMAGE RESPONSE, PHOSPHORYLATION AT SER-317 AND SER-345,
RP AND MUTAGENESIS OF LYS-38.
RX PubMed=12446774; DOI=10.1128/mcb.22.24.8552-8561.2002;
RA Heffernan T.P., Simpson D.A., Frank A.R., Heinloth A.N., Paules R.S.,
RA Cordeiro-Stone M., Kaufmann W.K.;
RT "An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation
RT following UVC-induced DNA damage.";
RL Mol. Cell. Biol. 22:8552-8561(2002).
RN [19]
RP SUBCELLULAR LOCATION, ACTIVITY REGULATION, AND INTERACTION WITH BRCA1.
RX PubMed=11836499; DOI=10.1038/ng837;
RA Yarden R.I., Pardo-Reoyo S., Sgagias M., Cowan K.H., Brody L.C.;
RT "BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA
RT damage.";
RL Nat. Genet. 30:285-289(2002).
RN [20]
RP FUNCTION IN DNA DAMAGE RESPONSE.
RX PubMed=12399544; DOI=10.1073/pnas.182557299;
RA Zhao H., Watkins J.L., Piwnica-Worms H.;
RT "Disruption of the checkpoint kinase 1/cell division cycle 25A pathway
RT abrogates ionizing radiation-induced S and G2 checkpoints.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:14795-14800(2002).
RN [21]
RP FUNCTION IN CDC25A TURNOVER, PHOSPHORYLATION AT SER-317 AND SER-345, AND
RP MUTAGENESIS OF SER-317 AND SER-345.
RX PubMed=12676583; DOI=10.1016/s1535-6108(03)00048-5;
RA Soerensen C.S., Syljuaesen R.G., Falck J., Schroeder T., Roennstrand L.,
RA Khanna K.K., Zhou B.-B., Bartek J., Lukas J.;
RT "Chk1 regulates the S phase checkpoint by coupling the physiological
RT turnover and ionizing radiation-induced accelerated proteolysis of
RT Cdc25A.";
RL Cancer Cell 3:247-258(2003).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF TLK1, CATALYTIC ACTIVITY, INTERACTION WITH
RP TLK1, AND PHOSPHORYLATION AT SER-317.
RX PubMed=12660173; DOI=10.1093/emboj/cdg151;
RA Groth A., Lukas J., Nigg E.A., Sillje H.H.W., Wernstedt C., Bartek J.,
RA Hansen K.;
RT "Human tousled like kinases are targeted by an ATM- and Chk1-dependent DNA
RT damage checkpoint.";
RL EMBO J. 22:1676-1687(2003).
RN [23]
RP FUNCTION IN CDC25A TURNOVER, AND MUTAGENESIS OF ASP-130.
RX PubMed=14681206; DOI=10.1101/gad.1157503;
RA Jin J., Shirogane T., Xu L., Nalepa G., Qin J., Elledge S.J., Harper J.W.;
RT "SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein
RT phosphatase.";
RL Genes Dev. 17:3062-3074(2003).
RN [24]
RP PHOSPHORYLATION AT SER-317, AND MUTAGENESIS OF ASP-130; SER-317 AND
RP SER-345.
RX PubMed=12588868; DOI=10.1074/jbc.m210862200;
RA Gatei M., Sloper K., Soerensen C., Syljuaesen R., Falck J., Hobson K.,
RA Savage K., Lukas J., Zhou B.-B., Bartek J., Khanna K.K.;
RT "Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of
RT Chk1 on ser-317 in response to ionizing radiation.";
RL J. Biol. Chem. 278:14806-14811(2003).
RN [25]
RP FUNCTION IN CDC25A TURNOVER, AND PHOSPHORYLATION AT SER-345.
RX PubMed=12676925; DOI=10.1074/jbc.m300229200;
RA Xiao Z., Chen Z., Gunasekera A.H., Sowin T.J., Rosenberg S.H., Fesik S.,
RA Zhang H.;
RT "Chk1 mediates S and G2 arrests through Cdc25A degradation in response to
RT DNA-damaging agents.";
RL J. Biol. Chem. 278:21767-21773(2003).
RN [26]
RP INTERACTION WITH YWHAZ AND XPO1, SUBCELLULAR LOCATION, ASSOCIATION WITH
RP CHROMATIN, PHOSPHORYLATION AT SER-317 AND SER-345, AND MUTAGENESIS OF
RP SER-317; PHE-344; SER-345 AND MET-353.
RX PubMed=12676962; DOI=10.1074/jbc.m300070200;
RA Jiang K., Pereira E., Maxfield M., Russell B., Goudelock D.M., Sanchez Y.;
RT "Regulation of Chk1 includes chromatin association and 14-3-3 binding
RT following phosphorylation on ser-345.";
RL J. Biol. Chem. 278:25207-25217(2003).
RN [27]
RP FUNCTION IN CDC25A TURNOVER.
RX PubMed=12759351; DOI=10.1074/jbc.m302704200;
RA Hassepass I., Voit R., Hoffmann I.;
RT "Phosphorylation at serine 75 is required for UV-mediated degradation of
RT human Cdc25A phosphatase at the S-phase checkpoint.";
RL J. Biol. Chem. 278:29824-29829(2003).
RN [28]
RP INTERACTION WITH CLSPN, AND ACTIVITY REGULATION.
RX PubMed=12766152; DOI=10.1074/jbc.m301136200;
RA Chini C.C.S., Chen J.;
RT "Human claspin is required for replication checkpoint control.";
RL J. Biol. Chem. 278:30057-30062(2003).
RN [29]
RP FUNCTION IN MITOSIS, CATALYTIC ACTIVITY, AND FUNCTION IN PHOSPHORYLATION OF
RP CDC25A.
RX PubMed=14559997; DOI=10.1128/mcb.23.21.7488-7497.2003;
RA Chen M.-S., Ryan C.E., Piwnica-Worms H.;
RT "Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase
RT through 14-3-3 binding.";
RL Mol. Cell. Biol. 23:7488-7497(2003).
RN [30]
RP REGULATION OF TLK1.
RX PubMed=12955071; DOI=10.1038/sj.onc.1206691;
RA Krause D.R., Jonnalagadda J.C., Gatei M.H., Sillje H.H.W., Zhou B.-B.,
RA Nigg E.A., Khanna K.;
RT "Suppression of tousled-like kinase activity after DNA damage or
RT replication block requires ATM, NBS1 and Chk1.";
RL Oncogene 22:5927-5937(2003).
RN [31]
RP PHOSPHORYLATION AT SER-317.
RX PubMed=14657349; DOI=10.1073/pnas.2536810100;
RA Wang Y., Qin J.;
RT "MSH2 and ATR form a signaling module and regulate two branches of the
RT damage response to DNA methylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003).
RN [32]
RP FUNCTION, AND PHOSPHORYLATION AT SER-345.
RX PubMed=14988723; DOI=10.1038/sj.emboj.7600113;
RA Pichierri P., Rosselli F.;
RT "The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-
RT NBS1-FANCD2 pathways.";
RL EMBO J. 23:1178-1187(2004).
RN [33]
RP DOMAIN, MITOTIC PHOSPHORYLATION, PHOSPHORYLATION AT SER-345, AND
RP MUTAGENESIS OF LYS-38.
RX PubMed=14681223; DOI=10.1074/jbc.m312215200;
RA Ng C.-P., Lee H.C., Ho C.W., Arooz T., Siu W.Y., Lau A., Poon R.Y.C.;
RT "Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by
RT their regulatory domains.";
RL J. Biol. Chem. 279:8808-8819(2004).
RN [34]
RP FUNCTION IN MITOSIS, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ASP-130.
RX PubMed=15311285; DOI=10.1038/ncb1165;
RA Kraemer A., Mailand N., Lukas C., Syljuaesen R.G., Wilkinson C.J.,
RA Nigg E.A., Bartek J., Lukas J.;
RT "Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1
RT kinase.";
RL Nat. Cell Biol. 6:884-891(2004).
RN [35]
RP INTERACTION WITH CLSPN, AND PHOSPHORYLATION AT SER-296; SER-317 AND
RP SER-345.
RX PubMed=15707391; DOI=10.1042/bj20041966;
RA Clarke C.A.L., Clarke P.R.;
RT "DNA-dependent phosphorylation of Chk1 and claspin in a human cell-free
RT system.";
RL Biochem. J. 388:705-712(2005).
RN [36]
RP SUBCELLULAR LOCATION.
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 [37]
RP INTERACTION WITH PPM1D, PHOSPHORYLATION AT SER-317 AND SER-345, AND
RP DEPHOSPHORYLATION BY PPM1D.
RX PubMed=15870257; DOI=10.1101/gad.1291305;
RA Lu X., Nannenga B., Donehower L.A.;
RT "PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle
RT checkpoints.";
RL Genes Dev. 19:1162-1174(2005).
RN [38]
RP FUNCTION IN PHOSPHORYLATION OF TP53, FUNCTION IN TP53-DEPENDENT
RP TRANSCRIPTION, AND CATALYTIC ACTIVITY.
RX PubMed=15659650; DOI=10.1091/mbc.e04-08-0689;
RA Ou Y.-H., Chung P.-H., Sun T.-P., Shieh S.-Y.;
RT "p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the
RT regulation of DNA-damage-induced C-terminal acetylation.";
RL Mol. Biol. Cell 16:1684-1695(2005).
RN [39]
RP INTERACTION WITH TIMELESS.
RX PubMed=15798197; DOI=10.1128/mcb.25.8.3109-3116.2005;
RA Uensal-Kacmaz K., Mullen T.E., Kaufmann W.K., Sancar A.;
RT "Coupling of human circadian and cell cycles by the timeless protein.";
RL Mol. Cell. Biol. 25:3109-3116(2005).
RN [40]
RP FUNCTION IN HOMOLOGOUS RECOMBINATION REPAIR, FUNCTION IN PHOSPHORYLATION OF
RP RAD51, CATALYTIC ACTIVITY, INTERACTION WITH RAD51, AND MUTAGENESIS OF
RP SER-317 AND SER-345.
RX PubMed=15665856; DOI=10.1038/ncb1212;
RA Soerensen C.S., Hansen L.T., Dziegielewski J., Syljuaesen R.G., Lundin C.,
RA Bartek J., Helleday T.;
RT "The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous
RT recombination repair.";
RL Nat. Cell Biol. 7:195-201(2005).
RN [41]
RP FUNCTION IN MITOTIC EXIT, AND PHOSPHORYLATION AT SER-345.
RX PubMed=15650047; DOI=10.1073/pnas.0409130102;
RA Huang X., Tran T., Zhang L., Hatcher R., Zhang P.;
RT "DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent
RT mitotic exit DNA damage checkpoint.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:1065-1070(2005).
RN [42]
RP FUNCTION IN TP53 ACTIVATION, FUNCTION IN PHOSPHORYLATION OF MDM4, AND
RP CATALYTIC ACTIVITY.
RX PubMed=16511572; DOI=10.1038/sj.emboj.7601010;
RA Jin Y., Dai M.S., Lu S.Z., Xu Y., Luo Z., Zhao Y., Lu H.;
RT "14-3-3gamma binds to MDMX that is phosphorylated by UV-activated Chk1,
RT resulting in p53 activation.";
RL EMBO J. 25:1207-1218(2006).
RN [43]
RP FUNCTION IN PHOSPHORYLATION OF CLSPN, INTERACTION WITH CLSPN, ACTIVITY
RP REGULATION, AND CATALYTIC ACTIVITY.
RX PubMed=16963448; DOI=10.1074/jbc.m604373200;
RA Chini C.C., Chen J.;
RT "Repeated phosphopeptide motifs in human Claspin are phosphorylated by Chk1
RT and mediate Claspin function.";
RL J. Biol. Chem. 281:33276-33282(2006).
RN [44]
RP FUNCTION IN PHOSPHORYLATION OF RB1, AND CATALYTIC ACTIVITY.
RX PubMed=17380128; DOI=10.1038/sj.emboj.7601652;
RA Inoue Y., Kitagawa M., Taya Y.;
RT "Phosphorylation of pRB at Ser612 by Chk1/2 leads to a complex between pRB
RT and E2F-1 after DNA damage.";
RL EMBO J. 26:2083-2093(2007).
RN [45]
RP FUNCTION IN DNA CROSS-LINKS REPAIR, FUNCTION IN PHOSPHORYLATION OF FANCE,
RP AND CATALYTIC ACTIVITY.
RX PubMed=17296736; DOI=10.1128/mcb.02357-06;
RA Wang X., Kennedy R.D., Ray K., Stuckert P., Ellenberger T., D'Andrea A.D.;
RT "Chk1-mediated phosphorylation of FANCE is required for the Fanconi
RT anemia/BRCA pathway.";
RL Mol. Cell. Biol. 27:3098-3108(2007).
RN [46]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E.,
RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y.,
RA Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [47]
RP FUNCTION IN APOPTOSIS.
RX PubMed=18510930; DOI=10.1016/j.cell.2008.03.037;
RA Sidi S., Sanda T., Kennedy R.D., Hagen A.T., Jette C.A., Hoffmans R.,
RA Pascual J., Imamura S., Kishi S., Amatruda J.F., Kanki J.P., Green D.R.,
RA D'Andrea A.A., Look A.T.;
RT "Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses
RT p53, Bcl-2, and caspase-3.";
RL Cell 133:864-877(2008).
RN [48]
RP FUNCTION IN PHOSPHORYLATION OF NEK6, AND CATALYTIC ACTIVITY.
RX PubMed=18728393; DOI=10.4161/cc.7.17.6551;
RA Lee M.Y., Kim H.J., Kim M.A., Jee H.J., Kim A.J., Bae Y.S., Park J.I.,
RA Chung J.H., Yun J.;
RT "Nek6 is involved in G2/M phase cell cycle arrest through DNA damage-
RT induced phosphorylation.";
RL Cell Cycle 7:2705-2709(2008).
RN [49]
RP FUNCTION IN REPLICATION FORK MAINTENANCE, AND FUNCTION IN PCNA
RP UBIQUITINATION.
RX PubMed=18451105; DOI=10.1101/gad.1632808;
RA Yang X.H., Shiotani B., Classon M., Zou L.;
RT "Chk1 and Claspin potentiate PCNA ubiquitination.";
RL Genes Dev. 22:1147-1152(2008).
RN [50]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [51]
RP FUNCTION IN RAD51-MEDIATED DNA REPAIR, FUNCTION IN PHOSPHORYLATION OF BRCA2
RP AND RAD51, AND CATALYTIC ACTIVITY.
RX PubMed=18317453; DOI=10.1038/onc.2008.17;
RA Bahassi E.M., Ovesen J.L., Riesenberg A.L., Bernstein W.Z., Hasty P.E.,
RA Stambrook P.J.;
RT "The checkpoint kinases Chk1 and Chk2 regulate the functional associations
RT between hBRCA2 and Rad51 in response to DNA damage.";
RL Oncogene 27:3977-3985(2008).
RN [52]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [53]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [54]
RP INTERACTION WITH CDK5RAP3.
RX PubMed=19223857; DOI=10.1038/cr.2009.14;
RA Jiang H., Wu J., He C., Yang W., Li H.;
RT "Tumor suppressor protein C53 antagonizes checkpoint kinases to promote
RT cyclin-dependent kinase 1 activation.";
RL Cell Res. 19:458-468(2009).
RN [55]
RP PHOSPHORYLATION AT SER-345, UBIQUITINATION AT LYS-436, INTERACTION WITH
RP FBXO6, AND MUTAGENESIS OF SER-345; ARG-372; ARG-376; ARG-379 AND LYS-436.
RX PubMed=19716789; DOI=10.1016/j.molcel.2009.06.030;
RA Zhang Y.-W., Brognard J., Coughlin C., You Z., Dolled-Filhart M.,
RA Aslanian A., Manning G., Abraham R.T., Hunter T.;
RT "The F box protein Fbx6 regulates Chk1 stability and cellular sensitivity
RT to replication stress.";
RL Mol. Cell 35:442-453(2009).
RN [56]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-296, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [57]
RP FUNCTION IN NEK11 PHOSPHORYLATION.
RX PubMed=19734889; DOI=10.1038/ncb1969;
RA Melixetian M., Klein D.K., Soerensen C.S., Helin K.;
RT "NEK11 regulates CDC25A degradation and the IR-induced G2/M checkpoint.";
RL Nat. Cell Biol. 11:1247-1253(2009).
RN [58]
RP INTERACTION WITH FEM1B, AND ACTIVITY REGULATION.
RX PubMed=19330022; DOI=10.1038/onc.2009.58;
RA Sun T.P., Shieh S.Y.;
RT "Human FEM1B is required for Rad9 recruitment and CHK1 activation in
RT response to replication stress.";
RL Oncogene 28:1971-1981(2009).
RN [59]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-301, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [60]
RP FUNCTION IN CDC25A DEGRADATION.
RX PubMed=20090422; DOI=10.4161/cc.9.3.10513;
RA Soerensen C.S., Melixetian M., Klein D.K., Helin K.;
RT "NEK11: linking CHK1 and CDC25A in DNA damage checkpoint signaling.";
RL Cell Cycle 9:450-455(2010).
RN [61]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [62]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [63]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [64]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-280; SER-296; SER-301;
RP SER-331; SER-467 AND SER-468, AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [65]
RP FUNCTION IN PHOSPHORYLATION OF SPRTN, CATALYTIC ACTIVITY, SUBCELLULAR
RP LOCATION, PROTEOLYTIC CLEAVAGE, ACTIVITY REGULATION, AND PHOSPHORYLATION AT
RP SER-345.
RX PubMed=31316063; DOI=10.1038/s41467-019-11095-y;
RA Halder S., Torrecilla I., Burkhalter M.D., Popovic M., Fielden J., Vaz B.,
RA Oehler J., Pilger D., Lessel D., Wiseman K., Singh A.N., Vendrell I.,
RA Fischer R., Philipp M., Ramadan K.;
RT "SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards
RT DNA replication.";
RL Nat. Commun. 10:3142-3142(2019).
RN [66]
RP FUNCTION.
RX PubMed=33108758; DOI=10.1016/j.molcel.2020.10.008;
RA Li F., Kozono D., Deraska P., Branigan T., Dunn C., Zheng X.F., Parmar K.,
RA Nguyen H., DeCaprio J., Shapiro G.I., Chowdhury D., D'Andrea A.D.;
RT "CHK1 Inhibitor Blocks Phosphorylation of FAM122A and Promotes Replication
RT Stress.";
RL Mol. Cell 0:0-0(2020).
RN [67]
RP FUNCTION, UBIQUITINATION BY TRAF4, AND MUTAGENESIS OF LYS-132.
RX PubMed=32357935; DOI=10.1186/s13045-020-00869-3;
RA Yu X., Li W., Liu H., Deng Q., Wang X., Hu H., Xu-Monette Z.Y., Xiong W.,
RA Lu Z., Young K.H., Wang W., Li Y.;
RT "Ubiquitination of the DNA-damage checkpoint kinase CHK1 by TRAF4 is
RT required for CHK1 activation.";
RL J. Hematol. Oncol. 13:40-40(2020).
RN [68]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-289.
RX PubMed=10761933; DOI=10.1016/s0092-8674(00)80704-7;
RA Chen P., Luo C., Deng Y., Ryan K., Register J., Margosiak S.,
RA Tempczyk-Russell A., Nguyen B., Myers P., Lundgren K., Kan C.-C.,
RA O'Connor P.M.;
RT "The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1:
RT implications for Chk1 regulation.";
RL Cell 100:681-692(2000).
RN [69]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-289.
RX PubMed=12244092; DOI=10.1074/jbc.m201233200;
RA Zhao B., Bower M.J., McDevitt P.J., Zhao H., Davis S.T., Johanson K.O.,
RA Green S.M., Concha N.O., Zhou B.-B.S.;
RT "Structural basis for Chk1 inhibition by UCN-01.";
RL J. Biol. Chem. 277:46609-46615(2002).
RN [70]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-289.
RX PubMed=15974586; DOI=10.1021/jm049022c;
RA Foloppe N., Fisher L.M., Howes R., Kierstan P., Potter A.,
RA Robertson A.G.S., Surgenor A.E.;
RT "Structure-based design of novel Chk1 inhibitors: insights into hydrogen
RT bonding and protein-ligand affinity.";
RL J. Med. Chem. 48:4332-4345(2005).
RN [71]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-223 AND MET-312.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
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:11535615, PubMed:12446774, PubMed:12399544, PubMed:14559997,
CC PubMed:14988723, PubMed:15311285, PubMed:15665856, PubMed:15650047,
CC PubMed:32357935). May also negatively regulate cell cycle progression
CC during unperturbed cell cycles (PubMed:11535615, PubMed:12446774,
CC PubMed:12399544, PubMed:14559997, PubMed:14988723, PubMed:15311285,
CC PubMed:15665856, PubMed:15650047). This regulation is achieved by a
CC number of mechanisms that together help to preserve the integrity of
CC the genome (PubMed:11535615, PubMed:12446774, PubMed:12399544,
CC PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856,
CC PubMed:15650047). Recognizes the substrate consensus sequence [R-X-X-
CC S/T] (PubMed:11535615, PubMed:12446774, PubMed:12399544,
CC PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15665856,
CC PubMed:15650047). Binds to and phosphorylates CDC25A, CDC25B and CDC25C
CC (PubMed:9278511, PubMed:12676583, PubMed:14681206, PubMed:12676925,
CC PubMed:12759351, PubMed:19734889, PubMed:14559997). Phosphorylation of
CC CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at
CC 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit
CC CDC25A and CDC25C (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-
CC 76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis
CC of CDC25A (PubMed:9278511, PubMed:12676583, PubMed:14681206,
CC PubMed:12676925, PubMed:12759351, PubMed:19734889). Phosphorylation of
CC CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at
CC 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for
CC polyubiquitination and degradation of CDCD25A (PubMed:9278511,
CC PubMed:19734889, PubMed:20090422). Inhibition of CDC25 leads to
CC increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes
CC and blocks cell cycle progression (PubMed:9278511). Also phosphorylates
CC NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309',
CC which promotes the release of RAD51 from BRCA2 and enhances the
CC association of RAD51 with chromatin, thereby promoting DNA repair by
CC homologous recombination (PubMed:15665856). Phosphorylates multiple
CC sites within the C-terminus of TP53, which promotes activation of TP53
CC by acetylation and promotes cell cycle arrest and suppression of
CC cellular proliferation (PubMed:10673501, PubMed:15659650,
CC PubMed:16511572). Also promotes repair of DNA cross-links through
CC phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates
CC TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of
CC the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071).
CC This may enhance chromatin assembly both in the presence or absence of
CC DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in
CC replication fork maintenance through regulation of PCNA
CC (PubMed:18451105). May regulate the transcription of genes that
CC regulate cell-cycle progression through the phosphorylation of histones
CC (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which
CC leads to epigenetic inhibition of a subset of genes (By similarity).
CC May also phosphorylate RB1 to promote its interaction with the E2F
CC family of transcription factors and subsequent cell cycle arrest
CC (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to
CC chromatin (PubMed:31316063). Reduces replication stress and activates
CC the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A
CC and promoting the serine/threonine-protein phosphatase 2A-mediated
CC dephosphorylation and stabilization of WEE1 levels and activity
CC (PubMed:33108758). {ECO:0000250|UniProtKB:O35280,
CC ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615,
CC ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774,
CC ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583,
CC ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351,
CC ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997,
CC ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723,
CC ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047,
CC ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856,
CC ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736,
CC ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105,
CC ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889,
CC ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063,
CC ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758,
CC ECO:0000269|PubMed:9278511}.
CC -!- FUNCTION: [Isoform 2]: Endogenous repressor of isoform 1, interacts
CC with, and antagonizes CHK1 to promote the S to G2/M phase transition.
CC {ECO:0000269|PubMed:22184239}.
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:10673501, ECO:0000269|PubMed:12660173,
CC ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:15659650,
CC ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572,
CC ECO:0000269|PubMed:16963448, ECO:0000269|PubMed:17296736,
CC ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18317453,
CC ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:31316063,
CC ECO:0000269|PubMed:9278511};
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:10673501,
CC ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:14559997,
CC ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856,
CC ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:16963448,
CC ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128,
CC ECO:0000269|PubMed:18317453, ECO:0000269|PubMed:18728393,
CC ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:9278511};
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 (PubMed:11390642, PubMed:12588868, PubMed:12676583,
CC PubMed:12676962, PubMed:15665856, PubMed:19716789). Activation is
CC modulated by several mediators including CLSPN, BRCA1 and FEM1B
CC (PubMed:11836499, PubMed:12766152, PubMed:16963448, PubMed:19330022).
CC Proteolytic cleavage at the C-terminus by SPRTN during normal DNA
CC replication activates the protein kinase activity (PubMed:31316063).
CC {ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:11836499,
CC ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583,
CC ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:12766152,
CC ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16963448,
CC ECO:0000269|PubMed:19330022, ECO:0000269|PubMed:19716789,
CC ECO:0000269|PubMed:31316063}.
CC -!- SUBUNIT: Interacts (phosphorylated by ATR) with RAD51
CC (PubMed:15665856). Interacts with and phosphorylates CLSPN, an adapter
CC protein that regulates the ATR-dependent phosphorylation of CHEK1
CC (PubMed:16963448). Interacts with BRCA1 (PubMed:11836499). Interacts
CC with and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:9278511).
CC Interacts with FBXO6, which regulates CHEK1 (PubMed:19716789).
CC Interacts with PPM1D, which regulates CHEK1 through dephosphorylation
CC (PubMed:15870257). Interacts with TIMELESS; DNA damage-dependent
CC (PubMed:15798197). Interacts with FEM1B; activates CHEK1 in response to
CC stress (PubMed:19330022). Interacts with TLK1 (PubMed:12660173).
CC Interacts with XPO1 and YWHAZ (PubMed:12676962). Interacts with
CC CDK5RAP3; antagonizes CHEK1 (PubMed:19223857).
CC {ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12660173,
CC ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:12766152,
CC ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:15707391,
CC ECO:0000269|PubMed:15798197, ECO:0000269|PubMed:15870257,
CC ECO:0000269|PubMed:16963448, ECO:0000269|PubMed:19223857,
CC ECO:0000269|PubMed:19330022, ECO:0000269|PubMed:19716789,
CC ECO:0000269|PubMed:9278511}.
CC -!- SUBUNIT: [Isoform 1]: Isoform 1 associates with isoform 2, the
CC interaction is disrupted upon phosphorylation by ATR.
CC {ECO:0000269|PubMed:22184239}.
CC -!- INTERACTION:
CC O14757; P38398: BRCA1; NbExp=3; IntAct=EBI-974488, EBI-349905;
CC O14757; P30307: CDC25C; NbExp=2; IntAct=EBI-974488, EBI-974439;
CC O14757; Q9HAW4: CLSPN; NbExp=5; IntAct=EBI-974488, EBI-1369377;
CC O14757; Q9UJM3: ERRFI1; NbExp=2; IntAct=EBI-974488, EBI-2941912;
CC O14757; P08238: HSP90AB1; NbExp=3; IntAct=EBI-974488, EBI-352572;
CC O14757; O00255: MEN1; NbExp=2; IntAct=EBI-974488, EBI-592789;
CC O14757; Q06609: RAD51; NbExp=3; IntAct=EBI-974488, EBI-297202;
CC O14757; P06400: RB1; NbExp=3; IntAct=EBI-974488, EBI-491274;
CC O14757; Q9HCE7-2: SMURF1; NbExp=4; IntAct=EBI-974488, EBI-9845742;
CC O14757; Q9UNS1: TIMELESS; NbExp=2; IntAct=EBI-974488, EBI-2212315;
CC O14757; P61981: YWHAG; NbExp=7; IntAct=EBI-974488, EBI-359832;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11836499,
CC ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15311285,
CC ECO:0000269|PubMed:15710331, ECO:0000269|PubMed:9278511}. Chromosome
CC {ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:31316063,
CC ECO:0000269|PubMed:9382850}. Cytoplasm {ECO:0000269|PubMed:12676962}.
CC Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:15311285}. Note=Nuclear export is mediated at least
CC in part by XPO1/CRM1 (PubMed:12676962). Also localizes to the
CC centrosome specifically during interphase, where it may protect
CC centrosomal CDC2 kinase from inappropriate activation by cytoplasmic
CC CDC25B (PubMed:15311285). Proteolytic cleavage at the C-terminus by
CC SPRTN promotes removal from chromatin (PubMed:31316063).
CC {ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15311285,
CC ECO:0000269|PubMed:31316063}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O14757-1; Sequence=Displayed;
CC Name=2; Synonyms=Chk1-short {ECO:0000303|PubMed:22184239}, Chk1-S
CC {ECO:0000303|PubMed:22184239};
CC IsoId=O14757-2; Sequence=VSP_044008, VSP_044009;
CC Name=3;
CC IsoId=O14757-3; Sequence=VSP_045075;
CC -!- TISSUE SPECIFICITY: Expressed ubiquitously with the most abundant
CC expression in thymus, testis, small intestine and colon.
CC {ECO:0000269|PubMed:9278511, ECO:0000269|PubMed:9382850}.
CC -!- DOMAIN: The autoinhibitory region (AIR) inhibits the activity of the
CC kinase domain. {ECO:0000269|PubMed:14681223}.
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:10859164, ECO:0000269|PubMed:11390642,
CC ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12588868,
CC ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583,
CC ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12676962,
CC ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14681223,
CC ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15650047,
CC ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:15870257,
CC ECO:0000269|PubMed:19716789}.
CC -!- PTM: Ubiquitinated. Mono or diubiquitination promotes nuclear exclusion
CC (By similarity). The activated form (phosphorylated on Ser-345) is
CC polyubiquitinated at Lys-436 by some SCF-type E3 ubiquitin ligase
CC complex containing FBXO6 promoting its degradation. Ubiquitination and
CC degradation are required to terminate the checkpoint and ensure that
CC activated CHEK1 does not accumulate as cells progress through S phase,
CC when replication forks encounter transient impediments during normal
CC DNA replication. 'Lys-63'-mediated ubiquitination by TRAF4 at Lys-132
CC activates cell cycle arrest and activation of DNA repair
CC (PubMed:32357935). {ECO:0000250, ECO:0000269|PubMed:10859164,
CC ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12446774,
CC ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925,
CC ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:14681223,
CC ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15650047,
CC ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:15870257,
CC ECO:0000269|PubMed:19716789}.
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:0000269|PubMed:31316063}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. NIM1 subfamily. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/chek1/";
CC ---------------------------------------------------------------------------
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DR EMBL; AF016582; AAC51736.1; -; mRNA.
DR EMBL; AF032874; AAB88852.1; -; mRNA.
DR EMBL; AB032387; BAA84577.1; -; Genomic_DNA.
DR EMBL; JF289264; AEB71796.1; -; mRNA.
DR EMBL; AK292549; BAF85238.1; -; mRNA.
DR EMBL; AK293143; BAG56691.1; -; mRNA.
DR EMBL; AK299783; BAG61665.1; -; mRNA.
DR EMBL; AF527555; AAM78553.1; -; Genomic_DNA.
DR EMBL; AB451222; BAG70036.1; -; mRNA.
DR EMBL; AB451345; BAG70159.1; -; mRNA.
DR EMBL; AP001132; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW67644.1; -; Genomic_DNA.
DR EMBL; BC004202; AAH04202.1; -; mRNA.
DR EMBL; BC017575; AAH17575.1; -; mRNA.
DR CCDS; CCDS58191.1; -. [O14757-3]
DR CCDS; CCDS81645.1; -. [O14757-2]
DR CCDS; CCDS8459.1; -. [O14757-1]
DR RefSeq; NP_001107593.1; NM_001114121.2. [O14757-1]
DR RefSeq; NP_001107594.1; NM_001114122.2. [O14757-1]
DR RefSeq; NP_001231775.1; NM_001244846.1. [O14757-3]
DR RefSeq; NP_001265.2; NM_001274.5. [O14757-1]
DR RefSeq; NP_001317357.1; NM_001330428.1. [O14757-2]
DR RefSeq; XP_016872635.1; XM_017017146.1. [O14757-1]
DR PDB; 1IA8; X-ray; 1.70 A; A=1-289.
DR PDB; 1NVQ; X-ray; 2.00 A; A=1-289.
DR PDB; 1NVR; X-ray; 1.80 A; A=1-289.
DR PDB; 1NVS; X-ray; 1.80 A; A=1-289.
DR PDB; 1ZLT; X-ray; 1.74 A; A=1-289.
DR PDB; 1ZYS; X-ray; 1.70 A; A=1-273.
DR PDB; 2AYP; X-ray; 2.90 A; A=1-269.
DR PDB; 2BR1; X-ray; 2.00 A; A=1-289.
DR PDB; 2BRB; X-ray; 2.10 A; A=1-289.
DR PDB; 2BRG; X-ray; 2.10 A; A=1-289.
DR PDB; 2BRH; X-ray; 2.10 A; A=1-289.
DR PDB; 2BRM; X-ray; 2.20 A; A=1-289.
DR PDB; 2BRN; X-ray; 2.80 A; A=1-289.
DR PDB; 2BRO; X-ray; 2.20 A; A=1-289.
DR PDB; 2C3J; X-ray; 2.10 A; A=1-289.
DR PDB; 2C3K; X-ray; 2.60 A; A=1-289.
DR PDB; 2C3L; X-ray; 2.35 A; A=1-289.
DR PDB; 2CGU; X-ray; 2.50 A; A=1-289.
DR PDB; 2CGV; X-ray; 2.60 A; A=1-289.
DR PDB; 2CGW; X-ray; 2.20 A; A=1-289.
DR PDB; 2CGX; X-ray; 2.20 A; A=1-289.
DR PDB; 2E9N; X-ray; 2.50 A; A=2-270.
DR PDB; 2E9O; X-ray; 2.10 A; A=2-270.
DR PDB; 2E9P; X-ray; 2.60 A; A=2-270.
DR PDB; 2E9U; X-ray; 2.00 A; A=2-270.
DR PDB; 2E9V; X-ray; 2.00 A; A/B=2-269.
DR PDB; 2GDO; X-ray; 3.00 A; A=1-289.
DR PDB; 2GHG; X-ray; 3.50 A; A=2-270.
DR PDB; 2HOG; X-ray; 1.90 A; A=2-307.
DR PDB; 2HXL; X-ray; 1.80 A; A=2-307.
DR PDB; 2HXQ; X-ray; 2.00 A; A=2-307.
DR PDB; 2HY0; X-ray; 1.70 A; A=2-307.
DR PDB; 2QHM; X-ray; 2.00 A; A=1-307.
DR PDB; 2QHN; X-ray; 1.70 A; A=1-307.
DR PDB; 2R0U; X-ray; 1.90 A; A=1-307.
DR PDB; 2WMQ; X-ray; 2.48 A; A=1-289.
DR PDB; 2WMR; X-ray; 2.43 A; A=1-289.
DR PDB; 2WMS; X-ray; 2.70 A; A=1-289.
DR PDB; 2WMT; X-ray; 2.55 A; A=1-289.
DR PDB; 2WMU; X-ray; 2.60 A; A=1-289.
DR PDB; 2WMV; X-ray; 2.01 A; A=1-289.
DR PDB; 2WMW; X-ray; 2.43 A; A=1-289.
DR PDB; 2WMX; X-ray; 2.45 A; A=1-289.
DR PDB; 2X8D; X-ray; 1.90 A; A=1-289.
DR PDB; 2X8E; X-ray; 2.50 A; A=1-276.
DR PDB; 2X8I; X-ray; 1.92 A; A=1-289.
DR PDB; 2XEY; X-ray; 2.70 A; A=1-289.
DR PDB; 2XEZ; X-ray; 2.25 A; A=1-289.
DR PDB; 2XF0; X-ray; 2.40 A; A=1-289.
DR PDB; 2YDI; X-ray; 1.60 A; A=1-289.
DR PDB; 2YDJ; X-ray; 1.85 A; A/B=1-276.
DR PDB; 2YDK; X-ray; 1.90 A; A=1-276.
DR PDB; 2YER; X-ray; 1.83 A; A=1-276.
DR PDB; 2YEX; X-ray; 1.30 A; A=1-276.
DR PDB; 2YM3; X-ray; 2.01 A; A=1-289.
DR PDB; 2YM4; X-ray; 2.35 A; A=1-289.
DR PDB; 2YM5; X-ray; 2.03 A; A=1-289.
DR PDB; 2YM6; X-ray; 2.01 A; A=1-289.
DR PDB; 2YM7; X-ray; 1.81 A; A=1-289.
DR PDB; 2YM8; X-ray; 2.07 A; A=1-289.
DR PDB; 2YWP; X-ray; 2.90 A; A=2-270.
DR PDB; 3F9N; X-ray; 1.90 A; A=2-307.
DR PDB; 3JVR; X-ray; 1.76 A; A=2-272.
DR PDB; 3JVS; X-ray; 1.90 A; A=2-272.
DR PDB; 3NLB; X-ray; 1.90 A; A=1-289.
DR PDB; 3OT3; X-ray; 1.44 A; A=2-274.
DR PDB; 3OT8; X-ray; 1.65 A; A=2-274.
DR PDB; 3PA3; X-ray; 1.40 A; A=2-274.
DR PDB; 3PA4; X-ray; 1.59 A; A=2-274.
DR PDB; 3PA5; X-ray; 1.70 A; A=2-274.
DR PDB; 3TKH; X-ray; 1.79 A; A=1-307.
DR PDB; 3TKI; X-ray; 1.60 A; A=1-307.
DR PDB; 3U9N; X-ray; 1.85 A; A=2-274.
DR PDB; 4FSM; X-ray; 2.30 A; A=2-280.
DR PDB; 4FSN; X-ray; 2.10 A; A=4-280.
DR PDB; 4FSQ; X-ray; 2.40 A; A=2-280.
DR PDB; 4FSR; X-ray; 2.50 A; A=2-280.
DR PDB; 4FST; X-ray; 1.90 A; A=2-270.
DR PDB; 4FSU; X-ray; 2.10 A; A=2-280.
DR PDB; 4FSW; X-ray; 2.30 A; A=2-280.
DR PDB; 4FSY; X-ray; 2.30 A; A=2-280.
DR PDB; 4FSZ; X-ray; 2.30 A; A=2-280.
DR PDB; 4FT0; X-ray; 2.30 A; A=2-280.
DR PDB; 4FT3; X-ray; 2.50 A; A=2-280.
DR PDB; 4FT5; X-ray; 2.40 A; A=2-280.
DR PDB; 4FT7; X-ray; 2.20 A; A=2-280.
DR PDB; 4FT9; X-ray; 2.20 A; A=2-280.
DR PDB; 4FTA; X-ray; 2.40 A; A=2-280.
DR PDB; 4FTC; X-ray; 2.00 A; A=2-280.
DR PDB; 4FTI; X-ray; 2.20 A; A=2-280.
DR PDB; 4FTJ; X-ray; 2.20 A; A=2-280.
DR PDB; 4FTK; X-ray; 2.30 A; A=2-280.
DR PDB; 4FTL; X-ray; 2.50 A; A=2-280.
DR PDB; 4FTM; X-ray; 1.90 A; A=2-280.
DR PDB; 4FTN; X-ray; 2.02 A; A=2-280.
DR PDB; 4FTO; X-ray; 2.10 A; A=2-280.
DR PDB; 4FTQ; X-ray; 2.00 A; A=2-280.
DR PDB; 4FTR; X-ray; 2.25 A; A=2-280.
DR PDB; 4FTT; X-ray; 2.30 A; A=2-280.
DR PDB; 4FTU; X-ray; 2.10 A; A=2-280.
DR PDB; 4GH2; X-ray; 2.03 A; A=2-280.
DR PDB; 4HYH; X-ray; 1.70 A; A=1-289.
DR PDB; 4HYI; X-ray; 1.40 A; A=1-289.
DR PDB; 4JIK; X-ray; 1.90 A; A=2-274.
DR PDB; 4QYE; X-ray; 2.05 A; A=1-289.
DR PDB; 4QYF; X-ray; 2.15 A; A=1-289.
DR PDB; 4QYG; X-ray; 1.75 A; A/B=1-289.
DR PDB; 4QYH; X-ray; 1.90 A; A/B=1-289.
DR PDB; 4RVK; X-ray; 1.85 A; A=1-289.
DR PDB; 4RVL; X-ray; 1.85 A; A=1-289.
DR PDB; 4RVM; X-ray; 1.86 A; A=1-289.
DR PDB; 5DLS; X-ray; 2.15 A; A=1-289.
DR PDB; 5F4N; X-ray; 1.91 A; A=1-273.
DR PDB; 5OOP; X-ray; 1.70 A; A=1-289.
DR PDB; 5OOR; X-ray; 1.90 A; A=1-289.
DR PDB; 5OOT; X-ray; 2.10 A; A=1-289.
DR PDB; 5OP2; X-ray; 1.90 A; A=1-289.
DR PDB; 5OP4; X-ray; 2.00 A; A=1-289.
DR PDB; 5OP5; X-ray; 1.90 A; A=1-289.
DR PDB; 5OP7; X-ray; 1.80 A; A=1-289.
DR PDB; 5OPB; X-ray; 1.55 A; A=1-289.
DR PDB; 5OPR; X-ray; 1.95 A; A=1-289.
DR PDB; 5OPS; X-ray; 2.00 A; A=1-289.
DR PDB; 5OPU; X-ray; 1.55 A; A=1-289.
DR PDB; 5OPV; X-ray; 1.90 A; A=1-289.
DR PDB; 5OQ5; X-ray; 1.40 A; A=1-289.
DR PDB; 5OQ6; X-ray; 1.95 A; A=1-289.
DR PDB; 5OQ7; X-ray; 2.10 A; A/B=1-289.
DR PDB; 5OQ8; X-ray; 2.00 A; A=1-289.
DR PDB; 5WI2; X-ray; 2.50 A; A/B=377-476.
DR PDB; 6FC8; X-ray; 1.61 A; A=1-276.
DR PDB; 6FCF; X-ray; 1.85 A; A=1-276.
DR PDB; 6FCK; X-ray; 1.90 A; A=1-276.
DR PDB; 7AKM; X-ray; 1.93 A; A/B=2-287.
DR PDB; 7AKO; X-ray; 1.80 A; A/B=2-289.
DR PDB; 7BJD; X-ray; 2.00 A; A=1-289.
DR PDB; 7BJE; X-ray; 1.80 A; A=1-289.
DR PDB; 7BJH; X-ray; 1.80 A; A=1-289.
DR PDB; 7BJJ; X-ray; 1.80 A; A=1-289.
DR PDB; 7BJM; X-ray; 2.30 A; A=1-289.
DR PDB; 7BJO; X-ray; 2.30 A; A=1-289.
DR PDB; 7BJR; X-ray; 1.90 A; A=1-289.
DR PDB; 7BJX; X-ray; 2.40 A; A/B=1-289.
DR PDB; 7BK1; X-ray; 2.00 A; A=1-289.
DR PDB; 7BK2; X-ray; 2.00 A; A=1-289.
DR PDB; 7BK3; X-ray; 2.00 A; A=1-289.
DR PDB; 7BKN; X-ray; 2.74 A; A=1-289.
DR PDB; 7BKO; X-ray; 2.30 A; A=1-289.
DR PDB; 7MCK; X-ray; 1.65 A; A=1-289.
DR PDB; 7SUF; X-ray; 1.48 A; A=1-289.
DR PDB; 7SUG; X-ray; 1.48 A; A=1-289.
DR PDB; 7SUH; X-ray; 2.46 A; A=1-289.
DR PDB; 7SUI; X-ray; 2.12 A; A=1-289.
DR PDB; 7SUJ; X-ray; 2.30 A; A/B=1-289.
DR PDBsum; 1IA8; -.
DR PDBsum; 1NVQ; -.
DR PDBsum; 1NVR; -.
DR PDBsum; 1NVS; -.
DR PDBsum; 1ZLT; -.
DR PDBsum; 1ZYS; -.
DR PDBsum; 2AYP; -.
DR PDBsum; 2BR1; -.
DR PDBsum; 2BRB; -.
DR PDBsum; 2BRG; -.
DR PDBsum; 2BRH; -.
DR PDBsum; 2BRM; -.
DR PDBsum; 2BRN; -.
DR PDBsum; 2BRO; -.
DR PDBsum; 2C3J; -.
DR PDBsum; 2C3K; -.
DR PDBsum; 2C3L; -.
DR PDBsum; 2CGU; -.
DR PDBsum; 2CGV; -.
DR PDBsum; 2CGW; -.
DR PDBsum; 2CGX; -.
DR PDBsum; 2E9N; -.
DR PDBsum; 2E9O; -.
DR PDBsum; 2E9P; -.
DR PDBsum; 2E9U; -.
DR PDBsum; 2E9V; -.
DR PDBsum; 2GDO; -.
DR PDBsum; 2GHG; -.
DR PDBsum; 2HOG; -.
DR PDBsum; 2HXL; -.
DR PDBsum; 2HXQ; -.
DR PDBsum; 2HY0; -.
DR PDBsum; 2QHM; -.
DR PDBsum; 2QHN; -.
DR PDBsum; 2R0U; -.
DR PDBsum; 2WMQ; -.
DR PDBsum; 2WMR; -.
DR PDBsum; 2WMS; -.
DR PDBsum; 2WMT; -.
DR PDBsum; 2WMU; -.
DR PDBsum; 2WMV; -.
DR PDBsum; 2WMW; -.
DR PDBsum; 2WMX; -.
DR PDBsum; 2X8D; -.
DR PDBsum; 2X8E; -.
DR PDBsum; 2X8I; -.
DR PDBsum; 2XEY; -.
DR PDBsum; 2XEZ; -.
DR PDBsum; 2XF0; -.
DR PDBsum; 2YDI; -.
DR PDBsum; 2YDJ; -.
DR PDBsum; 2YDK; -.
DR PDBsum; 2YER; -.
DR PDBsum; 2YEX; -.
DR PDBsum; 2YM3; -.
DR PDBsum; 2YM4; -.
DR PDBsum; 2YM5; -.
DR PDBsum; 2YM6; -.
DR PDBsum; 2YM7; -.
DR PDBsum; 2YM8; -.
DR PDBsum; 2YWP; -.
DR PDBsum; 3F9N; -.
DR PDBsum; 3JVR; -.
DR PDBsum; 3JVS; -.
DR PDBsum; 3NLB; -.
DR PDBsum; 3OT3; -.
DR PDBsum; 3OT8; -.
DR PDBsum; 3PA3; -.
DR PDBsum; 3PA4; -.
DR PDBsum; 3PA5; -.
DR PDBsum; 3TKH; -.
DR PDBsum; 3TKI; -.
DR PDBsum; 3U9N; -.
DR PDBsum; 4FSM; -.
DR PDBsum; 4FSN; -.
DR PDBsum; 4FSQ; -.
DR PDBsum; 4FSR; -.
DR PDBsum; 4FST; -.
DR PDBsum; 4FSU; -.
DR PDBsum; 4FSW; -.
DR PDBsum; 4FSY; -.
DR PDBsum; 4FSZ; -.
DR PDBsum; 4FT0; -.
DR PDBsum; 4FT3; -.
DR PDBsum; 4FT5; -.
DR PDBsum; 4FT7; -.
DR PDBsum; 4FT9; -.
DR PDBsum; 4FTA; -.
DR PDBsum; 4FTC; -.
DR PDBsum; 4FTI; -.
DR PDBsum; 4FTJ; -.
DR PDBsum; 4FTK; -.
DR PDBsum; 4FTL; -.
DR PDBsum; 4FTM; -.
DR PDBsum; 4FTN; -.
DR PDBsum; 4FTO; -.
DR PDBsum; 4FTQ; -.
DR PDBsum; 4FTR; -.
DR PDBsum; 4FTT; -.
DR PDBsum; 4FTU; -.
DR PDBsum; 4GH2; -.
DR PDBsum; 4HYH; -.
DR PDBsum; 4HYI; -.
DR PDBsum; 4JIK; -.
DR PDBsum; 4QYE; -.
DR PDBsum; 4QYF; -.
DR PDBsum; 4QYG; -.
DR PDBsum; 4QYH; -.
DR PDBsum; 4RVK; -.
DR PDBsum; 4RVL; -.
DR PDBsum; 4RVM; -.
DR PDBsum; 5DLS; -.
DR PDBsum; 5F4N; -.
DR PDBsum; 5OOP; -.
DR PDBsum; 5OOR; -.
DR PDBsum; 5OOT; -.
DR PDBsum; 5OP2; -.
DR PDBsum; 5OP4; -.
DR PDBsum; 5OP5; -.
DR PDBsum; 5OP7; -.
DR PDBsum; 5OPB; -.
DR PDBsum; 5OPR; -.
DR PDBsum; 5OPS; -.
DR PDBsum; 5OPU; -.
DR PDBsum; 5OPV; -.
DR PDBsum; 5OQ5; -.
DR PDBsum; 5OQ6; -.
DR PDBsum; 5OQ7; -.
DR PDBsum; 5OQ8; -.
DR PDBsum; 5WI2; -.
DR PDBsum; 6FC8; -.
DR PDBsum; 6FCF; -.
DR PDBsum; 6FCK; -.
DR PDBsum; 7AKM; -.
DR PDBsum; 7AKO; -.
DR PDBsum; 7BJD; -.
DR PDBsum; 7BJE; -.
DR PDBsum; 7BJH; -.
DR PDBsum; 7BJJ; -.
DR PDBsum; 7BJM; -.
DR PDBsum; 7BJO; -.
DR PDBsum; 7BJR; -.
DR PDBsum; 7BJX; -.
DR PDBsum; 7BK1; -.
DR PDBsum; 7BK2; -.
DR PDBsum; 7BK3; -.
DR PDBsum; 7BKN; -.
DR PDBsum; 7BKO; -.
DR PDBsum; 7MCK; -.
DR PDBsum; 7SUF; -.
DR PDBsum; 7SUG; -.
DR PDBsum; 7SUH; -.
DR PDBsum; 7SUI; -.
DR PDBsum; 7SUJ; -.
DR AlphaFoldDB; O14757; -.
DR SMR; O14757; -.
DR BioGRID; 107536; 203.
DR CORUM; O14757; -.
DR DIP; DIP-24182N; -.
DR ELM; O14757; -.
DR IntAct; O14757; 58.
DR MINT; O14757; -.
DR STRING; 9606.ENSP00000388648; -.
DR BindingDB; O14757; -.
DR ChEMBL; CHEMBL4630; -.
DR DrugBank; DB07647; (2R)-1-[(5,6-DIPHENYL-7H-PYRROLO[2,3-D]PYRIMIDIN-4-YL)AMINO]PROPAN-2-OL.
DR DrugBank; DB07648; (2R)-3-{[(4Z)-5,6-DIPHENYL-6,7-DIHYDRO-4H-PYRROLO[2,3-D]PYRIMIDIN-4-YLIDENE]AMINO}PROPANE-1,2-DIOL.
DR DrugBank; DB07037; (2S)-1-AMINO-3-[(5-NITROQUINOLIN-8-YL)AMINO]PROPAN-2-OL.
DR DrugBank; DB07243; (3-ENDO)-8-METHYL-8-AZABICYCLO[3.2.1]OCT-3-YL 1H-PYRROLO[2,3-B]PYRIDINE-3-CARBOXYLATE.
DR DrugBank; DB07078; (3Z)-6-(4-HYDROXY-3-METHOXYPHENYL)-3-(1H-PYRROL-2-YLMETHYLENE)-1,3-DIHYDRO-2H-INDOL-2-ONE.
DR DrugBank; DB07654; (5,6-DIPHENYL-FURO[2,3-D]PYRIMIDIN-4-YLAMINO)-ACETIC.
DR DrugBank; DB07213; (5-{3-[5-(PIPERIDIN-1-YLMETHYL)-1H-INDOL-2-YL]-1H-INDAZOL-6-YL}-2H-1,2,3-TRIAZOL-4-YL)METHANOL.
DR DrugBank; DB07314; 1-(5-CHLORO-2,4-DIMETHOXYPHENYL)-3-(5-CYANOPYRAZIN-2-YL)UREA.
DR DrugBank; DB07228; 1-(5-CHLORO-2-METHOXYPHENYL)-3-{6-[2-(DIMETHYLAMINO)-1-METHYLETHOXY]PYRAZIN-2-YL}UREA.
DR DrugBank; DB08781; 1-[(2S)-4-(5-BROMO-1H-PYRAZOLO[3,4-B]PYRIDIN-4-YL)MORPHOLIN-2-YL]METHANAMINE.
DR DrugBank; DB08774; 1-[(2S)-4-(5-phenyl-1H-pyrazolo[3,4-b]pyridin-4-yl)morpholin-2-yl]methanamine.
DR DrugBank; DB07311; 18-CHLORO-11,12,13,14-TETRAHYDRO-1H,10H-8,4-(AZENO)-9,15,1,3,6-BENZODIOXATRIAZACYCLOHEPTADECIN-2-ONE.
DR DrugBank; DB07034; 2,2'-{[9-(HYDROXYIMINO)-9H-FLUORENE-2,7-DIYL]BIS(OXY)}DIACETIC ACID.
DR DrugBank; DB07038; 2-(cyclohexylamino)benzoic acid.
DR DrugBank; DB08779; 2-(methylsulfanyl)-5-(thiophen-2-ylmethyl)-1H-imidazol-4-ol.
DR DrugBank; DB08393; 2-[(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)AMINO]ETHANOL.
DR DrugBank; DB08392; 2-[5,6-BIS-(4-METHOXY-PHENYL)-FURO[2,3-D]PYRIMIDIN-4-YLAMINO]-ETHANOL.
DR DrugBank; DB07959; 3-(1H-BENZIMIDAZOL-2-YL)-1H-INDAZOLE.
DR DrugBank; DB07075; 3-(5-{[4-(AMINOMETHYL)PIPERIDIN-1-YL]METHYL}-1H-INDOL-2-YL)-1H-INDAZOLE-6-CARBONITRILE.
DR DrugBank; DB07025; 3-(5-{[4-(AMINOMETHYL)PIPERIDIN-1-YL]METHYL}-1H-INDOL-2-YL)QUINOLIN-2(1H)-ONE.
DR DrugBank; DB07655; 3-AMINO-3-BENZYL-[4.3.0]BICYCLO-1,6-DIAZANONAN-2-ONE.
DR DrugBank; DB07320; 4-(6-{[(4-METHYLCYCLOHEXYL)AMINO]METHYL}-1,4-DIHYDROINDENO[1,2-C]PYRAZOL-3-YL)BENZOIC ACID.
DR DrugBank; DB07336; 4-[3-(1H-BENZIMIDAZOL-2-YL)-1H-INDAZOL-6-YL]-2-METHOXYPHENOL.
DR DrugBank; DB08777; 5,6,7,8-TETRAHYDRO[1]BENZOTHIENO[2,3-D]PYRIMIDIN-4(3H)-ONE.
DR DrugBank; DB07158; 5-ETHYL-3-METHYL-1,5-DIHYDRO-4H-PYRAZOLO[4,3-C]QUINOLIN-4-ONE.
DR DrugBank; DB08780; 6-MORPHOLIN-4-YL-9H-PURINE.
DR DrugBank; DB08778; [4-amino-2-(tert-butylamino)-1,3-thiazol-5-yl](phenyl)methanone.
DR DrugBank; DB06852; CHIR-124.
DR DrugBank; DB06486; Enzastaurin.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB08776; N-(4-OXO-5,6,7,8-TETRAHYDRO-4H-[1,3]THIAZOLO[5,4-C]AZEPIN-2-YL)ACETAMIDE.
DR DrugBank; DB07653; N-(5,6-DIPHENYLFURO[2,3-D]PYRIMIDIN-4-YL)GLYCINE.
DR DrugBank; DB06876; N-{5-[4-(4-METHYLPIPERAZIN-1-YL)PHENYL]-1H-PYRROLO[2,3-B]PYRIDIN-3-YL}NICOTINAMIDE.
DR DrugBank; DB08683; REL-(9R,12S)-9,10,11,12-TETRAHYDRO-9,12-EPOXY-1H-DIINDOLO[1,2,3-FG:3',2',1'-KL]PYRROLO[3,4-I][1,6]BENZODIAZOCINE-1,3(2H)-DIONE.
DR DrugBank; DB05149; XL844.
DR DrugCentral; O14757; -.
DR GuidetoPHARMACOLOGY; 1987; -.
DR iPTMnet; O14757; -.
DR MetOSite; O14757; -.
DR PhosphoSitePlus; O14757; -.
DR BioMuta; CHEK1; -.
DR CPTAC; CPTAC-3223; -.
DR CPTAC; CPTAC-3282; -.
DR CPTAC; CPTAC-922; -.
DR EPD; O14757; -.
DR jPOST; O14757; -.
DR MassIVE; O14757; -.
DR MaxQB; O14757; -.
DR PaxDb; O14757; -.
DR PeptideAtlas; O14757; -.
DR PRIDE; O14757; -.
DR ProteomicsDB; 27577; -.
DR ProteomicsDB; 48208; -. [O14757-1]
DR ProteomicsDB; 48209; -. [O14757-2]
DR Antibodypedia; 3671; 1892 antibodies from 48 providers.
DR CPTC; O14757; 6 antibodies.
DR DNASU; 1111; -.
DR Ensembl; ENST00000278916.8; ENSP00000278916.4; ENSG00000149554.14. [O14757-3]
DR Ensembl; ENST00000428830.6; ENSP00000412504.2; ENSG00000149554.14. [O14757-1]
DR Ensembl; ENST00000438015.7; ENSP00000388648.1; ENSG00000149554.14. [O14757-1]
DR Ensembl; ENST00000524737.6; ENSP00000432890.1; ENSG00000149554.14. [O14757-1]
DR Ensembl; ENST00000532449.6; ENSP00000481616.2; ENSG00000149554.14. [O14757-1]
DR Ensembl; ENST00000534070.5; ENSP00000435371.1; ENSG00000149554.14. [O14757-1]
DR Ensembl; ENST00000544373.5; ENSP00000442317.2; ENSG00000149554.14. [O14757-2]
DR GeneID; 1111; -.
DR KEGG; hsa:1111; -.
DR MANE-Select; ENST00000438015.7; ENSP00000388648.1; NM_001114122.3; NP_001107594.1.
DR UCSC; uc001qcf.5; human. [O14757-1]
DR CTD; 1111; -.
DR DisGeNET; 1111; -.
DR GeneCards; CHEK1; -.
DR HGNC; HGNC:1925; CHEK1.
DR HPA; ENSG00000149554; Tissue enhanced (bone marrow, lymphoid tissue, seminal vesicle).
DR MIM; 603078; gene.
DR neXtProt; NX_O14757; -.
DR OpenTargets; ENSG00000149554; -.
DR PharmGKB; PA110; -.
DR VEuPathDB; HostDB:ENSG00000149554; -.
DR eggNOG; KOG0590; Eukaryota.
DR GeneTree; ENSGT00940000159682; -.
DR InParanoid; O14757; -.
DR OMA; KRSQGHV; -.
DR PhylomeDB; O14757; -.
DR TreeFam; TF351441; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; O14757; -.
DR Reactome; R-HSA-1433557; Signaling by SCF-KIT.
DR Reactome; R-HSA-176187; Activation of ATR in response to replication stress.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-69601; Ubiquitin Mediated Degradation of Phosphorylated Cdc25A.
DR Reactome; R-HSA-75035; Chk1/Chk2(Cds1) mediated inactivation of Cyclin B:Cdk1 complex.
DR Reactome; R-HSA-8953750; Transcriptional Regulation by E2F6.
DR SignaLink; O14757; -.
DR SIGNOR; O14757; -.
DR BioGRID-ORCS; 1111; 839 hits in 1122 CRISPR screens.
DR ChiTaRS; CHEK1; human.
DR EvolutionaryTrace; O14757; -.
DR GeneWiki; CHEK1; -.
DR GenomeRNAi; 1111; -.
DR Pharos; O14757; Tchem.
DR PRO; PR:O14757; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O14757; protein.
DR Bgee; ENSG00000149554; Expressed in secondary oocyte and 128 other tissues.
DR ExpressionAtlas; O14757; baseline and differential.
DR Genevisible; O14757; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0000794; C:condensed nuclear chromosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:CAFA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:CAFA.
DR GO; GO:0005657; C:replication fork; IEA:Ensembl.
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; IPI:CAFA.
DR GO; GO:0004672; F:protein kinase activity; IMP:CACAO.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IDA:UniProtKB.
DR GO; GO:1902742; P:apoptotic process involved in development; IEA:Ensembl.
DR GO; GO:0071313; P:cellular response to caffeine; IEA:Ensembl.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:UniProtKB.
DR GO; GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:UniProtKB.
DR GO; GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0006260; P:DNA replication; TAS:Reactome.
DR GO; GO:0045815; P:epigenetic maintenance of chromatin in transcription-competent conformation; ISS:UniProtKB.
DR GO; GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Ensembl.
DR GO; GO:0001833; P:inner cell mass cell proliferation; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007095; P:mitotic G2 DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0044818; P:mitotic G2/M transition checkpoint; IMP:UniProtKB.
DR GO; GO:2000279; P:negative regulation of DNA biosynthetic process; IEA:Ensembl.
DR GO; GO:0070317; P:negative regulation of G0 to G1 transition; TAS:Reactome.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; IDA:UniProtKB.
DR GO; GO:0006997; P:nucleus organization; IEA:Ensembl.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IDA:UniProtKB.
DR GO; GO:0045787; P:positive regulation of cell cycle; IDA:CAFA.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
DR GO; GO:2000615; P:regulation of histone H3-K9 acetylation; ISS:UniProtKB.
DR GO; GO:0046602; P:regulation of mitotic centrosome separation; IDA:UniProtKB.
DR GO; GO:1901796; P:regulation of signal transduction by p53 class mediator; TAS:Reactome.
DR GO; GO:0010767; P:regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage; ISS:UniProtKB.
DR GO; GO:0090399; P:replicative senescence; NAS:BHF-UCL.
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 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Chromosome;
KW Cytoplasm; 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_0000085848"
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 270..327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 391..476
FT /note="Autoinhibitory region"
FT COMPBIAS 281..327
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 130
FT /note="Proton acceptor"
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"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:20068231"
FT MOD_RES 296
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:15707391,
FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19369195,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 301
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163"
FT MOD_RES 317
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:11390642,
FT ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12588868,
FT ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583,
FT ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:14657349,
FT ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:15870257"
FT MOD_RES 331
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 345
FT /note="Phosphoserine; by ATM and ATR"
FT /evidence="ECO:0000269|PubMed:10859164,
FT ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12446774,
FT ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925,
FT ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:14681223,
FT ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15650047,
FT ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:15870257,
FT ECO:0000269|PubMed:19716789, ECO:0000269|PubMed:31316063"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 468
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 132
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:32357935"
FT CROSSLNK 436
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:19716789"
FT VAR_SEQ 1..94
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:22184239"
FT /id="VSP_044008"
FT VAR_SEQ 95..97
FT /note="RIE -> MEK (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:22184239"
FT /id="VSP_044009"
FT VAR_SEQ 412..445
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045075"
FT VARIANT 156
FT /note="R -> Q (in dbSNP:rs3731410)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_021123"
FT VARIANT 223
FT /note="E -> V (in dbSNP:rs35817404)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040407"
FT VARIANT 312
FT /note="V -> M (in dbSNP:rs34097480)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040408"
FT VARIANT 471
FT /note="I -> V (in dbSNP:rs506504)"
FT /evidence="ECO:0000269|PubMed:10717241,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:19054851, ECO:0000269|PubMed:9278511,
FT ECO:0000269|PubMed:9382850, ECO:0000269|Ref.6,
FT ECO:0000269|Ref.9"
FT /id="VAR_024571"
FT MUTAGEN 38
FT /note="K->R: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:12446774,
FT ECO:0000269|PubMed:14681223"
FT MUTAGEN 130
FT /note="D->A: Abolishes kinase activity."
FT /evidence="ECO:0000269|PubMed:10673501,
FT ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:11535615,
FT ECO:0000269|PubMed:11821419, ECO:0000269|PubMed:12588868,
FT ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:15311285,
FT ECO:0000269|PubMed:9278511"
FT MUTAGEN 132
FT /note="K->R: Strong reduction of chromatin-associated CHK1
FT ubiquitination."
FT /evidence="ECO:0000269|PubMed:32357935"
FT MUTAGEN 317
FT /note="S->A: Abrogates interaction with RAD51; when
FT associated with A-345. Reduces phosphorylation and impairs
FT activation by hydroxyurea and ionizing radiation. Abrogates
FT nuclear retention upon checkpoint activation. Impairs
FT interaction with FBXO6."
FT /evidence="ECO:0000269|PubMed:11390642,
FT ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583,
FT ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856"
FT MUTAGEN 317
FT /note="S->E: Enhances interaction with RAD51; when
FT associated with E-345."
FT /evidence="ECO:0000269|PubMed:11390642,
FT ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583,
FT ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856"
FT MUTAGEN 344
FT /note="F->A: Impairs nuclear export."
FT /evidence="ECO:0000269|PubMed:12676962"
FT MUTAGEN 345
FT /note="S->A: Abrogates interaction with RAD51; when
FT associated with A-317. Reduces phosphorylation and impairs
FT activation by hydroxyurea and ionizing radiation. Impairs
FT interaction with YWHAZ which is required for nuclear
FT retention after checkpoint activation."
FT /evidence="ECO:0000269|PubMed:11390642,
FT ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583,
FT ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856,
FT ECO:0000269|PubMed:19716789"
FT MUTAGEN 345
FT /note="S->E: Enhances interaction with RAD51; when
FT associated with E-317."
FT /evidence="ECO:0000269|PubMed:11390642,
FT ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583,
FT ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856,
FT ECO:0000269|PubMed:19716789"
FT MUTAGEN 353
FT /note="M->A: Impairs nuclear export."
FT /evidence="ECO:0000269|PubMed:12676962"
FT MUTAGEN 357
FT /note="S->A: No effect on phosphorylation induced by
FT hydroxyurea."
FT /evidence="ECO:0000269|PubMed:11390642"
FT MUTAGEN 366
FT /note="S->A: No effect on phosphorylation induced by
FT hydroxyurea."
FT /evidence="ECO:0000269|PubMed:11390642"
FT MUTAGEN 372
FT /note="R->E: In 3RE mutant. Disrupts the folding and/or
FT conformation, allowing increased accessibility to FBXO6
FT component of SCF-type E3 ubiquitin ligase complex; when
FT associated with E-376 and E-379."
FT /evidence="ECO:0000269|PubMed:19716789"
FT MUTAGEN 376
FT /note="R->E: In 3RE mutant. Disrupts the folding and/or
FT conformation, allowing increased accessibility to FBXO6
FT component of SCF-type E3 ubiquitin ligase complex; when
FT associated with E-372 and E-379."
FT /evidence="ECO:0000269|PubMed:19716789"
FT MUTAGEN 379
FT /note="R->E: In 3RE mutant. Disrupts the folding and/or
FT conformation, allowing increased accessibility to FBXO6
FT component of SCF-type E3 ubiquitin ligase complex; when
FT associated with E-372 and E-376."
FT /evidence="ECO:0000269|PubMed:19716789"
FT MUTAGEN 436
FT /note="K->R: Enhances stability of the protein, probably by
FT preventing ubiquitination at this site."
FT /evidence="ECO:0000269|PubMed:19716789"
FT MUTAGEN 468
FT /note="S->A: No effect on phosphorylation induced by
FT hydroxyurea."
FT /evidence="ECO:0000269|PubMed:11390642"
FT CONFLICT 163
FT /note="L -> S (in Ref. 5; BAG56691)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="D -> G (in Ref. 4; BAG61665)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="F -> L (in Ref. 4; BAG61665)"
FT /evidence="ECO:0000305"
FT HELIX 3..8
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 9..17
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 19..28
FT /evidence="ECO:0007829|PDB:2YEX"
FT TURN 29..31
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 34..41
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 42..44
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 48..60
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 70..76
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 88..91
FT /evidence="ECO:0007829|PDB:2GDO"
FT HELIX 92..95
FT /evidence="ECO:0007829|PDB:2YEX"
FT TURN 98..100
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 104..123
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:2GHG"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 136..138
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:2C3J"
FT STRAND 153..157
FT /evidence="ECO:0007829|PDB:7SUF"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 176..179
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 186..203
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:4HYI"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:2XEY"
FT HELIX 216..222
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 227..229
FT /evidence="ECO:0007829|PDB:2E9U"
FT HELIX 231..233
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 236..245
FT /evidence="ECO:0007829|PDB:2YEX"
FT TURN 250..252
FT /evidence="ECO:0007829|PDB:2YEX"
FT HELIX 256..259
FT /evidence="ECO:0007829|PDB:2YEX"
FT TURN 263..266
FT /evidence="ECO:0007829|PDB:2YEX"
FT STRAND 379..384
FT /evidence="ECO:0007829|PDB:5WI2"
FT HELIX 386..399
FT /evidence="ECO:0007829|PDB:5WI2"
FT STRAND 403..417
FT /evidence="ECO:0007829|PDB:5WI2"
FT STRAND 423..432
FT /evidence="ECO:0007829|PDB:5WI2"
FT STRAND 434..446
FT /evidence="ECO:0007829|PDB:5WI2"
FT HELIX 448..461
FT /evidence="ECO:0007829|PDB:5WI2"
FT HELIX 463..465
FT /evidence="ECO:0007829|PDB:5WI2"
SQ SEQUENCE 476 AA; 54434 MW; 0ABD0FAB67E60F67 CRC64;
MAVPFVEDWD LVQTLGEGAY GEVQLAVNRV TEEAVAVKIV DMKRAVDCPE NIKKEICINK
MLNHENVVKF YGHRREGNIQ YLFLEYCSGG ELFDRIEPDI GMPEPDAQRF FHQLMAGVVY
LHGIGITHRD IKPENLLLDE RDNLKISDFG LATVFRYNNR ERLLNKMCGT LPYVAPELLK
RREFHAEPVD VWSCGIVLTA MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA
LLHKILVENP SARITIPDIK KDRWYNKPLK KGAKRPRVTS GGVSESPSGF SKHIQSNLDF
SPVNSASSEE NVKYSSSQPE PRTGLSLWDT SPSYIDKLVQ GISFSQPTCP DHMLLNSQLL
GTPGSSQNPW QRLVKRMTRF FTKLDADKSY QCLKETCEKL GYQWKKSCMN QVTISTTDRR
NNKLIFKVNL LEMDDKILVD FRLSKGDGLE FKRHFLKIKG KLIDIVSSQK IWLPAT
