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 27-MAR-2024, entry version 247. 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 PHOSPHORYLATION AT SER-345. RX PubMed=25083873; DOI=10.1016/j.cell.2014.05.046; RA Kumar A., Mazzanti M., Mistrik M., Kosar M., Beznoussenko G.V., RA Mironov A.A., Garre M., Parazzoli D., Shivashankar G.V., Scita G., RA Bartek J., Foiani M.; RT "ATR mediates a checkpoint at the nuclear envelope in response to RT mechanical stress."; RL Cell 158:633-646(2014). RN [66] 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 [67] 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 [68] 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 [69] 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 [70] 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 [71] 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 [72] 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=8; 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 (PubMed:10859164, PubMed:11390642, PubMed:12446774, PubMed:12588868, CC PubMed:12676583, PubMed:12676925, PubMed:12676962, PubMed:14681223, CC PubMed:14988723, PubMed:15650047, PubMed:15707391, PubMed:15870257, CC PubMed:25083873, PubMed:31316063). Phosphorylated by ATM in response to CC ionizing irradiation (PubMed:12588868, PubMed:12676583). ATM and ATR CC can both phosphorylate Ser-317 and Ser-345 and this results in enhanced CC kinase activity (PubMed:11390642, PubMed:12446774, PubMed:12676583, CC PubMed:12660173, PubMed:12588868, PubMed:12676962, PubMed:14657349, CC PubMed:15707391, PubMed:15870257, PubMed:15665856, PubMed:25083873). CC Phosphorylation at Ser-345 induces a change in the conformation of the CC protein, activates the kinase activity and is a prerequisite for CC interaction with FBXO6 and subsequent ubiquitination at Lys-436 CC (PubMed:19716789). Phosphorylation at Ser-345 also increases binding to CC 14-3-3 proteins and promotes nuclear retention (PubMed:12676962). CC Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to CC exit from checkpoint mediated cell cycle arrest (PubMed:15870257). CC Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or CC diubiquitination. Also phosphorylated at undefined residues during CC mitotic arrest, resulting in decreased activity (By similarity). CC {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10859164, CC ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12446774, CC ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12660173, CC ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, CC ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:14657349, CC ECO:0000269|PubMed:14681223, ECO:0000269|PubMed:14988723, CC ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15665856, CC ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:15870257, CC ECO:0000269|PubMed:19716789, ECO:0000269|PubMed:25083873, CC ECO:0000269|PubMed:31316063}. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. 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 PDB; 8E80; X-ray; 1.49 A; A=1-289. DR PDB; 8E81; X-ray; 1.62 A; A=1-289. DR PDB; 8SIV; X-ray; 1.76 A; A=1-289. DR PDB; 8SIW; X-ray; 1.88 A; A/B=1-289. DR PDB; 8SIX; X-ray; 1.55 A; A=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 PDBsum; 8E80; -. DR PDBsum; 8E81; -. DR PDBsum; 8SIV; -. DR PDBsum; 8SIW; -. DR PDBsum; 8SIX; -. DR AlphaFoldDB; O14757; -. DR SMR; O14757; -. DR BioGRID; 107536; 235. DR CORUM; O14757; -. DR DIP; DIP-24182N; -. DR ELM; O14757; -. DR IntAct; O14757; 61. DR MINT; O14757; -. DR STRING; 9606.ENSP00000391090; -. 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; DB12284; LY-2608204. 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; DB12611; PF-477736. DR DrugBank; DB12008; Prexasertib. 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 GlyGen; O14757; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O14757; -. DR MetOSite; O14757; -. DR PhosphoSitePlus; O14757; -. DR BioMuta; CHEK1; -. DR CPTAC; CPTAC-3223; -. DR CPTAC; CPTAC-3282; -. DR CPTAC; CPTAC-5888; -. DR CPTAC; CPTAC-922; -. DR EPD; O14757; -. DR jPOST; O14757; -. DR MassIVE; O14757; -. DR MaxQB; O14757; -. DR PaxDb; 9606-ENSP00000388648; -. DR PeptideAtlas; O14757; -. DR ProteomicsDB; 27577; -. DR ProteomicsDB; 48208; -. [O14757-1] DR ProteomicsDB; 48209; -. [O14757-2] DR Pumba; O14757; -. DR Antibodypedia; 3671; 2113 antibodies from 48 providers. DR CPTC; O14757; 6 antibodies. DR DNASU; 1111; -. DR Ensembl; ENST00000278916.8; ENSP00000278916.4; ENSG00000149554.15. [O14757-3] DR Ensembl; ENST00000428830.6; ENSP00000412504.2; ENSG00000149554.15. [O14757-1] DR Ensembl; ENST00000438015.7; ENSP00000388648.1; ENSG00000149554.15. [O14757-1] DR Ensembl; ENST00000524737.6; ENSP00000432890.1; ENSG00000149554.15. [O14757-1] DR Ensembl; ENST00000532449.6; ENSP00000481616.2; ENSG00000149554.15. [O14757-1] DR Ensembl; ENST00000534070.5; ENSP00000435371.1; ENSG00000149554.15. [O14757-1] DR Ensembl; ENST00000544373.5; ENSP00000442317.2; ENSG00000149554.15. [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 AGR; HGNC:1925; -. 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; GYTCKVG; -. DR OrthoDB; 1341507at2759; -. 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; 875 hits in 1208 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 130 other cell types or tissues. DR ExpressionAtlas; O14757; baseline and differential. 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 H3T11 kinase activity; 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:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB. DR GO; GO:0006338; P:chromatin remodeling; ISS:UniProtKB. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IMP:UniProtKB. DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB. DR GO; GO:0006260; P:DNA replication; TAS:Reactome. 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:0045814; P:negative regulation of gene expression, epigenetic; ISS:UniProtKB. 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: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:0090399; P:replicative senescence; NAS:BHF-UCL. DR GO; GO:0042770; P:signal transduction in response to DNA damage; IDA:UniProtKB. DR CDD; cd14069; STKc_Chk1; 1. DR Gene3D; 3.30.310.80; Kinase associated domain 1, KA1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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 PANTHER; PTHR24346; MAP/MICROTUBULE AFFINITY-REGULATING KINASE; 1. DR PANTHER; PTHR24346:SF73; SERINE_THREONINE-PROTEIN KINASE CHK1; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. DR Genevisible; O14757; HS. 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:25083873, FT 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 //