Reviewed, UniProtKB/Swiss-Prot O14757 (CHK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase Chk1
    EC=2.7.11.1

Gene names

Name:	CHEK1
Synonyms:	CHK1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	476 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Required for checkpoint mediated cell cycle arrest in response to DNA damage or the presence of unreplicated DNA. May also negatively regulate cell cycle progression during unperturbed cell cycles. Recognizes the substrate consensus sequence [R-X-X-S/T]. Binds to and phosphorylates CDC25A, CDC25B and CDC25C. Phosphorylation of CDC25A at 'Ser-178' and 'Thr-507' and phosphorylation of CDC25C at 'Ser-216' creates binding sites for 14-3-3 proteins which inhibit CDC25A and CDC25C. Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A. Inhibition of CDC25 activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Binds to and phosphorylates RAD51 at 'Thr-309', which may enhance the association of RAD51 with chromatin and promote DNA repair by homologous recombination. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may affect chromatin assembly during S phase or DNA repair. May also phosphorylate multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and enhances suppression of cellular proliferation. Ref.1 Ref.6 Ref.9 Ref.13 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.22 Ref.24 Ref.25 Ref.27 Ref.29 Ref.33 Ref.35 Ref.36
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Subunit structure	Interacts with BRCA1, CLSPN, PPM1D, RAD51, TIMELESS, XPO1/CRM1 and YWHAZ/14-3-3 zeta. Ref.1 Ref.35 Ref.14 Ref.21 Ref.23 Ref.30 Ref.32 Ref.34
Subcellular location	Nucleus. Cytoplasm. Note: Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B. Ref.1 Ref.29 Ref.14 Ref.21 Ref.31
Tissue specificity	Expressed ubiquitously with the most abundant expression in thymus, testis, small intestine and colon. Ref.1
Domain	The autoinhibitory region (AIR) inhibits the activity of the kinase domain. Ref.28
Post-translational modification	Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication. Phosphorylated by ATM in response to ionizing irradiation. ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity. Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention. Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell cycle arrest. May also be phosphorylated at Ser-280 by AKT1/PKB, which may promote mono and/or diubiquitination. Also phosphorylated at undefined residues during mitotic arrest, which results in decreased activity. Ref.1 Ref.9 Ref.13 Ref.16 Ref.17 Ref.20 Ref.27 Ref.36 Ref.21 Ref.30 Ref.32 Ref.28 Ref.8 Ref.10 Ref.19 Ref.26 Ref.38 Ref.39 Ref.40 Ubiquitinated. Mono or diubiquitination promotes nuclear exclusion By similarity.
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. NIM1 subfamily. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Cell cycle DNA damage DNA repair
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Isopeptide bond Phosphoprotein Ubl conjugation
Technical term	3D-structure
Gene Ontology (GO)
Biological process	DNA damage checkpoint Ref.1 Traceable author statement. Source: ProtInc DNA repair Inferred from electronic annotation. Source: UniProtKB-KW DNA replication Inferred from Experiment. Source: Reactome gamete generation Ref.2 Traceable author statement. Source: ProtInc negative regulation of cell proliferation Ref.1 Traceable author statement. Source: ProtInc reciprocal meiotic recombination Ref.1 Traceable author statement. Source: ProtInc regulation of cyclin-dependent protein kinase activity Ref.1 Traceable author statement. Source: ProtInc
Cellular component	condensed nuclear chromosome Ref.2 Traceable author statement. Source: ProtInc cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleoplasm Ref.15 Inferred from Experiment. Source: Reactome
Molecular function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from Experiment. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AATF	Q9NY61	1	EBI-974488,EBI-372428
BRCA1	P38398	1	EBI-974488,EBI-349905
CDC25A	P30304	1	EBI-974488,EBI-747671
CDC25C	P30307	2	EBI-974488,EBI-974439
CLSPN	Q9HAW4	4	EBI-974488,EBI-1369377
HSP90AB1	P08238	1	EBI-974488,EBI-352572
TIMELESS	Q9UNS1	2	EBI-974488,EBI-2212315

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 476

476

Serine/threonine-protein kinase Chk1

PRO_0000085848

Regions

Domain

9 – 265

257

Protein kinase

Nucleotide binding

15 – 23

9

ATP By similarity

Region

391 – 476

86

Autoinhibitory region

Sites

Active site

130

1

Proton acceptor

Binding site

38

1

ATP By similarity

Amino acid modifications

Modified residue

280

1

Phosphoserine; by PKB/AKT1 By similarity

Modified residue

286

1

Phosphoserine Ref.39 Ref.40

Modified residue

296

1

Phosphoserine Ref.30 Ref.40

Modified residue

301

1

Phosphoserine Ref.39 Ref.40

Modified residue

308

1

Phosphoserine Ref.38 Ref.39

Modified residue

317

1

Phosphoserine; by ATM and ATR Ref.13 Ref.16 Ref.17 Ref.21 Ref.30 Ref.32 Ref.10 Ref.19 Ref.26 Ref.38 Ref.39

Modified residue

331

1

Phosphoserine Ref.39

Modified residue

345

1

Phosphoserine; by ATM and ATR Ref.13 Ref.16 Ref.20 Ref.27 Ref.36 Ref.21 Ref.30 Ref.32 Ref.28 Ref.8 Ref.10

Modified residue

468

1

Phosphoserine Ref.39

Cross-link

436

Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) Ref.37

Natural variations

Natural variant

156

1

R → Q: dbSNP rs3731410. Ref.4

VAR_021123

Natural variant

223

1

E → V Ref.45

VAR_040407

Natural variant

312

1

V → M Ref.45

VAR_040408

Natural variant

471

1

V → I: dbSNP rs506504.

VAR_024571

Experimental info

Mutagenesis

38

1

K → R: Abolishes kinase activity. Ref.13 Ref.28

Mutagenesis

130

1

D → A: Abolishes kinase activity. Ref.1 Ref.6 Ref.9 Ref.18 Ref.29 Ref.10 Ref.19 Ref.11

Mutagenesis

317

1

S → A: Abrogates interaction with RAD51; when associated with A-345. Reduces phosphorylation and impairs activation by hydroxyurea and ionizing radiation. Abrogates nuclear retention upon checkpoint activation. Ref.16 Ref.35 Ref.21 Ref.10 Ref.19

Mutagenesis

317

1

S → E: Enhances interaction with RAD51; when associated with E-345. Ref.16 Ref.35 Ref.21 Ref.10 Ref.19

Mutagenesis

344

1

F → A: Impairs nuclear export. Ref.21

Mutagenesis

345

1

S → A: Abrogates interaction with RAD51; when associated with A-317. Reduces phosphorylation and impairs activation by hydroxyurea and ionizing radiation. Impairs interaction with YWHAZ which is required for nuclear retention after checkpoint activation. Ref.16 Ref.35 Ref.21 Ref.10 Ref.19

Mutagenesis

345

1

S → E: Enhances interaction with RAD51; when associated with E-317. Ref.16 Ref.35 Ref.21 Ref.10 Ref.19

Mutagenesis

353

1

M → A: Impairs nuclear export. Ref.21

Mutagenesis

357

1

S → A: No effect on phosphorylation induced by hydroxyurea. Ref.10

Mutagenesis

366

1

S → A: No effect on phosphorylation induced by hydroxyurea. Ref.10

Mutagenesis

468

1

S → A: No effect on phosphorylation induced by hydroxyurea. Ref.10

Secondary structure

1

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476

Helix Strand Turn

Details...

Helix

4 – 7

4

Beta strand

9 – 16

8

Beta strand

22 – 28

7

Turn

29 – 31

3

Beta strand

34 – 41

8

Helix

49 – 61

13

Beta strand

70 – 74

5

Beta strand

79 – 85

7

Helix

92 – 95

4

Turn

98 – 100

3

Helix

104 – 123

20

Helix

133 – 135

3

Beta strand

136 – 138

3

Beta strand

144 – 146

3

Helix

171 – 173

3

Helix

176 – 180

5

Helix

186 – 203

18

Beta strand

209 – 211

3

Helix

216 – 222

7

Helix

231 – 233

3

Helix

237 – 245

9

Turn

250 – 252

3

Helix

256 – 259

4

Turn

263 – 266

4

Sequences

	Sequence		Length	Mass (Da)
	O14757-1 [UniParc]. Last modified January 1, 1998. Version 1. Checksum: 0ABD0FAB67F49F67	FASTA	476	54,420
	10 20 30 40 50 60 MAVPFVEDWD LVQTLGEGAY GEVQLAVNRV TEEAVAVKIV DMKRAVDCPE NIKKEICINK 70 80 90 100 110 120 MLNHENVVKF YGHRREGNIQ YLFLEYCSGG ELFDRIEPDI GMPEPDAQRF FHQLMAGVVY 130 140 150 160 170 180 LHGIGITHRD IKPENLLLDE RDNLKISDFG LATVFRYNNR ERLLNKMCGT LPYVAPELLK 190 200 210 220 230 240 RREFHAEPVD VWSCGIVLTA MLAGELPWDQ PSDSCQEYSD WKEKKTYLNP WKKIDSAPLA 250 260 270 280 290 300 LLHKILVENP SARITIPDIK KDRWYNKPLK KGAKRPRVTS GGVSESPSGF SKHIQSNLDF 310 320 330 340 350 360 SPVNSASSEE NVKYSSSQPE PRTGLSLWDT SPSYIDKLVQ GISFSQPTCP DHMLLNSQLL 370 380 390 400 410 420 GTPGSSQNPW QRLVKRMTRF FTKLDADKSY QCLKETCEKL GYQWKKSCMN QVTISTTDRR 430 440 450 460 470 NNKLIFKVNL LEMDDKILVD FRLSKGDGLE FKRHFLKIKG KLIDIVSSQK VWLPAT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Conservation of the Chk1 checkpoint pathway in mammals: linkage of DNA damage to Cdk regulation through Cdc25." Sanchez Y., Wong C., Thoma R.S., Richman R., Wu Z., Piwnica-Worms H., Elledge S.J. Science 277:1497-1501(1997) [PubMed: 9278511] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH CDC25A; CDC25B AND CDC25C, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, PHOSPHORYLATION, MUTAGENESIS OF ASP-130.
[2]	"Atm-dependent interactions of a mammalian chk1 homolog with meiotic chromosomes." Flaggs G., Plug A.W., Dunks K.M., Mundt K.E., Ford J.C., Quiggle M.R.E., Taylor E.M., Westphal C.H., Ashley T., Hoekstra M.F., Carr A.M. Curr. Biol. 7:977-986(1997) [PubMed: 9382850] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Analysis of the candidate target genes for mutation in microsatellite instability-positive cancers of the colorectum, stomach, and endometrium." Semba S., Ouyang H., Han S.-Y., Kato Y., Horii A. Int. J. Oncol. 16:731-737(2000) [PubMed: 10717241] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT GLN-156.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Bone marrow and Muscle.
[6]	"The human homologs of checkpoint kinases Chk1 and Cds1 (Chk2) phosphorylate p53 at multiple DNA damage-inducible sites." Shieh S.-Y., Ahn J., Tamai K., Taya Y., Prives C. Genes Dev. 14:289-300(2000) [PubMed: 10673501] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-130.
[7]	Erratum Shieh S.-Y., Ahn J., Tamai K., Taya Y., Prives C. Genes Dev. 14:750-750(2000)
[8]	"Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint." Liu Q., Guntuku S., Cui X.-S., Matsuoka S., Cortez D., Tamai K., Luo G., Carattini-Rivera S., DeMayo F., Bradley A., Donehower L.A., Elledge S.J. Genes Dev. 14:1448-1459(2000) [PubMed: 10859164] [Abstract] Cited for: PHOSPHORYLATION AT SER-345.
[9]	"Activation of mammalian Chk1 during DNA replication arrest: a role for Chk1 in the intra-S phase checkpoint monitoring replication origin firing." Feijoo C., Hall-Jackson C., Wu R., Jenkins D., Leitch J., Gilbert D.M., Smythe C. J. Cell Biol. 154:913-923(2001) [PubMed: 11535615] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION BY ATR, MUTAGENESIS OF ASP-130.
[10]	"ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1." Zhao H., Piwnica-Worms H. Mol. Cell. Biol. 21:4129-4139(2001) [PubMed: 11390642] [Abstract] Cited for: PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF ASP-130; SER-317; SER-345; SER-357; SER-366 AND SER-468.
[11]	"Determination of substrate motifs for human Chk1 and hCds1/Chk2 by the oriented peptide library approach." O'Neill T., Giarratani L., Chen P., Iyer L., Lee C.-H., Bobiak M., Kanai F., Zhou B.-B., Chung J.H., Rathbun G.A. J. Biol. Chem. 277:16102-16115(2002) [PubMed: 11821419] [Abstract] Cited for: SUBSTRATE SPECIFICITY, MUTAGENESIS OF ASP-130.
[12]	Erratum O'Neill T., Giarratani L., Chen P., Iyer L., Lee C.-H., Bobiak M., Kanai F., Zhou B.-B., Chung J.H., Rathbun G.A. J. Biol. Chem. 277:35776-35777(2002)
[13]	"An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage." Heffernan T.P., Simpson D.A., Frank A.R., Heinloth A.N., Paules R.S., Cordeiro-Stone M., Kaufmann W.K. Mol. Cell. Biol. 22:8552-8561(2002) [PubMed: 12446774] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF LYS-38.
[14]	"BRCA1 regulates the G2/M checkpoint by activating Chk1 kinase upon DNA damage." Yarden R.I., Pardo-Reoyo S., Sgagias M., Cowan K.H., Brody L.C. Nat. Genet. 30:285-289(2002) [PubMed: 11836499] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH BRCA1.
[15]	"Disruption of the checkpoint kinase 1/cell division cycle 25A pathway abrogates ionizing radiation-induced S and G2 checkpoints." Zhao H., Watkins J.L., Piwnica-Worms H. Proc. Natl. Acad. Sci. U.S.A. 99:14795-14800(2002) [PubMed: 12399544] [Abstract] Cited for: FUNCTION.
[16]	"Chk1 regulates the S phase checkpoint by coupling the physiological turnover and ionizing radiation-induced accelerated proteolysis of Cdc25A." Soerensen C.S., Syljuaesen R.G., Falck J., Schroeder T., Roennstrand L., Khanna K.K., Zhou B.-B., Bartek J., Lukas J. Cancer Cell 3:247-258(2003) [PubMed: 12676583] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF SER-317 AND SER-345.
[17]	"Human tousled like kinases are targeted by an ATM- and Chk1-dependent DNA damage checkpoint." Groth A., Lukas J., Nigg E.A., Sillje H.H.W., Wernstedt C., Bartek J., Hansen K. EMBO J. 22:1676-1687(2003) [PubMed: 12660173] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-317.
[18]	"SCFbeta-TRCP links Chk1 signaling to degradation of the Cdc25A protein phosphatase." Jin J., Shirogane T., Xu L., Nalepa G., Qin J., Elledge S.J., Harper J.W. Genes Dev. 17:3062-3074(2003) [PubMed: 14681206] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF ASP-130.
[19]	"Ataxia-telangiectasia-mutated (ATM) and NBS1-dependent phosphorylation of Chk1 on ser-317 in response to ionizing radiation." Gatei M., Sloper K., Soerensen C., Syljuaesen R., Falck J., Hobson K., Savage K., Lukas J., Zhou B.-B., Bartek J., Khanna K.K. J. Biol. Chem. 278:14806-14811(2003) [PubMed: 12588868] [Abstract] Cited for: PHOSPHORYLATION AT SER-317, MUTAGENESIS OF ASP-130; SER-317 AND SER-345.
[20]	"Chk1 mediates S and G2 arrests through Cdc25A degradation in response to DNA-damaging agents." Xiao Z., Chen Z., Gunasekera A.H., Sowin T.J., Rosenberg S.H., Fesik S., Zhang H. J. Biol. Chem. 278:21767-21773(2003) [PubMed: 12676925] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-345.
[21]	"Regulation of Chk1 includes chromatin association and 14-3-3 binding following phosphorylation on ser-345." Jiang K., Pereira E., Maxfield M., Russell B., Goudelock D.M., Sanchez Y. J. Biol. Chem. 278:25207-25217(2003) [PubMed: 12676962] [Abstract] Cited for: INTERACTION WITH YWHAZ AND XPO1, SUBCELLULAR LOCATION, ASSOCIATION WITH CHROMATIN, PHOSPHORYLATION AT SER-317 AND SER-345, MUTAGENESIS OF SER-317; PHE-344; SER-345 AND MET-353.
[22]	"Phosphorylation at serine 75 is required for UV-mediated degradation of human Cdc25A phosphatase at the S-phase checkpoint." Hassepass I., Voit R., Hoffmann I. J. Biol. Chem. 278:29824-29829(2003) [PubMed: 12759351] [Abstract] Cited for: FUNCTION.
[23]	"Human claspin is required for replication checkpoint control." Chini C.C.S., Chen J. J. Biol. Chem. 278:30057-30062(2003) [PubMed: 12766152] [Abstract] Cited for: INTERACTION WITH CLSPN.
[24]	"Chk1 kinase negatively regulates mitotic function of Cdc25A phosphatase through 14-3-3 binding." Chen M.-S., Ryan C.E., Piwnica-Worms H. Mol. Cell. Biol. 23:7488-7497(2003) [PubMed: 14559997] [Abstract] Cited for: FUNCTION.
[25]	"Suppression of tousled-like kinase activity after DNA damage or replication block requires ATM, NBS1 and Chk1." Krause D.R., Jonnalagadda J.C., Gatei M.H., Sillje H.H.W., Zhou B.-B., Nigg E.A., Khanna K. Oncogene 22:5927-5937(2003) [PubMed: 12955071] [Abstract] Cited for: FUNCTION.
[26]	"MSH2 and ATR form a signaling module and regulate two branches of the damage response to DNA methylation." Wang Y., Qin J. Proc. Natl. Acad. Sci. U.S.A. 100:15387-15392(2003) [PubMed: 14657349] [Abstract] Cited for: PHOSPHORYLATION AT SER-317.
[27]	"The DNA crosslink-induced S-phase checkpoint depends on ATR-CHK1 and ATR-NBS1-FANCD2 pathways." Pichierri P., Rosselli F. EMBO J. 23:1178-1187(2004) [PubMed: 14988723] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-345.
[28]	"Differential mode of regulation of the checkpoint kinases CHK1 and CHK2 by their regulatory domains." Ng C.-P., Lee H.C., Ho C.W., Arooz T., Siu W.Y., Lau A., Poon R.Y.C. J. Biol. Chem. 279:8808-8819(2004) [PubMed: 14681223] [Abstract] Cited for: DOMAIN, MITOTIC PHOSPHORYLATION, PHOSPHORYLATION AT SER-345, MUTAGENESIS OF LYS-38.
[29]	"Centrosome-associated Chk1 prevents premature activation of cyclin-B-Cdk1 kinase." Kraemer A., Mailand N., Lukas C., Syljuaesen R.G., Wilkinson C.J., Nigg E.A., Bartek J., Lukas J. Nat. Cell Biol. 6:884-891(2004) [PubMed: 15311285] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-130.
[30]	"DNA-dependent phosphorylation of Chk1 and claspin in a human cell-free system." Clarke C.A.L., Clarke P.R. Biochem. J. 388:705-712(2005) [PubMed: 15707391] [Abstract] Cited for: INTERACTION WITH CLSPN, PHOSPHORYLATION AT SER-296; SER-317 AND SER-345.
[31]	"Lack of PTEN sequesters CHK1 and initiates genetic instability." Puc J., Keniry M., Li H.S., Pandita T.K., Choudhury A.D., Memeo L., Mansukhani M., Murty V.V.V.S., Gaciong Z., Meek S.E.M., Piwnica-Worms H., Hibshoosh H., Parsons R. Cancer Cell 7:193-204(2005) [PubMed: 15710331] [Abstract] Cited for: SUBCELLULAR LOCATION.
[32]	"PPM1D dephosphorylates Chk1 and p53 and abrogates cell cycle checkpoints." Lu X., Nannenga B., Donehower L.A. Genes Dev. 19:1162-1174(2005) [PubMed: 15870257] [Abstract] Cited for: INTERACTION WITH PPM1D, PHOSPHORYLATION AT SER-317 AND SER-345.
[33]	"p53 C-terminal phosphorylation by CHK1 and CHK2 participates in the regulation of DNA-damage-induced C-terminal acetylation." Ou Y.-H., Chung P.-H., Sun T.-P., Shieh S.-Y. Mol. Biol. Cell 16:1684-1695(2005) [PubMed: 15659650] [Abstract] Cited for: FUNCTION.
[34]	"Coupling of human circadian and cell cycles by the timeless protein." Uensal-Kacmaz K., Mullen T.E., Kaufmann W.K., Sancar A. Mol. Cell. Biol. 25:3109-3116(2005) [PubMed: 15798197] [Abstract] Cited for: INTERACTION WITH TIMELESS.
[35]	"The cell-cycle checkpoint kinase Chk1 is required for mammalian homologous recombination repair." Soerensen C.S., Hansen L.T., Dziegielewski J., Syljuaesen R.G., Lundin C., Bartek J., Helleday T. Nat. Cell Biol. 7:195-201(2005) [PubMed: 15665856] [Abstract] Cited for: FUNCTION, INTERACTION WITH RAD51, MUTAGENESIS OF SER-317 AND SER-345.
[36]	"DNA damage-induced mitotic catastrophe is mediated by the Chk1-dependent mitotic exit DNA damage checkpoint." Huang X., Tran T., Zhang L., Hatcher R., Zhang P. Proc. Natl. Acad. Sci. U.S.A. 102:1065-1070(2005) [PubMed: 15650047] [Abstract] Cited for: FUNCTION, PHOSPHORYLATION AT SER-345.
[37]	"Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry." Denis N.J., Vasilescu J., Lambert J.-P., Smith J.C., Figeys D. Proteomics 7:868-874(2007) [PubMed: 17370265] [Abstract] Cited for: UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-436, MASS SPECTROMETRY.
[38]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-308 AND SER-317, MASS SPECTROMETRY.
[39]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-301; SER-308; SER-317; SER-331 AND SER-468, MASS SPECTROMETRY.
[40]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-286; SER-296 AND SER-301, MASS SPECTROMETRY.
[41]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[42]	"The 1.7 A crystal structure of human cell cycle checkpoint kinase Chk1: implications for Chk1 regulation." Chen P., Luo C., Deng Y., Ryan K., Register J., Margosiak S., Tempczyk-Russell A., Nguyen B., Myers P., Lundgren K., Kan C.-C., O'Connor P.M. Cell 100:681-692(2000) [PubMed: 10761933] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 1-289.
[43]	"Structural basis for Chk1 inhibition by UCN-01." Zhao B., Bower M.J., McDevitt P.J., Zhao H., Davis S.T., Johanson K.O., Green S.M., Concha N.O., Zhou B.-B.S. J. Biol. Chem. 277:46609-46615(2002) [PubMed: 12244092] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-289.
[44]	"Structure-based design of novel Chk1 inhibitors: insights into hydrogen bonding and protein-ligand affinity." Foloppe N., Fisher L.M., Howes R., Kierstan P., Potter A., Robertson A.G.S., Surgenor A.E. J. Med. Chem. 48:4332-4345(2005) [PubMed: 15974586] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 1-289.
[45]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] VAL-223 AND MET-312.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBLGenBankDDBJ

AF016582 mRNA. Translation: AAC51736.1.
AF032874 mRNA. Translation: AAB88852.1.
AB032387 Genomic DNA. Translation: BAA84577.1.
AF527555 Genomic DNA. Translation: AAM78553.1.
BC004202 mRNA. Translation: AAH04202.1.
BC017575 mRNA. Translation: AAH17575.1.

IPI

IPI00023664.

RefSeq

NP_001107593.1.
NP_001107594.1.
NP_001265.2.

UniGene

Hs.24529

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IA8	X-ray	1.70	A	1-289	[»]
1NVQ	X-ray	2.00	A	1-289	[»]
1NVR	X-ray	1.80	A	1-289	[»]
1NVS	X-ray	1.80	A	1-289	[»]
1ZLT	X-ray	1.74	A	1-289	[»]
1ZYS	X-ray	1.70	A	1-273	[»]
2AYP	X-ray	2.90	A	1-269	[»]
2BR1	X-ray	2.00	A	1-289	[»]
2BRB	X-ray	2.10	A	1-289	[»]
2BRG	X-ray	2.10	A	1-289	[»]
2BRH	X-ray	2.10	A	1-289	[»]
2BRM	X-ray	2.20	A	1-289	[»]
2BRN	X-ray	2.80	A	1-289	[»]
2BRO	X-ray	2.20	A	1-289	[»]
2C3J	X-ray	2.10	A	1-289	[»]
2C3K	X-ray	2.60	A	1-289	[»]
2C3L	X-ray	2.35	A	1-289	[»]
2CGU	X-ray	2.50	A	1-289	[»]
2CGV	X-ray	2.60	A	1-289	[»]
2CGW	X-ray	2.20	A	1-289	[»]
2CGX	X-ray	2.20	A	1-289	[»]
2E9N	X-ray	2.50	A	2-270	[»]
2E9O	X-ray	2.10	A	2-270	[»]
2E9P	X-ray	2.60	A	2-270	[»]
2E9U	X-ray	2.00	A	2-270	[»]
2E9V	X-ray	2.00	A/B	2-269	[»]
2GDO	X-ray	3.00	A	1-289	[»]
2GHG	X-ray	3.50	A	2-270	[»]
2HOG	X-ray	1.90	A	2-307	[»]
2HXL	X-ray	1.80	A	2-307	[»]
2HXQ	X-ray	2.00	A	2-307	[»]
2HY0	X-ray	1.70	A	2-307	[»]
2QHM	X-ray	2.00	A	1-307	[»]
2QHN	X-ray	1.70	A	1-307	[»]
2R0U	X-ray	1.90	A	1-307	[»]
2YWP	X-ray	2.90	A	2-270	[»]
3F9N	X-ray	1.90	A	2-307	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:24182N.

IntAct

O14757. 8 interactions.

PTM databases

PhosphoSite

O14757.

Proteomic databases

PRIDE

O14757.

Genome annotation databases

Ensembl

ENSG00000149554. Homo sapiens. [Contig view]

GeneID

1111.

KEGG

hsa:1111.

Organism-specific databases

GeneCards

GC11P125001.

H-InvDB

HIX0020525.

HGNC

HGNC:1925. CHEK1.

HPA

CAB002049.

MIM

603078. gene.

PharmGKB

PA110.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

O14757.

HOVERGEN

O14757.

Enzyme and pathway databases

BRENDA

2.7.11.1. 247.

Pathway_Interaction_DB

circadianpathway. Circadian rhythm pathway.

Reactome

REACT_1538. Cell Cycle Checkpoints.

Gene expression databases

ArrayExpress

O14757.

Bgee

O14757.

CleanEx

HS_CHEK1.

GermOnline

ENSG00000149554. Homo sapiens.

Family and domain databases

InterPro

IPR000719. Prot_kinase_core.
IPR017441. Protein_kinase_ATP_BS.
IPR017442. Se/Thr_pkinase-rel.
IPR015729. Ser/Thr_Checkpoint-1_Hal4.
IPR008271. Ser_thr_pkin_AS.
IPR002290. Ser_thr_pkinase.
[Graphical view]

PANTHER

PTHR22982:SF11. Ser_thr_Chk1_Hal4. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

ProDom

PD000001. Prot_kinase. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

BindingDB

O14757.

NextBio

4608.

SOURCE

Search...

Entry information

Entry name

CHK1_HUMAN

Accession

Primary (citable) accession number: O14757

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 1, 1998
Last modified:	June 16, 2009
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)