CHEK1
entrez
1111
canonical
uniprot
O14757
canonical
ensembl
ENSG00000149554
resolver
ensp
ENSP00000278916
resolver
ensp
ENSP00000388648
resolver
ensp
ENSP00000391090
resolver
ensp
ENSP00000412504
resolver
ensp
ENSP00000435371
resolver
ensp
ENSP00000442317
resolver
ensp
ENSP00000518558
resolver
ensp
ENSP00000572716
resolver
ensp
ENSP00000588705
resolver
enst
ENST00000427383
resolver
enst
ENST00000711049
resolver
genesymbol
CHEK1
resolver
genesymbol_syn
CHK1
resolver
hgnc
HGNC:1925
resolver
uniprot
A8K934
resolver
uniprot
B4DDD0
resolver
uniprot
B4DSK3
resolver
uniprot
B4DT73
resolver
uniprot
B5BTY6
resolver
uniprot
E7EPP6
resolver
uniprot
F5H7S4
resolver
uniprot
H2BI51
resolver
uniprot_entry
B4DT73_HUMAN
resolver
uniprot_entry
CHK1_HUMAN
resolver
uniprot_entry
E7EPP6_HUMAN
resolver
uniprot_sec
A8K934
resolver
uniprot_sec
B4DDD0
resolver
uniprot_sec
B4DSK3
resolver
uniprot_sec
B5BTY6
resolver
uniprot_sec
F5H7S4
resolver
uniprot_sec
H2BI51
resolver
activity_regulation
ACTIVITY REGULATION: Activated through phosphorylation predominantly by ATR but also by ATM in response to DNA damage or inhibition of DNA replication (PubMed:11390642, PubMed:12588868, PubMed:12676583, PubMed:12676962, PubMed:15665856, PubMed:19716789). Activation is modulated by several mediators including CLSPN, BRCA1 and FEM1B (PubMed:11836499, PubMed:12766152, PubMed:16963448, PubMed:19330022). Proteolytic cleavage at the C-terminus by SPRTN during normal DNA replication activates the protein kinase activity (PubMed:31316063). {ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:12766152, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16963448, ECO:0000269|PubMed:19330022, ECO:0000269|PubMed:19716789, ECO:0000269|PubMed:31316063}.
uniprot
proteins
amino_acid_sequence
MAVPFVEDWDLVQTLGEGAYGEVQLAVNRVTEEAVAVKIVDMKRAVDCPENIKKEICINKMLNHENVVKFYGHRREGNIQYLFLEYCSGGELFDRIEPDIGMPEPDAQRFFHQLMAGVVYLHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRYNNRERLLNKMCGTLPYVAPELLKRREFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLALLHKILVENPSARITIPDIKKDRWYNKPLKKGAKRPRVTSGGVSESPSGFSKHIQSNLDFSPVNSASSEENVKYSSSQPEPRTGLSLWDTSPSYIDKLVQGISFSQPTCPDHMLLNSQLLGTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETCEKLGYQWKKSCMNQVTISTTDRRNNKLIFKVNLLEMDDKILVDFRLSKGDGLEFKRHFLKIKGKLIDIVSSQKIWLPAT
uniprot
proteins
disease_involvement
DISEASE: Oocyte/zygote/embryo maturation arrest 21 (OZEMA21) [MIM:620610]: An autosomal dominant, female infertility disorder characterized by zygote development arrest due to failure of pronuclei fusion. {ECO:0000269|PubMed:33948904, ECO:0000269|PubMed:33953335}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest and activation of DNA repair in response to the presence of DNA damage or unreplicated DNA (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856, PubMed:32357935). May also negatively regulate cell cycle progression during unperturbed cell cycles (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Recognizes the substrate consensus sequence [R-X-X-S/T] (PubMed:11535615, PubMed:12399544, PubMed:12446774, PubMed:14559997, PubMed:14988723, PubMed:15311285, PubMed:15650047, PubMed:15665856). Binds to and phosphorylates CDC25A, CDC25B and CDC25C (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14559997, PubMed:14681206, PubMed:19734889, PubMed:9278511). 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 (PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76', 'Ser-124', 'Ser-178', 'Ser-279' and 'Ser-293' promotes proteolysis of CDC25A (PubMed:12676583, PubMed:12676925, PubMed:12759351, PubMed:14681206, PubMed:19734889, PubMed:9278511). Phosphorylation of CDC25A at 'Ser-76' primes the protein for subsequent phosphorylation at 'Ser-79', 'Ser-82' and 'Ser-88' by NEK11, which is required for polyubiquitination and degradation of CDCD25A (PubMed:19734889, PubMed:20090422, PubMed:9278511). Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression (PubMed:9278511). Also phosphorylates NEK6 (PubMed:18728393). Binds to and phosphorylates RAD51 at 'Thr-309', which promotes the release of RAD51 from BRCA2 and enhances the association of RAD51 with chromatin, thereby promoting DNA repair by homologous recombination (PubMed:15665856). Phosphorylates multiple sites within the C-terminus of TP53, which promotes activation of TP53 by acetylation and promotes cell cycle arrest and suppression of cellular proliferation (PubMed:10673501, PubMed:15659650, PubMed:16511572). Also promotes repair of DNA cross-links through phosphorylation of FANCE (PubMed:17296736). Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A (PubMed:12660173, PubMed:12955071). This may enhance chromatin assembly both in the presence or absence of DNA damage (PubMed:12660173, PubMed:12955071). May also play a role in replication fork maintenance through regulation of PCNA (PubMed:18451105). May regulate the transcription of genes that regulate cell-cycle progression through the phosphorylation of histones (By similarity). Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes (By similarity). May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest (PubMed:17380128). Phosphorylates SPRTN, promoting SPRTN recruitment to chromatin (PubMed:31316063). Reduces replication stress and activates the G2/M checkpoint, by phosphorylating and inactivating PABIR1/FAM122A and promoting the serine/threonine-protein phosphatase 2A-mediated dephosphorylation and stabilization of WEE1 levels and activity (PubMed:33108758). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:12399544, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12759351, ECO:0000269|PubMed:12955071, ECO:0000269|PubMed:14559997, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15659650, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:16511572, ECO:0000269|PubMed:17296736, ECO:0000269|PubMed:17380128, ECO:0000269|PubMed:18451105, ECO:0000269|PubMed:18728393, ECO:0000269|PubMed:19734889, ECO:0000269|PubMed:20090422, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32357935, ECO:0000269|PubMed:33108758, ECO:0000269|PubMed:9278511}.; FUNCTION: [Isoform 2]: Endogenous repressor of isoform 1, interacts with, and antagonizes CHK1 to promote the S to G2/M phase transition. {ECO:0000269|PubMed:22184239}.
uniprot
proteins
mass_dalton
54434
uniprot
proteins
mutagenesis
MUTAGEN 38; /note="K->R: Abolishes kinase activity."; /evidence="ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:14681223"; MUTAGEN 130; /note="D->A: Abolishes kinase activity."; /evidence="ECO:0000269|PubMed:10673501, ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:11535615, ECO:0000269|PubMed:11821419, ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:14681206, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:9278511"; MUTAGEN 132; /note="K->R: Strong reduction of chromatin-associated CHK1 ubiquitination."; /evidence="ECO:0000269|PubMed:32357935"; MUTAGEN 317; /note="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. Impairs interaction with FBXO6."; /evidence="ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856"; MUTAGEN 317; /note="S->E: Enhances interaction with RAD51; when associated with E-345."; /evidence="ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856"; MUTAGEN 344; /note="F->A: Impairs nuclear export."; /evidence="ECO:0000269|PubMed:12676962"; MUTAGEN 345; /note="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."; /evidence="ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:19716789"; MUTAGEN 345; /note="S->E: Enhances interaction with RAD51; when associated with E-317."; /evidence="ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:19716789"; MUTAGEN 353; /note="M->A: Impairs nuclear export."; /evidence="ECO:0000269|PubMed:12676962"; MUTAGEN 357; /note="S->A: No effect on phosphorylation induced by hydroxyurea."; /evidence="ECO:0000269|PubMed:11390642"; MUTAGEN 366; /note="S->A: No effect on phosphorylation induced by hydroxyurea."; /evidence="ECO:0000269|PubMed:11390642"; MUTAGEN 372; /note="R->E: In 3RE mutant. Disrupts the folding and/or conformation, allowing increased accessibility to FBXO6 component of SCF-type E3 ubiquitin ligase complex; when associated with E-376 and E-379."; /evidence="ECO:0000269|PubMed:19716789"; MUTAGEN 376; /note="R->E: In 3RE mutant. Disrupts the folding and/or conformation, allowing increased accessibility to FBXO6 component of SCF-type E3 ubiquitin ligase complex; when associated with E-372 and E-379."; /evidence="ECO:0000269|PubMed:19716789"; MUTAGEN 379; /note="R->E: In 3RE mutant. Disrupts the folding and/or conformation, allowing increased accessibility to FBXO6 component of SCF-type E3 ubiquitin ligase complex; when associated with E-372 and E-376."; /evidence="ECO:0000269|PubMed:19716789"; MUTAGEN 436; /note="K->R: Enhances stability of the protein, probably by preventing ubiquitination at this site."; /evidence="ECO:0000269|PubMed:19716789"; MUTAGEN 468; /note="S->A: No effect on phosphorylation induced by hydroxyurea."; /evidence="ECO:0000269|PubMed:11390642
uniprot
proteins
post_translational_modification
PTM: Phosphorylated by ATR in a RAD17-dependent manner in response to ultraviolet irradiation and inhibition of DNA replication (PubMed:10859164, PubMed:11390642, PubMed:12446774, PubMed:12588868, PubMed:12676583, PubMed:12676925, PubMed:12676962, PubMed:14681223, PubMed:14988723, PubMed:15650047, PubMed:15707391, PubMed:15870257, PubMed:25083873, PubMed:31316063). Phosphorylated by ATM in response to ionizing irradiation (PubMed:12588868, PubMed:12676583). ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity (PubMed:11390642, PubMed:12446774, PubMed:12588868, PubMed:12660173, PubMed:12676583, PubMed:12676962, PubMed:14657349, PubMed:15665856, PubMed:15707391, PubMed:15870257, PubMed:25083873). Phosphorylation at Ser-345 induces a change in the conformation of the protein, activates the kinase activity and is a prerequisite for interaction with FBXO6 and subsequent ubiquitination at Lys-436 (PubMed:19716789). Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention (PubMed:12676962). Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell cycle arrest (PubMed:15870257). Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination. Also phosphorylated at undefined residues during mitotic arrest, resulting in decreased activity (By similarity). {ECO:0000250|UniProtKB:O35280, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12588868, ECO:0000269|PubMed:12660173, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:14657349, ECO:0000269|PubMed:14681223, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15665856, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:15870257, ECO:0000269|PubMed:19716789, ECO:0000269|PubMed:25083873, ECO:0000269|PubMed:31316063}.; PTM: Ubiquitinated. Mono or diubiquitination promotes nuclear exclusion (By similarity). The activated form (phosphorylated on Ser-345) is polyubiquitinated at Lys-436 by some SCF-type E3 ubiquitin ligase complex containing FBXO6 promoting its degradation. Ubiquitination and degradation are required to terminate the checkpoint and ensure that activated CHEK1 does not accumulate as cells progress through S phase, when replication forks encounter transient impediments during normal DNA replication. 'Lys-63'-mediated ubiquitination by TRAF4 at Lys-132 activates cell cycle arrest and activation of DNA repair (PubMed:32357935). {ECO:0000250, ECO:0000269|PubMed:10859164, ECO:0000269|PubMed:11390642, ECO:0000269|PubMed:12446774, ECO:0000269|PubMed:12676583, ECO:0000269|PubMed:12676925, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:14681223, ECO:0000269|PubMed:14988723, ECO:0000269|PubMed:15650047, ECO:0000269|PubMed:15707391, ECO:0000269|PubMed:15870257, ECO:0000269|PubMed:19716789}.; PTM: Proteolytically cleaved at the C-terminus by SPRTN during normal DNA replication, thereby promoting CHEK1 removal from chromatin and activating the protein kinase activity. {ECO:0000269|PubMed:31316063}.
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
NIM1 subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10673501
uniprot
proteins
pubmed
10717241
uniprot
proteins
pubmed
10761933
uniprot
proteins
pubmed
10859164
uniprot
proteins
pubmed
11390642
uniprot
proteins
pubmed
11535615
uniprot
proteins
pubmed
11821419
uniprot
proteins
pubmed
11836499
uniprot
proteins
pubmed
12244092
uniprot
proteins
pubmed
12399544
uniprot
proteins
pubmed
12446774
uniprot
proteins
pubmed
12588868
uniprot
proteins
pubmed
12660173
uniprot
proteins
pubmed
12676583
uniprot
proteins
pubmed
12676925
uniprot
proteins
pubmed
12676962
uniprot
proteins
pubmed
12759351
uniprot
proteins
pubmed
12766152
uniprot
proteins
pubmed
12955071
uniprot
proteins
pubmed
14559997
uniprot
proteins
pubmed
14657349
uniprot
proteins
pubmed
14681206
uniprot
proteins
pubmed
14681223
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14988723
uniprot
proteins
pubmed
15311285
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15650047
uniprot
proteins
pubmed
15659650
uniprot
proteins
pubmed
15665856
uniprot
proteins
pubmed
15707391
uniprot
proteins
pubmed
15710331
uniprot
proteins
pubmed
15798197
uniprot
proteins
pubmed
15870257
uniprot
proteins
pubmed
15974586
uniprot
proteins
pubmed
16511572
uniprot
proteins
pubmed
16554811
uniprot
proteins
pubmed
16963448
uniprot
proteins
pubmed
17296736
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17380128
uniprot
proteins
pubmed
17525332
uniprot
proteins
pubmed
18317453
uniprot
proteins
pubmed
18451105
uniprot
proteins
pubmed
18510930
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18728393
uniprot
proteins
pubmed
19054851
uniprot
proteins
pubmed
19223857
uniprot
proteins
pubmed
19330022
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19716789
uniprot
proteins
pubmed
19734889
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20090422
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22184239
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
25083873
uniprot
proteins
pubmed
31316063
uniprot
proteins
pubmed
32357935
uniprot
proteins
pubmed
33108758
uniprot
proteins
pubmed
33948904
uniprot
proteins
pubmed
33953335
uniprot
proteins
pubmed
36243983
uniprot
proteins
pubmed
9278511
uniprot
proteins
pubmed
9382850
uniprot
proteins
sequence_length
476
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11836499, ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:15710331, ECO:0000269|PubMed:9278511}. Chromosome {ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:9382850}. Cytoplasm {ECO:0000269|PubMed:12676962}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:15311285}. Note=Nuclear export is mediated at least in part by XPO1/CRM1 (PubMed:12676962). Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 kinase from inappropriate activation by cytoplasmic CDC25B (PubMed:15311285). Proteolytic cleavage at the C-terminus by SPRTN promotes removal from chromatin (PubMed:31316063). {ECO:0000269|PubMed:12676962, ECO:0000269|PubMed:15311285, ECO:0000269|PubMed:31316063}.
uniprot
proteins