UniProt Accession

 CHK1_HUMAN; O14757; A8K934; B4DDD0; B4DSK3; B5BTY6; F5H7S4; H2BI51 

Genbank Protein ID

 AF016582; AF032874; AB032387; JF289264; AK292549; AK293143; AK299783; AF527555; AB451222; AB451345; AP001132; CH471065; BC004202; BC017575 

Genbank Nucleotide ID

 AAC51736.1; AAB88852.1; BAA84577.1; AEB71796.1; BAF85238.1; BAG56691.1; BAG61665.1; AAM78553.1; BAG70036.1; BAG70159.1; EAW67644.1; AAH04202.1; AAH17575.1 

Protein Name

 Serine/threonine-protein kinase Chk1 

Protein Synonyms/Alias

 CHK1 checkpoint homolog; Cell cycle checkpoint kinase; Checkpoint kinase-1 

Gene Name

 CHEK1 

Gene Synonyms/Alias

 CHK1 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
53	VDCPENIKKEICINK	ubiquitination	[1]
54	DCPENIKKEICINKM	ubiquitination	[1]
60	KKEICINKMLNHENV	ubiquitination	[1]
132	GITHRDIKPENLLLD	ubiquitination	[1]
145	LDERDNLKISDFGLA	ubiquitination	[1, 2]
166	NRERLLNKMCGTLPY	ubiquitination	[1]
180	YVAPELLKRREFHAE	ubiquitination	[1]
225	YSDWKEKKTYLNPWK	ubiquitination	[1]
233	TYLNPWKKIDSAPLA	ubiquitination	[1]
244	APLALLHKILVENPS	ubiquitination	[1]
260	RITIPDIKKDRWYNK	ubiquitination	[1]
261	ITIPDIKKDRWYNKP	ubiquitination	[1]
292	ESPSGFSKHIQSNLD	ubiquitination	[1, 2]
313	ASSEENVKYSSSQPE	ubiquitination	[1, 2]
383	RMTRFFTKLDADKSY	ubiquitination	[2]
388	FTKLDADKSYQCLKE	ubiquitination	[1]
399	CLKETCEKLGYQWKK	ubiquitination	[1, 3]
405	EKLGYQWKKSCMNQV	ubiquitination	[1]
406	KLGYQWKKSCMNQVT	ubiquitination	[1]
436	NLLEMDDKILVDFRL	ubiquitination	[4, 5]
461	HFLKIKGKLIDIVSS	ubiquitination	[1]

Reference

 [1] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [2] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [3] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [4] Tryptic digestion of ubiquitin standards reveals an improved strategy for identifying ubiquitinated proteins by mass spectrometry.
 Denis NJ, Vasilescu J, Lambert JP, Smith JC, Figeys D.
 Proteomics. 2007 Mar;7(6):868-74. [PMID: 17370265]
 [5] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789] 

Functional Description

 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. May also negatively regulate cell cycle progression during unperturbed cell cycles. This regulation is achieved by a number of mechanisms that together help to preserve the integrity of the genome. 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. 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. Inhibition of CDC25 leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. Also phosphorylates NEK6. 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. 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. Also promotes repair of DNA cross-links through phosphorylation of FANCE. Binds to and phosphorylates TLK1 at 'Ser-743', which prevents the TLK1-dependent phosphorylation of the chromatin assembly factor ASF1A. This may enhance chromatin assembly both in the presence or absence of DNA damage. May also play a role in replication fork maintenance through regulation of PCNA. May regulate the transcription of genes that regulate cell- cycle progression through the phosphorylation of histones. Phosphorylates histone H3.1 (to form H3T11ph), which leads to epigenetic inhibition of a subset of genes. May also phosphorylate RB1 to promote its interaction with the E2F family of transcription factors and subsequent cell cycle arrest. 

Sequence Annotation

 DOMAIN 9 265 Protein kinase.
 NP_BIND 15 23 ATP (By similarity).
 REGION 1 265 Interaction with CLSPN (By similarity).
 REGION 391 476 Autoinhibitory region.
 ACT_SITE 130 130 Proton acceptor.
 BINDING 38 38 ATP (By similarity).
 MOD_RES 280 280 Phosphoserine; by PKB/AKT1 (By
 MOD_RES 286 286 Phosphoserine.
 MOD_RES 296 296 Phosphoserine.
 MOD_RES 301 301 Phosphoserine.
 MOD_RES 317 317 Phosphoserine; by ATM and ATR.
 MOD_RES 345 345 Phosphoserine; by ATM and ATR.
 CROSSLNK 436 436 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 3D-structure; Alternative splicing; ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; Isopeptide bond; Kinase; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 476 AA 

Protein Sequence

Gene Ontology

 GO:0005813; C:centrosome; IDA:UniProtKB.
 GO:0000785; C:chromatin; ISS:UniProtKB.
 GO:0000794; C:condensed nuclear chromosome; IDA:UniProtKB.
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005654; C:nucleoplasm; TAS:Reactome.
 GO:0005657; C:replication fork; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0035402; F:histone kinase activity (H3-T11 specific); IDA:UniProtKB.
 GO:0071313; P:cellular response to caffeine; IEA:Compara.
 GO:0071260; P:cellular response to mechanical stimulus; IEP:UniProtKB.
 GO:0048096; P:chromatin-mediated maintenance of transcription; ISS:UniProtKB.
 GO:0006975; P:DNA damage induced protein phosphorylation; IDA:UniProtKB.
 GO:0006281; P:DNA repair; IMP:UniProtKB.
 GO:0006260; P:DNA replication; TAS:Reactome.
 GO:0031572; P:G2 DNA damage checkpoint; IMP:UniProtKB.
 GO:0000086; P:G2/M transition of mitotic cell cycle; IEA:Compara.
 GO:0045839; P:negative regulation of mitosis; IDA:UniProtKB.
 GO:0042127; P:regulation of cell proliferation; IEA:Compara.
 GO:0010569; P:regulation of double-strand break repair via homologous recombination; IDA:UniProtKB.
 GO:2000615; P:regulation of histone H3-K9 acetylation; ISS:UniProtKB.
 GO:0046602; P:regulation of mitotic centrosome separation; IDA:UniProtKB.
 GO:0033261; P:regulation of S phase; IEA:Compara.
 GO:0010767; P:regulation of transcription from RNA polymerase II promoter in response to UV-induced DNA damage; ISS:UniProtKB.
 GO:0090399; P:replicative senescence; NAS:BHF-UCL. 

Interpro

 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS. 

Pfam

 PF00069; Pkinase 

SMART

 SM00220; S_TKc 

PROSITE

 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 

PRINTS