CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-001706
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase Chk2 
Protein Synonyms/Alias
 CHK2 checkpoint homolog; Cds1 homolog; Hucds1; hCds1; Checkpoint kinase 2 
Gene Name
 CHEK2 
Gene Synonyms/Alias
 CDS1; CHK2; RAD53 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
174CFDEPLLKRTDKYRTubiquitination[1]
267RDEYIMSKTLGSGACubiquitination[1]
416ITDFGHSKILGETSLubiquitination[1]
480HRTQVSLKDQITSGKubiquitination[1]
508KALDLVKKLLVVDPKubiquitination[1]
537QDEDMKRKFQDLLSEubiquitination[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] 
Functional Description
 Serine/threonine-protein kinase which is required for checkpoint-mediated cell cycle arrest, activation of DNA repair and apoptosis in response to the presence of DNA double-strand breaks. May also negatively regulate cell cycle progression during unperturbed cell cycles. Following activation, phosphorylates numerous effectors preferentially at the consensus sequence [L-X- R-X-X-S/T]. Regulates cell cycle checkpoint arrest through phosphorylation of CDC25A, CDC25B and CDC25C, inhibiting their activity. Inhibition of CDC25 phosphatase activity leads to increased inhibitory tyrosine phosphorylation of CDK-cyclin complexes and blocks cell cycle progression. May also phosphorylate NEK6 which is involved in G2/M cell cycle arrest. Regulates DNA repair through phosphorylation of BRCA2, enhancing the association of RAD51 with chromatin which promotes DNA repair by homologous recombination. Also stimulates the transcription of genes involved in DNA repair (including BRCA2) through the phosphorylation and activation of the transcription factor FOXM1. Regulates apoptosis through the phosphorylation of p53/TP53, MDM4 and PML. Phosphorylation of p53/TP53 at 'Ser-20' by CHEK2 may alleviate inhibition by MDM2, leading to accumulation of active p53/TP53. Phosphorylation of MDM4 may also reduce degradation of p53/TP53. Also controls the transcription of pro-apoptotic genes through phosphorylation of the transcription factor E2F1. Tumor suppressor, it may also have a DNA damage-independent function in mitotic spindle assembly by phosphorylating BRCA1. Its absence may be a cause of the chromosomal instability observed in some cancer cells. 
Sequence Annotation
 DOMAIN 113 175 FHA.
 DOMAIN 220 486 Protein kinase.
 NP_BIND 227 234 ATP.
 NP_BIND 302 308 ATP.
 NP_BIND 351 352 ATP.
 REGION 368 394 T-loop/activation segment.
 ACT_SITE 347 347 Proton acceptor.
 BINDING 249 249 ATP.
 BINDING 368 368 ATP.
 MOD_RES 62 62 Phosphoserine; by PLK3.
 MOD_RES 68 68 Phosphothreonine; by ATM and MLTK.
 MOD_RES 73 73 Phosphoserine; by PLK3.
 MOD_RES 379 379 Phosphoserine; by autocatalysis.
 MOD_RES 383 383 Phosphothreonine; by autocatalysis.
 MOD_RES 387 387 Phosphothreonine; by autocatalysis.
 MOD_RES 456 456 Phosphoserine.  
Keyword
 3D-structure; Alternative splicing; Apoptosis; ATP-binding; Cell cycle; Cell division; Complete proteome; Disease mutation; DNA damage; DNA repair; Kinase; Li-Fraumeni syndrome; Magnesium; Metal-binding; Mitosis; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transcription; Transcription regulation; Transferase; Tumor suppressor; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 543 AA 
Protein Sequence
MSRESDVEAQ QSHGSSACSQ PHGSVTQSQG SSSQSQGISS SSTSTMPNSS QSSHSSSGTL 60
SSLETVSTQE LYSIPEDQEP EDQEPEEPTP APWARLWALQ DGFANLETES GHVTQSDLEL 120
LLSSDPPASA SQSAGIRGVR HHPRPVCSLK CVNDNYWFGR DKSCEYCFDE PLLKRTDKYR 180
TYSKKHFRIF REVGPKNSYI AYIEDHSGNG TFVNTELVGK GKRRPLNNNS EIALSLSRNK 240
VFVFFDLTVD DQSVYPKALR DEYIMSKTLG SGACGEVKLA FERKTCKKVA IKIISKRKFA 300
IGSAREADPA LNVETEIEIL KKLNHPCIIK IKNFFDAEDY YIVLELMEGG ELFDKVVGNK 360
RLKEATCKLY FYQMLLAVQY LHENGIIHRD LKPENVLLSS QEEDCLIKIT DFGHSKILGE 420
TSLMRTLCGT PTYLAPEVLV SVGTAGYNRA VDCWSLGVIL FICLSGYPPF SEHRTQVSLK 480
DQITSGKYNF IPEVWAEVSE KALDLVKKLL VVDPKARFTT EEALRHPWLQ DEDMKRKFQD 540
LLSEENESTA LPQVLAQPST SRKRPREGEA EGAETTKRPA VCAAVL 586 
Gene Ontology
 GO:0016605; C:PML body; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
 GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0051301; P:cell division; IEA:UniProtKB-KW.
 GO:0044257; P:cellular protein catabolic process; IMP:UniProtKB.
 GO:0006975; P:DNA damage induced protein phosphorylation; IMP:UniProtKB.
 GO:0006302; P:double-strand break repair; IMP:UniProtKB.
 GO:0000086; P:G2/M transition of mitotic cell cycle; IMP:UniProtKB.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IDA:UniProtKB.
 GO:0045893; P:positive regulation of transcription, DNA-dependent; IDA:UniProtKB.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0050821; P:protein stabilization; IDA:UniProtKB.
 GO:0042176; P:regulation of protein catabolic process; IMP:UniProtKB.
 GO:0090399; P:replicative senescence; NAS:BHF-UCL.
 GO:0010332; P:response to gamma radiation; IEA:Compara.
 GO:0072428; P:signal transduction involved in intra-S DNA damage checkpoint; IMP:UniProtKB.
 GO:0090307; P:spindle assembly involved in mitosis; IMP:UniProtKB.
 GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW. 
Interpro
 IPR000253; FHA_dom.
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS.
 IPR008984; SMAD_FHA_domain. 
Pfam
 PF00498; FHA
 PF00069; Pkinase 
SMART
 SM00240; FHA
 SM00220; S_TKc 
PROSITE
 PS50006; FHA_DOMAIN
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST 
PRINTS