O96017

※ Protein Information

Tag	Content
UniProt Accession	CHK2_HUMAN; O96017;
Entrez ID	11200
GenBank Protein ID	NM_001005735.1; NM_001257387.1; NM_007194.3; NM_145862.2; XM_011529845.2; XM_017028561.1;
GenBank Nucleotide ID	NP_001005735.1; NP_001244316.1; NP_009125.1; NP_665861.1; XP_011528147.1; XP_016884050.1;
Protein Name	Serine/threonine-protein kinase Chk2 (EC 2.7.11.1) (CHK2 checkpoint homolog) (Cds1 homolog) (Hucds1) (hCds1) (Checkpoint kinase 2)
Gene Name	CHEK2; CDS1; CHK2; RAD53
Organism	Homo sapiens
NCBI Taxa ID	9606
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 le(view all) 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. Promotes the CCAR2-SIRT1 association and is required for CCAR2-mediated SIRT1 inhibition (PubMed:25361978).
Sequence (Fasta)	MSRESDVEAQ QSHGSSACSQ PHGSVTQSQG SSSQSQGISS SSTSTMPNSS QSSHSSSGTL 60 SSLETVSTQE LYSIPEDQEP EDQEPEEPTP APWARLWALQ DGFANLECVN DNYWFGRDKS 120 CEYCFDEPLL KRTDKYRTYS KKHFRIFREV GPKNSYIAYI EDHSGNGTFV NTELVGKGKR 180 RPLNNNSEIA LSLSRNKVFV FFDLTVDDQS VYPKALRDEY IMSKTLGSGA CGEVKLAFER 240 KTCKKVAIKI ISKRKFAIGS AREADPALNV ETEIEILKKL NHPCIIKIKN FFDAEDYYIV 300 LELMEGGELF DKVVGNKRLK EATCKLYFYQ MLLAVQYLHE NGIIHRDLKP ENVLLSSQEE 360 DCLIKITDFG HSKILGETSL MRTLCGTPTY LAPEVLVSVG TAGYNRAVDC WSLGVILFIC 420 LSGYPPFSEH RTQVSLKDQI TSGKYNFIPE VWAEVSEKAL DLVKKLLVVD PKARFTTEEA 480 LRHPWLQDED MKRKFQDLLS EENESTALPQ VLAQPSTSRK RPREGEAEGA ETTKRPAVCA 540 AVL 544 Fasta Sequence >O96017\|CHEK2; CDS1; CHK2; RAD53\|Homo sapiens (Human) MSRESDVEAQQSHGSSACSQPHGSVTQSQGSSSQSQGISSSSTSTMPNSSQSSHSSSGTLSSLETVSTQELYSIPEDQEPEDQEPEEPTPAPWARLWALQDGFANLECVNDNYWFGRDKSCEYCFDEPLLKRTDKYRTYSKKHFRIFREVGPKNSYIAYIEDHSGNGTFVNTELVGKGKRRPLNNNSEIALSLSRNKVFVFFDLTVDDQSVYPKALRDEYIMSKTLGSGACGEVKLAFERKTCKKVAIKIISKRKFAIGSAREADPALNVETEIEILKKLNHPCIIKIKNFFDAEDYYIVLELMEGGELFDKVVGNKRLKEATCKLYFYQMLLAVQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGHSKILGETSLMRTLCGTPTYLAPEVLVSVGTAGYNRAVDCWSLGVILFICLSGYPPFSEHRTQVSLKDQITSGKYNFIPEVWAEVSEKALDLVKKLLVVDPKARFTTEEALRHPWLQDEDMKRKFQDLLSEENESTALPQVLAQPSTSRKRPREGEAEGAETTKRPAVCAAVL

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Phosphorylation	Lung hyperplasias		P		15829965
1	[Reference]: We analysed a panel of human lung hyperplasias, all of which retained wild-type p53 genes and had no signs of gross chromosomal instability, and found signs of a DNA damage response, including histone H2AX and Chk2 phosphorylation, p53 accumulation, focal staining of p53 binding protein 1 (53BP1) and apoptosis.
2	Threonine Phosphorylation	Bladder cancer	tumor tissue	U	T68	15361851
2	[Reference]: Furthermore, the vast majority of the tumours showed 'unscheduled' activatory phosphorylation on Thr68 of Chk2 in the absence of any DNA-damaging treatment.
3	Threonine Phosphorylation	Bloom syndrome	cell lines	U	T68	17634426
3	[Reference]: Here, we report that BLM-deficient cell lines and primary fibroblasts display an endogenously activated DNA double-strand break checkpoint response with prominent levels of phosphorylated histone H2AX (gamma-H2AX), Chk2 (p(T68)Chk2), and ATM (p(S1981)ATM) colocalizing in nuclear foci.?
4	Threonine Phosphorylation	Non-small cell lung cancer/carcinoma	tumor tissue	U	T68	16705183
4	[Reference]: Moreover, and consistent with p14ARF being a determinant of CHK2 phosphorylation in lung carcinogenesis, a strong correlation between p14ARF and phospho-CHK2 (Thr68) protein expression is observed in human lung tumors (P < 0.00006).

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	breast familial breast cancer
CTD (Curated) (count: 14) (view all)	MESH:D001943 ; Breast Neoplasms MESH:D018567 ; Breast Neoplasms, Male MESH:D015179 ; Colorectal Neoplasms MESH:D018450 ; Disease Progression MESH:D016864 ; Li-Fraumeni Syndrome MESH:C563755 ; Li-Fraumeni Syndrome 2 MESH:D008175 ; Lung Neoplasms MESH:D018307 ; Neoplasms, Squamous Cell MESH:D009447 ; Neuroblastoma MESH:D008228 ; Lymphoma, Non-Hodgkin MESH:D012516 ; Osteosarcoma MESH:C537243 ; Prostate cancer, familial MESH:D011471 ; Prostatic Neoplasms MESH:D013274 ; Stomach Neoplasms
DisGeNet (Curated) (count: 43) (view all)	C0001618; Tumors of Adrenal Cortex C0006142; Malignant neoplasm of breast C0007114; Malignant neoplasm of skin C0009375; Colonic Neoplasms C0009404; Colorectal Neoplasms C0017638; Glioma C0024121; Lung Neoplasms C0024299; Lymphoma C0024305; Lymphoma, Non-Hodgkin C0025286; Meningioma C0027766; Nervous System Neoplasms C0027819; Neuroblastoma C0029463; Osteosarcoma C0030193; Pain C0030297; Pancreatic Neoplasm C0033578; Prostatic Neoplasms C0035335; Retinoblastoma C0037286; Skin Neoplasms C0038356; Stomach Neoplasms C0085390; Li-Fraumeni Syndrome C0152031; Joint swelling C0206720; Squamous Cell Neoplasms C0221204; Lytic lesion C0242788; Breast Neoplasms, Male C0346647; Malignant neoplasm of pancreas C0376358; Malignant neoplasm of prostate C0524801; Retinal Neoplasms C0677776; Hereditary Breast and Ovarian Cancer Syndrome C0678222; Breast Carcinoma C0699791; Stomach Carcinoma C0750857; Alkaline phosphatase serum increased C1261473; Sarcoma C1458155; Mammary Neoplasms C1836482; Li-Fraumeni Syndrome 2 C1838578; Encephalopathy, progressive C1842408; Increased risk of pancreatic cancer C2931456; Prostate cancer, familial C4021768; Abnormality of metabolism/homeostasis C4025038; Abnormality of the tibial metaphysis C4025040; Abnormality of the femoral metaphysis C4073168; Abnormal lactate dehydrogenase activity C4280444; Abnormality of the wide portion of the femoral bone C4280575; Progressive brain disease
HGMD (count: 40) (view all)	CD993416; Li-Fraumeni syndrome; Small deletions CD077681; Reduced activity, association with; Small deletions CD064528; Breast cancer; Small deletions CD077682; Reduced activity, association with; Small deletions CD030580; Prostate cancer; Small deletions CD993415; Li-Fraumeni syndrome; Small deletions CG065898; Prostate cancer; Gross deletions CG065899; Breast cancer; Gross deletions CM023347; Multiple cancers; Missense/nonsense CM030414; Prostate cancer; Missense/nonsense CM077521; Reduced activity, association with; Missense/nonsense CM023898; Breast cancer; Missense/nonsense CM023899; Breast cancer; Missense/nonsense CM077520; Reduced activity, association with; Missense/nonsense CM092017; Colorectal cancer ?; Missense/nonsense CM030415; Prostate cancer; Missense/nonsense CM013593; Li-Fraumeni syndrome; Missense/nonsense CM993368; Li-Fraumeni syndrome, increased risk; Missense/nonsense CM086681; Breast cancer ?; Missense/nonsense CM030416; Prostate cancer; Missense/nonsense CM086682; Breast cancer ?; Missense/nonsense CM086683; Breast cancer ?; Missense/nonsense CM030417; Prostate cancer; Missense/nonsense CM030418; Prostate cancer; Missense/nonsense CM030419; Prostate cancer; Missense/nonsense CM030420; Prostate cancer; Missense/nonsense CM030421; Prostate cancer; Missense/nonsense CM030422; Prostate cancer; Missense/nonsense CM030423; Prostate cancer; Missense/nonsense CM030424; Prostate cancer; Missense/nonsense CM062510; Prostate cancer; Missense/nonsense CM030425; Prostate cancer; Missense/nonsense CM030426; Prostate cancer; Missense/nonsense CM051021; Breast cancer, association with; Missense/nonsense CM077522; Reduced activity, association with; Missense/nonsense CM030427; Prostate cancer; Missense/nonsense CR068233; Ovarian cancer ?; Regulatory CS086685; Breast cancer ?; Splicing CS030536; Prostate cancer; Splicing CS086684; Breast cancer ?; Splicing
GWASdb (count: 8) (view all)	rs1547014; Vertical cup-disc ratio; optic nerve disease\|open-angle glaucoma\|myopia rs1547014; Lung function (forced expiratory volume in 1 second to forced vital capacity ratio); lung disease rs4822983; Esophageal cancer (squamous cell); esophageal cancer rs17879961; Lung cancer; lung cancer rs738722; Esophageal cancer and gastric cancer; esophageal cancer\|stomach cancer rs738722; Lung function (forced expiratory volume in 1 second to forced vital capacity ratio); lung disease rs5762763; Multiple complex diseases; Null rs5762766; Alzheimer's disease; Alzheimer's disease

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 45) (view all)	12 SDVEAQQSHGSSACS dbPAF 120 YWFGRDKSCEYCFDE dbPAF 140 TDKYRTYSKKHFRIF dbPAF 15 EAQQSHGSSACSQPH dbPAF 164 IAYIEDHSGNGTFVN dbPAF 19 SHGSSACSQPHGSVT dbPAF 205 VFVFFDLTVDDQSVY dbPAF 210 DLTVDDQSVYPKALR dbPAF 225 DEYIMSKTLGSGACG dbPAF 24 ACSQPHGSVTQSQGS dbPAF 26 SQPHGSVTQSQGSSS dbPAF 260 KRKFAIGSAREADPA dbPAF 28 PHGSVTQSQGSSSQS dbPAF 33 TQSQGSSSQSQGISS dbPAF 35 SQGSSSQSQGISSSS dbPAF 356 KPENVLLSSQEEDCL dbPAF 357 PENVLLSSQEEDCLI dbPAF 372 KITDFGHSKILGETS dbPAF 378 HSKILGETSLMRTLC dbPAF 379 SKILGETSLMRTLCG dbPAF 383 GETSLMRTLCGTPTY dbPAF 387 LMRTLCGTPTYLAPE dbPAF 389 RTLCGTPTYLAPEVL dbPAF 39 SSQSQGISSSSTSTM dbPAF 390 TLCGTPTYLAPEVLV dbPAF 40 SQSQGISSSSTSTMP dbPAF 41 QSQGISSSSTSTMPN dbPAF 42 SQGISSSSTSTMPNS dbPAF 43 QGISSSSTSTMPNSS dbPAF 432 PPFSEHRTQVSLKDQ dbPAF 435 SEHRTQVSLKDQITS dbPAF 44 GISSSSTSTMPNSSQ dbPAF 45 ISSSSTSTMPNSSQS dbPAF 456 PEVWAEVSEKALDLV dbPAF 50 TSTMPNSSQSSHSSS dbPAF 516 PQVLAQPSTSRKRPR dbPAF 517 QVLAQPSTSRKRPRE dbPAF 518 VLAQPSTSRKRPREG dbPAF 52 TMPNSSQSSHSSSGT dbPAF 55 NSSQSSHSSSGTLSS dbPAF 62 SSSGTLSSLETVSTQ dbPAF 65 GTLSSLETVSTQELY dbPAF 67 LSSLETVSTQELYSI dbPAF 68 SSLETVSTQELYSIP dbPAF 73 VSTQELYSIPEDQEP dbPAF
Acetylation (count: 1)	153 IFREVGPKNSYIAYI PLMD
Ubiquitination (count: 6)	131 CFDEPLLKRTDKYRT PLMD 224 RDEYIMSKTLGSGAC PLMD 373 ITDFGHSKILGETSL PLMD 437 HRTQVSLKDQITSGK PLMD 465 KALDLVKKLLVVDPK PLMD 494 QDEDMKRKFQDLLSE PLMD

※ Protein-Protein Interaction

Network

Interaction

Source

F5GXF0	O96017	IntAct
O96017	O96017	MINT
O96017	P04637	MINT;HPRD
O96017	P06400	MINT
O96017	P18887	MINT
O96017	P30304	MINT
O96017	P38398	IntAct
O96017	P52292	MINT
O96017	P53350	DIP; IntAct;HPRD
O96017	P55072	IntAct
O96017	P56645	MINT
O96017	P62875	IntAct
O96017	Q00987	MINT
O96017	Q01094	HPRD
O96017	Q07960	IntAct
O96017	Q12888	IntAct
O96017	Q13315	HPRD
O96017	Q13362	IntAct
O96017	Q14738	IntAct
O96017	Q15172	IntAct
O96017	Q15173	IntAct
O96017	Q16537	IntAct
O96017	Q92878	IntAct
O96017	Q9NY61	IntAct
O96017	Q9Y248	IntAct
O96017	Q9Y3F4	MINT

PTMD Annotation Information

※ Protein Information

Functional Description

Fasta Sequence

※ PTM-Disease Association

※ Disease Cross-ref Annotation

※ PTM Sites

※ Protein-Protein Interaction