CHK2_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CHK2_MOUSE
• UniProt AC: Q9Z265
• Protein Name: Serine/threonine-protein kinase Chk2
• Gene Name: Chek2
• Organism: Mus musculus (Mouse).
• Sequence Length: 546
• Subcellular Localization: Nucleus, PML body. Nucleus, nucleoplasm. Recruited into PML bodies together with TP53..
• Protein 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 (By similarity)..
• Protein Sequence: MKSHHQSHSSTSSKAHDSASCSQSQGGFSQPQGTPSQLHELSQYQGSSSSSTGTVPSSSQSSHSSSGTLSSLETVSTQELCSIPEDQEPEEPGPAPWARLWALQDGFSNLDCVNDNYWFGRDKSCEYCFDGPLLRRTDKYRTYSKKHFRIFREMGPKNCYIVYIEDHSGNGTFVNTELIGKGKRCPLSNNSEIALSLCRNKVFVFFDLTVDDQSVYPKELRDEYIMSKTLGSGACGEVKMAFERKTCQKVAIKIISKRRFALGSSREADTAPSVETEIEILKKLNHPCIIKIKDVFDAEDYYIVLELMEGGELFDRVVGNKRLKEATCKLYFYQMLVAVQYLHENGIIHRDLKPENVLLSSQEEDCLIKITDFGQSKILGETSLMRTLCGTPTYLAPEVLVSNGTAGYSRAVDCWSLGVILFICLSGYPPFSEHKTQVSLKDQITSGKYNFIPEVWTDVSEEALDLVKKLLVVDPKARLTTEEALNHPWLQDEYMKKKFQDLLVQEKNSVTLPVAPAQTSSQKRPLELEVEGMPSTKRLSVCGAVL

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
68	Phosphorylation	SSHSSSGTLSSLETV CCCCCCCCCCCCEEE	25.97	-
71	Phosphorylation	SSSGTLSSLETVSTQ CCCCCCCCCEEECHH	33.08	-
77	Phosphorylation	SSLETVSTQELCSIP CCCEEECHHHHHCCC	23.02	20371347
82	Phosphorylation	VSTQELCSIPEDQEP ECHHHHHCCCCCCCC	54.53	-
264	Phosphorylation	KRRFALGSSREADTA HCCCCCCCCCCCCCC	27.37	26239621
265	Phosphorylation	RRFALGSSREADTAP CCCCCCCCCCCCCCC	32.13	26239621
270	Phosphorylation	GSSREADTAPSVETE CCCCCCCCCCCHHHH	47.73	23984901
382	Phosphorylation	QSKILGETSLMRTLC CCCCCCCHHHHHHHC	25.92	29472430
383	Phosphorylation	SKILGETSLMRTLCG CCCCCCHHHHHHHCC	18.83	22817900
387	Phosphorylation	GETSLMRTLCGTPTY CCHHHHHHHCCCCCE	16.66	-
391	Phosphorylation	LMRTLCGTPTYLAPE HHHHHCCCCCEECCE	16.09	-
393	Phosphorylation	RTLCGTPTYLAPEVL HHHCCCCCEECCEEE	30.88	24759943
460	Phosphorylation	PEVWTDVSEEALDLV CCHHCCCCHHHHHHH	32.31	-
540	Phosphorylation	MPSTKRLSVCGAVL- CCCCCEEEECEECC-	21.28	22817900

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
68	T	Phosphorylation	Kinase	MAP3K20	Q9ESL4	Uniprot
71	S	Phosphorylation	Kinase	PLK3	Q60806	Uniprot
77	T	Phosphorylation	Kinase	ATM	Q62388	Uniprot
77	T	Phosphorylation	Kinase	MAP3K20	Q9ESL4	Uniprot
82	S	Phosphorylation	Kinase	PLK3	Q60806	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
77	T	Phosphorylation	Phosphorylated at Ser-82 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-77 by ATM and the G2/M transition checkpoint.	-
77	T	Phosphorylation	Phosphorylation at Thr-77 induces homodimerization.	-
82	S	Phosphorylation	Phosphorylated at Ser-82 by PLK3 in response to DNA damage, promoting phosphorylation at Thr-77 by ATM and the G2/M transition checkpoint.	-
383	S	Phosphorylation	DNA damage-induced autophosphorylation at Ser-383 induces CUL1-mediated ubiquitination and regulates the pro-apoptotic function.	-
387	T	Phosphorylation	Autophosphorylates at Thr-387 and Thr-391 in the T-loop/activation segment upon dimerization to become fully active.	-
391	T	Phosphorylation	Autophosphorylates at Thr-387 and Thr-391 in the T-loop/activation segment upon dimerization to become fully active.	-
460	S	Phosphorylation	Phosphorylation at Ser-460 also regulates ubiquitination.	-

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of CHK2_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
BRD8_HUMAN	BRD8	physical	20360068
CHK2_HUMAN	CHEK2	physical	20360068
STK38_HUMAN	STK38	physical	20360068
JPH1_HUMAN	JPH1	physical	20360068

Drug and Disease Associations

• Kegg Drug
• DrugBank
• There are no disease associations of PTM sites.