CHK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CHK1_MOUSE
• UniProt AC: O35280
• Protein Name: Serine/threonine-protein kinase Chk1
• Gene Name: Chek1
• Organism: Mus musculus (Mouse).
• Sequence Length: 476
• Subcellular Localization: Nucleus. Cytoplasm. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Nuclear export is mediated at least in part by XPO1/CRM1. Also localizes to the centrosome specifically during interphase, where it may protect centrosomal CDC2 k
• Protein 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. This inhibits their activity through proteasomal degradation, nucleo-cytoplasmic shuttling and inhibition by proteins of the 13-3-3 family. 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, 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 (By similarity). 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..
• Protein Sequence: MAVPFVEDWDLVQTLGEGAYGEVQLAVNRITEEAVAVKIVDMKRAIDCPENIKKEICINKMLSHENVVKFYGHRREGHIQYLFLEYCSGGELFDRIEPDIGMPEQDAQRFFHQLMAGVVYLHGIGITHRDIKPENLLLDERDNLKISDFGLATVFRHNNRERLLNKMCGTLPYVAPELLKRKEFHAEPVDVWSCGIVLTAMLAGELPWDQPSDSCQEYSDWKEKKTYLNPWKKIDSAPLALLHKILVETPSARITIPDIKKDRWYNKPLNRGAKRPRATSGGMSESSSGFSKHIHSNLDFSPVNNGSSEETVKFSSSQPEPRTGLSLWDTGPSNVDKLVQGISFSQPTCPEHMLVNSQLLGTPGSSQNPWQRLVKRMTRFFTKLDADKSYQCLKETFEKLGYQWKKSCMNQVTVSTTDRRNNKLIFKINLVEMDEKILVDFRLSKGDGLEFKRHFLKIKGKLSDVVSSQKVWFPVT

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
279	Phosphorylation	GAKRPRATSGGMSES CCCCCCCCCCCCCCC	29.23	25263469
280	Phosphorylation	AKRPRATSGGMSESS CCCCCCCCCCCCCCC	32.15	26824392
284	Phosphorylation	RATSGGMSESSSGFS CCCCCCCCCCCCCCH	37.29	22345495
286	Phosphorylation	TSGGMSESSSGFSKH CCCCCCCCCCCCHHC	23.61	22817900
287	Phosphorylation	SGGMSESSSGFSKHI CCCCCCCCCCCHHCC	30.35	23984901
288	Phosphorylation	GGMSESSSGFSKHIH CCCCCCCCCCHHCCC	53.81	23984901
291	Phosphorylation	SESSSGFSKHIHSNL CCCCCCCHHCCCCCC	27.18	23984901
296	Phosphorylation	GFSKHIHSNLDFSPV CCHHCCCCCCCCCCC	38.19	22322096
301	Phosphorylation	IHSNLDFSPVNNGSS CCCCCCCCCCCCCCC	27.83	28973931
308	Phosphorylation	SPVNNGSSEETVKFS CCCCCCCCCCEEECC	40.63	22322096
315	Phosphorylation	SEETVKFSSSQPEPR CCCEEECCCCCCCCC	24.30	22322096
316	Phosphorylation	EETVKFSSSQPEPRT CCEEECCCCCCCCCC	35.80	27600695
317	Phosphorylation	ETVKFSSSQPEPRTG CEEECCCCCCCCCCC	48.86	17525332
323	Phosphorylation	SSQPEPRTGLSLWDT CCCCCCCCCCCCCCC	53.87	26643407
326	Phosphorylation	PEPRTGLSLWDTGPS CCCCCCCCCCCCCCC	28.85	26643407
345	Phosphorylation	LVQGISFSQPTCPEH HHHCCCCCCCCCCCH	28.58	21921034
463	Phosphorylation	LKIKGKLSDVVSSQK HEECCCHHHCCCCCE	31.67	27600695
467	Phosphorylation	GKLSDVVSSQKVWFP CCHHHCCCCCEEEEE	27.22	27149854
468	Phosphorylation	KLSDVVSSQKVWFPV CHHHCCCCCEEEEEC	23.55	27841257

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
280	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
286	S	Phosphorylation	Kinase	CDK1	P06493	PSP
301	S	Phosphorylation	Kinase	CDK1	P06493	PSP
317	S	Phosphorylation	Kinase	ATM	Q62388	Uniprot
317	S	Phosphorylation	Kinase	ATR	Q9JKK8	Uniprot
345	S	Phosphorylation	Kinase	ATR	Q9JKK8	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Fbxo6	Q9QZN4	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
280	S	Phosphorylation	Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination.	15710331
280	S	ubiquitylation	Phosphorylation at Ser-280 by AKT1/PKB, may promote mono and/or diubiquitination.	15710331
317	S	Phosphorylation	ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity.	17376776
345	S	Phosphorylation	ATM and ATR can both phosphorylate Ser-317 and Ser-345 and this results in enhanced kinase activity.	15710331
345	S	Phosphorylation	Conversely, dephosphorylation at Ser-345 by PPM1D may contribute to exit from checkpoint mediated cell cycle arrest.	15710331
345	S	Phosphorylation	Phosphorylation at Ser-345 also increases binding to 14-3-3 proteins and promotes nuclear retention.	15710331
345	S	Phosphorylation	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.	15710331
345	S	Phosphorylation	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 (By similarity).	15710331
345	S	ubiquitylation	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.	15710331
345	S	ubiquitylation	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 (By similarity).	15710331
436	K	Phosphorylation	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.	15710331
436	K	Phosphorylation	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 (By similarity).	15710331
436	K	ubiquitylation	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.	15710331
436	K	ubiquitylation	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 (By similarity).	15710331

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CHK1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CHK1_HUMAN	CHEK1	physical	20360068
H32_MOUSE	Hist1h3f	physical	18243098
ACSL3_HUMAN	ACSL3	physical	26496610
PKD2_HUMAN	PKD2	physical	26496610
NELFA_HUMAN	NELFA	physical	26496610
NO40_HUMAN	ZCCHC17	physical	26496610
HDGR2_HUMAN	HDGFRP2	physical	26496610
RAVR1_HUMAN	RAVER1	physical	26496610

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"ATM and ATR substrate analysis reveals extensive protein networksresponsive to DNA damage.";
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
Science 316:1160-1166(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-317, AND MASSSPECTROMETRY.
PubMed: 17525332

"Lack of PTEN sequesters CHK1 and initiates genetic instability.";
Puc J., Keniry M., Li H.S., Pandita T.K., Choudhury A.D., Memeo L.,Mansukhani M., Murty V.V.V.S., Gaciong Z., Meek S.E.M.,Piwnica-Worms H., Hibshoosh H., Parsons R.;
Cancer Cell 7:193-204(2005).
Cited for: SUBCELLULAR LOCATION, UBIQUITINATION, PHOSPHORYLATION AT SER-280 ANDSER-345, AND MUTAGENESIS OF SER-280.
PubMed: 15710331