MSH6_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: MSH6_MOUSE
• UniProt AC: P54276
• Protein Name: DNA mismatch repair protein Msh6 {ECO:0000303|PubMed:9390556}
• Gene Name: Msh6 {ECO:0000312|MGI:MGI:1343961}
• Organism: Mus musculus (Mouse).
• Sequence Length: 1358
• Subcellular Localization: Nucleus . Chromosome . Associates with H3K36me3 via its PWWP domain.
• Protein Description: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction (By similarity)..
• Protein Sequence: MSRQSTLYSFFPKSPALGDTKKAAAEASRQGAAASGASASRGGDAAWSEAEPGSRSAAVSASSPEAKDLNGGLRRASSSAQAVPPSSCDFSPGDLVWAKMEGYPWWPCLVYNHPFDGTFIRKKGKSVRVHVQFFDDSPTRGWVSKRMLKPYTGSKSKEAQKGGHFYSSKSEILRAMQRADEALSKDTAERLQLAVCDEPSEPEEEEETEVHEAYLSDKSEEDNYNESEEEAQPSVQGPRRSSRQVKKRRVISDSESDIGGSDVEFKPDTKQEGSSDDASSGVGDSDSEDLGTFGKGAPKRKRAMVAQGGLRRKSLKKETGSAKRATPILSETKSTLSAFSAPQNSESQTHVSGGGNDSSGPTVWYHETLEWLKPEKRRDEHRRRPDHPEFNPTTLYVPEEFLNSCTPGMRKWWQLKSQNFDLVIFYKVGKFYELYHMDAVIGVSELGLIFMKGNWAHSGFPEIAFGRFSDSLVQKGYKVARVEQTETPEMMEARCRKMAHVSKFDRVVRREICRIITKGTQTYSVLDGDPSENYSRYLLSLKEKEEETSGHTRVYGVCFVDTSLGKFFIGQFSDDRHCSRFRTLVAHYPPVQILFEKGNLSTETKTVLKGSLSSCLQEGLIPGSQFWDATKTLRTLLEGGYFTGNGDSSTVLPLVLKGMTSESDSVGLTPGEESELALSALGGIVFYLKKCLIDQELLSMANFEEYFPLDSDTVSTVKPGAVFTKASQRMVLDAVTLNNLEIFLNGTNGSTEGTLLERLDTCHTPFGKRLLKQWLCAPLCSPSAISDRLDAVEDLMAVPDKVTEVADLLKKLPDLERLLSKIHNVGSPLKSQNHPDSRAIMYEETTYSKKKIIDFLSALEGFKVMCKVSGLLEEVAGGFTSKTLKQVVTLQSKSPKGRFPDLTAELQRWDTAFDHEKARKTGLITPKAGFDSDYDQALADIRENEQSLLEYLDKQRSRLGCKSIVYWGIGRNRYQLEIPENFATRNLPEEYELKSTKKGCKRYWTKTIEKKLANLINAEERRDTSLKDCMRRLFCNFDKNHKDWQSAVECIAVLDVLLCLANYSQGGDGPMCRPEIVLPGEDTHPFLEFKGSRHPCITKTFFGDDFIPNDILIGCEEEAEEHGKAYCVLVTGPNMGGKSTLIRQAGLLAVMAQLGCYVPAEKCRLTPVDRVFTRLGASDRIMSGESTFFVELSETASILRHATAHSLVLVDELGRGTATFDGTAIANAVVKELAETIKCRTLFSTHYHSLVEDYSKSVCVRLGHMACMVENECEDPSQETITFLYKFIKGACPKSYGFNAARLANLPEEVIQKGHRKAREFERMNQSLQLFREVCLATEKPTINGEAIHRLLALINGL

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
5	Phosphorylation	---MSRQSTLYSFFP ---CCCCCHHHHHCC	21.19	24719451
6	Phosphorylation	--MSRQSTLYSFFPK --CCCCCHHHHHCCC	22.75	25168779
8	Phosphorylation	MSRQSTLYSFFPKSP CCCCCHHHHHCCCCC	11.97	28576409
9	Phosphorylation	SRQSTLYSFFPKSPA CCCCHHHHHCCCCCC	24.43	25266776
14	Phosphorylation	LYSFFPKSPALGDTK HHHHCCCCCCCCCHH	18.68	26824392
20	Phosphorylation	KSPALGDTKKAAAEA CCCCCCCHHHHHHHH	32.42	23984901
38	Phosphorylation	GAAASGASASRGGDA HHHHCCCCCCCCCCC	30.24	-
40	Phosphorylation	AASGASASRGGDAAW HHCCCCCCCCCCCCC	29.03	-
48	Phosphorylation	RGGDAAWSEAEPGSR CCCCCCCCCCCCCCC	23.39	26525534
56	Phosphorylation	EAEPGSRSAAVSASS CCCCCCCEECEECCC	23.44	28833060
60	Phosphorylation	GSRSAAVSASSPEAK CCCEECEECCCCCHH	20.08	27087446
62	Phosphorylation	RSAAVSASSPEAKDL CEECEECCCCCHHHC	38.63	27087446
63	Phosphorylation	SAAVSASSPEAKDLN EECEECCCCCHHHCC	26.86	27087446
67	Acetylation	SASSPEAKDLNGGLR ECCCCCHHHCCCCCC	62.17	-
77	Phosphorylation	NGGLRRASSSAQAVP CCCCCCCCCCCCCCC	24.02	27087446
78	Phosphorylation	GGLRRASSSAQAVPP CCCCCCCCCCCCCCC	28.80	22942356
79	Phosphorylation	GLRRASSSAQAVPPS CCCCCCCCCCCCCCH	23.16	27087446
86	Phosphorylation	SAQAVPPSSCDFSPG CCCCCCCHHCCCCCC	37.21	26745281
87	Phosphorylation	AQAVPPSSCDFSPGD CCCCCCHHCCCCCCC	24.39	25777480
91	Phosphorylation	PPSSCDFSPGDLVWA CCHHCCCCCCCEEEE	18.09	25777480
137	Phosphorylation	HVQFFDDSPTRGWVS EEEECCCCCCCCCCC	29.98	27087446
139	Phosphorylation	QFFDDSPTRGWVSKR EECCCCCCCCCCCHH	45.85	22942356
144	Phosphorylation	SPTRGWVSKRMLKPY CCCCCCCCHHCCCCC	14.18	23984901
149	Acetylation	WVSKRMLKPYTGSKS CCCHHCCCCCCCCCC	27.00	7720385
155	Acetylation	LKPYTGSKSKEAQKG CCCCCCCCCHHHHCC	67.88	7677683
170	Phosphorylation	GHFYSSKSEILRAMQ CCCCCCHHHHHHHHH	31.64	25338131
200	Phosphorylation	LAVCDEPSEPEEEEE EEECCCCCCCCCHHC	64.83	21659605
208	Phosphorylation	EPEEEEETEVHEAYL CCCCHHCHHHHHHHH	46.73	25293948
214	Phosphorylation	ETEVHEAYLSDKSEE CHHHHHHHHCCCCCC	12.07	25293948
216	Phosphorylation	EVHEAYLSDKSEEDN HHHHHHHCCCCCCCC	30.25	21659605
219	Phosphorylation	EAYLSDKSEEDNYNE HHHHCCCCCCCCCCC	51.73	26239621
224	Phosphorylation	DKSEEDNYNESEEEA CCCCCCCCCCCHHHH	32.40	18846507
227	Phosphorylation	EEDNYNESEEEAQPS CCCCCCCCHHHHCCC	46.82	23375375
234	Phosphorylation	SEEEAQPSVQGPRRS CHHHHCCCCCCCCCC	18.26	23375375
252	Phosphorylation	VKKRRVISDSESDIG HHHEEEECCCCCCCC	32.02	23684622
254	Phosphorylation	KRRVISDSESDIGGS HEEEECCCCCCCCCC	32.01	23684622
256	Phosphorylation	RVISDSESDIGGSDV EEECCCCCCCCCCCC	38.18	26824392
261	Phosphorylation	SESDIGGSDVEFKPD CCCCCCCCCCEECCC	33.02	26824392
269	Phosphorylation	DVEFKPDTKQEGSSD CCEECCCCCCCCCCC	43.06	25619855
274	Phosphorylation	PDTKQEGSSDDASSG CCCCCCCCCCCCCCC	29.82	22006019
275	Phosphorylation	DTKQEGSSDDASSGV CCCCCCCCCCCCCCC	50.82	25293948
279	Phosphorylation	EGSSDDASSGVGDSD CCCCCCCCCCCCCCC	34.32	25293948
280	Phosphorylation	GSSDDASSGVGDSDS CCCCCCCCCCCCCCH	38.94	25293948
285	Phosphorylation	ASSGVGDSDSEDLGT CCCCCCCCCHHCCCC	36.79	21149613
287	Phosphorylation	SGVGDSDSEDLGTFG CCCCCCCHHCCCCCC	36.64	26525534
292	Phosphorylation	SDSEDLGTFGKGAPK CCHHCCCCCCCCCCH	36.19	21149613
314	Phosphorylation	QGGLRRKSLKKETGS CCCCCHHHHCHHCCC	43.54	29514104
326	Phosphorylation	TGSAKRATPILSETK CCCCCCCCCCHHHHH	18.20	28973931
330	Phosphorylation	KRATPILSETKSTLS CCCCCCHHHHHHHHH	43.89	28833060
332	Phosphorylation	ATPILSETKSTLSAF CCCCHHHHHHHHHCC	27.24	28833060
345	Phosphorylation	AFSAPQNSESQTHVS CCCCCCCCCCCCCCC	33.12	22802335
347	Phosphorylation	SAPQNSESQTHVSGG CCCCCCCCCCCCCCC	39.95	22802335
349	Phosphorylation	PQNSESQTHVSGGGN CCCCCCCCCCCCCCC	33.26	22802335
352	Phosphorylation	SESQTHVSGGGNDSS CCCCCCCCCCCCCCC	24.90	22802335
475	Ubiquitination	FSDSLVQKGYKVARV CHHHHHHCCCEEEEE	57.64	-
485	Phosphorylation	KVARVEQTETPEMME EEEEEECCCCHHHHH	28.46	24899341
487	Phosphorylation	ARVEQTETPEMMEAR EEEECCCCHHHHHHH	28.12	-
502	Phosphorylation	CRKMAHVSKFDRVVR HHHHHHHHHHHHHHH	20.10	-
503	Acetylation	RKMAHVSKFDRVVRR HHHHHHHHHHHHHHH	50.63	23806337
725	Ubiquitination	KPGAVFTKASQRMVL CCCCEEEHHHHCCEE	34.28	-
827	Phosphorylation	SKIHNVGSPLKSQNH HHHHHCCCCCCCCCC	23.83	26824392
842	Phosphorylation	PDSRAIMYEETTYSK CCCCCCCCEECCCCH	12.42	25293948
845	Phosphorylation	RAIMYEETTYSKKKI CCCCCEECCCCHHHH	21.06	25293948
846	Phosphorylation	AIMYEETTYSKKKII CCCCEECCCCHHHHH	29.13	25293948
869	Phosphorylation	FKVMCKVSGLLEEVA CHHHHHHHCHHHHHH	14.82	20139300
882	Ubiquitination	VAGGFTSKTLKQVVT HHCCCCCCCHHHHHE	55.61	22790023
883	Phosphorylation	AGGFTSKTLKQVVTL HCCCCCCCHHHHHEE	38.67	20139300
892	Phosphorylation	KQVVTLQSKSPKGRF HHHHEECCCCCCCCC	37.91	20139300
894	Phosphorylation	VVTLQSKSPKGRFPD HHEECCCCCCCCCCH	36.77	20139300
932	Phosphorylation	TPKAGFDSDYDQALA CCCCCCCCCHHHHHH	35.49	26745281
934	Phosphorylation	KAGFDSDYDQALADI CCCCCCCHHHHHHHH	17.57	26239621
1007	Phosphorylation	CKRYWTKTIEKKLAN HHHHHHHHHHHHHHH	27.30	-
1099	Ubiquitination	SRHPCITKTFFGDDF CCCCCEEEECCCCCC	24.35	-
1217	Phosphorylation	VDELGRGTATFDGTA EEECCCCEEEECHHH	22.59	21659604
1219	Phosphorylation	ELGRGTATFDGTAIA ECCCCEEEECHHHHH	23.30	21659604
1231	Acetylation	AIANAVVKELAETIK HHHHHHHHHHHHHHC	40.17	22826441
1231	Ubiquitination	AIANAVVKELAETIK HHHHHHHHHHHHHHC	40.17	-
1327	Phosphorylation	EFERMNQSLQLFREV HHHHHHHHHHHHHHH	17.06	22006019

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

Oops, there are no upstream regulatory protein records of MSH6_MOUSE !!

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of MSH6_MOUSE !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of MSH6_MOUSE !!

Protein-Protein Interaction

Oops, there are no PPI records of MSH6_MOUSE !!

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Phosphorylation

"Large-scale phosphorylation analysis of mouse liver.";
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-261, AND MASSSPECTROMETRY.
PubMed: 17242355