dbPTM

MSH2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	MSH2_HUMAN
UniProt AC	P43246
Protein Name	DNA mismatch repair protein Msh2
Gene Name	MSH2
Organism	Homo sapiens (Human).
Sequence Length	934
Subcellular Localization	Nucleus .
Protein Description	Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2-MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis..
Protein Sequence	MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPAGAKNLQSVVLSKMNFESFVKDLLLVRQYRVEVYKNRAGNKASKENDWYLAYKASPGNLSQFEDILFGNNDMSASIGVVGVKMSAVDGQRQVGVGYVDSIQRKLGLCEFPDNDQFSNLEALLIQIGPKECVLPGGETAGDMGKLRQIIQRGGILITERKKADFSTKDIYQDLNRLLKGKKGEQMNSAVLPEMENQVAVSSLSAVIKFLELLSDDSNFGQFELTTFDFSQYMKLDIAAVRALNLFQGSVEDTTGSQSLAALLNKCKTPQGQRLVNQWIKQPLMDKNRIEERLNLVEAFVEDAELRQTLQEDLLRRFPDLNRLAKKFQRQAANLQDCYRLYQGINQLPNVIQALEKHEGKHQKLLLAVFVTPLTDLRSDFSKFQEMIETTLDMDQVENHEFLVKPSFDPNLSELREIMNDLEKKMQSTLISAARDLGLDPGKQIKLDSSAQFGYYFRVTCKEEKVLRNNKNFSTVDIQKNGVKFTNSKLTSLNEEYTKNKTEYEEAQDAIVKEIVNISSGYVEPMQTLNDVLAQLDAVVSFAHVSNGAPVPYVRPAILEKGQGRIILKASRHACVEVQDEIAFIPNDVYFEKDKQMFHIITGPNMGGKSTYIRQTGVIVLMAQIGCFVPCESAEVSIVDCILARVGAGDSQLKGVSTFMAEMLETASILRSATKDSLIIIDELGRGTSTYDGFGLAWAISEYIATKIGAFCMFATHFHELTALANQIPTVNNLHVTALTTEETLTMLYQVKKGVCDQSFGIHVAELANFPKHVIECAKQKALELEEFQYIGESQGYDIMEPAAKKCYLEREQGEKIIQEFLSKVKQMPFTEMSEENITIKLKQLKAEVIAKNNSFVNEIISRIKVTT

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MAVQPKETL ------CCCCCCCCE	14.51	22814378
31	Phosphorylation	QGMPEKPTTTVRLFD CCCCCCCCCEEEEEE	46.28	20068231
32	Phosphorylation	GMPEKPTTTVRLFDR CCCCCCCCEEEEEEC	31.64	20068231
33	Phosphorylation	MPEKPTTTVRLFDRG CCCCCCCEEEEEECC	13.20	20068231
65	Ubiquitination	FKTQGVIKYMGPAGA HHHHCCHHHCCCCHH	27.12	-
65	Acetylation	FKTQGVIKYMGPAGA HHHHCCHHHCCCCHH	27.12	23236377
66	Phosphorylation	KTQGVIKYMGPAGAK HHHCCHHHCCCCHHC	9.00	-
73	Ubiquitination	YMGPAGAKNLQSVVL HCCCCHHCCHHHHHH	58.22	21890473
73	Acetylation	YMGPAGAKNLQSVVL HCCCCHHCCHHHHHH	58.22	23954790
73	Ubiquitination	YMGPAGAKNLQSVVL HCCCCHHCCHHHHHH	58.22	21890473
77	Phosphorylation	AGAKNLQSVVLSKMN CHHCCHHHHHHHHCC	19.84	-
104	Methylation	QYRVEVYKNRAGNKA HHHHEEEECCCCCCC	45.17	-
104	Acetylation	QYRVEVYKNRAGNKA HHHHEEEECCCCCCC	45.17	7851203
104	2-Hydroxyisobutyrylation	QYRVEVYKNRAGNKA HHHHEEEECCCCCCC	45.17	-
104	Trimethylation	QYRVEVYKNRAGNKA HHHHEEEECCCCCCC	45.17	-
113	Acetylation	RAGNKASKENDWYLA CCCCCCCCCCCEEEE	66.45	23236377
172	Ubiquitination	YVDSIQRKLGLCEFP HHHHHHHHHCCCCCC	30.45	-
206	Phosphorylation	CVLPGGETAGDMGKL CCCCCCCCCCHHHHH	38.93	20068231
212	Ubiquitination	ETAGDMGKLRQIIQR CCCCHHHHHHHHHHH	33.58	-
219	Methylation	KLRQIIQRGGILITE HHHHHHHHCCEEEEE	34.59	115483861
235	Ubiquitination	KKADFSTKDIYQDLN CCCCCCHHHHHHHHH	40.71	-
235	Acetylation	KKADFSTKDIYQDLN CCCCCCHHHHHHHHH	40.71	23236377
238	Phosphorylation	DFSTKDIYQDLNRLL CCCHHHHHHHHHHHH	13.20	25159151
249	Ubiquitination	NRLLKGKKGEQMNSA HHHHCCCCCCCCCCC	76.09	21890473
255	Phosphorylation	KKGEQMNSAVLPEME CCCCCCCCCCHHHHH	17.89	22210691
268	Phosphorylation	MENQVAVSSLSAVIK HHHHHHHHHHHHHHH	18.80	22210691
332	Ubiquitination	SLAALLNKCKTPQGQ HHHHHHHCCCCHHHH	36.76	21890473
347	Ubiquitination	RLVNQWIKQPLMDKN HHHHHHHHCCCCCCC	42.79	-
430	Sumoylation	KHEGKHQKLLLAVFV HCCCCCHHHHEEHHH	40.60	-
430	Sumoylation	KHEGKHQKLLLAVFV HCCCCCHHHHEEHHH	40.60	28112733
479	Phosphorylation	PSFDPNLSELREIMN CCCCCCHHHHHHHHH	41.02	25159151
489	Ubiquitination	REIMNDLEKKMQSTL HHHHHHHHHHHHHHH	54.19	19608861
489	Acetylation	REIMNDLEKKMQSTL HHHHHHHHHHHHHHH	54.19	19608861
491	2-Hydroxyisobutyrylation	IMNDLEKKMQSTLIS HHHHHHHHHHHHHHH	32.56	-
491	Ubiquitination	IMNDLEKKMQSTLIS HHHHHHHHHHHHHHH	32.56	-
494	Phosphorylation	DLEKKMQSTLISAAR HHHHHHHHHHHHHHH	22.98	25627689
495	Phosphorylation	LEKKMQSTLISAARD HHHHHHHHHHHHHHH	15.95	25627689
509	Ubiquitination	DLGLDPGKQIKLDSS HCCCCCCCCEEECCC	54.99	-
515	Phosphorylation	GKQIKLDSSAQFGYY CCCEEECCCCCCEEE	37.70	26074081
516	Phosphorylation	KQIKLDSSAQFGYYF CCEEECCCCCCEEEE	26.25	26074081
521	Phosphorylation	DSSAQFGYYFRVTCK CCCCCCEEEEEEEEC	10.75	26074081
522	Phosphorylation	SSAQFGYYFRVTCKE CCCCCEEEEEEEECH	5.81	26074081
526	Phosphorylation	FGYYFRVTCKEEKVL CEEEEEEEECHHHHH	17.38	26074081
531	Acetylation	RVTCKEEKVLRNNKN EEEECHHHHHHCCCC	47.89	26051181
531	Ubiquitination	RVTCKEEKVLRNNKN EEEECHHHHHHCCCC	47.89	-
537	Ubiquitination	EKVLRNNKNFSTVDI HHHHHCCCCCCCEEE	64.02	-
540	Phosphorylation	LRNNKNFSTVDIQKN HHCCCCCCCEEEHHC	36.59	27134283
550	Acetylation	DIQKNGVKFTNSKLT EEHHCCEEECCCCCC	48.12	7427807
555	Sumoylation	GVKFTNSKLTSLNEE CEEECCCCCCCCCHH	58.83	19608861
555	Ubiquitination	GVKFTNSKLTSLNEE CEEECCCCCCCCCHH	58.83	21906983
555	Acetylation	GVKFTNSKLTSLNEE CEEECCCCCCCCCHH	58.83	19608861
557	Phosphorylation	KFTNSKLTSLNEEYT EECCCCCCCCCHHHH	34.60	21406692
558	Phosphorylation	FTNSKLTSLNEEYTK ECCCCCCCCCHHHHC	39.37	22617229
563	Phosphorylation	LTSLNEEYTKNKTEY CCCCCHHHHCCCCHH	19.48	21406692
564	Phosphorylation	TSLNEEYTKNKTEYE CCCCHHHHCCCCHHH	31.27	21406692
565	Ubiquitination	SLNEEYTKNKTEYEE CCCHHHHCCCCHHHH	56.39	21890473
565	Acetylation	SLNEEYTKNKTEYEE CCCHHHHCCCCHHHH	56.39	23236377
567	Ubiquitination	NEEYTKNKTEYEEAQ CHHHHCCCCHHHHHH	44.27	21906983
567	Sumoylation	NEEYTKNKTEYEEAQ CHHHHCCCCHHHHHH	44.27	-
567	Acetylation	NEEYTKNKTEYEEAQ CHHHHCCCCHHHHHH	44.27	27452117
569	Acetylation	EYTKNKTEYEEAQDA HHHCCCCHHHHHHHH	53.19	19608861
570	Phosphorylation	YTKNKTEYEEAQDAI HHCCCCHHHHHHHHH	25.05	-
627	2-Hydroxyisobutyrylation	VRPAILEKGQGRIIL CCHHHHHCCCCEEEE	53.76	-
635	Acetylation	GQGRIILKASRHACV CCCEEEEEECCCEEE	33.63	19608861
635	Ubiquitination	GQGRIILKASRHACV CCCEEEEEECCCEEE	33.63	19608861
668	Phosphorylation	KQMFHIITGPNMGGK CCEEEEEECCCCCCC	46.08	24043423
717	Phosphorylation	ARVGAGDSQLKGVST HHCCCCCHHHCCHHH	36.17	28348404
720	Ubiquitination	GAGDSQLKGVSTFMA CCCCHHHCCHHHHHH	50.02	-
723	Phosphorylation	DSQLKGVSTFMAEML CHHHCCHHHHHHHHH	25.29	20068231
724	Phosphorylation	SQLKGVSTFMAEMLE HHHCCHHHHHHHHHH	18.28	20068231
732	Phosphorylation	FMAEMLETASILRSA HHHHHHHHHHHHHHC	23.03	20068231
734	Phosphorylation	AEMLETASILRSATK HHHHHHHHHHHHCCC	29.58	20068231
738	Phosphorylation	ETASILRSATKDSLI HHHHHHHHCCCCCEE	36.52	27251275
740	Phosphorylation	ASILRSATKDSLIII HHHHHHCCCCCEEEE	36.31	27251275
741	Ubiquitination	SILRSATKDSLIIID HHHHHCCCCCEEEEE	45.07	-
743	Phosphorylation	LRSATKDSLIIIDEL HHHCCCCCEEEEECC	24.03	21712546
845	Acetylation	KHVIECAKQKALELE HHHHHHHHHHCCHHH	65.08	26051181
845	Ubiquitination	KHVIECAKQKALELE HHHHHHHHHHCCHHH	65.08	-
856	Phosphorylation	LELEEFQYIGESQGY CHHHHHHHCCCCCCC	19.06	27732954
860	Phosphorylation	EFQYIGESQGYDIME HHHHCCCCCCCCCCC	24.56	17525332
863	Phosphorylation	YIGESQGYDIMEPAA HCCCCCCCCCCCHHH	8.48	27732954
871	Ubiquitination	DIMEPAAKKCYLERE CCCCHHHHHHHHHHH	45.54	21906983
872	Ubiquitination	IMEPAAKKCYLEREQ CCCHHHHHHHHHHHH	24.32	-
882	Ubiquitination	LEREQGEKIIQEFLS HHHHHHHHHHHHHHH	52.51	21890473
882	Ubiquitination	LEREQGEKIIQEFLS HHHHHHHHHHHHHHH	52.51	21890473
889	Phosphorylation	KIIQEFLSKVKQMPF HHHHHHHHHHCCCCC	40.50	26074081
890	Acetylation	IIQEFLSKVKQMPFT HHHHHHHHHCCCCCC	56.45	26051181
892	Ubiquitination	QEFLSKVKQMPFTEM HHHHHHHCCCCCCCC	44.61	-
897	Phosphorylation	KVKQMPFTEMSEENI HHCCCCCCCCCCCCE	25.55	26074081
900	Phosphorylation	QMPFTEMSEENITIK CCCCCCCCCCCEEEE	35.21	22817900
907	Ubiquitination	SEENITIKLKQLKAE CCCCEEEEHHHHHHH	40.77	-
909	Ubiquitination	ENITIKLKQLKAEVI CCEEEEHHHHHHHHH	48.89	-
912	Ubiquitination	TIKLKQLKAEVIAKN EEEHHHHHHHHHHHC	39.75	-
918	Ubiquitination	LKAEVIAKNNSFVNE HHHHHHHHCCHHHHH	45.60	-
921	Phosphorylation	EVIAKNNSFVNEIIS HHHHHCCHHHHHHHH	39.71	9559627

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
238	Y	Phosphorylation	Kinase	NPM-ALK	AAA58698	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
Oops, there are no descriptions of PTM sites of MSH2_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of MSH2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
BLM_HUMAN	BLM	physical	10783165
CHK1_HUMAN	CHEK1	physical	15647386
CHK2_HUMAN	CHEK2	physical	15647386
ATM_HUMAN	ATM	physical	10783165
MLH1_HUMAN	MLH1	physical	10783165
MSH6_HUMAN	MSH6	physical	10783165
RFC1_HUMAN	RFC1	physical	10783165
MSH3_HUMAN	MSH3	physical	14657349
MSH6_HUMAN	MSH6	physical	14657349
ATR_HUMAN	ATR	physical	14657349
ATRIP_HUMAN	ATRIP	physical	14657349
MSH3_HUMAN	MSH3	physical	9774676
MSH6_HUMAN	MSH6	physical	9774676
MSH3_HUMAN	MSH3	physical	10029069
MSH6_HUMAN	MSH6	physical	10029069
MSH2_HUMAN	MSH2	physical	8942985
MSH3_HUMAN	MSH3	physical	8942985
MSH6_HUMAN	MSH6	physical	8942985
EXO1_HUMAN	EXO1	physical	10856833
EXO1_HUMAN	EXO1	physical	9788596
EXO1_HUMAN	EXO1	physical	19015241
SLX4_HUMAN	SLX4	physical	19596235
KPCZ_HUMAN	PRKCZ	physical	15808853
XPA_HUMAN	XPA	physical	19468048
RFA4_HUMAN	RPA4	physical	19468048
P53_HUMAN	TP53	physical	12101417
ESR1_HUMAN	ESR1	physical	15886699
ESR2_HUMAN	ESR2	physical	15886699
ATR_HUMAN	ATR	physical	21285353
EXO1_HUMAN	EXO1	physical	22222486
MSH6_HUMAN	MSH6	physical	10748159
MSH3_HUMAN	MSH3	physical	8805365
MLH1_HUMAN	MLH1	physical	12799449
PMS2_HUMAN	PMS2	physical	12799449
MSH6_HUMAN	MSH6	physical	22939629
MSH3_HUMAN	MSH3	physical	22939629
SRSF5_HUMAN	SRSF5	physical	22939629
SNUT1_HUMAN	SART1	physical	22939629
SRS11_HUMAN	SRSF11	physical	22939629
SRSF7_HUMAN	SRSF7	physical	22939629
RED_HUMAN	IK	physical	22939629
RBM25_HUMAN	RBM25	physical	22939629
SMCA5_HUMAN	SMARCA5	physical	22939629
SRS10_HUMAN	SRSF10	physical	22939629
RS24_HUMAN	RPS24	physical	22939629
TOP2B_HUMAN	TOP2B	physical	22939629
SEPT9_HUMAN	SEPT9	physical	22939629
RAD21_HUMAN	RAD21	physical	22939629
SP16H_HUMAN	SUPT16H	physical	22939629
MSH6_HUMAN	MSH6	physical	9428522
XPF_HUMAN	ERCC4	physical	14706347
ERCC1_HUMAN	ERCC1	physical	14706347
MSH6_HUMAN	MSH6	physical	19377479
MSH3_HUMAN	MSH3	physical	19377479
PCNA_HUMAN	PCNA	physical	15225546
VATB2_HUMAN	ATP6V1B2	physical	22863883
CUL2_HUMAN	CUL2	physical	22863883
PLAK_HUMAN	JUP	physical	22863883
DPYL3_HUMAN	DPYSL3	physical	22863883
NRDC_HUMAN	NRD1	physical	22863883
PDE3A_HUMAN	PDE3A	physical	22863883
SC23A_HUMAN	SEC23A	physical	22863883
F10A1_HUMAN	ST13	physical	22863883
STAT3_HUMAN	STAT3	physical	22863883
SPT5H_HUMAN	SUPT5H	physical	22863883
XRCC6_HUMAN	XRCC6	physical	22863883
REV1_HUMAN	REV1	physical	24038355
ANXA6_HUMAN	ANXA6	physical	26344197
DNJC9_HUMAN	DNAJC9	physical	26344197
EIF3B_HUMAN	EIF3B	physical	26344197
FEN1_HUMAN	FEN1	physical	26344197
MSH6_HUMAN	MSH6	physical	26344197
NMD3_HUMAN	NMD3	physical	26344197
RFA1_HUMAN	RPA1	physical	26344197
SNX27_HUMAN	SNX27	physical	26344197
TIPRL_HUMAN	TIPRL	physical	26344197
TPP2_HUMAN	TPP2	physical	26344197
TCTP_HUMAN	TPT1	physical	26344197
MSH6_HUMAN	MSH6	physical	25241761
E2F3_HUMAN	E2F3	physical	25241761
MLH1_HUMAN	MLH1	physical	25241761
UBP10_HUMAN	USP10	physical	26975374
RAF1_HUMAN	RAF1	physical	27173435
FTM_HUMAN	RPGRIP1L	physical	27173435
HDAC6_HUMAN	HDAC6	physical	24882211
MCM9_HUMAN	MCM9	physical	26300262
MCM8_HUMAN	MCM8	physical	26300262

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
120435	Hereditary non-polyposis colorectal cancer 1 (HNPCC1)
158320	Muir-Torre syndrome (MRTES)
608089	Endometrial cancer (ENDMC)
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of MSH2_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Lysine acetylation targets protein complexes and co-regulates majorcellular functions."; Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.,Olsen J.V., Mann M.; Science 325:834-840(2009). Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-555 AND LYS-635, AND MASSSPECTROMETRY.	19608861 [Abstract]
Phosphorylation
Reference	PubMed
"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-860, AND MASSSPECTROMETRY.	17525332 [Abstract]