Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures
Basic Information
Protein Name :  DNA mismatch repair protein Msh2  

UniProtKB / Swiss-Prot ID :  MSH2_HUMAN

Gene Name (Synonyms) : 
MSH2  

Species :  Homo sapiens (Human). 

Subcellular Localization :  Nucleus (Potential). 

Protein Function :  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 MAVQPKETLQLESAAEVGFVRFFQGMPEKPTTTVRLFDRGDFYTAHGEDALLAAREVFKTQGVIKYMGPA...
Predicted Secondary Structure CCCCCCCCCCCCHHHHCCHHHHHHHHHHCCCCEEEEEEECCHHHHHHHHHHHHHHHHHHHHHHHHHCCCC...
Protein Variant
LocationDescription
2A -> T (in HNPCC1). VAR_054511
8T -> M (could be associated withincreased colorectal cancer
13S -> I (in colorectal cancer). VAR_043736
17V -> F (in gastric cancer; uncertainpathogenicity; cryptic acceptor splice
33T -> P (in HNPCC1; shows slightly reducedmismatch binding or release efficiency).
40G -> S (in CRC). VAR_043739
43Y -> C (in dbSNP:rs17217723). VAR_019233
44T -> M (in HNPCC1; repair proficient). VAR_043740
45A -> V (in HNPCC1; repair proficient). VAR_043741
46H -> Q (in HNPCC1; dbSNP:rs33946261). VAR_004470
92Missing (in HNPCC1; uncertainpathogenicity; has no effect on ex vivo
93L -> F (in HNPCC1). VAR_043743
96R -> H. VAR_004471
98Y -> C (in HNPCC1; uncertainpathogenicity).
102V -> I (in HNPCC1). VAR_043745
106R -> K (in dbSNP:rs41295286). VAR_038026
110K -> T (in HNPCC1; somatic mutation). VAR_043746
127N -> S (in HNPCC1; shows no defects;dbSNP:rs17217772).
139N -> S (in HNPCC1). VAR_004472
145I -> M (in HNPCC1). VAR_004473
161V -> D (in HNPCC1; affects proteinstability; associated with an absence of
162G -> A (in HNPCC1). VAR_054512
162G -> R (in HNPCC1; shows a decreasedexpression level of the MutS alpha
163V -> D (in HNPCC1). VAR_043748
163V -> G (in HNPCC1). VAR_022670
164G -> R (in HNPCC1; affects proteinstability; associated with an absence of
165Y -> D (associated with HNPCC1; unknownpathological significance; repair
167D -> H (in HNPCC1; does not show adecreased expression level of the MutS
169I -> V (in HNPCC1; unknown pathologicalsignificance).
173L -> P (in HNPCC1; affects proteinstability; associated with an absence of
175L -> P (in HNPCC1). VAR_043752
177E -> H (associated with HNPCC1; requires2 nucleotide substitutions; unknown
187L -> P (in HNPCC1; affects proteinstability; associated with an absence of
198E -> G (in HNPCC1). VAR_054513
199C -> R (in glioma; also associated withHNPCC1; has no effect on ex vivo splicing
203G -> R (in CRC; uncertain pathogenicity;somatic mutation).
216I -> V (in HNPCC1; uncertain pathologicalsignificance; shows slightly reduced
246K -> Q (in HNPCC1; uncertainpathogenicity).
265Missing (in HNPCC1). VAR_004475
272A -> V (associated with HNPCC1; unknownpathological significance; shows slightly
283D -> Y (in HNPCC1). VAR_043757
305A -> T (in HNPCC1; repair proficient). VAR_004476
322G -> D (common polymorphism; may beassociated with increased colorectal
323S -> C (in HNPCC1; unknown pathologicalsignificance).
323S -> Y (in HNPCC1; unknown pathologicalsignificance).
331N -> D (associated with HNPCC1; has noeffect on ex vivo splicing assay).
333C -> Y (in HNPCC1; affects proteinstability; associated with an absence of
335T -> I (in HNPCC1; unknown pathologicalsignificance).
336P -> S (in HNPCC1). VAR_043761
342V -> I (in colorectal cancer). VAR_043762
349P -> L (in HNPCC1). VAR_043763
359R -> S (in HNPCC1; shows a decreasedexpression level of the MutS alpha comp
385P -> L (associated with HNPCC1; unknownpathological significance; repair
390L -> F (in HNPCC1; unknown pathologicalsignificance; the equivalent substitution
393K -> M (in HNPCC1). VAR_043765
419Q -> K (in CRC; uncertain pathogenicity;the equivalent substitution in yeast
440Missing (in HNPCC1). VAR_043766
470V -> E (associated with HNPCC1; has noeffect on ex vivo splicing assay).
492M -> V (in HNPCC1). VAR_043767
506D -> Y (in CRC; sporadic; early onset;the equivalent substitution in yeast
519F -> L (associated with HNPCC1; unknownpathological significance; repair
524R -> P (in HNPCC1; defective in mismatchrepair activity).
552T -> P (in HNPCC1). VAR_043768
554S -> R (in HNPCC1; uncertain pathologicalsignificance).
562E -> V (in HNPCC1). VAR_004480
564T -> A (in HNPCC1; uncertainpathogenicity; dbSNP:rs55778204).
583N -> S (in HNPCC1). VAR_043770
596N -> S (in HNPCC1; uncertain pathologicalsignificance; dbSNP:rs41295288).
596Missing (in HNPCC1; has no effect on exvivo splicing assay; repair deficient).
600A -> V (in HNPCC1). VAR_043771
603D -> N (in HNPCC1; affects proteinstability; associated with an absence of
610H -> N (associated with HNPCC1; has noeffect on ex vivo splicing assay).
619Y -> C (in CRC). VAR_043773
622P -> L (in HNPCC1; the equivalentsubstitution in yeast causes loss of
629Q -> R (in HNPCC1; uncertainpathogenicity).
636A -> P (in HNPCC1; partial functionalloss; mainly causes defects in mismatch
638R -> G (associated with HNPCC1; has noeffect on ex vivo splicing assay).
639H -> R (in HNPCC1; shows reduced mismatchbinding; repair proficient).
639H -> Y (in HNPCC1; the equivalentsubstitution in yeast does not affect
641C -> G. VAR_004484
645Q -> E (associated with HNPCC1; has noeffect on ex vivo splicing assay).
647E -> K (in HNPCC1). VAR_043776
656Y -> H (in HNPCC1; somatic mutation). VAR_043777
660D -> G (in HNPCC1). VAR_022671
669G -> R (in HNPCC1). VAR_067761
670P -> L (in dbSNP:rs41294982). VAR_038027
671N -> Y (in HNPCC1; uncertainpathogenicity).
674G -> R (in HNPCC1; confers resistance toATP-dependent mismatch release; repair
674G -> S (in HNPCC1; somatic mutation). VAR_004485
675K -> A (associated with HNPCC1; requires2 nucleotide substitutions; unknown
679I -> T (in HNPCC1; somatic mutation). VAR_043779
688M -> I (in HNPCC1). VAR_012945
692G -> R (in HNPCC1). VAR_009250
696P -> L (associated with HNPCC1; has noeffect on ex vivo splicing assay).
697C -> F (in HNPCC1; the equivalentsubstitution in yeast causes loss of
697C -> R (in HNPCC1; has no effect on exvivo splicing assay).
714A -> V (in HNPCC1; uncertainpathogenicity).
723S -> F (in HNPCC1; has no effect on exvivo splicing assay; repair deficient).
729M -> V (in HNPCC1; somatic mutation). VAR_043782
732T -> I (in HNPCC1; somatic mutation). VAR_043783
745Missing (in HNPCC1; mainly causes defectsin mismatch binding or release
748D -> Y (associated with HNPCC1; has noeffect on ex vivo splicing assay).
749E -> K (in HNPCC1; mainly causes defectsin mismatch binding or release
759G -> E (associated with HNPCC1; unknownpathological significance; repair
770I -> V. VAR_004487
779M -> I (in dbSNP:rs41295292). VAR_038028
805L -> V (associated with HNPCC1; unknownpathological significance; repair
807T -> S (in dbSNP:rs41295294). VAR_038029
813M -> V (in HNPCC1). VAR_043786
824Q -> E (in gastric cancer; uncertainpathogenicity).
834A -> T (in HNPCC1; shows no functionaldefects in gel shift assay; is
835N -> H (in dbSNP:rs41295296). VAR_038030
839H -> Q (associated with HNPCC1; has noeffect on ex vivo splicing assay).
839H -> R (in HNPCC1). VAR_043788
843C -> G (associated with HNPCC1; unknownpathological significance; repair
845K -> E (in HNPCC1). VAR_013172
853E -> A (in HNPCC1; uncertainpathogenicity).
860S -> L (associated with HNPCC1; unknownpathological significance; repair
868P -> A (in gastric cancer; uncertainpathogenicity).
870A -> G (in gastric cancer; uncertainpathogenicity).
873C -> G (in gastric cancer; uncertainpathogenicity).
886E -> G (in HNPCC1; repair proficient). VAR_043793
905T -> R (in HNPCC1; uncertain pathologicalsignificance).
911L -> R (in dbSNP:rs41295182). VAR_038031
923V -> E (in HNPCC1; uncertain pathologicalsignificance).
931K -> T (in HNPCC1). VAR_043795
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Overview of Protein Modification Sites with Functional and Structural Information
Accessible Surface Area (ASA)
Pred. Secondary
Real Secondary
Disorder Prediction
Protein Domain
&
Experimental PTM Sites
Predicted PTM Sites
Protein Variant
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Experimental Post-Translational Modification Sites Download
Locations
Modification
Substrate Sites
&
Secondary Structure
Accessible Surface Area (%)
Resource
Reference
Structural Characterization
Orthologous
Protein Cluster
32PhosphothreonineEKPTTTVRL
HCCCCEEEE
31.64HPRD
Link
73Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)PAGAKNLQS
CCCCCCCCC
58.22Phosphositeplus
Link
206PhosphothreoninePGGETAGDM
CCCCCHHHH
38.93HPRD
Link
206PhosphothreoninePGGETAGDM
CCCCCHHHH
38.93Phosphositeplus
Link
249Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)LKGKKGEQM
HCCCCCCCC
76.09Phosphositeplus
Link
332Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)ALLNKCKTP
HHHHCCCCH
36.76Phosphositeplus
Link
555Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)FTNSKLTSL
EECHHHHHH
58.83Phosphositeplus
Link
555N6-acetyllysineFTNSKLTSL
EECHHHHHH
58.83HPRD
Link
555N6-acetyllysineFTNSKLTSL
EECHHHHHH
58.83Phosphositeplus
Link
555N6-acetyllysine.FTNSKLTSL
EECHHHHHH
58.83UniProtKB
Link
565Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EEYTKNKTE
HHHHHHHHH
56.39Phosphositeplus
Link
567Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)YTKNKTEYE
HHHHHHHHH
44.27Phosphositeplus
Link
635N6-acetyllysineRIILKASRH
EEEEEECCC
33.63HPRD
Link
635N6-acetyllysineRIILKASRH
EEEEEECCC
33.63Phosphositeplus
Link
635N6-acetyllysine.RIILKASRH
EEEEEECCC
33.63UniProtKB
Link
732PhosphothreonineEMLETASIL
HHHHHHHHH
23.03HPRD
Link
734PhosphoserineLETASILRS
HHHHHHHHH
29.58HPRD
Link
860PhosphoserineYIGESQGYD
CCCCCCCHH
24.56HPRD
Link-
860PhosphoserineYIGESQGYD
CCCCCCCHH
24.56PhosphoELM
Link-
860PhosphoserineYIGESQGYD
CCCCCCCHH
24.56Phosphositeplus
Link-
860Phosphoserine.YIGESQGYD
CCCCCCCHH
24.56UniProtKB
Link-
871Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EPAAKKCYL
HCCCCHHHC
45.54Phosphositeplus
Link-
882Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)EQGEKIIQE
CCCHHHHHH
52.51Phosphositeplus
Link-
897PhosphothreonineQMPFTEMSE
CCCCCCCCH
25.55HPRD
Link-
897PhosphothreonineQMPFTEMSE
CCCCCCCCH
25.55Phosphositeplus
Link-
900PhosphoserineFTEMSEENI
CCCCCHHHH
35.21HPRD
Link-
900PhosphoserineFTEMSEENI
CCCCCHHHH
35.21Phosphositeplus
Link-
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Protein-Protein Interactions
      Interacting Protein      
Interaction type
Source ID
      Resource      
      Pubmed ID      
Domain-Domain Interactions
MSH3_HUMANphysical interactionMINT-18554MINT9774676
BRCA1_HUMANphysical interactionMINT-17604MINT10783165
MSH6_HUMANphysical interactionMINT-18943MINT9774676
BARD1_HUMANphysical interactionMINT-15047MINT11498787
MSH2_HUMANphysical interactionEBI-1164319
intact9774676
MSH3_HUMANphysical interaction
physical interaction
physical interaction
physical interaction
EBI-1164225
EBI-1164243
EBI-1
intact9774676
9774676
9774676
9774676
CBP_HUMANin vitro
in vivo
HPRD:00389HPRD16051665
MLH1_HUMANENSP00000233146STRING
MSH6_HUMANENSP00000233146STRING
MSH3_HUMANENSP00000233146STRING
RAD50_HUMANENSP00000233146STRING
PMS2_HUMANENSP00000233146STRING
PMS2_HUMANENSP00000233146STRING
PMS2_HUMANENSP00000233146STRING
PMS2L_HUMANENSP00000233146STRING
RAD51_HUMANENSP00000233146STRING
P53_HUMANENSP00000233146STRING
ATM_HUMANENSP00000233146STRING
EXO1_HUMANENSP00000233146STRING
MRE11_HUMANENSP00000233146STRING
CHK2_HUMANENSP00000233146STRING
PMS1_HUMANENSP00000233146STRING
BLM_HUMANENSP00000233146STRING
MLH3_HUMANENSP00000233146STRING
MAX_HUMANENSP00000233146STRING
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Disease Reference
Kegg disease
OMIM disease
120435Hereditary non-polyposis colorectal cancer 1 (HNPCC1)
158320Muir-Torre syndrome (MRTES)
608089Endometrial cancer (ENDMC)
Drug Reference
There are no disease associations of PTM sites.
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Related Literatures of Post-Translational Modification
Acetylation
ReferencePubMed
"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.
Phosphorylation
ReferencePubMed
"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.
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Basic Information | Overview of PTM Sites | Experimental PTM Sites | Protein-Protein Interactions | Drug and Disease Associations | Related Literatures