CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007641
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA mismatch repair protein Msh2 
Protein Synonyms/Alias
 MutS protein homolog 2 
Gene Name
 Msh2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
567NEEYTKNKGEYEEAQacetylation[1]
907SEESISAKLKQLKAEacetylation[2]
Reference
 [1] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [2] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 
Functional 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 (By similarity). 
Sequence Annotation
 NP_BIND 669 676 ATP (Potential).
 REGION 601 671 Interaction with EXO1 (By similarity).  
Keyword
 ATP-binding; Cell cycle; Complete proteome; DNA damage; DNA repair; DNA-binding; Nucleotide-binding; Nucleus; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 935 AA 
Protein Sequence
MAVQPKETLQ LEGAAEAGFV RFFEGMPEKP STTVRLFDRG DFYTAHGEDA LLAAREVFKT 60
QGVIKYMGPA GSKTLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNKAGNK ASKENEWYLA 120
FKASPGNLSQ FEDILFGNND MSASVGVMGI KMAVVDGQRH VGVGYVDSTQ RKLGLCEFPE 180
NDQFSNLEAL LIQIGPKECV LPGGETTGDM GKLRQVIQRG GILITERKRA DFSTKDIYQD 240
LNRLLKGKKG EQINSAALPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LATFDFSQYM 300
KLDMAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTAQGQR LVNQWIKQPL MDRNRIEERL 360
NLVEAFVEDS ELRQSLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPSVIQA 420
LEKYEGRHQA LLLAVFVTPL IDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE 480
LREVMDGLEK KMQSTLINAA RGLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS 540
TVDIQKNGVK FTNSELSSLN EEYTKNKGEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA 600
HLDAIVSFAH VSNAAPVPYV RPVILEKGKG RIILKASRHA CVEVQDEVAF IPNDVHFEKD 660
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK 720
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISDYI ATKIGAFCMF 780
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPRHV 840
IACAKQKALE LEEFQNIGTS LGCDEAEPAA KRRCLEREQG EKIILEFLSK VKQVPFTAMS 900
EESISAKLKQ LKAEVVAKNN SFVNEIISRI KAPAP 935 
Gene Ontology
 GO:0032301; C:MutSalpha complex; IDA:MGI.
 GO:0032302; C:MutSbeta complex; IBA:RefGenome.
 GO:0000228; C:nuclear chromosome; IBA:RefGenome.
 GO:0043531; F:ADP binding; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0019237; F:centromeric DNA binding; IDA:MGI.
 GO:0003684; F:damaged DNA binding; IMP:MGI.
 GO:0032181; F:dinucleotide repeat insertion binding; IEA:Compara.
 GO:0008094; F:DNA-dependent ATPase activity; IBA:RefGenome.
 GO:0000406; F:double-strand/single-strand DNA junction binding; IBA:RefGenome.
 GO:0000400; F:four-way junction DNA binding; IBA:RefGenome.
 GO:0032137; F:guanine/thymine mispair binding; ISO:MGI.
 GO:0000404; F:loop DNA binding; IBA:RefGenome.
 GO:0000287; F:magnesium ion binding; IEA:Compara.
 GO:0032357; F:oxidized purine DNA binding; IEA:Compara.
 GO:0032138; F:single base insertion or deletion binding; IBA:RefGenome.
 GO:0032142; F:single guanine insertion binding; IEA:Compara.
 GO:0032143; F:single thymine insertion binding; IEA:Compara.
 GO:0003697; F:single-stranded DNA binding; IEA:Compara.
 GO:0000403; F:Y-form DNA binding; IBA:RefGenome.
 GO:0030183; P:B cell differentiation; IMP:MGI.
 GO:0007050; P:cell cycle arrest; IMP:MGI.
 GO:0008340; P:determination of adult lifespan; IMP:MGI.
 GO:0006302; P:double-strand break repair; IMP:MGI.
 GO:0007281; P:germ cell development; IMP:MGI.
 GO:0001701; P:in utero embryonic development; IGI:MGI.
 GO:0031573; P:intra-S DNA damage checkpoint; IGI:MGI.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IGI:MGI.
 GO:0045190; P:isotype switching; IMP:MGI.
 GO:0043570; P:maintenance of DNA repeat elements; IBA:RefGenome.
 GO:0008584; P:male gonad development; IMP:MGI.
 GO:0006311; P:meiotic gene conversion; IBA:RefGenome.
 GO:0000710; P:meiotic mismatch repair; IBA:RefGenome.
 GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
 GO:0045128; P:negative regulation of reciprocal meiotic recombination; IBA:RefGenome.
 GO:0006119; P:oxidative phosphorylation; IMP:MGI.
 GO:0051096; P:positive regulation of helicase activity; IEA:Compara.
 GO:0006301; P:postreplication repair; ISS:UniProtKB.
 GO:0010224; P:response to UV-B; IMP:MGI.
 GO:0010165; P:response to X-ray; IMP:MGI.
 GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:MGI. 
Interpro
 IPR011184; DNA_mismatch_repair_MSH2.
 IPR007695; DNA_mismatch_repair_MutS-lik_N.
 IPR000432; DNA_mismatch_repair_MutS_C.
 IPR007861; DNA_mismatch_repair_MutS_clamp.
 IPR007696; DNA_mismatch_repair_MutS_core.
 IPR007860; DNA_mmatch_repair_MutS_con_dom.
 IPR027417; P-loop_NTPase. 
Pfam
 PF01624; MutS_I
 PF05188; MutS_II
 PF05192; MutS_III
 PF05190; MutS_IV
 PF00488; MutS_V 
SMART
 SM00534; MUTSac
 SM00533; MUTSd 
PROSITE
 PS00486; DNA_MISMATCH_REPAIR_2 
PRINTS