CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007640
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA mismatch repair protein Msh2 
Protein Synonyms/Alias
 hMSH2; MutS protein homolog 2 
Gene Name
 MSH2 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
73YMGPAGAKNLQSVVLubiquitination[1, 2, 3]
249NRLLKGKKGEQMNSAubiquitination[4, 5]
332SLAALLNKCKTPQGQubiquitination[4, 6]
537EKVLRNNKNFSTVDIubiquitination[2]
555GVKFTNSKLTSLNEEacetylation[7]
555GVKFTNSKLTSLNEEubiquitination[4]
565SLNEEYTKNKTEYEEubiquitination[4]
567NEEYTKNKTEYEEAQubiquitination[4]
635GQGRIILKASRHACVacetylation[7]
741SILRSATKDSLIIIDubiquitination[4]
871DIMEPAAKKCYLEREubiquitination[4]
882LEREQGEKIIQEFLSubiquitination[1, 2, 3]
907SEENITIKLKQLKAEubiquitination[5]
909ENITIKLKQLKAEVIubiquitination[5]
Reference
 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [3] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [4] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [5] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [6] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [7] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861] 
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. 
Sequence Annotation
 NP_BIND 669 676 ATP (Potential).
 REGION 601 671 Interaction with EXO1.
 MOD_RES 555 555 N6-acetyllysine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Disease mutation; DNA damage; DNA repair; DNA-binding; Hereditary nonpolyposis colorectal cancer; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Tumor suppressor. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 934 AA 
Protein Sequence
MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA LLAAREVFKT 60
QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV EVYKNRAGNK ASKENDWYLA 120
YKASPGNLSQ FEDILFGNND MSASIGVVGV KMSAVDGQRQ VGVGYVDSIQ RKLGLCEFPD 180
NDQFSNLEAL LIQIGPKECV LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD 240
LNRLLKGKKG EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM 300
KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL MDKNRIEERL 360
NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN LQDCYRLYQG INQLPNVIQA 420
LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF QEMIETTLDM DQVENHEFLV KPSFDPNLSE 480
LREIMNDLEK KMQSTLISAA RDLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS 540
TVDIQKNGVK FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA 600
QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF IPNDVYFEKD 660
KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA EVSIVDCILA RVGAGDSQLK 720
GVSTFMAEML ETASILRSAT KDSLIIIDEL GRGTSTYDGF GLAWAISEYI ATKIGAFCMF 780
ATHFHELTAL ANQIPTVNNL HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV 840
IECAKQKALE LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS 900
EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT 934 
Gene Ontology
 GO:0032301; C:MutSalpha complex; IDA:HGNC.
 GO:0032302; C:MutSbeta complex; IDA:HGNC.
 GO:0000228; C:nuclear chromosome; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0019237; F:centromeric DNA binding; IEA:Compara.
 GO:0003684; F:damaged DNA 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:0032137; F:guanine/thymine mispair binding; IMP:MGI.
 GO:0000404; F:loop DNA binding; IBA:RefGenome.
 GO:0042803; F:protein homodimerization activity; IDA:HGNC.
 GO:0000403; F:Y-form DNA binding; IBA:RefGenome.
 GO:0030183; P:B cell differentiation; ISS:BHF-UCL.
 GO:0007050; P:cell cycle arrest; IEA:Compara.
 GO:0008340; P:determination of adult lifespan; IEA:Compara.
 GO:0006302; P:double-strand break repair; IBA:RefGenome.
 GO:0007281; P:germ cell development; IEA:Compara.
 GO:0001701; P:in utero embryonic development; IEA:Compara.
 GO:0031573; P:intra-S DNA damage checkpoint; IBA:RefGenome.
 GO:0042771; P:intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator; IBA:RefGenome.
 GO:0045190; P:isotype switching; ISS:BHF-UCL.
 GO:0043570; P:maintenance of DNA repeat elements; IMP:HGNC.
 GO:0008584; P:male gonad development; ISS:BHF-UCL.
 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; ISS:BHF-UCL.
 GO:0045128; P:negative regulation of reciprocal meiotic recombination; IBA:RefGenome.
 GO:0006119; P:oxidative phosphorylation; IEA:Compara.
 GO:0051096; P:positive regulation of helicase activity; IDA:BHF-UCL.
 GO:0006301; P:postreplication repair; IDA:UniProtKB.
 GO:0010224; P:response to UV-B; ISS:BHF-UCL.
 GO:0010165; P:response to X-ray; ISS:BHF-UCL.
 GO:0016446; P:somatic hypermutation of immunoglobulin genes; IBA:RefGenome. 
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