CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-005463
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
 YOL090W; O0935 
Created Date
 July 27, 2013 
Organism
 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) 
NCBI Taxa ID
 559292 
Lysine Modification
Position
Peptide
Type
References
950AIANEPEKENDNYLKubiquitination[1]
Reference
 [1] Global analysis of phosphorylation and ubiquitylation cross-talk in protein degradation.
 Swaney DL, Beltrao P, Starita L, Guo A, Rush J, Fields S, Krogan NJ, Villén J.
 Nat Methods. 2013 Jul;10(7):676-82. [PMID: 23749301] 
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 bind to DNA mismatches thereby initiating DNA repair. MSH2 seems to act as a scaffold for the other MutS homologs that provide substrate-binding and substrate-specificity. When bound, heterodimers bend the DNA helix and shield approximately 20 base pairs. MutS alpha acts mainly to repair base-base and single insertion-deletion mismatches that occur during replication, but can also repair longer insertion-deletion loops (IDLs), although with decreasing efficiency as the size of the extrahelical loop increases. MutS beta acts mainly to repair IDLs from 2 to 13 nucleotides in size, but can also repair base-base and single insertion-deletion mismatches. After mismatch binding, MutS alpha or beta form a ternary complex with a MutL 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. Both subunits bind ATP, but with differing affinities, and their ATPase kinetics are also very different. MSH6 binds and hydrolyzes ATP rapidly, whereas MSH2 catalyzes ATP at a substantially slower rate. Binding to a mismatched base pair suppresses MSH6-catalyzed ATP hydrolysis, but not the activity of MSH2. ATP binding to both subunits is necessary to trigger a change in MutS alpha interaction with mismatched DNA, converting MutS alpha into a sliding clamp capable of hydrolysis-independent movement along DNA, and also facilitates formation of ternary complexes containing MutS and MutL proteins and the mismatch. MutS beta also has a role in regulation of heteroduplex formation during mitotic and meiotic recombination. MutS beta binds to DNA flap structures predicted to form during recombination, and is required for 3' non-homologous tail removal (NHTR). MutS beta- binding alters the DNA conformation of its substrate at the ds/ssDNA junction and may facilitate its recognition and/or cleavage by the downstream nucleotide excision repair (NER) RAD1- RAD10 endonuclease. 
Sequence Annotation
 NP_BIND 688 695 ATP (Potential).
 REGION 851 964 Interaction with MSH6.  
Keyword
 ATP-binding; Complete proteome; DNA damage; DNA repair; DNA-binding; Nucleotide-binding; Nucleus; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 964 AA 
Protein Sequence
MSSTRPELKF SDVSEERNFY KKYTGLPKKP LKTIRLVDKG DYYTVIGSDA IFVADSVYHT 60
QSVLKNCQLD PVTAKNFHEP TKYVTVSLQV LATLLKLCLL DLGYKVEIYD KGWKLIKSAS 120
PGNIEQVNEL MNMNIDSSII IASLKVQWNS QDGNCIIGVA FIDTTAYKVG MLDIVDNEVY 180
SNLESFLIQL GVKECLVQDL TSNSNSNAEM QKVINVIDRC GCVVTLLKNS EFSEKDVELD 240
LTKLLGDDLA LSLPQKYSKL SMGACNALIG YLQLLSEQDQ VGKYELVEHK LKEFMKLDAS 300
AIKALNLFPQ GPQNPFGSNN LAVSGFTSAG NSGKVTSLFQ LLNHCKTNAG VRLLNEWLKQ 360
PLTNIDEINK RHDLVDYLID QIELRQMLTS EYLPMIPDIR RLTKKLNKRG NLEDVLKIYQ 420
FSKRIPEIVQ VFTSFLEDDS PTEPVNELVR SVWLAPLSHH VEPLSKFEEM VETTVDLDAY 480
EENNEFMIKV EFNEELGKIR SKLDTLRDEI HSIHLDSAED LGFDPDKKLK LENHHLHGWC 540
MRLTRNDAKE LRKHKKYIEL STVKAGIFFS TKQLKSIANE TNILQKEYDK QQSALVREII 600
NITLTYTPVF EKLSLVLAHL DVIASFAHTS SYAPIPYIRP KLHPMDSERR THLISSRHPV 660
LEMQDDISFI SNDVTLESGK GDFLIITGPN MGGKSTYIRQ VGVISLMAQI GCFVPCEEAE 720
IAIVDAILCR VGAGDSQLKG VSTFMVEILE TASILKNASK NSLIIVDELG RGTSTYDGFG 780
LAWAIAEHIA SKIGCFALFA THFHELTELS EKLPNVKNMH VVAHIEKNLK EQKHDDEDIT 840
LLYKVEPGIS DQSFGIHVAE VVQFPEKIVK MAKRKANELD DLKTNNEDLK KAKLSLQEVN 900
EGNIRLKALL KEWIRKVKEE GLHDPSKITE EASQHKIQEL LRAIANEPEK ENDNYLKYIK 960
ALLL 964 
Gene Ontology
 GO:0032301; C:MutSalpha complex; IPI:SGD.
 GO:0032302; C:MutSbeta complex; IPI:SGD.
 GO:0000228; C:nuclear chromosome; IDA:SGD.
 GO:0005524; F:ATP binding; IDA:SGD.
 GO:0003684; F:damaged DNA binding; IBA:RefGenome.
 GO:0008094; F:DNA-dependent ATPase activity; IBA:RefGenome.
 GO:0000406; F:double-strand/single-strand DNA junction binding; IDA:SGD.
 GO:0000400; F:four-way junction DNA binding; IDA:SGD.
 GO:0030983; F:mismatched DNA binding; IEA:InterPro.
 GO:0030466; P:chromatin silencing at silent mating-type cassette; IGI:SGD.
 GO:0036297; P:interstrand cross-link repair; IGI:SGD.
 GO:0043570; P:maintenance of DNA repeat elements; IBA:RefGenome.
 GO:0006311; P:meiotic gene conversion; IMP:SGD.
 GO:0000710; P:meiotic mismatch repair; IMP:SGD.
 GO:0045128; P:negative regulation of reciprocal meiotic recombination; IBA:RefGenome.
 GO:0006301; P:postreplication repair; IBA:RefGenome.
 GO:0000735; P:removal of nonhomologous ends; IMP:SGD. 
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