CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008848
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA mismatch repair protein Msh6 
Protein Synonyms/Alias
 G/T mismatch-binding protein; GTBP; GTMBP; MutS-alpha 160 kDa subunit; p160 
Gene Name
 Msh6 
Gene Synonyms/Alias
 Gtmbp 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
503RKMAHVSKFDRVVRRacetylation[1]
882VAGGFTSKTLKQVVTubiquitination[2]
1231AIANAVVKELAETIKacetylation[3]
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 analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [3] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441] 
Functional Description
 Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, 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 (By similarity). 
Sequence Annotation
 DOMAIN 92 154 PWWP.
 NP_BIND 1132 1139 ATP (Potential).
 MOD_RES 14 14 Phosphoserine (By similarity).
 MOD_RES 38 38 Phosphoserine (By similarity).
 MOD_RES 40 40 Phosphoserine (By similarity).
 MOD_RES 67 67 N6-acetyllysine (By similarity).
 MOD_RES 91 91 Phosphoserine (By similarity).
 MOD_RES 137 137 Phosphoserine (By similarity).
 MOD_RES 200 200 Phosphoserine (By similarity).
 MOD_RES 219 219 Phosphoserine (By similarity).
 MOD_RES 227 227 Phosphoserine (By similarity).
 MOD_RES 252 252 Phosphoserine (By similarity).
 MOD_RES 254 254 Phosphoserine (By similarity).
 MOD_RES 256 256 Phosphoserine (By similarity).
 MOD_RES 261 261 Phosphoserine.
 MOD_RES 269 269 Phosphothreonine (By similarity).
 MOD_RES 274 274 Phosphoserine (By similarity).
 MOD_RES 275 275 Phosphoserine (By similarity).
 MOD_RES 279 279 Phosphoserine (By similarity).
 MOD_RES 280 280 Phosphoserine (By similarity).
 MOD_RES 503 503 N6-acetyllysine (By similarity).
 MOD_RES 827 827 Phosphoserine (By similarity).  
Keyword
 Acetylation; ATP-binding; Complete proteome; DNA damage; DNA repair; DNA-binding; Nucleotide-binding; Phosphoprotein; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1358 AA 
Protein Sequence
MSRQSTLYSF FPKSPALGDT KKAAAEASRQ GAAASGASAS RGGDAAWSEA EPGSRSAAVS 60
ASSPEAKDLN GGLRRASSSA QAVPPSSCDF SPGDLVWAKM EGYPWWPCLV YNHPFDGTFI 120
RKKGKSVRVH VQFFDDSPTR GWVSKRMLKP YTGSKSKEAQ KGGHFYSSKS EILRAMQRAD 180
EALSKDTAER LQLAVCDEPS EPEEEEETEV HEAYLSDKSE EDNYNESEEE AQPSVQGPRR 240
SSRQVKKRRV ISDSESDIGG SDVEFKPDTK QEGSSDDASS GVGDSDSEDL GTFGKGAPKR 300
KRAMVAQGGL RRKSLKKETG SAKRATPILS ETKSTLSAFS APQNSESQTH VSGGGNDSSG 360
PTVWYHETLE WLKPEKRRDE HRRRPDHPEF NPTTLYVPEE FLNSCTPGMR KWWQLKSQNF 420
DLVIFYKVGK FYELYHMDAV IGVSELGLIF MKGNWAHSGF PEIAFGRFSD SLVQKGYKVA 480
RVEQTETPEM MEARCRKMAH VSKFDRVVRR EICRIITKGT QTYSVLDGDP SENYSRYLLS 540
LKEKEEETSG HTRVYGVCFV DTSLGKFFIG QFSDDRHCSR FRTLVAHYPP VQILFEKGNL 600
STETKTVLKG SLSSCLQEGL IPGSQFWDAT KTLRTLLEGG YFTGNGDSST VLPLVLKGMT 660
SESDSVGLTP GEESELALSA LGGIVFYLKK CLIDQELLSM ANFEEYFPLD SDTVSTVKPG 720
AVFTKASQRM VLDAVTLNNL EIFLNGTNGS TEGTLLERLD TCHTPFGKRL LKQWLCAPLC 780
SPSAISDRLD AVEDLMAVPD KVTEVADLLK KLPDLERLLS KIHNVGSPLK SQNHPDSRAI 840
MYEETTYSKK KIIDFLSALE GFKVMCKVSG LLEEVAGGFT SKTLKQVVTL QSKSPKGRFP 900
DLTAELQRWD TAFDHEKARK TGLITPKAGF DSDYDQALAD IRENEQSLLE YLDKQRSRLG 960
CKSIVYWGIG RNRYQLEIPE NFATRNLPEE YELKSTKKGC KRYWTKTIEK KLANLINAEE 1020
RRDTSLKDCM RRLFCNFDKN HKDWQSAVEC IAVLDVLLCL ANYSQGGDGP MCRPEIVLPG 1080
EDTHPFLEFK GSRHPCITKT FFGDDFIPND ILIGCEEEAE EHGKAYCVLV TGPNMGGKST 1140
LIRQAGLLAV MAQLGCYVPA EKCRLTPVDR VFTRLGASDR IMSGESTFFV ELSETASILR 1200
HATAHSLVLV DELGRGTATF DGTAIANAVV KELAETIKCR TLFSTHYHSL VEDYSKSVCV 1260
RLGHMACMVE NECEDPSQET ITFLYKFIKG ACPKSYGFNA ARLANLPEEV IQKGHRKARE 1320
FERMNQSLQL FREVCLATEK PTINGEAIHR LLALINGL 1358 
Gene Ontology
 GO:0032301; C:MutSalpha complex; IDA:MGI.
 GO:0000790; C:nuclear chromatin; IDA:MGI.
 GO:0043531; F:ADP binding; IEA:Compara.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003682; F:chromatin binding; IDA:MGI.
 GO:0003684; F:damaged DNA binding; IMP:MGI.
 GO:0008094; F:DNA-dependent ATPase activity; IBA:RefGenome.
 GO:0000400; F:four-way junction DNA binding; IBA:RefGenome.
 GO:0032137; F:guanine/thymine mispair binding; IDA:MGI.
 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:0008340; P:determination of adult lifespan; IMP:MGI.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
 GO:0045190; P:isotype switching; IMP:MGI.
 GO:0043570; P:maintenance of DNA repeat elements; IBA:RefGenome.
 GO:0000710; P:meiotic mismatch repair; IBA:RefGenome.
 GO:0045910; P:negative regulation of DNA recombination; IMP:MGI.
 GO:0051096; P:positive regulation of helicase activity; IEA:Compara.
 GO:0007131; P:reciprocal meiotic recombination; IBA:RefGenome.
 GO:0009411; P:response to UV; IMP:MGI.
 GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:MGI. 
Interpro
 IPR017261; DNA_mismatch_repair_Msh6.
 IPR015536; DNA_mismatch_repair_MSH6_C.
 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.
 IPR016151; DNA_mismatch_repair_MutS_N.
 IPR007860; DNA_mmatch_repair_MutS_con_dom.
 IPR027417; P-loop_NTPase.
 IPR000313; PWWP. 
Pfam
 PF01624; MutS_I
 PF05188; MutS_II
 PF05192; MutS_III
 PF05190; MutS_IV
 PF00488; MutS_V
 PF00855; PWWP 
SMART
 SM00534; MUTSac
 SM00533; MUTSd
 SM00293; PWWP 
PROSITE
 PS00486; DNA_MISMATCH_REPAIR_2
 PS50812; PWWP 
PRINTS