CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-008527
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA mismatch repair protein Msh6 
Protein Synonyms/Alias
 hMSH6; G/T mismatch-binding protein; GTBP; GTMBP; MutS-alpha 160 kDa subunit; p160 
Gene Name
 MSH6 
Gene Synonyms/Alias
 GTBP 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
476YSDSLVQKGYKVARVubiquitination[1]
519EICRIITKGTQTYSVubiquitination[1, 2]
537DPSENYSKYLLSLKEubiquitination[1]
728RSGAIFTKAYQRMVLubiquitination[1]
Reference
 [1] 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]
 [2] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 
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. 
Sequence Annotation
 DOMAIN 92 154 PWWP.
 NP_BIND 1134 1141 ATP (Potential).
 MOD_RES 14 14 Phosphoserine.
 MOD_RES 41 41 Phosphoserine.
 MOD_RES 43 43 Phosphoserine.
 MOD_RES 70 70 N6-acetyllysine.
 MOD_RES 79 79 Phosphoserine.
 MOD_RES 91 91 Phosphoserine.
 MOD_RES 137 137 Phosphoserine.
 MOD_RES 200 200 Phosphoserine.
 MOD_RES 219 219 Phosphoserine.
 MOD_RES 227 227 Phosphoserine.
 MOD_RES 252 252 Phosphoserine.
 MOD_RES 254 254 Phosphoserine.
 MOD_RES 256 256 Phosphoserine.
 MOD_RES 261 261 Phosphoserine.
 MOD_RES 269 269 Phosphothreonine.
 MOD_RES 274 274 Phosphoserine.
 MOD_RES 275 275 Phosphoserine.
 MOD_RES 279 279 Phosphoserine.
 MOD_RES 280 280 Phosphoserine.
 MOD_RES 309 309 Phosphoserine.
 MOD_RES 504 504 N6-acetyllysine.
 MOD_RES 830 830 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Alternative splicing; ATP-binding; Complete proteome; Direct protein sequencing; Disease mutation; DNA damage; DNA repair; DNA-binding; Hereditary nonpolyposis colorectal cancer; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 1360 AA 
Protein Sequence
MSRQSTLYSF FPKSPALSDA NKASARASRE GGRAAAAPGA SPSPGGDAAW SEAGPGPRPL 60
ARSASPPKAK NLNGGLRRSV APAAPTSCDF SPGDLVWAKM EGYPWWPCLV YNHPFDGTFI 120
REKGKSVRVH VQFFDDSPTR GWVSKRLLKP YTGSKSKEAQ KGGHFYSAKP EILRAMQRAD 180
EALNKDKIKR LELAVCDEPS EPEEEEEMEV GTTYVTDKSE EDNEIESEEE VQPKTQGSRR 240
SSRQIKKRRV ISDSESDIGG SDVEFKPDTK EEGSSDEISS GVGDSESEGL NSPVKVARKR 300
KRMVTGNGSL KRKSSRKETP SATKQATSIS SETKNTLRAF SAPQNSESQA HVSGGGDDSS 360
RPTVWYHETL EWLKEEKRRD EHRRRPDHPD FDASTLYVPE DFLNSCTPGM RKWWQIKSQN 420
FDLVICYKVG KFYELYHMDA LIGVSELGLV FMKGNWAHSG FPEIAFGRYS DSLVQKGYKV 480
ARVEQTETPE MMEARCRKMA HISKYDRVVR REICRIITKG TQTYSVLEGD PSENYSKYLL 540
SLKEKEEDSS GHTRAYGVCF VDTSLGKFFI GQFSDDRHCS RFRTLVAHYP PVQVLFEKGN 600
LSKETKTILK SSLSCSLQEG LIPGSQFWDA SKTLRTLLEE EYFREKLSDG IGVMLPQVLK 660
GMTSESDSIG LTPGEKSELA LSALGGCVFY LKKCLIDQEL LSMANFEEYI PLDSDTVSTT 720
RSGAIFTKAY QRMVLDAVTL NNLEIFLNGT NGSTEGTLLE RVDTCHTPFG KRLLKQWLCA 780
PLCNHYAIND RLDAIEDLMV VPDKISEVVE LLKKLPDLER LLSKIHNVGS PLKSQNHPDS 840
RAIMYEETTY SKKKIIDFLS ALEGFKVMCK IIGIMEEVAD GFKSKILKQV ISLQTKNPEG 900
RFPDLTVELN RWDTAFDHEK ARKTGLITPK AGFDSDYDQA LADIRENEQS LLEYLEKQRN 960
RIGCRTIVYW GIGRNRYQLE IPENFTTRNL PEEYELKSTK KGCKRYWTKT IEKKLANLIN 1020
AEERRDVSLK DCMRRLFYNF DKNYKDWQSA VECIAVLGKT LNKLVLRL 1068 
Gene Ontology
 GO:0032301; C:MutSalpha complex; IDA:HGNC.
 GO:0000790; C:nuclear chromatin; IEA:Compara.
 GO:0000228; C:nuclear chromosome; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003682; F:chromatin binding; IEA:Compara.
 GO:0003684; F:damaged DNA binding; IEA:Compara.
 GO:0008094; F:DNA-dependent ATPase activity; IBA:RefGenome.
 GO:0032137; F:guanine/thymine mispair binding; IEA:Compara.
 GO:0008340; P:determination of adult lifespan; ISS:BHF-UCL.
 GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; ISS:BHF-UCL.
 GO:0045190; P:isotype switching; ISS:BHF-UCL.
 GO:0000710; P:meiotic mismatch repair; ISS:BHF-UCL.
 GO:0045910; P:negative regulation of DNA recombination; IDA:BHF-UCL.
 GO:0051096; P:positive regulation of helicase activity; IDA:BHF-UCL.
 GO:0007131; P:reciprocal meiotic recombination; IBA:RefGenome.
 GO:0009411; P:response to UV; ISS:BHF-UCL.
 GO:0016446; P:somatic hypermutation of immunoglobulin genes; ISS:BHF-UCL. 
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