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FLASH GENE
Symbol MSH6 contributors: mct - updated : 15-09-2016
HGNC name mutS homolog 6 (E. coli)
HGNC id 7329
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal region (NTR), with a PCNA binding motif, a large region of unknown function and a nonspecific DNA binding fragment , which binds to duplex DNA in a salt-sensitive, mismatch-independent manner
  • HATH domain (homologous to the N terminus of hepatoma derived growth factor HDGF)
  • a core region structurally and functionally similar to bacterial MutS
  • a PWWP domain, in the NTR, globular PWWP domain, binding double-stranded DNA, without any preference for mismatches or nicks, whereas its apparent affinity for single-stranded DNA is about 20 times lower
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies homolog to E.coli muts S,6
    homolog to murine Msh6
    homolog to C.elegans Y47G6A.11
    Homologene
    FAMILY
  • DNA mismatch repair MUTS family
    • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • restoring repair of base-base and single- nucleotide insertion-deletion mismatches
  • role in suppressing genome instability and radiation-induced mutations
  • in complex with MSH2, is the mismatch repair protein that mediates DNA repair through the recognition of 1- and 2-bp mismatches
  • mismatch recognition heterodimer MSH2-hMSH6 disassembles a nucleosome
  • is potentially involved in the somatic hypermutation (SHM) process
  • is potentially involved in both the induction and repair of DNA double-strand breaks in switch regions
  • mismatch repair protein MSH2-MSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate
    • CELLULAR PROCESS nucleotide, repair, mismatch repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    mismatch repair
    a component
  • complexing with MSH2 in mismatch repair (MUTS alpha heterodimer), functioning as a molecular switch between ADP and ATP bound forms, selective for repair or GT mispair and single deplaced bases
  • part of MSH2-MSH6-MLH1-PMS1 ternary complexes requiring ATP binding to only the MSH6 nucleotide-binding site, whereas the formation of MSH2-MSH6 sliding clamps requires ATP binding to both the MSH2 and MSH6 nucleotide-binding sites
    • INTERACTION
    DNA binding to GT
    RNA
    small molecule
    protein
  • MSH2 (heterodimer with MSH2 that is capable of recognizing a DNA mismatch)
  • MSH3 to tumor supression
  • MSH2 interacts with MSH6 or MSH3 to form the MutSalpha or MutSbeta complex, respectively, which recognize base-base mispairs and insertions/deletions and initiate the repair process
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) HNPCC5 , CMMRD
    related resource Hereditary Non-Polyposis Colorectal Cancer, HNPCC
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral   deletion    
    in sporadic colorectal cancer (early onset), putatively in Mt DNA metabolism
    tumoral germinal mutation      
    in early-onset colorectal cancer patients without family history and endometrial carcinoma
    tumoral     --low  
    in cervical cancer
    tumoral       loss of function
    in colon and uterus tumor
    tumoral germinal mutation      
    associated with Lynch syndrome cancers (accountng for 10-20p100 of Lynch syndrome colorectal cancers)
    tumoral germinal mutation     loss of function
    in patients with primary ovarian, fallopian tube, or peritoneal cancers
    Susceptibility to prostate cancer
    Variant & Polymorphism other rare genetic variants that confer a high risk of prostate cancer when mutated
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS