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FLASH GENE
Symbol MSH6 contributors: mct - updated : 15-09-2016
HGNC name mutS homolog 6 (E. coli)
HGNC id 7329
Corresponding disease
CMMRD constitutional mismatch repair-deficiency syndrome
HNPCC5 hereditary non polyposis colorectal cancer, type 5
Location 2p16.3      Physical location : 48.010.220 - 48.034.084
Synonym name
  • G/T mismatch binding protein
  • sperm-associated protein
  • DNA mismatch repair protein MSH6
  • MutS-alpha 160 kDa subunit
    • Synonym symbol(s) GTBP, HSAP, GTMBP, p160
    DNA
    TYPE functioning gene
    STRUCTURE 23.87 kb     10 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Binding site
    text structure GC rich site of translation initiation binding sites for Sp1, ETF, MTF1, AP1
    MAPPING cloned Y linked N status confirmed
    Map pter - LHCGR - D2S119 - FOXN2 - D2S2182 - MSH2 - MSH6 - D2S378 - D2S391 - PIGF - FSHR - D2S2227 - D2S123 - SPTBN1 - D2S2251 - D2S393 - D2S337 - cen
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    10 - 4435 160 1360 - 1997 9455487
    also called GTBP-N
    - splicing - - - - 1997 9455487
  • also called GTB-I
  • lacking a highly conserved region between GTB, MSH2, MSH3
    		•
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    blood / hematopoieticthymus    
    Cardiovascularheart    
    Reproductivemale systemtestis  highly
    Respiratoryrespiratory tracttrachea  highly
    Visualeye   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoieticbone marrow   
    Connectiveadipose  highly
    Lymphoid    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle, G1
    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