Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Orphanet Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol MSH2 contributors: np/shn/mct - updated : 15-09-2016
HGNC name mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
HGNC id 7325
Corresponding disease
CMMRD constitutional mismatch repair-deficiency syndrome
HNPCC1 hereditary nonpolyposis colorectal cancer, type 1
MTS Muir-Torre syndrome
Location 2p21      Physical location : 47.630.262 - 47.710.360
Synonym name
  • mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1)
  • MutS protein homolog 2
    • Synonym symbol(s) FCC1, COCA1, HNPCC, LCFS2, HNPCC1
    DNA
    TYPE functioning gene
    STRUCTURE 80.16 kb     16 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status confirmed
    Map pter - D2S288 - D2S2227 - MSH2 - D2S2739 - D2S1352 - cen
    RNA
    TRANSCRIPTS type messenger
    text several spliced transcripts lacking one or other exons,expressed in monocytes and normal colon mucosa (PMID: 10573010)
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    16 splicing 3145 - 934 - 2005 15886699
    16 splicing 3042 - 868 - 2005 15886699
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveintestinesmall intestine   
    Lymphoid/Immunelymph node    
     thymus   highly
     tonsils   highly
    Reproductivemale systemtestis  highly
    Skin/Tegumentskin    
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • N-terminal connector and lever domains (Domain 3 and 2) involved in protein stability (Ollila 2008)
  • a region of homology with other MutS or MutL homologs, with 150 aminoacids
  • a putative helix-turn-helix domain associated with an adenine nucleotide
  • magnesium binding site
  • the clamp domain (Domain 4)
  • an ATPase domain (Domain 5) involved in mismatch binding or release (Ollila 2008)
  • C-terminus containing a helix-turn-helix-motif, which stabilize the ATPase domains of the MutSa subunits
    • mono polymer heteromer , dimer
    HOMOLOGY
    interspecies ortholog to MSH2, Pan troglodytes
    ortholog to msh2, Danio rerio
    ortholog to Msh2, Rattus norvegicus
    ortholog to Msh2, Mus musculus
    Homologene
    FAMILY
  • DNA mismatch repair mutS family
    • CATEGORY DNA associated
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,chromatin/chromosome
    basic FUNCTION
  • regulates adenosine nucleotide processing by the MSH2-MSH6 mismatch recognition heterodimer
  • MSH2/MSH3, discriminates between a repair-competent and a repair-resistant loop by sensing the conformational dynamics of their junctions
  • MSH2-MSH3 interferes with Okazaki fragment processing to promote trinucleotide repeat expansions
  • MSH2-MSH3 is required for 3prime non-homologous tail removal in double-strand break repair and, MSH2-MSH3 binds double-strand/single-strand junctions and initiates repair in an ATP-dependent manner
  • MSH2-MSH3 suppresses chromosomal instability and modulates the tumor spectrum in TP53-deficient tumorigenesis and possibly has a role in other chromosomally unstable tumors as well
  • mismatch repair protein MSH2-MSH6 recognizes mismatches and forms sliding clamps within a D-loop recombination intermediate
  • MSH2-MSH3 plays an important role in shifting the expansion-contraction equilibrium toward expansion in the early stages of Trinucleotide repeat (TNR) tract expansion
  • having function in correcting nucleotide mismatches or insertions and deletions in duplex DNA caused by errors in DNA replication or recombination
    • CELLULAR PROCESS nucleotide, repair, mismatch repair
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    mismatch repair
    a component
  • complexing with GTBP (MUTS alpha heterodimer)
  • associated primarily with MSH6 in a heterodimer called MutSa
  • 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
  • MSH2-MSH3 heterodimer recognizes various DNA mispairs, including loops of DNA ranging from 1 to 14 nucleotides and some base-base mispairs
    • INTERACTION
    DNA
  • mismatched nucleotides
    • RNA
    small molecule nucleotide, other,
  • ADP and magnesium
    • protein
  • MSH3 and MSH6
  • exonuclease I, EXO1
  • MSH6, MLH1, and PMS2
  • BRCA1
  • 5'-3' exonuclease 1, EXO1/HEX1
  • p53
  • checkpoint kinase 2, CHK2
  • c-MYC and MAX
  • ATM- and Rad3-related, ATR
  • excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence), ERCC1
  • MSH2/6 formed a complex with BLM-p53-RAD51 in response to the damaged DNA forks during double-stranded break repair
  • Chk1 and Chk2
  • PKC zeta
  • Oestrogen receptor alpha/beta
  • Werner syndrome, RecQ helicase-like, WRN
  • FANCD2
  • MLH1-MLH3, a meiotic crossover and DNA mismatch repair factor, is a MSH2-MSH3-stimulated endonuclease
  • 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
    repressed by Bcl-2
    ASSOCIATED DISORDERS
    corresponding disease(s) HNPCC1 , MTS , CMMRD
    related resource InternationalGrouponHereditaryNon-PolyposisColorectalCancer
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral       loss of function
    in colon and uterus tumor
    tumoral germinal mutation      
    germline allele-specific and mosaic hypermethylation, without evidence of DNA mismatch repair gene mutation in early-onset colorectal or endometrial cancers
    tumoral germinal mutation      
    in epithelial ovarian cancer
    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
  • MSH2-/- mice are viable but develop lymphoid tumours
  • mouse Msh2-deficient cells have lost mismatch binding and have acquired microsatellite instability, a mutator phenotype, and tolerance to methylating agents. A significant fraction of Msh2-deficient mice develop lymphomas at an early age
  • MSH2-/- mice develop lymphoblastic lymphomas in association with aberrant expression of rhombotin-2 and Tal-1
  • ES cells from Msh2(+/-) and Msh2(-/-) mice accumulate oxidized bases as a consequence of low-level radiation exposure
  • absence of Msh2 in Hdh(Q111) mice is sufficient to abrogate progressive Huntington's disease CAG repeat expansion in striatum, eliminate striatal mutant huntingtin with somatically expanded glutamine tracts and to cause an approximately 5 month delay in nuclear mutant protein accumulation
  • MSH2 depletion caused cellular phenotypes associated with defective Fanconi Anemia pathway, including mitomycin C hypersensitivity and chromosomal instability
  • Msh2-null mice were also impaired in locomotive activity and had an abnormal response to heat