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    MSH6 mutS homolog 6 [ Homo sapiens (human) ]

    Gene ID: 2956, updated on 25-May-2017
    Official Symbol
    MSH6provided by HGNC
    Official Full Name
    mutS homolog 6provided by HGNC
    Primary source
    HGNC:HGNC:7329
    See related
    Ensembl:ENSG00000116062 MIM:600678; Vega:OTTHUMG00000129129
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    GTBP; HSAP; p160; GTMBP; HNPCC5
    Summary
    This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]
    Orthologs
    Location:
    2p16.3
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    108 current GRCh38.p7 (GCF_000001405.33) 2 NC_000002.12 (47783082..47806953)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (48010221..48034092)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC107985794 Neighboring gene uncharacterized LOC105374589 Neighboring gene ribosomal protein L36a pseudogene 15 Neighboring gene F-box protein 11 Neighboring gene ribosomal protein S27a pseudogene 7 Neighboring gene uncharacterized LOC100506235

    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Jun 15 11:32:44 2016

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Professional guidelines

    Description
    Professional guideline
    ACMG 2013

    The ACMG recommends that laboratories performing clinical sequencing seek and report mutations in MSH6 that are pathogenic or expected to be pathogenic.

    GuidelinePubMed

    Associated conditions

    Description Tests
    Endometrial carcinoma
    MedGen: C0476089 OMIM: 608089 GeneReviews: Not available
    Compare labs
    Hereditary nonpolyposis colorectal cancer type 5
    MedGen: C1833477 OMIM: 614350 GeneReviews: Not available
    Compare labs
    Turcot syndrome
    MedGen: C0265325 OMIM: 276300 GeneReviews: Lynch Syndrome
    Compare labs

    Copy number response

    Description
    Copy number response
    Triplosensitivity

    No evidence available (Last evaluated (2015-11-16)

    ClinGen Genome Curation Page
    Haploinsufficency

    Sufficient evidence for dosage pathogenicity (Last evaluated (2015-11-16)

    ClinGen Genome Curation PagePubMed

    NHGRI GWAS Catalog

    Description
    Genome-wide association study of smoking behaviours in patients with COPD.
    NHGRI GWA Catalog
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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    contributes_to ADP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to ATP binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to ATPase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to MutLalpha complex binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chromatin binding IEA
    Inferred from Electronic Annotation
    more info
     
    contributes_to double-stranded DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to four-way junction DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to guanine/thymine mispair binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to magnesium ion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    methylated histone binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    mismatched DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to mismatched DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to oxidized purine DNA binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    contributes_to protein binding IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    NOT protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    PubMed 
    contributes_to single guanine insertion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    contributes_to single thymine insertion binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    Process Evidence Code Pubs
    DNA repair IDA
    Inferred from Direct Assay
    more info
    PubMed 
    determination of adult lifespan ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    intrinsic apoptotic signaling pathway ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    intrinsic apoptotic signaling pathway in response to DNA damage ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    isotype switching ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    NOT maintenance of DNA repeat elements IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    meiotic mismatch repair ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    mismatch repair IDA
    Inferred from Direct Assay
    more info
    PubMed 
    mismatch repair IGI
    Inferred from Genetic Interaction
    more info
    PubMed 
    mismatch repair IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    mismatch repair TAS
    Traceable Author Statement
    more info
     
    negative regulation of DNA recombination IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of helicase activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of isotype switching IEA
    Inferred from Electronic Annotation
    more info
     
    response to UV ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    somatic hypermutation of immunoglobulin genes ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    somatic recombination of immunoglobulin gene segments ISS
    Inferred from Sequence or Structural Similarity
    more info
     
    viral process IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    Golgi apparatus IDA
    Inferred from Direct Assay
    more info
     
    MutSalpha complex IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cytosol IDA
    Inferred from Direct Assay
    more info
     
    intracellular membrane-bounded organelle IDA
    Inferred from Direct Assay
    more info
     
    nuclear chromatin IEA
    Inferred from Electronic Annotation
    more info
     
    nucleoplasm IDA
    Inferred from Direct Assay
    more info
     
    nucleoplasm TAS
    Traceable Author Statement
    more info
     
    Preferred Names
    DNA mismatch repair protein Msh6
    Names
    G/T mismatch-binding protein
    mutS protein homolog 6
    mutS-alpha 160 kDa subunit
    sperm-associated protein

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_007111.1 RefSeqGene

      Range
      4936..28807
      Download
      GenBank, FASTA, Sequence Viewer (Graphics), LRG_219

    mRNA and Protein(s)

    1. NM_000179.2NP_000170.1  DNA mismatch repair protein Msh6 isoform 1

      See identical proteins and their annotated locations for NP_000170.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest protein (isoform 1).
      Source sequence(s)
      BC071594, BC104665, DA857066, U28946
      Consensus CDS
      CCDS1836.1
      UniProtKB/Swiss-Prot
      P52701
      UniProtKB/TrEMBL
      Q3SWU9
      Related
      ENSP00000234420.4, OTTHUMP00000159397, ENST00000234420.9, OTTHUMT00000251180
      Conserved Domains (7) summary
      cd05837
      Location:88195
      MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...
      COG0249
      Location:4071336
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:407525
      MutS_I; MutS domain I
      pfam05188
      Location:538692
      MutS_II; MutS domain II
      pfam05190
      Location:9321024
      MutS_IV; MutS family domain IV
      pfam05192
      Location:739827
      MutS_III; MutS domain III
      cl21455
      Location:10911313
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
    2. NM_001281492.1NP_001268421.1  DNA mismatch repair protein Msh6 isoform 2

      See identical proteins and their annotated locations for NP_001268421.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site and lacks two exons in the 5' coding region compared to variant 1. The resulting protein (isoform 2) is shorter but has the same N- and C-termini compared to isoform 1.
      Source sequence(s)
      AK293921, BC071594
      Consensus CDS
      CCDS62906.1
      UniProtKB/Swiss-Prot
      P52701
      Related
      ENSP00000446475.1, ENST00000540021.5
      Conserved Domains (6) summary
      COG0249
      Location:2771206
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:277395
      MutS_I; MutS domain I
      pfam05188
      Location:408562
      MutS_II; MutS domain II
      pfam05190
      Location:802894
      MutS_IV; MutS family domain IV
      pfam05192
      Location:609697
      MutS_III; MutS domain III
      cl21455
      Location:9611183
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
    3. NM_001281493.1NP_001268422.1  DNA mismatch repair protein Msh6 isoform 3

      See identical proteins and their annotated locations for NP_001268422.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks an alternate in-frame exon and initiates translation at a downstream start codon compared to variant 1. The resulting protein (isoform 3) is shorter and has a distinct N-terminus compared to isoform 1. Variants 3 and 4 encode the same protein (isoform 3).
      Source sequence(s)
      AC006509, BC071594
      Consensus CDS
      CCDS62907.1
      UniProtKB/Swiss-Prot
      P52701
      Related
      ENSP00000477844.1, ENST00000614496.4
      Conserved Domains (6) summary
      COG0249
      Location:1051034
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:105223
      MutS_I; MutS domain I
      pfam05188
      Location:236390
      MutS_II; MutS domain II
      pfam05190
      Location:630722
      MutS_IV; MutS family domain IV
      pfam05192
      Location:437525
      MutS_III; MutS domain III
      cl21455
      Location:7891011
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
    4. NM_001281494.1NP_001268423.1  DNA mismatch repair protein Msh6 isoform 3

      See identical proteins and their annotated locations for NP_001268423.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) contains an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a dowstream start codon compared to variant 1. The encoded isoform (3) is shorter and has a distinct N-terminus compared to isoform 1. Variants 3 and 4 encode the same protein (isoform 3).
      Source sequence(s)
      AC006509, AK304735, BC071594
      Consensus CDS
      CCDS62907.1
      UniProtKB/Swiss-Prot
      P52701
      Related
      ENSP00000438580.1, ENST00000538136.1
      Conserved Domains (6) summary
      COG0249
      Location:1051034
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:105223
      MutS_I; MutS domain I
      pfam05188
      Location:236390
      MutS_II; MutS domain II
      pfam05190
      Location:630722
      MutS_IV; MutS family domain IV
      pfam05192
      Location:437525
      MutS_III; MutS domain III
      cl21455
      Location:7891011
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 108 details...Open this link in a new tab

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p7 Primary Assembly

    Genomic

    1. NC_000002.12 Reference GRCh38.p7 Primary Assembly

      Range
      47783082..47806953
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_011532799.1XP_011531101.1  DNA mismatch repair protein Msh6 isoform X2

      See identical proteins and their annotated locations for XP_011531101.1

      Conserved Domains (7) summary
      cd05837
      Location:196
      MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...
      COG0249
      Location:3081237
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:308426
      MutS_I; MutS domain I
      pfam05188
      Location:439593
      MutS_II; MutS domain II
      pfam05190
      Location:833925
      MutS_IV; MutS family domain IV
      pfam05192
      Location:640728
      MutS_III; MutS domain III
      cl21455
      Location:9921214
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases
    2. XM_011532798.1XP_011531100.1  DNA mismatch repair protein Msh6 isoform X1

      Conserved Domains (7) summary
      cd05837
      Location:27134
      MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...
      COG0249
      Location:3461275
      MutS; DNA mismatch repair ATPase MutS [Replication, recombination and repair]
      pfam01624
      Location:346464
      MutS_I; MutS domain I
      pfam05188
      Location:477631
      MutS_II; MutS domain II
      pfam05190
      Location:871963
      MutS_IV; MutS family domain IV
      pfam05192
      Location:678766
      MutS_III; MutS domain III
      cl21455
      Location:10301252
      P-loop_NTPase; P-loop containing Nucleoside Triphosphate Hydrolases

    Alternate CHM1_1.1

    Genomic

    1. NC_018913.2 Alternate CHM1_1.1

      Range
      47940665..47964487
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
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