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MSH6 mutS homolog 6 [ Homo sapiens (human) ]

Gene ID: 2956, updated on 21-Nov-2014
Official Symbol
MSH6provided by HGNC
Official Full Name
mutS homolog 6provided by HGNC
Primary source
HGNC:HGNC:7329
See related
Ensembl:ENSG00000116062; HPRD:07202; MIM:600678
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]
See MSH6 in Epigenomics, MapViewer
Location:
2p16
Exon count:
12
Annotation release Status Assembly Chr Location
106 current GRCh38 (GCF_000001405.26) 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 ribosomal protein L18a pseudogene 6 Neighboring gene NME/NM23 nucleoside diphosphate kinase 2 pseudogene Neighboring gene ribosomal protein L36a pseudogene 15 Neighboring gene F-box protein 11 Neighboring gene ribosomal protein S27a pseudogene 7 Neighboring gene uncharacterized LOC100506235

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
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 
DNA-dependent ATPase activity IBA
Inferred from Biological aspect of Ancestor
more info
 
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
ATP catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
 
ATP catabolic process IDA
Inferred from Direct Assay
more info
PubMed 
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 IBA
Inferred from Biological aspect of Ancestor
more info
 
intrinsic apoptotic signaling pathway in response to DNA damage ISS
Inferred from Sequence or Structural Similarity
more info
 
isotype switching IBA
Inferred from Biological aspect of Ancestor
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 IBA
Inferred from Biological aspect of Ancestor
more info
 
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 
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 
reciprocal meiotic recombination IBA
Inferred from Biological aspect of Ancestor
more info
 
response to UV IBA
Inferred from Biological aspect of Ancestor
more info
 
response to UV ISS
Inferred from Sequence or Structural Similarity
more info
 
somatic hypermutation of immunoglobulin genes IBA
Inferred from Biological aspect of Ancestor
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
 
Component Evidence Code Pubs
Golgi apparatus IDA
Inferred from Direct Assay
more info
 
MutSalpha complex IDA
Inferred from Direct Assay
more info
PubMed 
cytoplasm 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
 
nuclear chromosome IBA
Inferred from Biological aspect of Ancestor
more info
 
NOT nucleolus IDA
Inferred from Direct Assay
more info
 
nucleus IDA
Inferred from Direct Assay
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
 
Preferred Names
DNA mismatch repair protein Msh6
Names
DNA mismatch repair protein Msh6
sperm-associated protein
mutS-alpha 160 kDa subunit
G/T mismatch-binding 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 

    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 proteins identical to 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
    Conserved Domains (6) 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; Mismatch repair ATPase (MutS family) [DNA replication, recombination, and repair]
    pfam01624
    Location:407525
    MutS_I; MutS domain I
    pfam05188
    Location:538693
    MutS_II; MutS domain II
    pfam05192
    Location:7371064
    MutS_III; MutS domain III
    cl17201
    Location:10911313
    ABC_ATPase; ATP-binding cassette transporter nucleotide-binding domain
  2. NM_001281492.1NP_001268421.1  DNA mismatch repair protein Msh6 isoform 2

    See proteins identical to 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, ENST00000540021
    Conserved Domains (5) summary
    COG0249
    Location:2771206
    MutS; Mismatch repair ATPase (MutS family) [DNA replication, recombination, and repair]
    pfam01624
    Location:277395
    MutS_I; MutS domain I
    pfam05188
    Location:408563
    MutS_II; MutS domain II
    pfam05192
    Location:607934
    MutS_III; MutS domain III
    cl17201
    Location:9611183
    ABC_ATPase; ATP-binding cassette transporter nucleotide-binding domain
  3. NM_001281493.1NP_001268422.1  DNA mismatch repair protein Msh6 isoform 3

    See proteins identical to 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, ENST00000614496
    Conserved Domains (5) summary
    COG0249
    Location:1051034
    MutS; Mismatch repair ATPase (MutS family) [DNA replication, recombination, and repair]
    pfam01624
    Location:105223
    MutS_I; MutS domain I
    pfam05188
    Location:236391
    MutS_II; MutS domain II
    pfam05192
    Location:435762
    MutS_III; MutS domain III
    cl17201
    Location:7891011
    ABC_ATPase; ATP-binding cassette transporter nucleotide-binding domain
  4. NM_001281494.1NP_001268423.1  DNA mismatch repair protein Msh6 isoform 3

    See proteins identical to 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, ENST00000538136
    Conserved Domains (5) summary
    COG0249
    Location:1051034
    MutS; Mismatch repair ATPase (MutS family) [DNA replication, recombination, and repair]
    pfam01624
    Location:105223
    MutS_I; MutS domain I
    pfam05188
    Location:236391
    MutS_II; MutS domain II
    pfam05192
    Location:435762
    MutS_III; MutS domain III
    cl17201
    Location:7891011
    ABC_ATPase; ATP-binding cassette transporter nucleotide-binding domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 106

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

Alternate HuRef

Genomic

  1. AC_000134.1 

    Range
    47746516..47770575
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Reference GRCh38 Primary Assembly

Genomic

  1. NC_000002.12 

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

mRNA and Protein(s)

  1. XM_005264271.1XP_005264328.1  

    Conserved Domains (6) 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; Mismatch repair ATPase (MutS family) [DNA replication, recombination, and repair]
    pfam01624
    Location:308426
    MutS_I; MutS domain I
    pfam05188
    Location:439594
    MutS_II; MutS domain II
    pfam05192
    Location:638965
    MutS_III; MutS domain III
    cl17201
    Location:9921214
    ABC_ATPase; ATP-binding cassette transporter nucleotide-binding domain

Alternate CHM1_1.1

Genomic

  1. NC_018913.2 

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