Human Gene MSH3 (uc003kgz.4) Description and Page Index
  Description: Homo sapiens mutS homolog 3 (E. coli) (MSH3), mRNA.
RefSeq Summary (NM_002439): The protein encoded by this gene forms a heterodimer with MSH2 to form MutS beta, part of the post-replicative DNA mismatch repair system. MutS beta initiates mismatch repair by binding to a mismatch and then forming a complex with MutL alpha heterodimer. This gene contains a polymorphic 9 bp tandem repeat sequence in the first exon. The repeat is present 6 times in the reference genome sequence and 3-7 repeats have been reported. Defects in this gene are a cause of susceptibility to endometrial cancer. [provided by RefSeq, Mar 2011]. Publication Note: This RefSeq record includes a subset of the publications that are available for this gene. Please see the Gene record to access additional publications. ##Evidence-Data-START## Transcript exon combination :: U61981.1, SRR1803615.35610.1 [ECO:0000332] RNAseq introns :: single sample supports all introns SAMEA1965299, SAMEA1966682 [ECO:0000348] ##Evidence-Data-END## ##RefSeq-Attributes-START## MANE Ensembl match :: ENST00000265081.7/ ENSP00000265081.6 RefSeq Select criteria :: based on single protein-coding transcript ##RefSeq-Attributes-END##
Transcript (Including UTRs)
   Position: hg19 chr5:79,950,467-80,172,634 Size: 222,168 Total Exon Count: 24 Strand: +
Coding Region
   Position: hg19 chr5:79,950,547-80,171,681 Size: 221,135 Coding Exon Count: 24 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr5:79,950,467-80,172,634)mRNA (may differ from genome)Protein (1137 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
OMIMPubMedReactomeStanford SOURCEUniProtKBWikipedia

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=DNA mismatch repair protein Msh3; Short=hMSH3; AltName: Full=Divergent upstream protein; Short=DUP; AltName: Full=Mismatch repair protein 1; Short=MRP1;
FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS beta which binds to DNA mismatches thereby initiating DNA repair. When bound, the MutS beta heterodimer bends the DNA helix and shields approximately 20 base pairs. MutS beta recognizes large insertion- deletion loops (IDL) up to 13 nucleotides long. After mismatch binding, forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis.
SUBUNIT: Heterodimer consisting of MSH2-MSH3 (MutS beta). Forms a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1.
INTERACTION: P43246:MSH2; NbExp=4; IntAct=EBI-1164205, EBI-355888;
PTM: Phosphorylated upon DNA damage, probably by ATM or ATR.
DISEASE: Defects in MSH3 are a cause of susceptibility to endometrial cancer (ENDMC) [MIM:608089].
SIMILARITY: Belongs to the DNA mismatch repair MutS family. MSH3 subfamily.
SEQUENCE CAUTION: Sequence=AAH11817.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence;
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="";

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MSH3
CDC HuGE Published Literature: MSH3
Positive Disease Associations: head and neck cancer lung cancer , Intercellular Adhesion Molecule-1 , microsatellite instability , prostate cancer
Related Studies:
  1. head and neck cancer lung cancer
    Michiels, S. et al. 2007, Polymorphism discovery in 62 DNA repair genes and haplotype-associations with risks for lung, and head and neck cancers, Carcinogenesis 2007. [PubMed 17494052]
  2. Intercellular Adhesion Molecule-1
    Emelia J Benjamin et al. BMC medical genetics 2007, Genome-wide association with select biomarker traits in the Framingham Heart Study., BMC medical genetics. [PubMed 17903293]
    The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.
  3. Intercellular Adhesion Molecule-1
    Emelia J Benjamin et al. BMC medical genetics 2007, Genome-wide association with select biomarker traits in the Framingham Heart Study., BMC medical genetics. [PubMed 17903293]
    The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: MSH3
Diseases sorted by gene-association score: familial adenomatous polyposis 4* (919), endometrial cancer* (758), gastric leiomyoma (9), superficial urinary bladder cancer (9), phlebotomus fever (7), lynch syndrome (7), colorectal cancer (6)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 5.97 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 135.22 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -35.2080-0.440 Picture PostScript Text
3' UTR -250.49953-0.263 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR007695 - DNA_mismatch_repair_MutS-lik_N
IPR000432 - DNA_mismatch_repair_MutS_C
IPR007861 - DNA_mismatch_repair_MutS_clamp
IPR007860 - DNA_mismatch_repair_MutS_connt
IPR007696 - DNA_mismatch_repair_MutS_core
IPR016151 - DNA_mismatch_repair_MutS_N

Pfam Domains:
PF00488 - MutS domain V
PF01624 - MutS domain I
PF05188 - MutS domain II
PF05192 - MutS domain III

SCOP Domains:
48334 - DNA repair protein MutS, domain III
52540 - P-loop containing nucleoside triphosphate hydrolases
53150 - DNA repair protein MutS, domain II
55271 - DNA repair protein MutS, domain I

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

- X-ray MuPIT

- X-ray MuPIT
To conserve bandwidth, only the images from the first 3 structures are shown.
3THZ - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P20585
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserNo orthologNo orthologGenome Browser
 Gene Details   Gene Details
 Gene Sorter   Gene Sorter
 RGDEnsembl  SGD
 Protein SequenceProtein Sequence  Protein Sequence
 AlignmentAlignment  Alignment

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0000403 Y-form DNA binding
GO:0000404 heteroduplex DNA loop binding
GO:0000406 double-strand/single-strand DNA junction binding
GO:0003677 DNA binding
GO:0003684 damaged DNA binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008094 DNA-dependent ATPase activity
GO:0019899 enzyme binding
GO:0030983 mismatched DNA binding
GO:0003697 single-stranded DNA binding
GO:0032139 dinucleotide insertion or deletion binding
GO:0032142 single guanine insertion binding
GO:0032181 dinucleotide repeat insertion binding
GO:0032137 guanine/thymine mispair binding
GO:0042803 protein homodimerization activity
GO:0032357 oxidized purine DNA binding

Biological Process:
GO:0006281 DNA repair
GO:0006298 mismatch repair
GO:0006974 cellular response to DNA damage stimulus
GO:0016447 somatic recombination of immunoglobulin gene segments
GO:0043570 maintenance of DNA repeat elements
GO:0045910 negative regulation of DNA recombination
GO:0051096 positive regulation of helicase activity

Cellular Component:
GO:0005654 nucleoplasm
GO:0016020 membrane
GO:0032302 MutSbeta complex

-  Descriptions from all associated GenBank mRNAs
  LF209855 - JP 2014500723-A/17358: Polycomb-Associated Non-Coding RNAs.
BC130434 - Homo sapiens mutS homolog 3 (E. coli), mRNA (cDNA clone MGC:163306 IMAGE:40146465), complete cds.
BC130436 - Homo sapiens mutS homolog 3 (E. coli), mRNA (cDNA clone MGC:163308 IMAGE:40146467), complete cds.
GQ900965 - Homo sapiens clone HEL-T-77 epididymis secretory sperm binding protein mRNA, complete cds.
AK289856 - Homo sapiens cDNA FLJ75589 complete cds, highly similar to Homo sapiens mutS homolog 3 (E. coli) (MSH3), mRNA.
J04810 - Human MSH3 gene, complete cds.
BC004177 - Homo sapiens mutS homolog 3 (E. coli), mRNA (cDNA clone IMAGE:2959447).
BC011817 - Homo sapiens mutS homolog 3 (E. coli), mRNA (cDNA clone IMAGE:3532592), partial cds.
BC098436 - Homo sapiens mutS homolog 3 (E. coli), mRNA (cDNA clone IMAGE:4906085).
U61981 - Human putative mismatch repair/binding protein hMSH3 (hMSH3) mRNA, complete cds.
BC017273 - Homo sapiens mutS homolog 3 (E. coli), mRNA (cDNA clone IMAGE:4811079).
MA445432 - JP 2018138019-A/17358: Polycomb-Associated Non-Coding RNAs.
LF332221 - JP 2014500723-A/139724: Polycomb-Associated Non-Coding RNAs.
LF332220 - JP 2014500723-A/139723: Polycomb-Associated Non-Coding RNAs.
MA567798 - JP 2018138019-A/139724: Polycomb-Associated Non-Coding RNAs.
MA567797 - JP 2018138019-A/139723: Polycomb-Associated Non-Coding RNAs.
LF332219 - JP 2014500723-A/139722: Polycomb-Associated Non-Coding RNAs.
LF332212 - JP 2014500723-A/139715: Polycomb-Associated Non-Coding RNAs.
LF332200 - JP 2014500723-A/139703: Polycomb-Associated Non-Coding RNAs.
LF332197 - JP 2014500723-A/139700: Polycomb-Associated Non-Coding RNAs.
MA567796 - JP 2018138019-A/139722: Polycomb-Associated Non-Coding RNAs.
MA567789 - JP 2018138019-A/139715: Polycomb-Associated Non-Coding RNAs.
MA567777 - JP 2018138019-A/139703: Polycomb-Associated Non-Coding RNAs.
MA567774 - JP 2018138019-A/139700: Polycomb-Associated Non-Coding RNAs.
JD244685 - Sequence 225709 from Patent EP1572962.
JD566706 - Sequence 547730 from Patent EP1572962.
JD300319 - Sequence 281343 from Patent EP1572962.
JD079392 - Sequence 60416 from Patent EP1572962.
JD429018 - Sequence 410042 from Patent EP1572962.
JD060792 - Sequence 41816 from Patent EP1572962.
JD315741 - Sequence 296765 from Patent EP1572962.
JD167641 - Sequence 148665 from Patent EP1572962.
JD481268 - Sequence 462292 from Patent EP1572962.
JD179365 - Sequence 160389 from Patent EP1572962.
JD381132 - Sequence 362156 from Patent EP1572962.
JD450867 - Sequence 431891 from Patent EP1572962.
JD097686 - Sequence 78710 from Patent EP1572962.
JD089062 - Sequence 70086 from Patent EP1572962.
JD534630 - Sequence 515654 from Patent EP1572962.
JD219255 - Sequence 200279 from Patent EP1572962.
JD486348 - Sequence 467372 from Patent EP1572962.
JD436979 - Sequence 418003 from Patent EP1572962.
JD136154 - Sequence 117178 from Patent EP1572962.
JD243194 - Sequence 224218 from Patent EP1572962.
JD079520 - Sequence 60544 from Patent EP1572962.
JD313435 - Sequence 294459 from Patent EP1572962.
JD138193 - Sequence 119217 from Patent EP1572962.
JD175667 - Sequence 156691 from Patent EP1572962.
JD299114 - Sequence 280138 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03430 - Mismatch repair
hsa05200 - Pathways in cancer
hsa05210 - Colorectal cancer

Reactome (by CSHL, EBI, and GO)

Protein P20585 (Reactome details) participates in the following event(s):

R-HSA-5444511 Formation of MSH2:MSH3 Complex
R-HSA-5358513 MSH2:MSH3 binds insertion/deletion loop of 2 bases or more
R-HSA-5358919 MSH2:MSH3 exchanges ADP for ATP
R-HSA-5358545 EXO1 interacts with MSH2:MSH3 (MutSbeta) and MLH1:PMS2 (MutLalpha)
R-HSA-5358512 MLH1:PMS2 makes single strand incision near insertion/deletion loop of 2 bases or more
R-HSA-5358519 MSH2:MSH3 recruits MLH1:PMS2 to mismatch and interacts with PCNA
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5632928 Defective Mismatch Repair Associated With MSH2
R-HSA-5632927 Defective Mismatch Repair Associated With MSH3
R-HSA-5358508 Mismatch Repair
R-HSA-5423599 Diseases of Mismatch Repair (MMR)
R-HSA-73894 DNA Repair
R-HSA-1643685 Disease

-  Other Names for This Gene
  Alternate Gene Symbols: A1L482, A6NMM6, DUC1, DUG, MSH3_HUMAN, NM_002439, NP_002430, P20585, Q6PJT5, Q86UQ6, Q92867, uc003kgz.3
UCSC ID: uc003kgz.4
RefSeq Accession: NM_002439
Protein: P20585 (aka MSH3_HUMAN)
CCDS: CCDS34195.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_002439.4
exon count: 24CDS single in 3' UTR: no RNA size: 4472
ORF size: 3414CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 6989.00frame shift in genome: no % Coverage: 99.44
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 1
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.