Homo sapiens Protein: MSH2
InnateDB Protein IDBP-50902.6
Last Modified 2014-10-13 [Report errors or provide feedback]
Gene Symbol MSH2
Protein Name mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)
Species Homo sapiens
Ensembl Protein ENSP00000233146
InnateDB Gene IDBG-50900 (MSH2)
Protein Structure
UniProt Annotation
Function Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2- MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta 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. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. {ECO:0000269PubMed:10078208, ECO:0000269PubMed:10660545, ECO:0000269PubMed:15064730, ECO:0000269PubMed:17611581, ECO:0000269PubMed:9564049, ECO:0000269PubMed:9822679, ECO:0000269PubMed:9822680}.
Subcellular Localization Nucleus {ECO:0000305}.
Disease Associations Hereditary non-polyposis colorectal cancer 1 (HNPCC1) [MIM:120435]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269PubMed:10375096, ECO:0000269PubMed:10386556, ECO:0000269PubMed:10528862, ECO:0000269PubMed:10573010, ECO:0000269PubMed:10612836, ECO:0000269PubMed:10777691, ECO:0000269PubMed:10829038, ECO:0000269PubMed:11726306, ECO:0000269PubMed:11870161, ECO:0000269PubMed:11920458, ECO:0000269PubMed:12112654, ECO:0000269PubMed:12124176, ECO:0000269PubMed:12132870, ECO:0000269PubMed:12200596, ECO:0000269PubMed:12362047, ECO:0000269PubMed:12373605, ECO:0000269PubMed:12655564, ECO:0000269PubMed:12655568, ECO:0000269PubMed:12658575, ECO:0000269PubMed:14635101, ECO:0000269PubMed:15046096, ECO:0000269PubMed:15300854, ECO:0000269PubMed:15342696, ECO:0000269PubMed:15365995, ECO:0000269PubMed:15613555, ECO:0000269PubMed:15870828, ECO:0000269PubMed:15896463, ECO:0000269PubMed:15991316, ECO:0000269PubMed:15996210, ECO:0000269PubMed:16451135, ECO:0000269PubMed:17101317, ECO:0000269PubMed:17128465, ECO:0000269PubMed:18561205, ECO:0000269PubMed:18625694, ECO:0000269PubMed:22371642, ECO:0000269PubMed:7874129, ECO:0000269PubMed:8261515, ECO:0000269PubMed:8700523, ECO:0000269PubMed:8872463, ECO:0000269PubMed:9048925, ECO:0000269PubMed:9240418, ECO:0000269PubMed:9298827, ECO:0000269PubMed:9311737, ECO:0000269PubMed:9419403, ECO:0000269PubMed:9559627, ECO:0000269PubMed:9718327}. Note=The disease is caused by mutations affecting the gene represented in this entry.Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy. {ECO:0000269PubMed:7713503}. Note=The disease is caused by mutations affecting the gene represented in this entry.Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
Tissue Specificity Ubiquitously expressed. {ECO:0000269PubMed:10856833}.
Number of Interactions This gene and/or its encoded proteins are associated with 130 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.
Experimentally validated
Total 132 [view]
Protein-Protein 132 [view]
Protein-DNA 0
Protein-RNA 0
Predicted by orthology
Total 3 [view]
Gene Ontology

Molecular Function
Accession GO Term
GO:0000287 magnesium ion binding
GO:0000400 four-way junction DNA 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:0003690 double-stranded DNA binding
GO:0003697 single-stranded DNA binding
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0008022 protein C-terminus binding
GO:0008094 DNA-dependent ATPase activity
GO:0016887 ATPase activity
GO:0019237 centromeric DNA binding
GO:0019899 enzyme binding
GO:0019901 protein kinase binding
GO:0030983 mismatched DNA binding
GO:0032137 guanine/thymine mispair binding
GO:0032139 dinucleotide insertion or deletion binding
GO:0032142 single guanine insertion binding
GO:0032143 single thymine insertion binding
GO:0032181 dinucleotide repeat insertion binding
GO:0032357 oxidized purine DNA binding
GO:0032405 MutLalpha complex binding
GO:0042803 protein homodimerization activity
GO:0043531 ADP binding
Biological Process
GO:0000710 meiotic mismatch repair
GO:0001701 in utero embryonic development
GO:0002204 somatic recombination of immunoglobulin genes involved in immune response
GO:0006119 oxidative phosphorylation
GO:0006200 ATP catabolic process
GO:0006281 DNA repair
GO:0006298 mismatch repair
GO:0006301 postreplication repair
GO:0006302 double-strand break repair
GO:0006311 meiotic gene conversion
GO:0006974 cellular response to DNA damage stimulus
GO:0007050 cell cycle arrest
GO:0007281 germ cell development
GO:0008340 determination of adult lifespan
GO:0008584 male gonad development
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0010165 response to X-ray
GO:0010224 response to UV-B
GO:0016446 somatic hypermutation of immunoglobulin genes
GO:0016447 somatic recombination of immunoglobulin gene segments
GO:0019724 B cell mediated immunity
GO:0030183 B cell differentiation
GO:0031573 intra-S DNA damage checkpoint
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043524 negative regulation of neuron apoptotic process
GO:0043570 maintenance of DNA repeat elements
GO:0045128 negative regulation of reciprocal meiotic recombination
GO:0045190 isotype switching
GO:0045910 negative regulation of DNA recombination
GO:0051096 positive regulation of helicase activity
Cellular Component
GO:0000228 nuclear chromosome
GO:0005634 nucleus
GO:0016020 membrane
GO:0032301 MutSalpha complex
GO:0032302 MutSbeta complex
Protein Structure and Domains
InterPro IPR000432 DNA mismatch repair protein MutS, C-terminal
IPR007695 DNA mismatch repair protein MutS-like, N-terminal
IPR007696 DNA mismatch repair protein MutS, core
IPR007860 DNA mismatch repair protein MutS, connector domain
IPR007861 DNA mismatch repair protein MutS, clamp
IPR011184 DNA mismatch repair protein, MSH2
IPR027417 P-loop containing nucleoside triphosphate hydrolase
PFAM PF00488
Post-translational Modifications
SwissProt P43246
PhosphoSite PhosphoSite-P43246
UniProt Splice Variant
Entrez Gene 4436
UniGene Hs.597656
RefSeq NP_000242
OMIM 609309
HPRD 00389
EMBL AC079775 AC138655 AF066081 AK296831 AK304496 AY601851 BC021566 BX649122 L47574 L47577 L47581 L47582 L47583 U03911 U04045 U41206 U41207 U41208 U41210 U41211 U41212 U41213 U41214 U41215 U41216 U41217 U41218 U41219 U41220 U41221
GenPept AAA18643 AAA61870 AAA76858 AAA82080 AAB59564 AAB59565 AAB59566 AAB59569 AAC27930 AAH21566 AAS99351 AAY15096 BAG59401 BAG65304