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Protein

DNA mismatch repair protein Msh2

Gene

MSH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.8 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi669 – 676ATPSequence analysis8

GO - Molecular functioni

  • ATPase activity Source: Ensembl
  • ATP binding Source: UniProtKB-KW
  • centromeric DNA binding Source: Ensembl
  • damaged DNA binding Source: Ensembl
  • DNA binding Source: UniProtKB
  • double-strand/single-strand DNA junction binding Source: GO_Central
  • enzyme binding Source: UniProtKB
  • guanine/thymine mispair binding Source: MGI
  • heteroduplex DNA loop binding Source: GO_Central
  • protein C-terminus binding Source: UniProtKB
  • protein homodimerization activity Source: HGNC
  • protein kinase binding Source: UniProtKB
  • Y-form DNA binding Source: GO_Central

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionDNA-binding
Biological processDNA damage, DNA repair
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000095002-MONOMER.
ReactomeiR-HSA-5358565. Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
R-HSA-5358606. Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta).
R-HSA-6796648. TP53 Regulates Transcription of DNA Repair Genes.
SIGNORiP43246.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA mismatch repair protein Msh2
Short name:
hMSH2
Alternative name(s):
MutS protein homolog 2
Gene namesi
Name:MSH2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:7325. MSH2.

Subcellular locationi

GO - Cellular componenti

  • membrane Source: UniProtKB
  • MutSalpha complex Source: UniProtKB
  • MutSbeta complex Source: HGNC
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nucleoplasm Source: Reactome

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 1 (HNPCC1)48 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:120435
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0545112A → T in HNPCC1. Corresponds to variant dbSNP:rs637504661 PublicationEnsembl.1
Natural variantiVAR_04373833T → P in HNPCC1; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637511073 PublicationsEnsembl.1
Natural variantiVAR_04374044T → M in HNPCC1; unknown pathological significance; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs5877790853 PublicationsEnsembl.1
Natural variantiVAR_04374145A → V in HNPCC1; unknown pathological significance; no decrease in mismatch repair activity. Corresponds to variant dbSNP:rs637502853 PublicationsEnsembl.1
Natural variantiVAR_00447046H → Q in HNPCC1. Corresponds to variant dbSNP:rs339462612 PublicationsEnsembl.1
Natural variantiVAR_04374292Missing in HNPCC1; unknown pathological significance. 3 Publications1
Natural variantiVAR_04374393L → F in HNPCC1. Corresponds to variant dbSNP:rs637514291 PublicationEnsembl.1
Natural variantiVAR_04374498Y → C in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637508871 PublicationEnsembl.1
Natural variantiVAR_043745102V → I in HNPCC1. Corresponds to variant dbSNP:rs1939223731 PublicationEnsembl.1
Natural variantiVAR_043746110K → T in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_019234127N → S in HNPCC1; presumed to enhance cancer risk considerably when associated with P-328; shows significantly decreased repair efficiency when associated with variant P-328. Corresponds to variant dbSNP:rs172177725 PublicationsEnsembl.1
Natural variantiVAR_004472139N → S in HNPCC1. 1
Natural variantiVAR_004473145I → M in HNPCC1; unknown pathological significance; normal mismatch repair activity. Corresponds to variant dbSNP:rs637501243 PublicationsEnsembl.1
Natural variantiVAR_012936161V → D in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. Corresponds to variant dbSNP:rs637501264 PublicationsEnsembl.1
Natural variantiVAR_054512162G → A in HNPCC1. Corresponds to variant dbSNP:rs637507731 PublicationEnsembl.1
Natural variantiVAR_043747162G → R in HNPCC1; decreased mismatch repair activity; associated with an abnormal subcellular localization pattern; affects protein stability; loss of protein expression. Corresponds to variant dbSNP:rs637506245 PublicationsEnsembl.1
Natural variantiVAR_043748163V → D in HNPCC1. Corresponds to variant dbSNP:rs637502141 PublicationEnsembl.1
Natural variantiVAR_022670163V → G in HNPCC1. Corresponds to variant dbSNP:rs637502141 PublicationEnsembl.1
Natural variantiVAR_043749164G → R in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. Corresponds to variant dbSNP:rs637505823 PublicationsEnsembl.1
Natural variantiVAR_067284165Y → D in HNPCC1; unknown pathological significance; decreased mismatch repair activity. Corresponds to variant dbSNP:rs5877791631 PublicationEnsembl.1
Natural variantiVAR_004474167D → H in HNPCC1; shows reduced mismatch binding; does not show a decreased expression level of the MutS alpha complex; not associated with an abnormal subcellular localization pattern; normal mismatch repair activity. Corresponds to variant dbSNP:rs637502556 PublicationsEnsembl.1
Natural variantiVAR_043750169I → V in HNPCC1 and CRC; unknown pathological significance. Corresponds to variant dbSNP:rs637507162 PublicationsEnsembl.1
Natural variantiVAR_043751173L → P in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. Corresponds to variant dbSNP:rs637500703 PublicationsEnsembl.1
Natural variantiVAR_043752175L → P in HNPCC1. Corresponds to variant dbSNP:rs637512911 PublicationEnsembl.1
Natural variantiVAR_067285177E → H in HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_043753187L → P in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. Corresponds to variant dbSNP:rs637514443 PublicationsEnsembl.1
Natural variantiVAR_076352187L → R in HNPCC1; decreased mismatch repair activity; loss of protein expression. Corresponds to variant dbSNP:rs637514441 PublicationEnsembl.1
Natural variantiVAR_054513198E → G in HNPCC1. Corresponds to variant dbSNP:rs63750327Ensembl.1
Natural variantiVAR_012937199C → R in glioma; also associated with HNPCC1; no effect on MSH2 splicing. Corresponds to variant dbSNP:rs637511102 PublicationsEnsembl.1
Natural variantiVAR_012938216I → V in HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency. Corresponds to variant dbSNP:rs637499361 PublicationEnsembl.1
Natural variantiVAR_043755246K → Q in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637508811 PublicationEnsembl.1
Natural variantiVAR_004475265 – 314Missing in HNPCC1. 1 PublicationAdd BLAST50
Natural variantiVAR_043756272A → V in HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency; results in partial MSH2 exon 5 skipping; normal mismatch repair activity. Corresponds to variant dbSNP:rs341369995 PublicationsEnsembl.1
Natural variantiVAR_043757283D → Y in HNPCC1. Corresponds to variant dbSNP:rs637503811 PublicationEnsembl.1
Natural variantiVAR_004476305A → T in HNPCC1; normal mismatch repair activity. Corresponds to variant dbSNP:rs637514542 PublicationsEnsembl.1
Natural variantiVAR_012939323S → C in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637507321 PublicationEnsembl.1
Natural variantiVAR_043758323S → Y in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637507321 PublicationEnsembl.1
Natural variantiVAR_054514331N → D in HNPCC1; no effect on MSH2 splicing. Corresponds to variant dbSNP:rs2676079381 PublicationEnsembl.1
Natural variantiVAR_043759333C → Y in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. Corresponds to variant dbSNP:rs637508283 PublicationsEnsembl.1
Natural variantiVAR_043760335T → I in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637506021 PublicationEnsembl.1
Natural variantiVAR_043761336P → S in HNPCC1. Corresponds to variant dbSNP:rs637510621 PublicationEnsembl.1
Natural variantiVAR_043763349P → L in HNPCC1. Corresponds to variant dbSNP:rs5877790671 PublicationEnsembl.1
Natural variantiVAR_043764359R → S in HNPCC1; shows a decreased expression level of the MutS alpha complex; associated with an abnormal subcellular localization pattern. Corresponds to variant dbSNP:rs637516172 PublicationsEnsembl.1
Natural variantiVAR_067286385P → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. Corresponds to variant dbSNP:rs5647361131 PublicationEnsembl.1
Natural variantiVAR_004478390L → F in HNPCC1 and CRC; unknown pathological significance; may decrease mismatch repair activity. Corresponds to variant dbSNP:rs172243679 PublicationsEnsembl.1
Natural variantiVAR_043765393K → M in HNPCC1. 1 Publication1
Natural variantiVAR_043766440Missing in HNPCC1. 1 Publication1
Natural variantiVAR_054515470V → E in HNPCC1; has no effect on ex vivo splicing assay. Corresponds to variant dbSNP:rs2676079591 PublicationEnsembl.1
Natural variantiVAR_043767492M → V in HNPCC1. 1
Natural variantiVAR_012941506D → Y in HNPCC1 and CRC; sporadic early-onset CRC; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637504924 PublicationsEnsembl.1
Natural variantiVAR_067287519F → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. 2 Publications1
Natural variantiVAR_004479524R → P in HNPCC1; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637512073 PublicationsEnsembl.1
Natural variantiVAR_043768552T → P in HNPCC1. Corresponds to variant dbSNP:rs637508381 PublicationEnsembl.1
Natural variantiVAR_012942554S → R in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637516561 PublicationEnsembl.1
Natural variantiVAR_004480562E → V in HNPCC1. Corresponds to variant dbSNP:rs637509971 PublicationEnsembl.1
Natural variantiVAR_043769564T → A in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs557782042 PublicationsEnsembl.1
Natural variantiVAR_043770583N → S in HNPCC1. Corresponds to variant dbSNP:rs2011181071 PublicationEnsembl.1
Natural variantiVAR_012943596N → S in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs412952883 PublicationsEnsembl.1
Natural variantiVAR_004481596Missing in HNPCC1; decreased mismatch repair activity; has no effect on MSH2 splicing. 9 Publications1
Natural variantiVAR_043771600A → V in HNPCC1. Corresponds to variant dbSNP:rs637512361 PublicationEnsembl.1
Natural variantiVAR_043772603D → N in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. Corresponds to variant dbSNP:rs637506574 PublicationsEnsembl.1
Natural variantiVAR_054516610H → N in HNPCC1; has no effect on MSH2 splicing. Corresponds to variant dbSNP:rs2676079801 PublicationEnsembl.1
Natural variantiVAR_004482622P → L in HNPCC1; decreased mismatch repair activity; confers multiple biochemical defects. Corresponds to variant dbSNP:rs289294835 PublicationsEnsembl.1
Natural variantiVAR_043774629Q → R in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs617564685 PublicationsEnsembl.1
Natural variantiVAR_012944636A → P in HNPCC1; decreased mismatch binding activity. Corresponds to variant dbSNP:rs637508755 PublicationsEnsembl.1
Natural variantiVAR_054517638R → G in HNPCC1; has no effect on MSH2 splicing. Corresponds to variant dbSNP:rs2676079811 PublicationEnsembl.1
Natural variantiVAR_043775639H → R in HNPCC1; decreased mismatch repair activity. Corresponds to variant dbSNP:rs5877791163 PublicationsEnsembl.1
Natural variantiVAR_004483639H → Y in HNPCC1; the equivalent substitution in yeast does not affect mismatch repair efficiency in vitro. Corresponds to variant dbSNP:rs289294842 PublicationsEnsembl.1
Natural variantiVAR_054518645Q → E in HNPCC1; has no effect on MSH2 splicing. Corresponds to variant dbSNP:rs2676079821 PublicationEnsembl.1
Natural variantiVAR_043776647E → K in HNPCC1. 1 Publication1
Natural variantiVAR_043777656Y → H in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_022671660D → G in HNPCC1. 1 Publication1
Natural variantiVAR_067761669G → R in HNPCC1. Corresponds to variant dbSNP:rs637516681 PublicationEnsembl.1
Natural variantiVAR_043778671N → Y in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637512322 PublicationsEnsembl.1
Natural variantiVAR_076353674G → A in HNPCC1; decreased mismatch repair activity. Corresponds to variant dbSNP:rs2676079962 PublicationsEnsembl.1
Natural variantiVAR_067288674G → R in HNPCC1; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637502343 PublicationsEnsembl.1
Natural variantiVAR_004485674G → S in HNPCC1; somatic mutation. Corresponds to variant dbSNP:rs637502341 PublicationEnsembl.1
Natural variantiVAR_067289675K → A in HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; decreased mismatch repair activity. Corresponds to variant dbSNP:rs5877791281 PublicationEnsembl.1
Natural variantiVAR_043779679I → T in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_012945688M → I in HNPCC1. Corresponds to variant dbSNP:rs637507903 PublicationsEnsembl.1
Natural variantiVAR_076354688M → V in HNPCC1; loss of protein expression. 1 Publication1
Natural variantiVAR_009250692G → R in HNPCC1. Corresponds to variant dbSNP:rs637502321 PublicationEnsembl.1
Natural variantiVAR_054519696P → L in HNPCC1; has no effect on ex vivo splicing assay. Corresponds to variant dbSNP:rs2676079941 PublicationEnsembl.1
Natural variantiVAR_004486697C → F in HNPCC1; decreased mismatch repair activity; loss of protein expression; confers multiple biochemical defects. Corresponds to variant dbSNP:rs637503987 PublicationsEnsembl.1
Natural variantiVAR_009251697C → R in HNPCC1; has no effect on MSH2 splicing. Corresponds to variant dbSNP:rs637509612 PublicationsEnsembl.1
Natural variantiVAR_043780714A → V in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637512241 PublicationEnsembl.1
Natural variantiVAR_076355722V → I Common polymorphism associated with HNPCC1. Corresponds to variant dbSNP:rs5877819961 PublicationEnsembl.1
Natural variantiVAR_043781723S → F in HNPCC1; decreased mismatch repair activity; has no effect on MSH2 splicing. Corresponds to variant dbSNP:rs637507943 PublicationsEnsembl.1
Natural variantiVAR_043782729M → V in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_043783732T → I in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_043784745 – 746Missing in HNPCC1; decreased mismatch repair activity. 3 Publications2
Natural variantiVAR_054520748D → Y in HNPCC1; has no effect on MSH2 splicing. Corresponds to variant dbSNP:rs2676080071 PublicationEnsembl.1
Natural variantiVAR_043785749E → K in HNPCC1; decreased mismatch repair activity; no loss of protein expression. Corresponds to variant dbSNP:rs637514773 PublicationsEnsembl.1
Natural variantiVAR_067290759G → E in HNPCC1; unknown pathological significance; decreased mismatch repair activity. Corresponds to variant dbSNP:rs3868334061 PublicationEnsembl.1
Natural variantiVAR_067291805L → V in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_043786813M → V in HNPCC1. Corresponds to variant dbSNP:rs637498411 PublicationEnsembl.1
Natural variantiVAR_004488834A → T in HNPCC1; decreased mismatch repair activity; shows no functional defects in gel shift assay. Corresponds to variant dbSNP:rs637507576 PublicationsEnsembl.1
Natural variantiVAR_054521839H → Q in HNPCC1; has no effect on MSH2 splicing. Corresponds to variant dbSNP:rs2676080161 PublicationEnsembl.1
Natural variantiVAR_043788839H → R in HNPCC1. Corresponds to variant dbSNP:rs637500271 PublicationEnsembl.1
Natural variantiVAR_067292843C → G in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_013172845K → E in HNPCC1. Corresponds to variant dbSNP:rs637505711 PublicationEnsembl.1
Natural variantiVAR_043789853E → A in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs637507972 PublicationsEnsembl.1
Natural variantiVAR_067293860S → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. Corresponds to variant dbSNP:rs637508491 PublicationEnsembl.1
Natural variantiVAR_043793886E → G in HNPCC1; unknown pathological significance; normal mismatch repair activity. Corresponds to variant dbSNP:rs637503503 PublicationsEnsembl.1
Natural variantiVAR_004489905T → R in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs2676080221 PublicationEnsembl.1
Natural variantiVAR_043794923V → E in HNPCC1; unknown pathological significance. Corresponds to variant dbSNP:rs1464212274 PublicationsEnsembl.1
Natural variantiVAR_043795931K → T in HNPCC1. Corresponds to variant dbSNP:rs2676080231 PublicationEnsembl.1
Muir-Torre syndrome (MRTES)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy.
See also OMIM:158320
Endometrial cancer (ENDMC)2 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:608089
Mismatch repair cancer syndrome (MMRCS)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients.
See also OMIM:276300
Colorectal cancer (CRC)4 Publications
Disease susceptibility may be associated with variations affecting the gene represented in this entry.
Disease descriptionA complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history.
See also OMIM:114500
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04373613S → I in CRC; unknown pathological significance. Corresponds to variant dbSNP:rs637499071 PublicationEnsembl.1
Natural variantiVAR_04373940G → S in CRC; unknown pathological significance. Corresponds to variant dbSNP:rs637512601 PublicationEnsembl.1
Natural variantiVAR_043750169I → V in HNPCC1 and CRC; unknown pathological significance. Corresponds to variant dbSNP:rs637507162 PublicationsEnsembl.1
Natural variantiVAR_043754203G → R in CRC; unknown pathological significance; somatic mutation. Corresponds to variant dbSNP:rs5877799731 PublicationEnsembl.1
Natural variantiVAR_043762342V → I in CRC; unknown pathological significance. Corresponds to variant dbSNP:rs637498791 PublicationEnsembl.1
Natural variantiVAR_004478390L → F in HNPCC1 and CRC; unknown pathological significance; may decrease mismatch repair activity. Corresponds to variant dbSNP:rs172243679 PublicationsEnsembl.1
Natural variantiVAR_012940419Q → K in CRC; unknown pathological significance; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637500064 PublicationsEnsembl.1
Natural variantiVAR_012941506D → Y in HNPCC1 and CRC; sporadic early-onset CRC; decreased mismatch repair activity. Corresponds to variant dbSNP:rs637504924 PublicationsEnsembl.1
Natural variantiVAR_043773619Y → C in CRC; unknown pathological significance. Corresponds to variant dbSNP:rs637499821 PublicationEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi675K → R: No effect on mismatch binding, complete loss of DNA repair function when associated with MSH6 mutant R-1140. 1 Publication1

Keywords - Diseasei

Disease mutation, Hereditary nonpolyposis colorectal cancer, Tumor suppressor

Organism-specific databases

DisGeNETi4436.
MalaCardsiMSH2.
MIMi114500. phenotype.
120435. phenotype.
158320. phenotype.
276300. phenotype.
608089. phenotype.
OpenTargetsiENSG00000095002.
Orphaneti252202. Constitutional mismatch repair deficiency syndrome.
144. Hereditary nonpolyposis colon cancer.
587. Muir-Torre syndrome.
99817. Non-polyposis Turcot syndrome.
PharmGKBiPA31133.

Polymorphism and mutation databases

BioMutaiMSH2.
DMDMi1171032.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001151832 – 934DNA mismatch repair protein Msh2Add BLAST933

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei555N6-acetyllysineCombined sources1
Modified residuei567N6-acetyllysineBy similarity1
Modified residuei921PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by PRKCZ, which may prevent MutS alpha degradation by the ubiquitin-proteasome pathway.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP43246.
MaxQBiP43246.
PaxDbiP43246.
PeptideAtlasiP43246.
PRIDEiP43246.

PTM databases

iPTMnetiP43246.
PhosphoSitePlusiP43246.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000095002.
CleanExiHS_MSH2.
ExpressionAtlasiP43246. baseline and differential.
GenevisibleiP43246. HS.

Organism-specific databases

HPAiCAB009572.
CAB070867.

Interactioni

Subunit structurei

Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta). Both heterodimer form a ternary complex with MutL alpha (MLH1-PMS1). Interacts with EXO1. Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with ATR. Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases. Interacts with SMARCAD1.10 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • enzyme binding Source: UniProtKB
  • protein C-terminus binding Source: UniProtKB
  • protein homodimerization activity Source: HGNC
  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi110573. 118 interactors.
DIPiDIP-35054N.
IntActiP43246. 46 interactors.
MINTiMINT-84789.
STRINGi9606.ENSP00000233146.

Structurei

Secondary structure

1934
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi14 – 24Combined sources11
Beta strandi33 – 38Combined sources6
Beta strandi40 – 46Combined sources7
Helixi48 – 56Combined sources9
Beta strandi59 – 61Combined sources3
Beta strandi65 – 71Combined sources7
Beta strandi75 – 81Combined sources7
Helixi82 – 94Combined sources13
Beta strandi99 – 105Combined sources7
Beta strandi117 – 124Combined sources8
Helixi129 – 131Combined sources3
Helixi132 – 135Combined sources4
Beta strandi147 – 152Combined sources6
Beta strandi155 – 158Combined sources4
Beta strandi160 – 167Combined sources8
Turni168 – 171Combined sources4
Beta strandi172 – 179Combined sources8
Helixi185 – 194Combined sources10
Beta strandi197 – 204Combined sources8
Helixi208 – 220Combined sources13
Beta strandi223 – 227Combined sources5
Helixi229 – 232Combined sources4
Helixi237 – 244Combined sources8
Turni252 – 254Combined sources3
Helixi255 – 257Combined sources3
Helixi259 – 262Combined sources4
Helixi264 – 277Combined sources14
Helixi279 – 281Combined sources3
Helixi283 – 285Combined sources3
Beta strandi289 – 293Combined sources5
Helixi296 – 298Combined sources3
Helixi304 – 309Combined sources6
Helixi326 – 330Combined sources5
Helixi336 – 347Combined sources12
Helixi353 – 367Combined sources15
Helixi370 – 377Combined sources8
Turni378 – 380Combined sources3
Helixi381 – 383Combined sources3
Helixi387 – 395Combined sources9
Helixi401 – 411Combined sources11
Helixi414 – 423Combined sources10
Beta strandi424 – 426Combined sources3
Beta strandi427 – 429Combined sources3
Helixi432 – 435Combined sources4
Helixi437 – 455Combined sources19
Helixi462 – 464Combined sources3
Turni472 – 474Combined sources3
Helixi476 – 502Combined sources27
Turni507 – 509Combined sources3
Beta strandi512 – 515Combined sources4
Turni517 – 519Combined sources3
Beta strandi521 – 525Combined sources5
Helixi527 – 530Combined sources4
Turni531 – 535Combined sources5
Beta strandi540 – 544Combined sources5
Beta strandi549 – 552Combined sources4
Helixi556 – 563Combined sources8
Turni564 – 567Combined sources4
Helixi568 – 585Combined sources18
Helixi586 – 588Combined sources3
Helixi589 – 613Combined sources25
Beta strandi615 – 617Combined sources3
Beta strandi623 – 625Combined sources3
Beta strandi631 – 637Combined sources7
Turni640 – 644Combined sources5
Beta strandi653 – 658Combined sources6
Turni659 – 661Combined sources3
Beta strandi664 – 668Combined sources5
Helixi675 – 691Combined sources17
Beta strandi695 – 703Combined sources9
Beta strandi706 – 711Combined sources6
Helixi724 – 738Combined sources15
Beta strandi744 – 749Combined sources6
Helixi756 – 772Combined sources17
Beta strandi777 – 783Combined sources7
Helixi785 – 792Combined sources8
Beta strandi797 – 807Combined sources11
Beta strandi810 – 820Combined sources11
Helixi827 – 833Combined sources7
Helixi838 – 850Combined sources13
Turni851 – 855Combined sources5
Helixi875 – 892Combined sources18
Helixi896 – 898Combined sources3
Helixi901 – 917Combined sources