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Protein

DNA mismatch repair protein Msh2

Gene

MSH2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containg DNA strand (PubMed:26300262). 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.9 Publications

Regions

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

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

Enzyme and pathway databases

ReactomeiR-HSA-5358565 Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha)
R-HSA-5358606 Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta)
R-HSA-5632927 Defective Mismatch Repair Associated With MSH3
R-HSA-5632928 Defective Mismatch Repair Associated With MSH2
R-HSA-5632968 Defective Mismatch Repair Associated With MSH6
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

EuPathDBiHostDB:ENSG00000095002.12
HGNCiHGNC:7325 MSH2
MIMi609309 gene
neXtProtiNX_P43246

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Involvement in diseasei

Hereditary non-polyposis colorectal cancer 1 (HNPCC1)54 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. 1 PublicationCorresponds to variant dbSNP:rs63750466EnsemblClinVar.1
Natural variantiVAR_04373833T → P in HNPCC1; decreased mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63751107EnsemblClinVar.1
Natural variantiVAR_04374044T → M in HNPCC1; unknown pathological significance; no decrease in mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779085EnsemblClinVar.1
Natural variantiVAR_04374145A → V in HNPCC1; unknown pathological significance; no decrease in mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750285EnsemblClinVar.1
Natural variantiVAR_00447046H → Q in HNPCC1. 2 PublicationsCorresponds to variant dbSNP:rs33946261EnsemblClinVar.1
Natural variantiVAR_04374292Missing in HNPCC1; unknown pathological significance. 3 Publications1
Natural variantiVAR_04374393L → F in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751429EnsemblClinVar.1
Natural variantiVAR_04374498Y → C in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750887EnsemblClinVar.1
Natural variantiVAR_043745102V → I in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs193922373EnsemblClinVar.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. 5 PublicationsCorresponds to variant dbSNP:rs17217772EnsemblClinVar.1
Natural variantiVAR_004472139N → S in HNPCC1. 1
Natural variantiVAR_004473145I → M in HNPCC1; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750124EnsemblClinVar.1
Natural variantiVAR_012936161V → D in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 4 PublicationsCorresponds to variant dbSNP:rs63750126EnsemblClinVar.1
Natural variantiVAR_054512162G → A in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750773EnsemblClinVar.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. 5 PublicationsCorresponds to variant dbSNP:rs63750624EnsemblClinVar.1
Natural variantiVAR_043748163V → D in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750214EnsemblClinVar.1
Natural variantiVAR_022670163V → G in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750214EnsemblClinVar.1
Natural variantiVAR_043749164G → R in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63750582EnsemblClinVar.1
Natural variantiVAR_067284165Y → D in HNPCC1; unknown pathological significance; decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779163EnsemblClinVar.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. 6 PublicationsCorresponds to variant dbSNP:rs63750255EnsemblClinVar.1
Natural variantiVAR_043751173L → P in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63750070EnsemblClinVar.1
Natural variantiVAR_043752175L → P in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751291EnsemblClinVar.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. 3 PublicationsCorresponds to variant dbSNP:rs63751444EnsemblClinVar.1
Natural variantiVAR_076352187L → R in HNPCC1; decreased mismatch repair activity; loss of protein expression. 1 PublicationCorresponds to variant dbSNP:rs63751444EnsemblClinVar.1
Natural variantiVAR_054513198E → G in HNPCC1. Corresponds to variant dbSNP:rs63750327EnsemblClinVar.1
Natural variantiVAR_012938216I → V in HNPCC1; unknown pathological significance; shows slightly reduced mismatch binding or release efficiency. 1 PublicationCorresponds to variant dbSNP:rs63749936EnsemblClinVar.1
Natural variantiVAR_043755246K → Q in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750881EnsemblClinVar.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. 5 PublicationsCorresponds to variant dbSNP:rs34136999EnsemblClinVar.1
Natural variantiVAR_043757283D → Y in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750381EnsemblClinVar.1
Natural variantiVAR_004476305A → T in HNPCC1; normal mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs63751454EnsemblClinVar.1
Natural variantiVAR_012939323S → C in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750732EnsemblClinVar.1
Natural variantiVAR_043758323S → Y in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750732EnsemblClinVar.1
Natural variantiVAR_054514331N → D in HNPCC1; no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607938EnsemblClinVar.1
Natural variantiVAR_043759333C → Y in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63750828EnsemblClinVar.1
Natural variantiVAR_043760335T → I in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63750602EnsemblClinVar.1
Natural variantiVAR_043761336P → S in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751062EnsemblClinVar.1
Natural variantiVAR_043763349P → L in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs587779067EnsemblClinVar.1
Natural variantiVAR_043764359R → S in HNPCC1; shows a decreased expression level of the MutS alpha complex; associated with an abnormal subcellular localization pattern. 2 PublicationsCorresponds to variant dbSNP:rs63751617EnsemblClinVar.1
Natural variantiVAR_067286385P → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs564736113EnsemblClinVar.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. 1 PublicationCorresponds to variant dbSNP:rs267607959EnsemblClinVar.1
Natural variantiVAR_043767492M → V in HNPCC1. 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. 3 PublicationsCorresponds to variant dbSNP:rs63751207EnsemblClinVar.1
Natural variantiVAR_043768552T → P in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750838EnsemblClinVar.1
Natural variantiVAR_012942554S → R in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751656EnsemblClinVar.1
Natural variantiVAR_004480562E → V in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750997EnsemblClinVar.1
Natural variantiVAR_043769564T → A in HNPCC1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs55778204EnsemblClinVar.1
Natural variantiVAR_043770583N → S in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs201118107EnsemblClinVar.1
Natural variantiVAR_012943596N → S in HNPCC1; unknown pathological significance. 3 PublicationsCorresponds to variant dbSNP:rs41295288EnsemblClinVar.1
Natural variantiVAR_004481596Missing in HNPCC1; decreased mismatch repair activity; has no effect on MSH2 splicing. 9 Publications1
Natural variantiVAR_043771600A → V in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751236EnsemblClinVar.1
Natural variantiVAR_043772603D → N in HNPCC1; decreased mismatch repair activity; affects protein stability; loss of protein expression. 4 PublicationsCorresponds to variant dbSNP:rs63750657EnsemblClinVar.1
Natural variantiVAR_054516610H → N in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607980EnsemblClinVar.1
Natural variantiVAR_004482622P → L in HNPCC1; decreased mismatch repair activity; confers multiple biochemical defects. 5 PublicationsCorresponds to variant dbSNP:rs28929483EnsemblClinVar.1
Natural variantiVAR_043774629Q → R in HNPCC1; unknown pathological significance. 5 PublicationsCorresponds to variant dbSNP:rs61756468EnsemblClinVar.1
Natural variantiVAR_012944636A → P in HNPCC1; decreased mismatch binding activity. 5 PublicationsCorresponds to variant dbSNP:rs63750875EnsemblClinVar.1
Natural variantiVAR_054517638R → G in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607981EnsemblClinVar.1
Natural variantiVAR_043775639H → R in HNPCC1; decreased mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs587779116EnsemblClinVar.1
Natural variantiVAR_004483639H → Y in HNPCC1; the equivalent substitution in yeast does not affect mismatch repair efficiency in vitro. 2 PublicationsCorresponds to variant dbSNP:rs28929484EnsemblClinVar.1
Natural variantiVAR_054518645Q → E in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267607982EnsemblClinVar.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 PublicationCorresponds to variant dbSNP:rs1085308057Ensembl.1
Natural variantiVAR_067761669G → R in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63751668EnsemblClinVar.1
Natural variantiVAR_043778671N → Y in HNPCC1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs63751232EnsemblClinVar.1
Natural variantiVAR_076353674G → A in HNPCC1; decreased mismatch repair activity. 2 PublicationsCorresponds to variant dbSNP:rs267607996Ensembl.1
Natural variantiVAR_067288674G → R in HNPCC1; decreased mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750234EnsemblClinVar.1
Natural variantiVAR_004485674G → S in HNPCC1; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs63750234EnsemblClinVar.1
Natural variantiVAR_067289675K → A in HNPCC1; requires 2 nucleotide substitutions; unknown pathological significance; decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs587779128EnsemblClinVar.1
Natural variantiVAR_043779679I → T in HNPCC1; somatic mutation. 1 Publication1
Natural variantiVAR_012945688M → I in HNPCC1. 3 PublicationsCorresponds to variant dbSNP:rs63750790EnsemblClinVar.1
Natural variantiVAR_076354688M → V in HNPCC1; loss of protein expression. 1 Publication1
Natural variantiVAR_009250692G → R in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750232EnsemblClinVar.1
Natural variantiVAR_054519696P → L in HNPCC1; has no effect on ex vivo splicing assay. 1 PublicationCorresponds to variant dbSNP:rs267607994EnsemblClinVar.1
Natural variantiVAR_004486697C → F in HNPCC1; decreased mismatch repair activity; loss of protein expression; confers multiple biochemical defects. 7 PublicationsCorresponds to variant dbSNP:rs63750398EnsemblClinVar.1
Natural variantiVAR_009251697C → R in HNPCC1; has no effect on MSH2 splicing. 2 PublicationsCorresponds to variant dbSNP:rs63750961EnsemblClinVar.1
Natural variantiVAR_043780714A → V in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751224EnsemblClinVar.1
Natural variantiVAR_043781723S → F in HNPCC1; decreased mismatch repair activity; has no effect on MSH2 splicing. 3 PublicationsCorresponds to variant dbSNP:rs63750794EnsemblClinVar.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. 1 PublicationCorresponds to variant dbSNP:rs267608007EnsemblClinVar.1
Natural variantiVAR_043785749E → K in HNPCC1; decreased mismatch repair activity; no loss of protein expression. 3 PublicationsCorresponds to variant dbSNP:rs63751477EnsemblClinVar.1
Natural variantiVAR_067290759G → E in HNPCC1; unknown pathological significance; decreased mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs386833406EnsemblClinVar.1
Natural variantiVAR_067291805L → V in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_043786813M → V in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63749841EnsemblClinVar.1
Natural variantiVAR_004488834A → T in HNPCC1; decreased mismatch repair activity; shows no functional defects in gel shift assay. 6 PublicationsCorresponds to variant dbSNP:rs63750757EnsemblClinVar.1
Natural variantiVAR_054521839H → Q in HNPCC1; has no effect on MSH2 splicing. 1 PublicationCorresponds to variant dbSNP:rs267608016EnsemblClinVar.1
Natural variantiVAR_043788839H → R in HNPCC1; decreases protein levels. 2 PublicationsCorresponds to variant dbSNP:rs63750027EnsemblClinVar.1
Natural variantiVAR_067292843C → G in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 Publication1
Natural variantiVAR_013172845K → E in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750571EnsemblClinVar.1
Natural variantiVAR_043789853E → A in HNPCC1; unknown pathological significance. 2 PublicationsCorresponds to variant dbSNP:rs63750797EnsemblClinVar.1
Natural variantiVAR_067293860S → L in HNPCC1; unknown pathological significance; normal mismatch repair activity. 1 PublicationCorresponds to variant dbSNP:rs63750849EnsemblClinVar.1
Natural variantiVAR_043793886E → G in HNPCC1; unknown pathological significance; normal mismatch repair activity. 3 PublicationsCorresponds to variant dbSNP:rs63750350EnsemblClinVar.1
Natural variantiVAR_004489905T → R in HNPCC1; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs267608022EnsemblClinVar.1
Natural variantiVAR_043794923V → E in HNPCC1; unknown pathological significance. 4 PublicationsCorresponds to variant dbSNP:rs146421227EnsemblClinVar.1
Natural variantiVAR_043795931K → T in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs267608023EnsemblClinVar.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. 1 PublicationCorresponds to variant dbSNP:rs63749907EnsemblClinVar.1
Natural variantiVAR_04373940G → S in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63751260EnsemblClinVar.1
Natural variantiVAR_043754203G → R in CRC; unknown pathological significance; somatic mutation. 1 PublicationCorresponds to variant dbSNP:rs587779973EnsemblClinVar.1
Natural variantiVAR_043762342V → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749879EnsemblClinVar.1
Natural variantiVAR_012940419Q → K in CRC; unknown pathological significance; decreased mismatch repair activity. 4 PublicationsCorresponds to variant dbSNP:rs63750006EnsemblClinVar.1
Natural variantiVAR_043773619Y → C in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749982EnsemblClinVar.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
GeneReviewsiMSH2
MalaCardsiMSH2
MIMi114500 phenotype
120435 phenotype
158320 phenotype
276300 phenotype
608089 phenotype
OpenTargetsiENSG00000095002
Orphaneti252202 Constitutional mismatch repair deficiency syndrome
144 Lynch syndrome
587 Muir-Torre 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
Cross-linki430Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
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, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP43246
MaxQBiP43246
PaxDbiP43246
PeptideAtlasiP43246
PRIDEiP43246
ProteomicsDBi55601

PTM databases

iPTMnetiP43246
PhosphoSitePlusiP43246

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000095002 Expressed in 212 organ(s), highest expression level in secondary oocyte
CleanExiHS_MSH2
ExpressionAtlasiP43246 baseline and differential
GenevisibleiP43246 HS

Organism-specific databases

HPAiCAB009572
CAB070867
HPA066845

Interactioni

Subunit structurei

Component of the DNA mismatch repair (MMR) complex composed at least of MSH2, MSH3, MSH6, PMS1 and MLH1 (PubMed:26300262). Heterodimer consisting of MSH2-MSH6 (MutS alpha) or MSH2-MSH3 (MutS beta) (PubMed:8942985). Both heterodimers form a ternary complex with MutL alpha (MLH1-PMS1) (PubMed:9788596, PubMed:10856833, PubMed:11427529, PubMed:11429708, PubMed:12414623, PubMed:14676842). Interacts with MCM9; the interaction recruits MCM9 to chromatin (PubMed:26300262). Interacts with MCM8 (PubMed:26300262). Interacts with EXO1 (PubMed:9788596, PubMed:10856833, PubMed:11427529, PubMed:11429708, PubMed:12414623, PubMed:14676842). 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 (PubMed:10783165). This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains (PubMed:10783165). Interacts with ATR (PubMed:14657349). Interacts with SLX4/BTBD12; this interaction is direct and links MutS beta to SLX4, a subunit of different structure-specific endonucleases (PubMed:19596235). Interacts with SMARCAD1 (PubMed:18675275).12 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110573, 136 interactors
ComplexPortaliCPX-77 DNA mismatch repair MutSbeta complex
CPX-80 DNA mismatch repair MutSalpha complex
CORUMiP43246
DIPiDIP-35054N
IntActiP43246, 50 interactors
MINTiP43246
STRINGi9606.ENSP00000233146

Structurei

Secondary structure

1934
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP43246
SMRiP43246
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP43246

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni601 – 671Interaction with EXO1Add BLAST71

Sequence similaritiesi

Belongs to the DNA mismatch repair MutS family.Curated

Phylogenomic databases

eggNOGiKOG0219 Eukaryota
COG0249 LUCA
GeneTreeiENSGT00550000074867
HOGENOMiHOG000196498
HOVERGENiHBG006399
InParanoidiP43246
KOiK08735
OMAiIPDILML
OrthoDBiEOG091G03SA
PhylomeDBiP43246
TreeFamiTF351780

Family and domain databases

Gene3Di3.30.420.110, 1 hit
3.40.1170.10, 1 hit
InterProiView protein in InterPro
IPR011184 DNA_mismatch_repair_Msh2
IPR007695 DNA_mismatch_repair_MutS-lik_N
IPR000432 DNA_mismatch_repair_MutS_C
IPR007861 DNA_mismatch_repair_MutS_clamp
IPR007696 DNA_mismatch_repair_MutS_core
IPR016151 DNA_mismatch_repair_MutS_N
IPR036187 DNA_mismatch_repair_MutS_sf
IPR007860 DNA_mmatch_repair_MutS_con_dom
IPR032642 Msh2
IPR036678 MutS_con_dom_sf
IPR027417 P-loop_NTPase
PANTHERiPTHR11361:SF35 PTHR11361:SF35, 1 hit
PfamiView protein in Pfam
PF01624 MutS_I, 1 hit
PF05188 MutS_II, 1 hit
PF05192 MutS_III, 1 hit
PF05190 MutS_IV, 1 hit
PF00488 MutS_V, 1 hit
PIRSFiPIRSF005813 MSH2, 1 hit
SMARTiView protein in SMART
SM00534 MUTSac, 1 hit
SM00533 MUTSd, 1 hit
SUPFAMiSSF48334 SSF48334, 1 hit
SSF52540 SSF52540, 1 hit
PROSITEiView protein in PROSITE
PS00486 DNA_MISMATCH_REPAIR_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 7 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: P43246-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MAVQPKETLQ LESAAEVGFV RFFQGMPEKP TTTVRLFDRG DFYTAHGEDA
60 70 80 90 100
LLAAREVFKT QGVIKYMGPA GAKNLQSVVL SKMNFESFVK DLLLVRQYRV
110 120 130 140 150
EVYKNRAGNK ASKENDWYLA YKASPGNLSQ FEDILFGNND MSASIGVVGV
160 170 180 190 200
KMSAVDGQRQ VGVGYVDSIQ RKLGLCEFPD NDQFSNLEAL LIQIGPKECV
210 220 230 240 250
LPGGETAGDM GKLRQIIQRG GILITERKKA DFSTKDIYQD LNRLLKGKKG
260 270 280 290 300
EQMNSAVLPE MENQVAVSSL SAVIKFLELL SDDSNFGQFE LTTFDFSQYM
310 320 330 340 350
KLDIAAVRAL NLFQGSVEDT TGSQSLAALL NKCKTPQGQR LVNQWIKQPL
360 370 380 390 400
MDKNRIEERL NLVEAFVEDA ELRQTLQEDL LRRFPDLNRL AKKFQRQAAN
410 420 430 440 450
LQDCYRLYQG INQLPNVIQA LEKHEGKHQK LLLAVFVTPL TDLRSDFSKF
460 470 480 490 500
QEMIETTLDM DQVENHEFLV KPSFDPNLSE LREIMNDLEK KMQSTLISAA
510 520 530 540 550
RDLGLDPGKQ IKLDSSAQFG YYFRVTCKEE KVLRNNKNFS TVDIQKNGVK
560 570 580 590 600
FTNSKLTSLN EEYTKNKTEY EEAQDAIVKE IVNISSGYVE PMQTLNDVLA
610 620 630 640 650
QLDAVVSFAH VSNGAPVPYV RPAILEKGQG RIILKASRHA CVEVQDEIAF
660 670 680 690 700
IPNDVYFEKD KQMFHIITGP NMGGKSTYIR QTGVIVLMAQ IGCFVPCESA
710 720 730 740 750
EVSIVDCILA RVGAGDSQLK GVSTFMAEML ETASILRSAT KDSLIIIDEL
760 770 780 790 800
GRGTSTYDGF GLAWAISEYI ATKIGAFCMF ATHFHELTAL ANQIPTVNNL
810 820 830 840 850
HVTALTTEET LTMLYQVKKG VCDQSFGIHV AELANFPKHV IECAKQKALE
860 870 880 890 900
LEEFQYIGES QGYDIMEPAA KKCYLEREQG EKIIQEFLSK VKQMPFTEMS
910 920 930
EENITIKLKQ LKAEVIAKNN SFVNEIISRI KVTT
Length:934
Mass (Da):104,743
Last modified:November 1, 1995 - v1
Checksum:i664A058C78242E05
GO
Isoform 2 (identifier: P43246-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: Missing.

Show »
Length:868
Mass (Da):97,323
Checksum:i1BC5218379005E26
GO

Computationally mapped potential isoform sequencesi

There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9PHA6E9PHA6_HUMAN
DNA mismatch repair protein
MSH2
921Annotation score:
A0A2R8Y6P0A0A2R8Y6P0_HUMAN
DNA mismatch repair protein
MSH2 hCG_17836
924Annotation score:
A0A2R8YG02A0A2R8YG02_HUMAN
DNA mismatch repair protein
MSH2
938Annotation score:
A0A2R8YFH0A0A2R8YFH0_HUMAN
DNA mismatch repair protein
MSH2
918Annotation score:
A0A2R8Y7S8A0A2R8Y7S8_HUMAN
DNA mismatch repair protein Msh2
MSH2
558Annotation score:
C9J809C9J809_HUMAN
DNA mismatch repair protein Msh2
MSH2
140Annotation score:
A0A2R8Y713A0A2R8Y713_HUMAN
DNA mismatch repair protein Msh2
MSH2
168Annotation score:

Sequence cautioni

The sequence AAC27930 differs from that shown. Reason: Frameshift at position 417. The frameshift is caused by a single nucleotide deletion which is found in a HNPCC kindred.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti784F → I in BX649122 (PubMed:17974005).Curated1
Sequence conflicti836F → S in BX649122 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0545112A → T in HNPCC1. 1 PublicationCorresponds to variant dbSNP:rs63750466EnsemblClinVar.1
Natural variantiVAR_0798225P → Q Polymorphism; decreases protein levels. 1 PublicationCorresponds to variant dbSNP:rs56170584EnsemblClinVar.1
Natural variantiVAR_0131718T → M3 PublicationsCorresponds to variant dbSNP:rs17217716EnsemblClinVar.1
Natural variantiVAR_04373613S → I in CRC; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs63749907EnsemblClinVar.1
Natural variantiVAR_04373717V → F in gastric cancer; unknown pathological significance; cryptic acceptor splice site suppressed on ex vivo splicing assay. 1 PublicationCorresponds to variant dbSNP:rs63750966EnsemblClinVar.1
Natural variantiVAR_04373833T → P in HNPCC1; decreased mismatch repair activity. 3 Publications