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Browse MSH2

Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Basic function annotation.
> Subcellular Location, Domain and Function
> Gene Ontology
> KEGG and Reactome Pathway
> Subcellular Location, Domain and Function
 
Subcellular Location Nucleus
Domain PF01624 MutS domain I
PF05188 MutS domain II
PF05192 MutS domain III
PF05190 MutS family domain IV
PF00488 MutS domain V
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.

> Gene Ontology
 
Biological Process GO:0000018 regulation of DNA recombination
GO:0000075 cell cycle checkpoint
GO:0000077 DNA damage checkpoint
GO:0000710 meiotic mismatch repair
GO:0001701 in utero embryonic development
GO:0002200 somatic diversification of immune receptors
GO:0002204 somatic recombination of immunoglobulin genes involved in immune response
GO:0002208 somatic diversification of immunoglobulins involved in immune response
GO:0002250 adaptive immune response
GO:0002263 cell activation involved in immune response
GO:0002285 lymphocyte activation involved in immune response
GO:0002312 B cell activation involved in immune response
GO:0002366 leukocyte activation involved in immune response
GO:0002377 immunoglobulin production
GO:0002381 immunoglobulin production involved in immunoglobulin mediated immune response
GO:0002440 production of molecular mediator of immune response
GO:0002443 leukocyte mediated immunity
GO:0002449 lymphocyte mediated immunity
GO:0002460 adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains
GO:0002521 leukocyte differentiation
GO:0002562 somatic diversification of immune receptors via germline recombination within a single locus
GO:0002566 somatic diversification of immune receptors via somatic mutation
GO:0006091 generation of precursor metabolites and energy
GO:0006119 oxidative phosphorylation
GO:0006298 mismatch repair
GO:0006301 postreplication repair
GO:0006302 double-strand break repair
GO:0006310 DNA recombination
GO:0006311 meiotic gene conversion
GO:0007050 cell cycle arrest
GO:0007093 mitotic cell cycle checkpoint
GO:0007126 meiotic nuclear division
GO:0007127 meiosis I
GO:0007131 reciprocal meiotic recombination
GO:0007281 germ cell development
GO:0007346 regulation of mitotic cell cycle
GO:0007548 sex differentiation
GO:0007568 aging
GO:0008340 determination of adult lifespan
GO:0008406 gonad development
GO:0008584 male gonad development
GO:0008630 intrinsic apoptotic signaling pathway in response to DNA damage
GO:0009116 nucleoside metabolic process
GO:0009119 ribonucleoside metabolic process
GO:0009123 nucleoside monophosphate metabolic process
GO:0009126 purine nucleoside monophosphate metabolic process
GO:0009141 nucleoside triphosphate metabolic process
GO:0009144 purine nucleoside triphosphate metabolic process
GO:0009150 purine ribonucleotide metabolic process
GO:0009161 ribonucleoside monophosphate metabolic process
GO:0009167 purine ribonucleoside monophosphate metabolic process
GO:0009199 ribonucleoside triphosphate metabolic process
GO:0009205 purine ribonucleoside triphosphate metabolic process
GO:0009314 response to radiation
GO:0009411 response to UV
GO:0009416 response to light stimulus
GO:0010165 response to X-ray
GO:0010212 response to ionizing radiation
GO:0010224 response to UV-B
GO:0010259 multicellular organism aging
GO:0010520 regulation of reciprocal meiotic recombination
GO:0010639 negative regulation of organelle organization
GO:0010948 negative regulation of cell cycle process
GO:0016064 immunoglobulin mediated immune response
GO:0016444 somatic cell DNA recombination
GO:0016445 somatic diversification of immunoglobulins
GO:0016446 somatic hypermutation of immunoglobulin genes
GO:0016447 somatic recombination of immunoglobulin gene segments
GO:0019724 B cell mediated immunity
GO:0022412 cellular process involved in reproduction in multicellular organism
GO:0030098 lymphocyte differentiation
GO:0030183 B cell differentiation
GO:0031570 DNA integrity checkpoint
GO:0031573 intra-S DNA damage checkpoint
GO:0035822 gene conversion
GO:0035825 reciprocal DNA recombination
GO:0040020 regulation of meiotic nuclear division
GO:0042113 B cell activation
GO:0042278 purine nucleoside metabolic process
GO:0042771 intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
GO:0043523 regulation of neuron apoptotic process
GO:0043524 negative regulation of neuron apoptotic process
GO:0043570 maintenance of DNA repeat elements
GO:0044773 mitotic DNA damage checkpoint
GO:0044774 mitotic DNA integrity checkpoint
GO:0045128 negative regulation of reciprocal meiotic recombination
GO:0045137 development of primary sexual characteristics
GO:0045190 isotype switching
GO:0045786 negative regulation of cell cycle
GO:0045835 negative regulation of meiotic nuclear division
GO:0045910 negative regulation of DNA recombination
GO:0045930 negative regulation of mitotic cell cycle
GO:0046034 ATP metabolic process
GO:0046128 purine ribonucleoside metabolic process
GO:0046546 development of primary male sexual characteristics
GO:0046661 male sex differentiation
GO:0048608 reproductive structure development
GO:0051052 regulation of DNA metabolic process
GO:0051053 negative regulation of DNA metabolic process
GO:0051095 regulation of helicase activity
GO:0051096 positive regulation of helicase activity
GO:0051321 meiotic cell cycle
GO:0051402 neuron apoptotic process
GO:0051445 regulation of meiotic cell cycle
GO:0051447 negative regulation of meiotic cell cycle
GO:0051783 regulation of nuclear division
GO:0051784 negative regulation of nuclear division
GO:0060631 regulation of meiosis I
GO:0061458 reproductive system development
GO:0070997 neuron death
GO:0072331 signal transduction by p53 class mediator
GO:0072332 intrinsic apoptotic signaling pathway by p53 class mediator
GO:0097193 intrinsic apoptotic signaling pathway
GO:1901214 regulation of neuron death
GO:1901215 negative regulation of neuron death
GO:1901657 glycosyl compound metabolic process
GO:1903046 meiotic cell cycle process
GO:2000241 regulation of reproductive process
GO:2000242 negative regulation of reproductive process
Molecular Function GO:0000217 DNA secondary structure binding
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:0003684 damaged DNA binding
GO:0003697 single-stranded DNA binding
GO:0008022 protein C-terminus binding
GO:0016887 ATPase activity
GO:0019237 centromeric DNA binding
GO:0030983 mismatched DNA binding
GO:0032135 DNA insertion or deletion binding
GO:0032137 guanine/thymine mispair binding
GO:0032138 single base insertion or deletion 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:0032356 oxidized DNA binding
GO:0032357 oxidized purine DNA binding
GO:0032404 mismatch repair complex binding
GO:0032405 MutLalpha complex binding
GO:0043531 ADP binding
GO:0043566 structure-specific DNA binding
Cellular Component GO:0000781 chromosome, telomeric region
GO:0000784 nuclear chromosome, telomeric region
GO:0032300 mismatch repair complex
GO:0032301 MutSalpha complex
GO:0032302 MutSbeta complex
GO:0044454 nuclear chromosome part
GO:0098687 chromosomal region
GO:1990391 DNA repair complex
> KEGG and Reactome Pathway
 
KEGG hsa03430 Mismatch repair
Reactome R-HSA-73894: DNA Repair
R-HSA-74160: Gene Expression
R-HSA-212436: Generic Transcription Pathway
R-HSA-5358508: Mismatch Repair
R-HSA-5358606: Mismatch repair (MMR) directed by MSH2
R-HSA-5358565: Mismatch repair (MMR) directed by MSH2
R-HSA-6796648: TP53 Regulates Transcription of DNA Repair Genes
R-HSA-3700989: Transcriptional Regulation by TP53
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Literatures that report relations between MSH2 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.
> Text Mining
 
  Literatures describing the relation between MSH2 and anti-tumor immunity in human cancer.
PMID Cancer type Relation to immunity Evidence sentences
28790115Prostate CarcinomaInhibit immunity (infiltration)MSH2 Loss in Primary Prostate Cancer. Loss of MSH2 protein is correlated with MSH2 inactivation, hypermutation, and higher tumor-infiltrating lymphocyte density, and appears most common among very high-grade primary tumors, for which routine screening may be warranted if validated in additional cohorts.
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.
> High-throughput Screening
  Statistical results of MSH2 in screening data sets for detecting immune reponses.
PMID Screening System Cancer Type Cell Line Data Set Statistical Results Relation to immunity
29301958CRISPR-Cas9 melanomaB16F10Pmel-1 T cell NA/NS NA/NS
29301958CRISPR-Cas9 melanomaB16F10OT-1 T cell NA/NS NA/NS
28783722CRISPR-Cas9 melanomaMel6242CT-CRISPR NA/NS NA/NS
28723893CRISPR-Cas9 melanomaB16GVAX+Anti-PD1 STARS Score: 4.03; FDR: 0.032 Sensitive to T cell-mediated killing
28723893CRISPR-Cas9 melanomaB16GVAX NA/NS NA/NS
25691366RNAiBreast cancerMCF7Luc-CTL assay NA/NS NA/NS
24476824shRNAmelanomaB16Primary screen NA/NS NA/NS
24476824shRNAmelanomaB16Secondary screen NA/NS NA/NS
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets.
> Expression difference between responders and non-responders
> Mutation difference between responders and non-responders
> Expression difference between responders and non-responders
 
Points in the above scatter plot represent the expression difference of MSH2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes Log2 (Fold Change) P value Anno
126997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)1412-0.0560.832
226997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)650.20.906
326997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)87-0.2460.849
428552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 9160.1990.608
528552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 59-0.1390.934
628552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 470.630.777
729033130MelanomaallAnti-PD-1 (nivolumab) 26230.0270.946
829033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 1511-0.0540.974
929033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 11120.1620.926
1029301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 48-0.0450.967
1129301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 2001
1229301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 280.330.837
1329443960Urothelial cancerallAnti-PD-L1 (atezolizumab) 682300.2330.00389
> Mutation difference between responders and non-responders
 
Points in the above scatter plot represent the mutation difference of MSH2 in various data sets.
No PMID Cancer type Group Drug # Res # NRes % Mut/Res % Mut/NRes % Diff (R vs NR) Pval Anno
125765070Non-small cell lung cancer (NSCLC)allAnti-PD-1 (pembrolizumab) 14177.107.10.452
225765070Non-small cell lung cancer (NSCLC)smokingAnti-PD-1 (pembrolizumab) 1030001
325765070Non-small cell lung cancer (NSCLC)non-smokingAnti-PD-1 (pembrolizumab) 414250250.222
426359337MelanomaallAnti-CTLA-4 (ipilimumab) 277314.82.712.10.0439
526359337MelanomaBRAFiAnti-CTLA-4 (ipilimumab) 0140001
626359337Melanomanon-BRAFiAnti-CTLA-4 (ipilimumab) 275914.83.411.40.0746
726997480MelanomaallAnti-PD-1 (pembrolizumab and nivolumab)21174.804.81
826997480MelanomaMAPKiAnti-PD-1 (pembrolizumab and nivolumab)8612.5012.51
926997480Melanomanon-MAPKiAnti-PD-1 (pembrolizumab and nivolumab)13110001
1028552987Urothelial cancerallAnti-PD-L1 (atezolizumab) 91611.1011.10.36
1128552987Urothelial cancersmokingAnti-PD-L1 (atezolizumab) 590001
1228552987Urothelial cancernon-smokingAnti-PD-L1 (atezolizumab) 47250250.364
1329033130MelanomaallAnti-PD-1 (nivolumab) 382703.7-3.70.415
1429033130MelanomaNIV3-PROGAnti-PD-1 (nivolumab) 22130001
1529033130MelanomaNIV3-NAIVEAnti-PD-1 (nivolumab) 161407.1-7.10.467
1629301960Clear cell renal cell carcinoma (ccRCC)allAnti-PD-1 (nivolumab) 11130001
1729301960Clear cell renal cell carcinoma (ccRCC)VEGFRiAnti-PD-1 (nivolumab) 610001
1829301960Clear cell renal cell carcinoma (ccRCC)non-VEGFRiAnti-PD-1 (nivolumab) 5120001
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of MSH2. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.
> Lymphocyte
 
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of MSH2. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by MSH2.
> Immunoinhibitor
> Immunostimulator
> MHC molecule
> Immunoinhibitor
 
> Immunostimulator
 
> MHC molecule
 
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of MSH2. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene.
> Chemokine
> Receptor
> Chemokine
 
> Receptor
 
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Distribution of MSH2 expression across immune and molecular subtypes.
> Immune subtype
> Molecular subtype
> Immune subtype
 
> Molecular subtype
 
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Associations between MSH2 and clinical features.
> Overall survival analysis
> Cancer stage
> Tumor grade
> Overall survival
 
> Stage
 
> Grade
 
Summary
SymbolMSH2
NamemutS homolog 2
Aliases HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location2p21
External Links HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content Drugs targeting MSH2 collected from DrugBank database.
> Drugs from DrugBank database
 

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