TISIDB

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
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 [ TOP ]
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 [ TOP ]
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 [ TOP ]
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
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
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

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Literatures describing the relation between MSH2 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
28790115	Prostate Carcinoma	Inhibit 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
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
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

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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
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	STARS Score: 4.03; FDR: 0.032	Sensitive to T cell-mediated killing
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
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

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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
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.056	0.832
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.2	0.906
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.246	0.849
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.199	0.608
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.139	0.934
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.63	0.777
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.027	0.946
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.054	0.974
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.162	0.926
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.045	0.967
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.33	0.837
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.233	0.00389

> Mutation difference between responders and non-responders

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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
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	25	0	25	0.222
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	14.8	2.7	12.1	0.0439
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	14.8	3.4	11.4	0.0746
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	11.1	0	11.1	0.36
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	25	0	25	0.364
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
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 [ TOP ]

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
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 [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
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 [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of MSH2 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between MSH2 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	MSH2
Name	mutS homolog 2
Aliases	HNPCC1; COCA1; mutS (E. coli) homolog 2 (colon cancer, nonpolyposis type 1); mutS homolog 2, colon cancer, n ......
Chromosomal Location	2p21
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting MSH2 collected from DrugBank database.

> Drugs from DrugBank database [ TOP ]
There is no record.

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