MSH2 [The Human Chemical-Genetic Interaction Map Project]

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======= MSH2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MSH2
  * **<color #00a2e8>Official Name</color>**: mutS homolog 2
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=4436|4436]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P43246|P43246]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MSH2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MSH2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/609309|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This locus is frequently mutated in hereditary nonpolyposis colon cancer (HNPCC). When cloned, it was discovered to be a human homolog of the E. coli mismatch repair gene mutS, consistent with the characteristic alterations in microsatellite sequences (RER+ phenotype) found in HNPCC. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2012]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2- MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B-induced cell cycle regulation and apoptosis. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:17611581, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|MutS II|
|MutS III|
|MutS IV|
|MutS V|
|MutS I|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|dinucleotide repeat insertion binding|
|double-strand/single-strand DNA junction binding|
|MutSbeta complex|
|single thymine insertion binding|
|MutSalpha complex|
|single guanine insertion binding|
|dinucleotide insertion or deletion binding|
|guanine/thymine mispair binding|
|positive regulation of isotype switching to IgA isotypes|
|regulation of isotype switching to IgA isotypes|
|centromeric DNA binding|
|positive regulation of helicase activity|
|oxidized purine DNA binding|
|MutLalpha complex binding|
|maintenance of DNA repeat elements|
|mismatched DNA binding|
|positive regulation of isotype switching to IgG isotypes|
|regulation of isotype switching to IgG isotypes|
|regulation of helicase activity|
|mismatch repair complex|
|intra-S DNA damage checkpoint|
|four-way junction DNA binding|
|determination of adult lifespan|
|response to UV-B|
|somatic hypermutation of immunoglobulin genes|
|somatic diversification of immunoglobulins involved in immune response|
|somatic recombination of immunoglobulin genes involved in immune response|
|isotype switching|
|somatic diversification of immune receptors via somatic mutation|
|somatic recombination of immunoglobulin gene segments|
|protein localization to chromatin|
|positive regulation of isotype switching|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator|
|response to X-ray|
|regulation of isotype switching|
|mismatch repair|
|multicellular organism aging|
|somatic cell DNA recombination|
|somatic diversification of immune receptors via germline recombination within a single locus|
|somatic diversification of immunoglobulins|
|positive regulation of B cell mediated immunity|
|positive regulation of immunoglobulin mediated immune response|
|ADP binding|
|positive regulation of DNA recombination|
|positive regulation of immunoglobulin production|
|B cell activation involved in immune response|
|DNA-dependent ATPase activity|
|negative regulation of DNA recombination|
|somatic diversification of immune receptors|
|intrinsic apoptotic signaling pathway by p53 class mediator|
|regulation of immunoglobulin mediated immune response|
|regulation of B cell mediated immunity|
|postreplication repair|
|positive regulation of ATPase activity|
|protein localization to chromosome|
|regulation of immunoglobulin production|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|regulation of ATPase activity|
|mitotic DNA damage checkpoint|
|positive regulation of production of molecular mediator of immune response|
|positive regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|double-stranded DNA binding|
|regulation of DNA recombination|
|mitotic DNA integrity checkpoint|
|positive regulation of lymphocyte mediated immunity|
|positive regulation of adaptive immune response|
|B cell differentiation|
|single-stranded DNA binding|
|nuclear chromosome, telomeric region|
|lymphocyte activation involved in immune response|
|oxidative phosphorylation|
|signal transduction by p53 class mediator|
|negative regulation of DNA metabolic process|
|DNA damage checkpoint|
|positive regulation of leukocyte mediated immunity|
|male gonad development|
|development of primary male sexual characteristics|
|regulation of production of molecular mediator of immune response|
|response to UV|
|DNA integrity checkpoint|
|negative regulation of neuron apoptotic process|
|regulation of adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|cell cycle arrest|
|intrinsic apoptotic signaling pathway|
|response to ionizing radiation|
|regulation of lymphocyte mediated immunity|
|mitotic cell cycle checkpoint|
|B cell activation|
|male sex differentiation|
|immunoglobulin production|
|regulation of adaptive immune response|
|positive regulation of B cell activation|
|production of molecular mediator of immune response|
|double-strand break repair|
|protein C-terminus binding|
|positive regulation of DNA metabolic process|
|cell cycle checkpoint|
|ATP metabolic process|
|regulation of leukocyte mediated immunity|
|regulation of neuron apoptotic process|
|negative regulation of neuron death|
|immunoglobulin mediated immune response|
|regulation of B cell activation|
|B cell mediated immunity|
|gonad development|
|magnesium ion binding|
|development of primary sexual characteristics|
|positive regulation of immune effector process|
|DNA recombination|
|ATPase activity|
|lymphocyte differentiation|
|germ cell development|
|sex differentiation|
|lymphocyte mediated immunity|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|aging|
|apoptotic signaling pathway|
|negative regulation of mitotic cell cycle|
|response to light stimulus|
|regulation of neuron death|
|leukocyte differentiation|
|enzyme binding|
|regulation of DNA metabolic process|
|cellular process involved in reproduction in multicellular organism|
|positive regulation of lymphocyte activation|
|in utero embryonic development|
|lymphocyte activation|
|chromatin binding|
|positive regulation of leukocyte activation|
|positive regulation of cell activation|
|generation of precursor metabolites and energy|
|reproductive structure development|
|reproductive system development|
|response to radiation|
|protein kinase binding|
|regulation of immune effector process|
|DNA repair|
|regulation of lymphocyte activation|
|hemopoiesis|
|negative regulation of cell cycle|
|mitotic cell cycle process|
|regulation of leukocyte activation|
|hematopoietic or lymphoid organ development|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|regulation of mitotic cell cycle|
|chordate embryonic development|
|regulation of cell activation|
|immune system development|
|embryo development ending in birth or egg hatching|
|developmental process involved in reproduction|
|mitotic cell cycle|
|gamete generation|
|protein localization to organelle|
|DNA metabolic process|
|leukocyte mediated immunity|
|positive regulation of hydrolase activity|
|cellular response to DNA damage stimulus|
|multicellular organismal reproductive process|
|sexual reproduction|
|multicellular organism reproduction|
|positive regulation of immune response|
|protein homodimerization activity|
|negative regulation of apoptotic process|
|negative regulation of programmed cell death|
|apoptotic process|
|leukocyte activation|
|embryo development|
|multi-organism reproductive process|
|negative regulation of cell death|
|cell cycle process|
|programmed cell death|
|chromosome organization|
|cell activation|
|cell death|
|immune effector process|
|positive regulation of immune system process|
|regulation of immune response|
|response to abiotic stimulus|
|regulation of cell cycle|
|regulation of hydrolase activity|
|phosphorylation|
|cell cycle|
|positive regulation of developmental process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|ATP binding|
|regulation of apoptotic process|
|regulation of programmed cell death|
|cellular protein localization|
|cellular macromolecule localization|
|cell development|
|regulation of immune system process|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of multicellular organismal process|
|positive regulation of molecular function|
|immune response|
|positive regulation of nucleobase-containing compound metabolic process|
|membrane|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp489|Hippuristanol 0.12μM R08 exp489 no dilution day6]]|-1.72|
|[[:results:exp29|Rapamycin 1μM R00 exp29]]|1.7|
|[[:results:exp48|Mubritinib 0.2μM R01 exp48]]|1.71|
|[[:results:exp19|Etoposide 1μM R00 exp19]]|1.73|
|[[:results:exp352|Dexamethasone 0.006 to 0.015μM on day4 R07 exp352]]|1.75|
|[[:results:exp60|Vinblastine 0.002μM R01 exp60]]|1.78|
|[[:results:exp59|UMK57 1μM R01 exp59]]|1.95|
|[[:results:exp11|CCCP 1μM R00 exp11]]|1.97|
|[[:results:exp365|I-BRD9 4μM R07 exp365]]|2.51|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 15627
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 4.55 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MSH2 Expression in NALM6 Cells: 4.55'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>