MSH6 [The Human Chemical-Genetic Interaction Map Project]

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======= MSH6 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: MSH6
  * **<color #00a2e8>Official Name</color>**: mutS homolog 6
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=2956|2956]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P52701|P52701]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MSH6&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MSH6|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600678|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a member of the DNA mismatch repair MutS family. In E. coli, the MutS protein helps in the recognition of mismatched nucleotides prior to their repair. A highly conserved region of approximately 150 aa, called the Walker-A adenine nucleotide binding motif, exists in MutS homologs. The encoded protein heterodimerizes with MSH2 to form a mismatch recognition complex that functions as a bidirectional molecular switch that exchanges ADP and ATP as DNA mismatches are bound and dissociated. Mutations in this gene may be associated with hereditary nonpolyposis colon cancer, colorectal cancer, and endometrial cancer. Transcripts variants encoding different isoforms have been described. [provided by RefSeq, Jul 2013]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MSH2 to form MutS alpha, which binds to DNA mismatches thereby initiating DNA repair. When bound, MutS alpha bends the DNA helix and shields approximately 20 base pairs, and recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. After mismatch binding, 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. Recruited on chromatin in G1 and early S phase via its PWWP domain that specifically binds trimethylated 'Lys-36' of histone H3 (H3K36me3): early recruitment to chromatin to be replicated allowing a quick identification of mismatch repair to initiate the DNA mismatch repair reaction. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:23622243, 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 V|
|MutS I|
|PWWP|
|MutS III|
|MutS IV|
|MutS II|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|single thymine insertion binding|
|MutSalpha complex|
|meiotic mismatch repair|
|single guanine insertion binding|
|guanine/thymine mispair binding|
|negative regulation of DNA endoreduplication|
|maintenance of DNA repeat elements|
|MutLalpha complex binding|
|oxidized purine DNA binding|
|positive regulation of helicase activity|
|mismatched DNA binding|
|regulation of DNA endoreduplication|
|pyrimidine dimer repair|
|regulation of helicase activity|
|mismatch repair complex|
|four-way junction DNA binding|
|determination of adult lifespan|
|somatic hypermutation of immunoglobulin genes|
|somatic recombination of immunoglobulin genes involved in immune response|
|isotype switching|
|somatic diversification of immune receptors via somatic mutation|
|somatic diversification of immunoglobulins involved in immune response|
|somatic recombination of immunoglobulin gene segments|
|negative regulation of DNA-dependent DNA replication|
|immunoglobulin production involved in immunoglobulin mediated immune response|
|mismatch repair|
|multicellular organism aging|
|somatic diversification of immune receptors via germline recombination within a single locus|
|somatic cell DNA recombination|
|somatic diversification of immunoglobulins|
|ADP binding|
|negative regulation of DNA replication|
|B cell activation involved in immune response|
|DNA-dependent ATPase activity|
|negative regulation of DNA recombination|
|somatic diversification of immune receptors|
|interstrand cross-link repair|
|regulation of DNA-dependent DNA replication|
|positive regulation of ATPase activity|
|methylated histone binding|
|intrinsic apoptotic signaling pathway in response to DNA damage|
|regulation of ATPase activity|
|double-stranded DNA binding|
|regulation of DNA recombination|
|regulation of DNA replication|
|lymphocyte activation involved in immune response|
|meiosis I cell cycle process|
|negative regulation of DNA metabolic process|
|response to UV|
|intrinsic apoptotic signaling pathway|
|B cell activation|
|immunoglobulin production|
|meiotic cell cycle process|
|production of molecular mediator of immune response|
|immunoglobulin mediated immune response|
|B cell mediated immunity|
|magnesium ion binding|
|DNA recombination|
|meiotic cell cycle|
|ATPase activity|
|nuclear chromatin|
|lymphocyte mediated immunity|
|aging|
|adaptive immune response based on somatic recombination of immune receptors built from immunoglobulin superfamily domains|
|apoptotic signaling pathway|
|response to light stimulus|
|negative regulation of cell cycle process|
|enzyme binding|
|regulation of DNA metabolic process|
|lymphocyte activation|
|chromatin binding|
|response to radiation|
|DNA repair|
|negative regulation of cell cycle|
|adaptive immune response|
|leukocyte activation involved in immune response|
|cell activation involved in immune response|
|immune system development|
|intracellular membrane-bounded organelle|
|viral process|
|DNA metabolic process|
|regulation of cell cycle process|
|leukocyte mediated immunity|
|positive regulation of hydrolase activity|
|cellular response to DNA damage stimulus|
|symbiotic process|
|interspecies interaction between organisms|
|protein homodimerization activity|
|apoptotic process|
|leukocyte activation|
|Golgi apparatus|
|cell cycle process|
|programmed cell death|
|chromosome organization|
|cell activation|
|cell death|
|immune effector process|
|response to abiotic stimulus|
|regulation of cell cycle|
|regulation of hydrolase activity|
|cell cycle|
|negative regulation of cellular macromolecule biosynthetic process|
|reproductive process|
|reproduction|
|positive regulation of catalytic activity|
|negative regulation of nucleobase-containing compound metabolic process|
|negative regulation of macromolecule biosynthetic process|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|negative regulation of biosynthetic process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of molecular function|
|immune response|
</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:exp429|Rapamycin 0.001μM R08 exp429]]|-1.77|
|[[:results:exp11|CCCP 1μM R00 exp11]]|1.75|
|[[:results:exp326|CCT251545 20μM R07 exp326]]|1.75|
|[[:results:exp242|Radicicol 0.16μM R05 exp242]]|1.76|
|[[:results:exp360|Genistein 15μM R07 exp360]]|1.9|
|[[:results:exp18|Doxycycline 10μM R00 exp18]]|1.95|
|[[:results:exp400|Senexin-A 25μM R07 exp400]]|2.01|
</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: 0/726
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/25|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/15|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/14|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/7|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 16248
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.6 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MSH6 Expression in NALM6 Cells: 7.6'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>