======= PMS2 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PMS2
  * **<color #00a2e8>Official Name</color>**: PMS1 homolog 2, mismatch repair system component
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=5395|5395]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P54278|P54278]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PMS2&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PMS2|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/600259|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  The protein encoded by this gene is a key component of the mismatch repair system that functions to correct DNA mismatches and small insertions and deletions that can occur during DNA replication and homologous recombination. This protein forms heterodimers with the gene product of the mutL homolog 1 (MLH1) gene to form the MutL-alpha heterodimer. The MutL-alpha heterodimer possesses an endonucleolytic activity that is activated following recognition of mismatches and insertion/deletion loops by the MutS-alpha and MutS-beta heterodimers, and is necessary for removal of the mismatched DNA. There is a DQHA(X)2E(X)4E motif found at the C-terminus of the protein encoded by this gene that forms part of the active site of the nuclease. Mutations in this gene have been associated with hereditary nonpolyposis colorectal cancer (HNPCC; also known as Lynch syndrome) and Turcot syndrome. [provided by RefSeq, Apr 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  Component of the post-replicative DNA mismatch repair system (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2- MSH6) binding to a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex. Assembly of the MutL-MutS-heteroduplex ternary complex in presence of RFC and PCNA is sufficient to activate endonuclease activity of PMS2. It introduces single-strand breaks near the mismatch and thus generates new entry points for the exonuclease EXO1 to degrade the strand containing the mismatch. DNA methylation would prevent cleavage and therefore assure that only the newly mutated DNA strand is going to be corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp loader subunits of DNA polymerase III, suggesting that it may play a role to recruit the DNA polymerase III to the site of the MMR. Also implicated in DNA damage signaling, a process which induces cell cycle arrest and can lead to apoptosis in case of major DNA damages. {ECO:0000269|PubMed:16873062, ECO:0000269|PubMed:18206974, ECO:0000269|PubMed:23709753}.

<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'>
|MutL C|
|HATPase c|
|DNA mis repair|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|single base insertion or deletion binding|
|MutSalpha complex binding|
|MutLalpha complex|
|mismatch repair complex|
|somatic hypermutation of immunoglobulin genes|
|somatic diversification of immune receptors via somatic mutation|
|mismatch repair|
|somatic diversification of immunoglobulins|
|endonuclease activity|
|somatic diversification of immune receptors|
|cytoplasmic ribonucleoprotein granule|
|single-stranded DNA binding|
|microtubule cytoskeleton|
|immunoglobulin production|
|production of molecular mediator of immune response|
|ATPase activity|
|nucleic acid phosphodiester bond hydrolysis|
|DNA repair|
|immune system development|
|DNA metabolic process|
|cellular response to DNA damage stimulus|
|response to drug|
|DNA binding|
|ATP binding|
|cellular response to stress|
</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:exp256|HMS-I1 10μM R06 exp256]]|1.87|
|[[:results:exp244|SB743921 0.001μM R05 exp244]]|1.87|
|[[:results:exp33|Rotenone 2μM R00 exp33]]|2.53|
|[[:results:exp208|Vinblastine 0.015μM R05 exp208]]|2.56|
|[[:results:exp24|Nocodazole 0.2μM R00 exp24]]|2.85|
|[[:results:exp94|Nocodazole 0.1μM R03 exp94]]|2.96|
|[[:results:exp111|R-DABN 8μM R03 exp111]]|3.22|
</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>**: 6555
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.17 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PMS2 Expression in NALM6 Cells: 6.17'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>