InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PMS2

Summary

InnateDB Protein

IDBP-7927.7

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PMS2

Protein Name

PMS2 postmeiotic segregation increased 2 (S. cerevisiae)

Synonyms

HNPCC4; PMS2CL; PMSL2;

Species

Homo sapiens

Ensembl Protein

ENSP00000371758

InnateDB Gene

IDBG-7921 (PMS2)

Protein Structure

UniProt Annotation

Function

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:0000269PubMed:16873062, ECO:0000269PubMed:18206974}.

Subcellular Localization

Nucleus.

Disease Associations

Hereditary non-polyposis colorectal cancer 4 (HNPCC4) [MIM:614337]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269PubMed:15887124, ECO:0000269PubMed:18178629}. Note=The disease is caused by mutations affecting the gene represented in this entry.Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: An autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients. {ECO:0000269PubMed:15077197, ECO:0000269PubMed:17557300, ECO:0000269PubMed:7661930, ECO:0000269PubMed:9419979}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 54 experimentally validated interaction(s) in this database.

Experimentally validated
Total	54 [view]
Protein-Protein	51 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003697	single-stranded DNA binding
GO:0004519	endonuclease activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016887	ATPase activity
GO:0030983	mismatched DNA binding
GO:0032138	single base insertion or deletion binding
GO:0032407	MutSalpha complex binding

Biological Process

GO:0006200	ATP catabolic process
GO:0006298	mismatch repair
GO:0016446	somatic hypermutation of immunoglobulin genes
GO:0090305	nucleic acid phosphodiester bond hydrolysis