Gene content    
PMS2 ( by HUGO)
PMS2 Postmeiotic Segregation Increased
Other
PMS2 Postmeiotic Segregation Increased 2 (S. Cerevisiae)
PMSL2
DNA Mismatch Repair Protein PMS2
PMS1 Protein Homolog 2
HNPCC4
Postmeiotic Segregation Increased (S. Cerevisiae) 2
H_DJ0042M02.9
PMS2CL
Mismatch Repair Endonuclease PMS2
EC 3.1.-.-
NCBI: 7p22.2    Ensembl: 7p22.1
PMS2_HUMANSize: 862 amino acidsMass: 95797 Da

  • Subunit: Heterodimer of PMS2 and MLH1 (MutL alpha). Forms a ternary complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of the BRCA1-associated genome surveillance complex (BASC), which contains BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1 protein complex. This association could be a dynamic process changing throughout the cell cycle and within subnuclear domains. Interacts with MTMR15/FAN1
  • Function:
    UniProtKB/Swiss-Prot Summary: PMS2_HUMAN, P54278 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
  • Similarity:
    Belongs to the DNA mismatch repair MutL/HexB family [IMAGE]

    • Protein Domain/Family    
    Source ID Domain Name Type
    InterProIPR002099DNA_mismatch_repair_famDNA mismatch repair proteinFamily
    IPR003594HATPase_ATP-bdATP-binding region, ATPase-likeDomain
    BlocksIPB002099DNA mismatch repair proteinDNA mismatch repair protein
    IPB003594ATP-binding regionATP-binding region, ATPase-like

    Gene Ontology    
    Type Term Evidence Source Pub
    Biological Process mismatch repair IDA GOA 10871409
    Cellular Component nucleus IC GOA 10871409
    Molecular Function contributes_to MutSalpha complex binding IDA GOA 16403449
    contributes_to single-stranded DNA binding IDA GOA 11809883
    DNA binding IDA GOA 10871409
    protein binding IPI GOA 11793469
    single base insertion or deletion binding IDA GOA 10871409

    Disorder & Mutation    
    Source Disease
    SWISS-PROTMismatch repair cancer syndrome (MMRCS) [MIM:276300]: Autosomal dominant disorder characterized by malignant tumors of the brain associated with multiple colorectal adenomas. Skin features include sebaceous cysts, hyperpigmented and cafe au lait spots. Note=The disease is caused by mutations affecting the gene represented in this entry
    SWISS-PROTHereditary 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. Note=The disease is caused by mutations affecting the gene represented in this entry

    PMS2 cross reference    
    PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene