Names & Taxonomy

Uniprot ID:
P54278
Entry Name:
PMS2_HUMAN
Status:
reviewed
Protein Names:
Mismatch repair endonuclease PMS2 (EC 3.1.-.-) (DNA mismatch repair protein PMS2) (PMS1 protein homolog 2)
Gene Names:
PMS2 PMSL2
Gene Names Primary:
PMS2
Organism:
Homo sapiens (Human)

Structure

Length:
862
Sequence:
MERAESSSTEPAKAIKPIDRKSVHQICSGQVVLSLSTAVKELVENSLDAGATNIDLKLKDYGVDLIEVSDNGCGVEEENFEGLTLKHHTSKIQEFADLTQVETFGFRGEALSSLCALSDVTISTCHASAKVGTRLMFDHNGKIIQKTPYPRPRGTTVSVQQLFSTLPVRHKEFQRNIKKEYAKMVQVLHAYCIISAGIRVSCTNQLGQGKRQPVVCTGGSPSIKENIGSVFGQKQLQSLIPFVQLPPSDSVCEEYGLSCSDALHNLFYISGFISQCTHGVGRSSTDRQFFFINRRPCDPAKVCRLVNEVYHMYNRHQYPFVVLNISVDSECVDINVTPDKRQILLQEEKLLLAVLKTSLIGMFDSDVNKLNVSQQPLLDVEGNLIKMHAADLEKPMVEKQDQSPSLRTGEEKKDVSISRLREAFSLRHTTENKPHSPKTPEPRRSPLGQKRGMLSSSTSGAISDKGVLRPQKEAVSSSHGPSDPTDRAEVEKDSGHGSTSVDSEGFSIPDTGSHCSSEYAASSPGDRGSQEHVDSQEKAPKTDDSFSDVDCHSNQEDTGCKFRVLPQPTNLATPNTKRFKKEEILSSSDICQKLVNTQDMSASQVDVAVKINKKVVPLDFSMSSLAKRIKQLHHEAQQSEGEQNYRKFRAKICPGENQAAEDELRKEISKTMFAEMEIIGQFNLGFIITKLNEDIFIVDQHATDEKYNFEMLQQHTVLQGQRLIAPQTLNLTAVNEAVLIENLEIFRKNGFDFVIDENAPVTERAKLISLPTSKNWTFGPQDVDELIFMLSDSPGVMCRPSRVKQMFASRACRKSVMIGTALNTSEMKKLITHMGEMDHPWNCPHGRPTMRHIANLGVISQN
Proteomes:
UP000005640

Subcellular location

Subcellular Location:
Nucleus

Function

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.
Gene Ontology Go:
cytoplasm
microtubule cytoskeleton
MutLalpha complex
nucleoplasm
nucleus
ATP binding
ATPase activity
DNA binding
endonuclease activity
single base insertion or deletion binding
DNA repair
mismatch repair
nucleic acid phosphodiester bond hydrolysis
response to drug
somatic hypermutation of immunoglobulin genes
Gene Ontology Biological Process:
DNA repair
mismatch repair
nucleic acid phosphodiester bond hydrolysis
response to drug
somatic hypermutation of immunoglobulin genes
Gene Ontology Molecular Function:
ATPase activity
ATP binding
DNA binding
endonuclease activity
single base insertion or deletion binding
Gene Ontology Cellular Component:
cytoplasm
microtubule cytoskeleton
MutLalpha complex
nucleoplasm
nucleus
Keywords:
3D-structure
Alternative splicing
Complete proteome
DNA damage
DNA repair
Disease mutation
Endonuclease
Hereditary nonpolyposis colorectal cancer
Hydrolase
Nuclease
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
Tumor suppressor
Interacts With:
P40692

Publication

PubMed ID:
8072530 14702039 12853948 15489334 10783165 15887124 16873062 18178629 18206974 16188885 16873053 18157157 20603073 20068231 11574484 7661930 9419979 10480359 11793469 15077197 17557300 23709753