UniProt Accession

 PMS2_HUMAN; P54278; B2R610; Q52LH6; Q5FBW9; Q5FBX1; Q5FBX2; Q75MR2 

Genbank Protein ID

 U13696; AB103082; AB103083; AB103085; U14658; AK312390; AC005995; BC093921 

Genbank Nucleotide ID

 AAA63923.1; BAD89425.1; BAD89426.1; BAD89428.1; AAA50390.1; BAG35307.1; AAS00390.1; AAH93921.1 

Protein Name

 Mismatch repair endonuclease PMS2 

Protein Synonyms/Alias

 DNA mismatch repair protein PMS2; PMS1 protein homolog 2 

Gene Name

 PMS2 

Gene Synonyms/Alias

 PMSL2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
146	HNGKIIQKTPYPRPR	ubiquitination	[1, 2, 3]
301	RRPCDPAKVCRLVNE	ubiquitination	[3]
748	ENLEIFRKNGFDFVI	ubiquitination	[3]

Reference

 [1] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [2] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [3] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 

Functional Description

 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. MulL 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. 

Sequence Annotation

 MOD_RES 181 181 Phosphotyrosine (By similarity).
 MOD_RES 597 597 Phosphothreonine.  

Keyword

 3D-structure; Alternative splicing; Complete proteome; Disease mutation; DNA damage; DNA repair; Endonuclease; Hereditary nonpolyposis colorectal cancer; Hydrolase; Nuclease; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Tumor suppressor. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 862 AA 

Protein Sequence

Gene Ontology

 GO:0032389; C:MutLalpha complex; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:InterPro.
 GO:0016887; F:ATPase activity; IBA:RefGenome.
 GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
 GO:0032138; F:single base insertion or deletion binding; IDA:HGNC.
 GO:0006298; P:mismatch repair; IDA:HGNC.
 GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IEA:GOC.
 GO:0007131; P:reciprocal meiotic recombination; IBA:RefGenome.
 GO:0042493; P:response to drug; IEA:Compara.
 GO:0016446; P:somatic hypermutation of immunoglobulin genes; IBA:RefGenome.
 GO:0016447; P:somatic recombination of immunoglobulin gene segments; IEA:Compara. 

Interpro

 IPR002099; DNA_mismatch_repair.
 IPR013507; DNA_mismatch_repair_C.
 IPR014762; DNA_mismatch_repair_CS.
 IPR014763; DNA_mismatch_repair_N.
 IPR003594; HATPase_ATP-bd.
 IPR014790; MutL_C.
 IPR020568; Ribosomal_S5_D2-typ_fold.
 IPR014721; Ribosomal_S5_D2-typ_fold_subgr. 

Pfam

 PF01119; DNA_mis_repair
 PF08676; MutL_C 

SMART

 SM00387; HATPase_c
 SM00853; MutL_C 

PROSITE

 PS00058; DNA_MISMATCH_REPAIR_1 

PRINTS