PMS2_MOUSE
ID PMS2_MOUSE Reviewed; 859 AA.
AC P54279;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 143.
DE RecName: Full=Mismatch repair endonuclease PMS2 {ECO:0000250|UniProtKB:P54278};
DE EC=3.1.-.-;
DE AltName: Full=DNA mismatch repair protein PMS2;
DE AltName: Full=PMS1 protein homolog 2 {ECO:0000250|UniProtKB:P54278};
GN Name=Pms2 {ECO:0000312|MGI:MGI:104288};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7628019; DOI=10.1016/0092-8674(95)90318-6;
RA Baker S.M., Bronner C.E., Zhang L., Plug A., Robatzek M., Warren G.,
RA Elliot E.A., Yu J., Ashley T., Arnheim N., Flavell R.A., Liskay R.M.;
RT "Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal
RT chromosome synapsis in meiosis.";
RL Cell 82:309-319(1995).
CC -!- FUNCTION: Component of the post-replicative DNA mismatch repair system
CC (MMR). Heterodimerizes with MLH1 to form MutL alpha. DNA repair is
CC initiated by MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3) binding to
CC a dsDNA mismatch, then MutL alpha is recruited to the heteroduplex.
CC Assembly of the MutL-MutS-heteroduplex ternary complex in presence of
CC RFC and PCNA is sufficient to activate endonuclease activity of PMS2.
CC It introduces single-strand breaks near the mismatch and thus generates
CC new entry points for the exonuclease EXO1 to degrade the strand
CC containing the mismatch. DNA methylation would prevent cleavage and
CC therefore assure that only the newly mutated DNA strand is going to be
CC corrected. MutL alpha (MLH1-PMS2) interacts physically with the clamp
CC loader subunits of DNA polymerase III, suggesting that it may play a
CC role to recruit the DNA polymerase III to the site of the MMR. Also
CC implicated in DNA damage signaling, a process which induces cell cycle
CC arrest and can lead to apoptosis in case of major DNA damages.
CC {ECO:0000250|UniProtKB:P54278}.
CC -!- SUBUNIT: Heterodimer of PMS2 and MLH1 (MutL alpha). Forms a ternary
CC complex with MutS alpha (MSH2-MSH6) or MutS beta (MSH2-MSH3). Part of
CC the BRCA1-associated genome surveillance complex (BASC), which contains
CC BRCA1, MSH2, MSH6, MLH1, ATM, BLM, PMS2 and the RAD50-MRE11-NBS1
CC protein complex. This association could be a dynamic process changing
CC throughout the cell cycle and within subnuclear domains. Interacts with
CC MTMR15/FAN1. {ECO:0000250|UniProtKB:P54278}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:P54278}.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC {ECO:0000305}.
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DR EMBL; U28724; AAA87031.1; -; mRNA.
DR AlphaFoldDB; P54279; -.
DR SMR; P54279; -.
DR STRING; 10090.ENSMUSP00000119875; -.
DR MoonProt; P54279; -.
DR iPTMnet; P54279; -.
DR PhosphoSitePlus; P54279; -.
DR EPD; P54279; -.
DR jPOST; P54279; -.
DR MaxQB; P54279; -.
DR PeptideAtlas; P54279; -.
DR PRIDE; P54279; -.
DR ProteomicsDB; 289702; -.
DR MGI; MGI:104288; Pms2.
DR eggNOG; KOG1978; Eukaryota.
DR InParanoid; P54279; -.
DR Reactome; R-MMU-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR ChiTaRS; Pms2; mouse.
DR PRO; PR:P54279; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; P54279; protein.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; ISO:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
DR GO; GO:0032389; C:MutLalpha complex; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0016887; F:ATP hydrolysis activity; IBA:GO_Central.
DR GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0004519; F:endonuclease activity; IEA:UniProtKB-KW.
DR GO; GO:0032407; F:MutSalpha complex binding; ISO:MGI.
DR GO; GO:0032138; F:single base insertion or deletion binding; ISO:MGI.
DR GO; GO:0003697; F:single-stranded DNA binding; ISO:MGI.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IMP:MGI.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0051321; P:meiotic cell cycle; TAS:MGI.
DR GO; GO:0006298; P:mismatch repair; IMP:MGI.
DR GO; GO:0048298; P:positive regulation of isotype switching to IgA isotypes; IMP:CAFA.
DR GO; GO:0048304; P:positive regulation of isotype switching to IgG isotypes; IMP:CAFA.
DR GO; GO:0016446; P:somatic hypermutation of immunoglobulin genes; IMP:CAFA.
DR GO; GO:0016447; P:somatic recombination of immunoglobulin gene segments; IMP:MGI.
DR Gene3D; 3.30.1370.100; -; 1.
DR Gene3D; 3.30.1540.20; -; 1.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR014762; DNA_mismatch_repair_CS.
DR InterPro; IPR002099; DNA_mismatch_repair_N.
DR InterPro; IPR013507; DNA_mismatch_S5_2-like.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR038973; MutL/Mlh/Pms.
DR InterPro; IPR014790; MutL_C.
DR InterPro; IPR042120; MutL_C_dimsub.
DR InterPro; IPR042121; MutL_C_regsub.
DR InterPro; IPR037198; MutL_C_sf.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR PANTHER; PTHR10073; PTHR10073; 1.
DR Pfam; PF01119; DNA_mis_repair; 1.
DR Pfam; PF08676; MutL_C; 1.
DR SMART; SM01340; DNA_mis_repair; 1.
DR SMART; SM00853; MutL_C; 1.
DR SUPFAM; SSF118116; SSF118116; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR TIGRFAMs; TIGR00585; mutl; 1.
DR PROSITE; PS00058; DNA_MISMATCH_REPAIR_1; 1.
PE 2: Evidence at transcript level;
KW DNA damage; DNA repair; Endonuclease; Hydrolase; Nuclease; Nucleus;
KW Reference proteome; Tumor suppressor.
FT CHAIN 1..859
FT /note="Mismatch repair endonuclease PMS2"
FT /id="PRO_0000178006"
FT REGION 392..413
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 427..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 469..555
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 496..532
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 859 AA; 95225 MW; 263B5A6BBBB2ACA9 CRC64;
MEQTEGVSTE CAKAIKPIDG KSVHQICSGQ VILSLSTAVK ELIENSVDAG ATTIDLRLKD
YGVDLIEVSD NGCGVEEENF EGLALKHHTS KIQEFADLTQ VETFGFRGEA LSSLCALSDV
TISTCHGSAS VGTRLVFDHN GKITQKTPYP RPKGTTVSVQ HLFYTLPVRY KEFQRNIKKE
YSKMVQVLQA YCIISAGVRV SCTNQLGQGK RHAVVCTSGT SGMKENIGSV FGQKQLQSLI
PFVQLPPSDA VCEEYGLSTS GRHKTFSTFR ASFHSARTAP GGVQQTGSFS SSIRGPVTQQ
RSLSLSMRFY HMYNRHQYPF VVLNVSVDSE CVDINVTPDK RQILLQEEKL LLAVLKTSLI
GMFDSDANKL NVNQQPLLDV EGNLVKLHTA ELEKPVPGKQ DNSPSLKSTA DEKRVASISR
LREAFSLHPT KEIKSRGPET AELTRSFPSE KRGVLSSYPS DVISYRGLRG SQDKLVSPTD
SPGDCMDREK IEKDSGLSST SAGSEEEFST PEVASSFSSD YNVSSLEDRP SQETINCGDL
DCRPPGTGQS LKPEDHGYQC KALPLARLSP TNAKRFKTEE RPSNVNISQR LPGPQSTSAA
EVDVAIKMNK RIVLLEFSLS SLAKRMKQLQ HLKAQNKHEL SYRKFRAKIC PGENQAAEDE
LRKEISKSMF AEMEILGQFN LGFIVTKLKE DLFLVDQHAA DEKYNFEMLQ QHTVLQAQRL
ITPQTLNLTA VNEAVLIENL EIFRKNGFDF VIDEDAPVTE RAKLISLPTS KNWTFGPQDI
DELIFMLSDS PGVMCRPSRV RQMFASRACR KSVMIGTALN ASEMKKLITH MGEMDHPWNC
PHGRPTMRHV ANLDVISQN
