ID   MLH1_YEAST              Reviewed;         769 AA.
AC   P38920; D6VZY9; Q2I028; Q2I029; Q2I031; Q2I032; Q2I033; Q2I034; Q2I035;
AC   Q2I036; Q2I038; Q2I039; Q2I041;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 210.
DE   RecName: Full=DNA mismatch repair protein MLH1;
DE   AltName: Full=MutL protein homolog 1;
DE   AltName: Full=Post meiotic segregation protein 2;
GN   Name=MLH1; Synonyms=PMS2; OrderedLocusNames=YMR167W;
GN   ORFNames=YM8520.16;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8264608; DOI=10.1128/mcb.14.1.407-415.1994;
RA   Prolla T.A., Christie D.-M., Liskay R.M.;
RT   "Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two
RT   homologs of the bacterial mutL gene.";
RL   Mol. Cell. Biol. 14:407-415(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-240; GLU-242; PRO-271;
RP   LEU-309; ASP-321; LYS-333; THR-375; GLY-452; ASN-465; SER-470; PHE-607;
RP   ASN-678; LEU-703 AND GLY-761.
RC   STRAIN=ATCC 200060 / W303, EAY1066, EAY1068, M2-8, M5-7, M7-8, SK1,
RC   YJM 145, YJM 269, YJM 280, YJM 320, YJM 326, YJM 339, and YJM 627;
RX   PubMed=16492773; DOI=10.1073/pnas.0510998103;
RA   Heck J.A., Argueso J.L., Gemici Z., Reeves R.G., Bernard A., Aquadro C.F.,
RA   Alani E.;
RT   "Negative epistasis between natural variants of the Saccharomyces
RT   cerevisiae MLH1 and PMS1 genes results in a defect in mismatch repair.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:3256-3261(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169872;
RA   Bowman S., Churcher C.M., Badcock K., Brown D., Chillingworth T.,
RA   Connor R., Dedman K., Devlin K., Gentles S., Hamlin N., Hunt S., Jagels K.,
RA   Lye G., Moule S., Odell C., Pearson D., Rajandream M.A., Rice P.,
RA   Skelton J., Walsh S.V., Whitehead S., Barrell B.G.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XIII.";
RL   Nature 387:90-93(1997).
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [5]
RP   MUTAGENESIS OF ALA-41; GLY-64; ILE-65; GLU-99; ILE-104; THR-114; ARG-214;
RP   VAL-216; ARG-265; ILE-326; GLN-552; ARG-672 AND ALA-694.
RX   PubMed=11555625; DOI=10.1093/hmg/10.18.1889;
RA   Ellison A.R., Lofing J., Bitter G.A.;
RT   "Functional analysis of human MLH1 and MSH2 missense variants and hybrid
RT   human-yeast MLH1 proteins in Saccharomyces cerevisiae.";
RL   Hum. Mol. Genet. 10:1889-1900(2001).
RN   [6]
RP   INTERACTION WITH PMS1, AND MUTAGENESIS OF ALA-41; PHE-96; ARG-97; GLY-98;
RP   LYS-764; PHE-766; GLU-767 AND CYS-769.
RX   PubMed=9234704; DOI=10.1128/mcb.17.8.4465;
RA   Pang Q., Prolla T.A., Liskay R.M.;
RT   "Functional domains of the Saccharomyces cerevisiae Mlh1p and Pms1p DNA
RT   mismatch repair proteins and their relevance to human hereditary
RT   nonpolyposis colorectal cancer-associated mutations.";
RL   Mol. Cell. Biol. 17:4465-4473(1997).
RN   [7]
RP   FUNCTION, AND SUBUNIT.
RX   PubMed=9545323; DOI=10.1074/jbc.273.16.9837;
RA   Habraken Y., Sung P., Prakash L., Prakash S.;
RT   "ATP-dependent assembly of a ternary complex consisting of a DNA mismatch
RT   and the yeast MSH2-MSH6 and MLH1-PMS1 protein complexes.";
RL   J. Biol. Chem. 273:9837-9841(1998).
RN   [8]
RP   FUNCTION, AND INTERACTION WITH MLH2; MLH3 AND PMS1.
RX   PubMed=10570173; DOI=10.1073/pnas.96.24.13914;
RA   Wang T.-F., Kleckner N., Hunter N.;
RT   "Functional specificity of MutL homologs in yeast: evidence for three Mlh1-
RT   based heterocomplexes with distinct roles during meiosis in recombination
RT   and mismatch correction.";
RL   Proc. Natl. Acad. Sci. U.S.A. 96:13914-13919(1999).
RN   [9]
RP   INTERACTION WITH PMS1, ATP-BINDING, AND MUTAGENESIS OF GLU-31 AND GLY-98.
RX   PubMed=10938116; DOI=10.1128/mcb.20.17.6390-6398.2000;
RA   Tran P.T., Liskay R.M.;
RT   "Functional studies on the candidate ATPase domains of Saccharomyces
RT   cerevisiae MutLalpha.";
RL   Mol. Cell. Biol. 20:6390-6398(2000).
RN   [10]
RP   DNA-BINDING.
RX   PubMed=12222686; DOI=10.1515/bc.2002.103;
RA   Drotschmann K., Hall M.C., Shcherbakova P.V., Wang H., Erie D.A.,
RA   Brownewell F.R., Kool E.T., Kunkel T.A.;
RT   "DNA binding properties of the yeast Msh2-Msh6 and Mlh1-Pms1
RT   heterodimers.";
RL   Biol. Chem. 383:969-975(2002).
RN   [11]
RP   ATP-BINDING, MUTAGENESIS OF GLU-31 AND ASN-35, AND BIOPHYSICOCHEMICAL
RP   PROPERTIES.
RX   PubMed=11717305; DOI=10.1074/jbc.m106120200;
RA   Hall M.C., Shcherbakova P.V., Kunkel T.A.;
RT   "Differential ATP binding and intrinsic ATP hydrolysis by amino-terminal
RT   domains of the yeast Mlh1 and Pms1 proteins.";
RL   J. Biol. Chem. 277:3673-3679(2002).
RN   [12]
RP   FUNCTION, AND MUTAGENESIS.
RX   PubMed=12529393; DOI=10.1128/mcb.23.3.873-886.2003;
RA   Argueso J.L., Kijas A.W., Sarin S., Heck J.A., Waase M., Alani E.;
RT   "Systematic mutagenesis of the Saccharomyces cerevisiae MLH1 gene reveals
RT   distinct roles for Mlh1p in meiotic crossing over and in vegetative and
RT   meiotic mismatch repair.";
RL   Mol. Cell. Biol. 23:873-886(2003).
RN   [13]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [14]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [15]
RP   DNA-BINDING, AND MUTAGENESIS OF ARG-273 AND ARG-274.
RX   PubMed=12682353; DOI=10.1093/nar/gkg324;
RA   Hall M.C., Shcherbakova P.V., Fortune J.M., Borchers C.H., Dial J.M.,
RA   Tomer K.B., Kunkel T.A.;
RT   "DNA binding by yeast Mlh1 and Pms1: implications for DNA mismatch
RT   repair.";
RL   Nucleic Acids Res. 31:2025-2034(2003).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-441, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA   Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT   "A multidimensional chromatography technology for in-depth phosphoproteome
RT   analysis.";
RL   Mol. Cell. Proteomics 7:1389-1396(2008).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
CC   -!- FUNCTION: Required for DNA mismatch repair (MMR), correcting base-base
CC       mismatches and insertion-deletion loops (IDLs) resulting from DNA
CC       replication, DNA damage or from recombination events between non-
CC       identical sequences during meiosis. Component of different MutL
CC       heterodimers that form a ternary complex with the MutS heterodimers,
CC       which initially recognize the DNA mismatches. This complex is thought
CC       to be responsible for directing the downstream MMR events, including
CC       strand discrimination, excision, and resynthesis. Plays a major role in
CC       maintaining the genetic stability of simple sequence repeats, the
CC       repair of heteroduplex sites present in meiotic recombination
CC       intermediates, and the promotion of meiotic crossing-over.
CC       {ECO:0000269|PubMed:10570173, ECO:0000269|PubMed:12529393,
CC       ECO:0000269|PubMed:9545323}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=69 uM for ATP {ECO:0000269|PubMed:11717305};
CC   -!- SUBUNIT: Heterodimer of MLH1 and PMS1, called MutLalpha, which is the
CC       major MMR MutL activity correcting base-base mismatches as well as
CC       IDLs. The heterodimer binds double strand DNA independently of a
CC       mismatch with positive cooperativity and has more than one DNA binding
CC       site. Forms a ternary complex with either the MSH2-MSH6 (MutSalpha) or
CC       the MSH2-MSH3 heterodimer (MutSbeta), which recognize and bind to
CC       mismatch DNA. Ternary complex formation is promoted by ATP binding.
CC       Heterodimer of MLH1 and MLH3, called MutLbeta, which is involved in
CC       correction of a specific subset of IDLs when associated with MutSbeta.
CC       Heterodimer of MLH1 and MLH2. {ECO:0000269|PubMed:9545323}.
CC   -!- INTERACTION:
CC       P38920; P39875: EXO1; NbExp=3; IntAct=EBI-11003, EBI-6738;
CC       P38920; Q07980: MLH2; NbExp=5; IntAct=EBI-11003, EBI-33369;
CC       P38920; Q12083: MLH3; NbExp=5; IntAct=EBI-11003, EBI-31634;
CC       P38920; Q08214: NTG2; NbExp=3; IntAct=EBI-11003, EBI-12303;
CC       P38920; P14242: PMS1; NbExp=12; IntAct=EBI-11003, EBI-13561;
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}.
CC   -!- MISCELLANEOUS: Present with 319 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC       {ECO:0000305}.
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DR   EMBL; U07187; AAA16835.1; -; Unassigned_DNA.
DR   EMBL; DQ356633; ABC86937.1; -; Genomic_DNA.
DR   EMBL; DQ356634; ABC86938.1; -; Genomic_DNA.
DR   EMBL; DQ356635; ABC86939.1; -; Genomic_DNA.
DR   EMBL; DQ356636; ABC86940.1; -; Genomic_DNA.
DR   EMBL; DQ356637; ABC86941.1; -; Genomic_DNA.
DR   EMBL; DQ356638; ABC86942.1; -; Genomic_DNA.
DR   EMBL; DQ356639; ABC86943.1; -; Genomic_DNA.
DR   EMBL; DQ356640; ABC86944.1; -; Genomic_DNA.
DR   EMBL; DQ356641; ABC86945.1; -; Genomic_DNA.
DR   EMBL; DQ356642; ABC86946.1; -; Genomic_DNA.
DR   EMBL; DQ356643; ABC86947.1; -; Genomic_DNA.
DR   EMBL; DQ356644; ABC86948.1; -; Genomic_DNA.
DR   EMBL; DQ356645; ABC86949.1; -; Genomic_DNA.
DR   EMBL; DQ356646; ABC86950.1; -; Genomic_DNA.
DR   EMBL; Z49705; CAA89803.1; -; Genomic_DNA.
DR   EMBL; BK006946; DAA10063.1; -; Genomic_DNA.
DR   PIR; S54525; S54525.
DR   RefSeq; NP_013890.1; NM_001182671.1.
DR   PDB; 4E4W; X-ray; 2.50 A; A=485-769.
DR   PDB; 4FMN; X-ray; 2.69 A; A=485-769.
DR   PDB; 4FMO; X-ray; 3.04 A; A=485-769.
DR   PDB; 6RMN; X-ray; 2.20 A; A=505-769.
DR   PDB; 6SHX; X-ray; 2.40 A; A=505-769.
DR   PDB; 6SNS; X-ray; 2.60 A; A=505-769.
DR   PDB; 6SNV; X-ray; 2.50 A; A/D=505-769.
DR   PDBsum; 4E4W; -.
DR   PDBsum; 4FMN; -.
DR   PDBsum; 4FMO; -.
DR   PDBsum; 6RMN; -.
DR   PDBsum; 6SHX; -.
DR   PDBsum; 6SNS; -.
DR   PDBsum; 6SNV; -.
DR   AlphaFoldDB; P38920; -.
DR   SMR; P38920; -.
DR   BioGRID; 35345; 237.
DR   ComplexPortal; CPX-1666; MutLalpha endonuclease complex.
DR   ComplexPortal; CPX-1667; MutLbeta endonuclease complex.
DR   ComplexPortal; CPX-1668; MLH1-MLH3 endonuclease complex.
DR   DIP; DIP-2412N; -.
DR   IntAct; P38920; 17.
DR   MINT; P38920; -.
DR   STRING; 4932.YMR167W; -.
DR   iPTMnet; P38920; -.
DR   MaxQB; P38920; -.
DR   PaxDb; 4932-YMR167W; -.
DR   PeptideAtlas; P38920; -.
DR   EnsemblFungi; YMR167W_mRNA; YMR167W; YMR167W.
DR   GeneID; 855203; -.
DR   KEGG; sce:YMR167W; -.
DR   AGR; SGD:S000004777; -.
DR   SGD; S000004777; MLH1.
DR   VEuPathDB; FungiDB:YMR167W; -.
DR   eggNOG; KOG1979; Eukaryota.
DR   GeneTree; ENSGT00800000124177; -.
DR   HOGENOM; CLU_004131_2_0_1; -.
DR   InParanoid; P38920; -.
DR   OMA; ANYHVKK; -.
DR   OrthoDB; 5475669at2759; -.
DR   BioCyc; YEAST:G3O-32857-MONOMER; -.
DR   BRENDA; 3.6.1.3; 984.
DR   Reactome; R-SCE-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR   SABIO-RK; P38920; -.
DR   BioGRID-ORCS; 855203; 0 hits in 10 CRISPR screens.
DR   PRO; PR:P38920; -.
DR   Proteomes; UP000002311; Chromosome XIII.
DR   RNAct; P38920; Protein.
DR   GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; HDA:SGD.
DR   GO; GO:0032389; C:MutLalpha complex; IPI:SGD.
DR   GO; GO:0032390; C:MutLbeta complex; IPI:SGD.
DR   GO; GO:0097587; C:MutLgamma complex; IPI:SGD.
DR   GO; GO:0005634; C:nucleus; HDA:SGD.
DR   GO; GO:0005524; F:ATP binding; IMP:SGD.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IDA:SGD.
DR   GO; GO:0140664; F:ATP-dependent DNA damage sensor activity; IEA:InterPro.
DR   GO; GO:0030983; F:mismatched DNA binding; IEA:InterPro.
DR   GO; GO:0000713; P:meiotic heteroduplex formation; IMP:SGD.
DR   GO; GO:0000710; P:meiotic mismatch repair; IDA:ComplexPortal.
DR   GO; GO:0006298; P:mismatch repair; IMP:SGD.
DR   GO; GO:0007131; P:reciprocal meiotic recombination; IMP:SGD.
DR   CDD; cd16926; HATPase_MutL-MLH-PMS-like; 1.
DR   CDD; cd03483; MutL_Trans_MLH1; 1.
DR   Gene3D; 3.30.230.10; -; 1.
DR   Gene3D; 3.30.565.10; Histidine kinase-like ATPase, C-terminal domain; 1.
DR   InterPro; IPR014762; DNA_mismatch_repair_CS.
DR   InterPro; IPR013507; DNA_mismatch_S5_2-like.
DR   InterPro; IPR036890; HATPase_C_sf.
DR   InterPro; IPR032189; Mlh1_C.
DR   InterPro; IPR002099; MutL/Mlh/PMS.
DR   InterPro; IPR038973; MutL/Mlh/Pms-like.
DR   InterPro; IPR020568; Ribosomal_Su5_D2-typ_SF.
DR   InterPro; IPR014721; Ribsml_uS5_D2-typ_fold_subgr.
DR   NCBIfam; TIGR00585; mutl; 1.
DR   PANTHER; PTHR10073; DNA MISMATCH REPAIR PROTEIN MLH, PMS, MUTL; 1.
DR   PANTHER; PTHR10073:SF12; DNA MISMATCH REPAIR PROTEIN MLH1; 1.
DR   Pfam; PF01119; DNA_mis_repair; 1.
DR   Pfam; PF13589; HATPase_c_3; 1.
DR   Pfam; PF16413; Mlh1_C; 1.
DR   SMART; SM01340; DNA_mis_repair; 1.
DR   SUPFAM; SSF55874; ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase; 1.
DR   SUPFAM; SSF54211; Ribosomal protein S5 domain 2-like; 1.
DR   PROSITE; PS00058; DNA_MISMATCH_REPAIR_1; 1.
PE   1: Evidence at protein level;
KW   3D-structure; DNA damage; DNA repair; Nucleus; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..769
FT                   /note="DNA mismatch repair protein MLH1"
FT                   /id="PRO_0000178008"
FT   REGION          1..335
FT                   /note="DNA- and ATP-binding"
FT   REGION          422..480
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          501..756
FT                   /note="Interaction with PMS1"
FT   COMPBIAS        422..445
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        446..480
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         441
FT                   /note="Phosphoserine; by ATM or ATR"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   VARIANT         240
FT                   /note="S -> R (in strain: SK1)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         242
FT                   /note="D -> E (in strain: YJM326 and YJM339)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         271
FT                   /note="L -> P (in strain: EAY1066, EAY1068, M2-8, M7-8,
FT                   M5-7, SK1, YJM269, YJM280, YJM320, YJM326, YJM339 and
FT                   YJM627)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         309
FT                   /note="P -> L (in strain: M2-8)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         321
FT                   /note="E -> D (in strain: EAY1066)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         333
FT                   /note="E -> K (in strain: SK1)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         375
FT                   /note="A -> T (in strain: YJM339)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         452
FT                   /note="S -> G (in strain: EAY1068, M2-8, M7-8, M5-7, YJM269
FT                   and YJM627)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         465
FT                   /note="D -> N (in strain: EAY1066 and YJM280)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         470
FT                   /note="P -> S (in strain: YJM339)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         607
FT                   /note="L -> F (in strain: EAY1068, M2-8, M7-8, M5-7 and
FT                   YJM627)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         678
FT                   /note="D -> N (in strain: SK1, YJM320 and YJM339)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         703
FT                   /note="P -> L (in strain: SK1, YJM320 and YJM339)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   VARIANT         761
FT                   /note="D -> G (in strain: EAY1066, EAY1068, M2-8, M7-8,
FT                   M5-7, SK1, YJM145, YJM269, YJM320, YJM339 and YJM627; forms
FT                   a non-functional heterodimer with PMS1 from strain S288c,
FT                   resulting in an accumulation of mutations in spore progeny
FT                   of crosses between these strains)"
FT                   /evidence="ECO:0000269|PubMed:16492773"
FT   MUTAGEN         31
FT                   /note="E->A: Reduces ATPase activity by 98%. Displays
FT                   3300-fold increase in spontaneous mutation accumulation."
FT                   /evidence="ECO:0000269|PubMed:10938116,
FT                   ECO:0000269|PubMed:11717305"
FT   MUTAGEN         35
FT                   /note="N->A: Abolishes ATP binding, reducing ATPase
FT                   activity by 95%. Displays 9800-fold increase in spontaneous
FT                   mutation accumulation."
FT                   /evidence="ECO:0000269|PubMed:11717305"
FT   MUTAGEN         41
FT                   /note="A->F: Defective in a mismatch repair assay.
FT                   Abolishes heterodimer formation. Displays an increases
FT                   spontaneous mutation accumulation."
FT                   /evidence="ECO:0000269|PubMed:11555625,
FT                   ECO:0000269|PubMed:9234704"
FT   MUTAGEN         41
FT                   /note="A->G: Reduces heterodimer formation. Displays an
FT                   weak increase in spontaneous mutation accumulation."
FT                   /evidence="ECO:0000269|PubMed:11555625,
FT                   ECO:0000269|PubMed:9234704"
FT   MUTAGEN         41
FT                   /note="A->S: Fully functional in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625,
FT                   ECO:0000269|PubMed:9234704"
FT   MUTAGEN         64
FT                   /note="G->R: Defective in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         65
FT                   /note="I->N: Defective in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         96
FT                   /note="F->A: Displays an increase in spontaneous mutation
FT                   accumulation. Does not impair heterodimer formation."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   MUTAGEN         97
FT                   /note="R->A: Displays an increase in spontaneous mutation
FT                   accumulation. Does not impair heterodimer formation."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   MUTAGEN         98
FT                   /note="G->A: Displays an increase in spontaneous mutation
FT                   accumulation. Does not impair heterodimer formation."
FT                   /evidence="ECO:0000269|PubMed:10938116,
FT                   ECO:0000269|PubMed:9234704"
FT   MUTAGEN         98
FT                   /note="G->V: Abolishes heterodimer formation. Displays an
FT                   increase in spontaneous mutation accumulation."
FT                   /evidence="ECO:0000269|PubMed:10938116,
FT                   ECO:0000269|PubMed:9234704"
FT   MUTAGEN         99
FT                   /note="E->K: Defective in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         104
FT                   /note="I->R: Defective in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         114
FT                   /note="T->R: Defective in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         214
FT                   /note="R->C: Partially defective in a mismatch repair
FT                   assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         216
FT                   /note="V->I: Fully functional in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         265
FT                   /note="R->C: Partially defective in a mismatch repair
FT                   assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         265
FT                   /note="R->H: Partially defective in a mismatch repair
FT                   assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         273
FT                   /note="R->E: Strongly reduces DNA-binding and displays
FT                   12000-fold increase in spontaneous mutation accumulation;
FT                   when associated with E-274."
FT                   /evidence="ECO:0000269|PubMed:12682353"
FT   MUTAGEN         274
FT                   /note="R->E: Reduces DNA-binding and displays a 1700-fold
FT                   increase in spontaneous mutation accumulation. Strongly
FT                   reduces DNA-binding and displays 12000-fold increase in
FT                   spontaneous mutation accumulation; when associated with
FT                   E-273."
FT                   /evidence="ECO:0000269|PubMed:12682353"
FT   MUTAGEN         326
FT                   /note="I->A: Partially defective in a mismatch repair
FT                   assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         326
FT                   /note="I->V: Fully functional in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         552
FT                   /note="Q->L: Defective in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         672
FT                   /note="R->P: Defective in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         694
FT                   /note="A->T: Fully functional in a mismatch repair assay."
FT                   /evidence="ECO:0000269|PubMed:11555625"
FT   MUTAGEN         764
FT                   /note="K->E: Displays an increase in spontaneous mutation
FT                   accumulation. Does not impair heterodimer formation."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   MUTAGEN         764
FT                   /note="K->R: No effect."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   MUTAGEN         766
FT                   /note="F->A: Displays an increase in spontaneous mutation
FT                   accumulation. Does not impair heterodimer formation."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   MUTAGEN         767
FT                   /note="E->D: Displays an increase in spontaneous mutation
FT                   accumulation. Does not impair heterodimer formation."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   MUTAGEN         769
FT                   /note="C->A: No effect."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   MUTAGEN         769
FT                   /note="C->S: Displays an increase in spontaneous mutation
FT                   accumulation. Does not impair heterodimer formation."
FT                   /evidence="ECO:0000269|PubMed:9234704"
FT   CONFLICT        258
FT                   /note="P -> L (in Ref. 1; AAA16835)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        288
FT                   /note="N -> F (in Ref. 1; AAA16835)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        708
FT                   /note="S -> L (in Ref. 1; AAA16835)"
FT                   /evidence="ECO:0000305"
FT   HELIX           512..524
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           527..534
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   STRAND          537..543
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   TURN            544..547
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   STRAND          548..553
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   STRAND          556..561
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           562..576
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   TURN            577..579
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   STRAND          582..585
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           591..593
FT                   /evidence="ECO:0007829|PDB:4E4W"
FT   HELIX           597..600
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           601..603
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           605..607
FT                   /evidence="ECO:0007829|PDB:6SHX"
FT   HELIX           610..621
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           624..631
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   STRAND          634..637
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           644..646
FT                   /evidence="ECO:0007829|PDB:4E4W"
FT   STRAND          647..654
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           663..665
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           666..675
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           682..697
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   STRAND          710..712
FT                   /evidence="ECO:0007829|PDB:6SNV"
FT   HELIX           714..733
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           735..742
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           747..752
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   STRAND          753..758
FT                   /evidence="ECO:0007829|PDB:6RMN"
FT   HELIX           759..765
FT                   /evidence="ECO:0007829|PDB:6RMN"
SQ   SEQUENCE   769 AA;  87062 MW;  B2DBB31DE3943171 CRC64;
     MSLRIKALDA SVVNKIAAGE IIISPVNALK EMMENSIDAN ATMIDILVKE GGIKVLQITD
     NGSGINKADL PILCERFTTS KLQKFEDLSQ IQTYGFRGEA LASISHVARV TVTTKVKEDR
     CAWRVSYAEG KMLESPKPVA GKDGTTILVE DLFFNIPSRL RALRSHNDEY SKILDVVGRY
     AIHSKDIGFS CKKFGDSNYS LSVKPSYTVQ DRIRTVFNKS VASNLITFHI SKVEDLNLES
     VDGKVCNLNF ISKKSISPIF FINNRLVTCD LLRRALNSVY SNYLPKGNRP FIYLGIVIDP
     AAVDVNVHPT KREVRFLSQD EIIEKIANQL HAELSAIDTS RTFKASSIST NKPESLIPFN
     DTIESDRNRK SLRQAQVVEN SYTTANSQLR KAKRQENKLV RIDASQAKIT SFLSSSQQFN
     FEGSSTKRQL SEPKVTNVSH SQEAEKLTLN ESEQPRDANT INDNDLKDQP KKKQKLGDYK
     VPSIADDEKN ALPISKDGYI RVPKERVNVN LTSIKKLREK VDDSIHRELT DIFANLNYVG
     VVDEERRLAA IQHDLKLFLI DYGSVCYELF YQIGLTDFAN FGKINLQSTN VSDDIVLYNL
     LSEFDELNDD ASKEKIISKI WDMSSMLNEY YSIELVNDGL DNDLKSVKLK SLPLLLKGYI
     PSLVKLPFFI YRLGKEVDWE DEQECLDGIL REIALLYIPD MVPKVDTSDA SLSEDEKAQF
     INRKEHISSL LEHVLFPCIK RRFLAPRHIL KDVVEIANLP DLYKVFERC
//