MLH1_YEAST
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 03-AUG-2022, entry version 202.
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; 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 downsteam 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; 231.
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; P38920; -.
DR PRIDE; P38920; -.
DR EnsemblFungi; YMR167W_mRNA; YMR167W; YMR167W.
DR GeneID; 855203; -.
DR KEGG; sce:YMR167W; -.
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 BioCyc; YEAST:G3O-32857-MON; -.
DR BRENDA; 3.6.1.3; 984.
DR Reactome; R-SCE-5358565; Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha).
DR PRO; PR:P38920; -.
DR Proteomes; UP000002311; Chromosome XIII.
DR RNAct; P38920; protein.
DR GO; GO:0005737; C:cytoplasm; HDA:SGD.
DR GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
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 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; IPR032189; Mlh1_C.
DR InterPro; IPR038973; MutL/Mlh/Pms.
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; PF16413; Mlh1_C; 1.
DR SMART; SM01340; DNA_mis_repair; 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 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, M5-
FT 7, SK1, YJM269, YJM280, YJM320, YJM326, YJM339 and 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, M5-
FT 7, SK1, YJM145, YJM269, YJM320, YJM339 and YJM627; forms a
FT 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 3300-
FT 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 E-
FT 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
