MLH3_YEAST
ID MLH3_YEAST Reviewed; 715 AA.
AC Q12083; D6W3K4;
DT 11-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=DNA mismatch repair protein MLH3;
DE AltName: Full=MutL protein homolog 3;
GN Name=MLH3; OrderedLocusNames=YPL164C; ORFNames=P2550;
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].
RC STRAIN=ATCC 204511 / S288c / AB972;
RX PubMed=8948103;
RX DOI=10.1002/(sici)1097-0061(199611)12:14<1483::aid-yea34>3.0.co;2-o;
RA Purnelle B., Coster F., Goffeau A.;
RT "The sequence of 55 kb on the left arm of yeast chromosome XVI identifies a
RT small nuclear RNA, a new putative protein kinase and two new putative
RT regulators.";
RL Yeast 12:1483-1492(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169875;
RA Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA Vo D.H., Hani J.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL Nature 387:103-105(1997).
RN [3]
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 [4]
RP FUNCTION, AND INTERACTION WITH MLH1.
RX PubMed=9770499; DOI=10.1073/pnas.95.21.12404;
RA Flores-Rozas H., Kolodner R.D.;
RT "The Saccharomyces cerevisiae MLH3 gene functions in MSH3-dependent
RT suppression of frameshift mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:12404-12409(1998).
RN [5]
RP FUNCTION, AND INTERACTION WITH MLH1.
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 [6]
RP FUNCTION.
RX PubMed=10679328; DOI=10.1016/s0960-9822(00)00314-6;
RA Harfe B.D., Minesinger B.K., Jinks-Robertson S.;
RT "Discrete in vivo roles for the MutL homologs Mlh2p and Mlh3p in the
RT removal of frameshift intermediates in budding yeast.";
RL Curr. Biol. 10:145-148(2000).
RN [7]
RP INTERACTION WITH SGS1.
RX PubMed=12200140; DOI=10.1016/s0006-291x(02)02034-x;
RA Wang T.-F., Kung W.M.;
RT "Supercomplex formation between Mlh1-Mlh3 and Sgs1-Top3 heterocomplexes in
RT meiotic yeast cells.";
RL Biochem. Biophys. Res. Commun. 296:949-953(2002).
CC -!- FUNCTION: Involved in DNA mismatch repair (MMR), correcting insertion-
CC deletion loops (IDLs) resulting from DNA replication, DNA damage or
CC from recombination events between non-identical sequences during
CC meiosis. Component of the MutLbeta heterodimer, which probably forms a
CC ternary complex with the MutSbeta heterodimer that initially recognizes
CC the DNA mismatches. This complex is thought to be responsible for
CC directing the downsteam MMR events, including strand discrimination,
CC excision, and resynthesis. Plays a major role in promoting meiotic
CC crossing-over and is involved in maintaining the genetic stability of
CC simple sequence repeats by correction of frameshift intermediates.
CC {ECO:0000269|PubMed:10570173, ECO:0000269|PubMed:10679328,
CC ECO:0000269|PubMed:9770499}.
CC -!- SUBUNIT: Heterodimer of MLH1 and MLH3, called MutLbeta, which is
CC involved in correction of a specific subset of IDLs when associated
CC with MutSbeta. Forms a ternary complex with a SGS1-TOP3 heterodimer
CC during meiosis.
CC -!- INTERACTION:
CC Q12083; P38920: MLH1; NbExp=5; IntAct=EBI-31634, EBI-11003;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC {ECO:0000305}.
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DR EMBL; X96770; CAA65557.1; -; Genomic_DNA.
DR EMBL; Z73520; CAA97869.1; -; Genomic_DNA.
DR EMBL; BK006949; DAA11270.1; -; Genomic_DNA.
DR PIR; S65175; S65175.
DR RefSeq; NP_015161.1; NM_001183978.1.
DR PDB; 6RMN; X-ray; 2.20 A; B=477-714.
DR PDB; 6SHX; X-ray; 2.40 A; B=477-715.
DR PDB; 6SNS; X-ray; 2.60 A; B=477-715.
DR PDB; 6SNV; X-ray; 2.50 A; B/E=477-715.
DR PDBsum; 6RMN; -.
DR PDBsum; 6SHX; -.
DR PDBsum; 6SNS; -.
DR PDBsum; 6SNV; -.
DR AlphaFoldDB; Q12083; -.
DR SMR; Q12083; -.
DR BioGRID; 36019; 186.
DR ComplexPortal; CPX-1668; MLH1-MLH3 endonuclease complex.
DR DIP; DIP-2414N; -.
DR IntAct; Q12083; 16.
DR STRING; 4932.YPL164C; -.
DR MaxQB; Q12083; -.
DR PaxDb; Q12083; -.
DR PRIDE; Q12083; -.
DR EnsemblFungi; YPL164C_mRNA; YPL164C; YPL164C.
DR GeneID; 855939; -.
DR KEGG; sce:YPL164C; -.
DR SGD; S000006085; MLH3.
DR VEuPathDB; FungiDB:YPL164C; -.
DR eggNOG; KOG1977; Eukaryota.
DR GeneTree; ENSGT00800000124176; -.
DR HOGENOM; CLU_005415_1_0_1; -.
DR InParanoid; Q12083; -.
DR OMA; RCAFPFQ; -.
DR BioCyc; YEAST:G3O-34060-MON; -.
DR BRENDA; 3.6.1.3; 984.
DR PRO; PR:Q12083; -.
DR Proteomes; UP000002311; Chromosome XVI.
DR RNAct; Q12083; protein.
DR GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
DR GO; GO:0097587; C:MutLgamma complex; IPI:SGD.
DR GO; GO:0005634; C:nucleus; IPI:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0016887; F:ATP hydrolysis activity; ISS: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:0000710; P:meiotic mismatch repair; IMP:SGD.
DR GO; GO:0006298; P:mismatch repair; IMP:SGD.
DR GO; GO:0007131; P:reciprocal meiotic recombination; IMP:SGD.
DR Gene3D; 3.30.1540.20; -; 2.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR InterPro; IPR013507; DNA_mismatch_S5_2-like.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR028830; Mlh3.
DR InterPro; IPR038973; MutL/Mlh/Pms.
DR InterPro; IPR014790; MutL_C.
DR InterPro; IPR042120; MutL_C_dimsub.
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 PANTHER; PTHR10073:SF47; PTHR10073:SF47; 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.
PE 1: Evidence at protein level;
KW 3D-structure; DNA damage; DNA repair; Nucleus; Reference proteome.
FT CHAIN 1..715
FT /note="DNA mismatch repair protein MLH3"
FT /id="PRO_0000245570"
FT HELIX 481..491
FT /evidence="ECO:0007829|PDB:6RMN"
FT STRAND 494..499
FT /evidence="ECO:0007829|PDB:6RMN"
FT TURN 500..502
FT /evidence="ECO:0007829|PDB:6RMN"
FT STRAND 503..507
FT /evidence="ECO:0007829|PDB:6RMN"
FT STRAND 519..523
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 524..545
FT /evidence="ECO:0007829|PDB:6RMN"
FT STRAND 558..561
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 563..577
FT /evidence="ECO:0007829|PDB:6RMN"
FT TURN 578..580
FT /evidence="ECO:0007829|PDB:6RMN"
FT STRAND 582..586
FT /evidence="ECO:0007829|PDB:6RMN"
FT STRAND 593..600
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 602..608
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 612..627
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 650..652
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 654..656
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 659..672
FT /evidence="ECO:0007829|PDB:6RMN"
FT HELIX 682..692
FT /evidence="ECO:0007829|PDB:6RMN"
FT STRAND 695..697
FT /evidence="ECO:0007829|PDB:6SNS"
FT STRAND 706..710
FT /evidence="ECO:0007829|PDB:6RMN"
SQ SEQUENCE 715 AA; 82001 MW; 970FD7F57EB6E3B1 CRC64;
MSQHIRKLDS DVSERLKSQA CTVSLASAVR EIVQNSVDAH ATTIDVMIDL PNLSFAVYDD
GIGLTRSDLN ILATQNYTSK IRKMNDLVTM KTYGYRGDAL YSISNVSNLF VCSKKKDYNS
AWMRKFPSKS VMLSENTILP IDPFWKICPW SRTKSGTVVI VEDMLYNLPV RRRILKEEPP
FKTFNTIKAD MLQILVMHPM ISLNVQYTDK LRINTEVLFR SKNITEGLTK HQQMSQVLRN
VFGAIIPPDM LKKVSLKFNE YQIEGIISKM PVGLKDLQFI YINGRRYADS AFQGYVDSLF
QAQDFGEKGM SLLKTKSVGK PYRSHPVFIL DVRCPQTIDD LLQDPAKKIV KPSHIRTIEP
LIVKTIRSFL TFQGYLTPDK SDSSFEIVNC SQKTATLPDS RIQISKRNQV LNSKMKIARI
NSYIGKPAVN GCRINNSTIN YEKIKNIRID GQKSRLRNKL SSRPYDSGFT EDYDSIGKTI
TDFSISRSVL AKYEVINQVD KKFILIRCLD QSIHNCPLLV LVDQHACDER IRLEELFYSL
LTEVVTGTFV ARDLKDCCIE VDRTEADLFK HYQSEFKKWG IGYETIEGTM ETSLLEIKTL
PEMLTSKYNG DKDYLKMVLL QHAHDLKDFK KLPMDLSHFE NYTSVDKLYW WKYSSCVPTV
FHEILNSKAC RSAVMFGDEL TRQECIILIS KLSRCHNPFE CAHGRPSMVP IAELK
