ID   MLH3_ARATH              Reviewed;        1155 AA.
AC   F4JN26; O81785;
DT   03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT   03-APR-2013, sequence version 2.
DT   03-AUG-2022, entry version 70.
DE   RecName: Full=DNA mismatch repair protein MLH3;
DE   AltName: Full=MutL protein homolog 3;
GN   Name=MLH3; OrderedLocusNames=At4g35520; ORFNames=F8D20.30;
OS   Arabidopsis thaliana (Mouse-ear cress).
OC   Eukaryota; Viridiplantae; Streptophyta; Embryophyta; Tracheophyta;
OC   Spermatophyta; Magnoliopsida; eudicotyledons; Gunneridae; Pentapetalae;
OC   rosids; malvids; Brassicales; Brassicaceae; Camelineae; Arabidopsis.
OX   NCBI_TaxID=3702;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=cv. Columbia;
RX   PubMed=10617198; DOI=10.1038/47134;
RA   Mayer K.F.X., Schueller C., Wambutt R., Murphy G., Volckaert G., Pohl T.,
RA   Duesterhoeft A., Stiekema W., Entian K.-D., Terryn N., Harris B.,
RA   Ansorge W., Brandt P., Grivell L.A., Rieger M., Weichselgartner M.,
RA   de Simone V., Obermaier B., Mache R., Mueller M., Kreis M., Delseny M.,
RA   Puigdomenech P., Watson M., Schmidtheini T., Reichert B., Portetelle D.,
RA   Perez-Alonso M., Boutry M., Bancroft I., Vos P., Hoheisel J.,
RA   Zimmermann W., Wedler H., Ridley P., Langham S.-A., McCullagh B.,
RA   Bilham L., Robben J., van der Schueren J., Grymonprez B., Chuang Y.-J.,
RA   Vandenbussche F., Braeken M., Weltjens I., Voet M., Bastiaens I., Aert R.,
RA   Defoor E., Weitzenegger T., Bothe G., Ramsperger U., Hilbert H., Braun M.,
RA   Holzer E., Brandt A., Peters S., van Staveren M., Dirkse W., Mooijman P.,
RA   Klein Lankhorst R., Rose M., Hauf J., Koetter P., Berneiser S., Hempel S.,
RA   Feldpausch M., Lamberth S., Van den Daele H., De Keyser A., Buysshaert C.,
RA   Gielen J., Villarroel R., De Clercq R., van Montagu M., Rogers J.,
RA   Cronin A., Quail M.A., Bray-Allen S., Clark L., Doggett J., Hall S.,
RA   Kay M., Lennard N., McLay K., Mayes R., Pettett A., Rajandream M.A.,
RA   Lyne M., Benes V., Rechmann S., Borkova D., Bloecker H., Scharfe M.,
RA   Grimm M., Loehnert T.-H., Dose S., de Haan M., Maarse A.C., Schaefer M.,
RA   Mueller-Auer S., Gabel C., Fuchs M., Fartmann B., Granderath K., Dauner D.,
RA   Herzl A., Neumann S., Argiriou A., Vitale D., Liguori R., Piravandi E.,
RA   Massenet O., Quigley F., Clabauld G., Muendlein A., Felber R., Schnabl S.,
RA   Hiller R., Schmidt W., Lecharny A., Aubourg S., Chefdor F., Cooke R.,
RA   Berger C., Monfort A., Casacuberta E., Gibbons T., Weber N., Vandenbol M.,
RA   Bargues M., Terol J., Torres A., Perez-Perez A., Purnelle B., Bent E.,
RA   Johnson S., Tacon D., Jesse T., Heijnen L., Schwarz S., Scholler P.,
RA   Heber S., Francs P., Bielke C., Frishman D., Haase D., Lemcke K.,
RA   Mewes H.-W., Stocker S., Zaccaria P., Bevan M., Wilson R.K.,
RA   de la Bastide M., Habermann K., Parnell L., Dedhia N., Gnoj L., Schutz K.,
RA   Huang E., Spiegel L., Sekhon M., Murray J., Sheet P., Cordes M.,
RA   Abu-Threideh J., Stoneking T., Kalicki J., Graves T., Harmon G.,
RA   Edwards J., Latreille P., Courtney L., Cloud J., Abbott A., Scott K.,
RA   Johnson D., Minx P., Bentley D., Fulton B., Miller N., Greco T., Kemp K.,
RA   Kramer J., Fulton L., Mardis E., Dante M., Pepin K., Hillier L.W.,
RA   Nelson J., Spieth J., Ryan E., Andrews S., Geisel C., Layman D., Du H.,
RA   Ali J., Berghoff A., Jones K., Drone K., Cotton M., Joshu C., Antonoiu B.,
RA   Zidanic M., Strong C., Sun H., Lamar B., Yordan C., Ma P., Zhong J.,
RA   Preston R., Vil D., Shekher M., Matero A., Shah R., Swaby I.K.,
RA   O'Shaughnessy A., Rodriguez M., Hoffman J., Till S., Granat S., Shohdy N.,
RA   Hasegawa A., Hameed A., Lodhi M., Johnson A., Chen E., Marra M.A.,
RA   Martienssen R., McCombie W.R.;
RT   "Sequence and analysis of chromosome 4 of the plant Arabidopsis thaliana.";
RL   Nature 402:769-777(1999).
RN   [2]
RP   GENOME REANNOTATION.
RC   STRAIN=cv. Columbia;
RX   PubMed=27862469; DOI=10.1111/tpj.13415;
RA   Cheng C.Y., Krishnakumar V., Chan A.P., Thibaud-Nissen F., Schobel S.,
RA   Town C.D.;
RT   "Araport11: a complete reannotation of the Arabidopsis thaliana reference
RT   genome.";
RL   Plant J. 89:789-804(2017).
RN   [3]
RP   DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND
RP   FUNCTION.
RX   PubMed=16856855; DOI=10.1042/bst0340542;
RA   Franklin F.C., Higgins J.D., Sanchez-Moran E., Armstrong S.J., Osman K.E.,
RA   Jackson N., Jones G.H.;
RT   "Control of meiotic recombination in Arabidopsis: role of the MutL and MutS
RT   homologues.";
RL   Biochem. Soc. Trans. 34:542-544(2006).
RN   [4]
RP   TISSUE SPECIFICITY, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION
RP   PHENOTYPE, AND FUNCTION.
RX   PubMed=16467846; DOI=10.1038/sj.emboj.7600992;
RA   Jackson N., Sanchez-Moran E., Buckling E., Armstrong S.J., Jones G.H.,
RA   Franklin F.C.;
RT   "Reduced meiotic crossovers and delayed prophase I progression in AtMLH3-
RT   deficient Arabidopsis.";
RL   EMBO J. 25:1315-1323(2006).
RN   [5]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=21771883; DOI=10.1242/jcs.088229;
RA   Macaisne N., Vignard J., Mercier R.;
RT   "SHOC1 and PTD form an XPF-ERCC1-like complex that is required for
RT   formation of class I crossovers.";
RL   J. Cell Sci. 124:2687-2691(2011).
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:16467846, ECO:0000269|PubMed:16856855}.
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. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16467846,
CC       ECO:0000269|PubMed:16856855}.
CC   -!- TISSUE SPECIFICITY: Expressed in reproductive tissues.
CC       {ECO:0000269|PubMed:16467846}.
CC   -!- DEVELOPMENTAL STAGE: Expressed during prophase I of meiosis.
CC       {ECO:0000269|PubMed:16467846, ECO:0000269|PubMed:16856855}.
CC   -!- DISRUPTION PHENOTYPE: Reduced fertility and meiotic defects: 60 per
CC       cent reduction in crossovers and delayed prophase I progression.
CC       {ECO:0000269|PubMed:16467846, ECO:0000269|PubMed:16856855,
CC       ECO:0000269|PubMed:21771883}.
CC   -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA20022.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC       Sequence=CAB80268.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AL031135; CAA20022.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AL161587; CAB80268.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; CP002687; AEE86526.2; -; Genomic_DNA.
DR   PIR; T04657; T04657.
DR   RefSeq; NP_001320143.1; NM_001342354.1.
DR   AlphaFoldDB; F4JN26; -.
DR   SMR; F4JN26; -.
DR   STRING; 3702.AT4G35520.1; -.
DR   PaxDb; F4JN26; -.
DR   PRIDE; F4JN26; -.
DR   EnsemblPlants; AT4G35520.1; AT4G35520.1; AT4G35520.
DR   GeneID; 829704; -.
DR   Gramene; AT4G35520.1; AT4G35520.1; AT4G35520.
DR   KEGG; ath:AT4G35520; -.
DR   Araport; AT4G35520; -.
DR   TAIR; locus:2127923; AT4G35520.
DR   eggNOG; KOG1977; Eukaryota.
DR   HOGENOM; CLU_009113_0_0_1; -.
DR   InParanoid; F4JN26; -.
DR   PRO; PR:F4JN26; -.
DR   Proteomes; UP000006548; Chromosome 4.
DR   ExpressionAtlas; F4JN26; baseline and differential.
DR   Genevisible; F4JN26; AT.
DR   GO; GO:0005694; C:chromosome; IDA:TAIR.
DR   GO; GO:0032300; C:mismatch repair complex; IBA:GO_Central.
DR   GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
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:0030983; F:mismatched DNA binding; IEA:InterPro.
DR   GO; GO:0006298; P:mismatch repair; IBA:GO_Central.
DR   GO; GO:0007131; P:reciprocal meiotic recombination; IMP:TAIR.
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; 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; IPR042121; MutL_C_regsub.
DR   InterPro; IPR037198; MutL_C_sf.
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; SM00853; MutL_C; 1.
DR   SUPFAM; SSF118116; SSF118116; 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; Nucleus; Reference proteome.
FT   CHAIN           1..1155
FT                   /note="DNA mismatch repair protein MLH3"
FT                   /id="PRO_0000421834"
SQ   SEQUENCE   1155 AA;  129285 MW;  07AA8C00F58691EB CRC64;
     MKTIKPLPEG VRHSMRSGII MFDMARVVEE LVFNSLDAGA TKVSIFVGVV SCSVKVVDDG
     SGVSRDDLVL LGERYATSKF HDFTNVETAS ETFGFRGEAL ASISDISLLE VRTKAIGRPN
     GYRKVMKGSK CLHLGIDDDR KDSGTTVTVR DLFYSQPVRR KYMQSSPKKV LESIKKCVFR
     IALVHSNVSF SVLDIESDEE LFQTNPSSSA FSLLMRDAGT EAVNSLCKVN VTDGMLNVSG
     FECADDWKPT DGQQTGRRNR LQSNPGYILC IACPRRLYEF SFEPSKTHVE FKKWGPVLAF
     IERITLANWK KDRILELFDG GADILAKGDR QDLIDDKIRL QNGSLFSILH FLDADWPEAM
     EPAKKKLKRS NDHAPCSSLL FPSADFKQDG DYFSPRKDVW SPECEVELKI QNPKEQGTVA
     GFESRTDSLL QSRDIEMQTN EDFPQVTDLL ETSLVADSKC RKQFLTRCQI TTPVNINHDF
     MKDSDVLNFQ FQGLKDELDV SNCIGKHLLR GCSSRVSLTF HEPKLSHVEG YESVVPMIPN
     EKQSSPRVLE TREGGSYCDV YSDKTPDCSL GSSWQDTDWF TPQCSSDRGC VGIGEDFNIT
     PIDTAEFDSY DEKVGSKKYL SSVNVGSSVT GSFCLSSEWS PMYSTPSATK WESEYQKGCR
     ILEQSLRLGR MPDPEFCFSA ANNIKFDHEV IPEMDCCETG TDSFTAIQNC TQLADKICKS
     SWGHADDVRI DQYSIRKEKF SYMDGTQNNA GKQRSKRSRS APPFYREKKR FISLSCKSDT
     KPKNSDPSEP DDLECLTQPC NASQMHLKCS ILDDVSYDHI QETEKRLSSA SDLKASAGCR
     TVHSETQDED VHEDFSSEEF LDPIKSTTKW RHNCAVSQVP KESHELHGQD GVFDISSGLL
     HLRSDESLVP ESINRHSLED AKVLQQVDKK YIPIVACGTV AIVDQHAADE RIRLEELRTK
     VLAGKARTVT YLSADQELVL PEMGYQLLQS YSEQIRDWGW ICNITVEGST SFKKNMSIIQ
     RKPTPITLNA VPCILGVNLS DVDLLEFLQQ LADTDGSSTI PPSVLRVLNS KACRGAIMFG
     DSLLPSECSL IIDGLKQTSL CFQCAHGRPT TVPLVDLKAL HKQIAKLSGR QVWHGLQRRE
     ITLDRAKSRL DNAKS