ID MLH1_ARATH Reviewed; 737 AA.
AC Q9ZRV4; Q9C5F9;
DT 03-APR-2013, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 24-JAN-2024, entry version 161.
DE RecName: Full=DNA mismatch repair protein MLH1;
DE AltName: Full=MutL protein homolog 1;
DE AltName: Full=Protein MUTL-HOMOLOGUE 1;
DE Short=AtMLH1;
GN Name=MLH1; OrderedLocusNames=At4g09140; ORFNames=F23J3.170, T8A17.9;
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 [MRNA].
RC STRAIN=cv. Columbia;
RX PubMed=10628846; DOI=10.1007/s004380051126;
RA Jean M., Pelletier J., Hilpert M., Belzille F., Kunze R.;
RT "Isolation and characterization of AtMLH1, a MutL homologue from
RT Arabidopsis thaliana.";
RL Mol. Gen. Genet. 262:633-642(1999).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 6-737.
RC STRAIN=cv. Columbia;
RX PubMed=14593172; DOI=10.1126/science.1088305;
RA Yamada K., Lim J., Dale J.M., Chen H., Shinn P., Palm C.J., Southwick A.M.,
RA Wu H.C., Kim C.J., Nguyen M., Pham P.K., Cheuk R.F., Karlin-Newmann G.,
RA Liu S.X., Lam B., Sakano H., Wu T., Yu G., Miranda M., Quach H.L.,
RA Tripp M., Chang C.H., Lee J.M., Toriumi M.J., Chan M.M., Tang C.C.,
RA Onodera C.S., Deng J.M., Akiyama K., Ansari Y., Arakawa T., Banh J.,
RA Banno F., Bowser L., Brooks S.Y., Carninci P., Chao Q., Choy N., Enju A.,
RA Goldsmith A.D., Gurjal M., Hansen N.F., Hayashizaki Y., Johnson-Hopson C.,
RA Hsuan V.W., Iida K., Karnes M., Khan S., Koesema E., Ishida J., Jiang P.X.,
RA Jones T., Kawai J., Kamiya A., Meyers C., Nakajima M., Narusaka M.,
RA Seki M., Sakurai T., Satou M., Tamse R., Vaysberg M., Wallender E.K.,
RA Wong C., Yamamura Y., Yuan S., Shinozaki K., Davis R.W., Theologis A.,
RA Ecker J.R.;
RT "Empirical analysis of transcriptional activity in the Arabidopsis
RT genome.";
RL Science 302:842-846(2003).
RN [5]
RP DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION, AND 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 [6]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
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 [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17559505; DOI=10.1111/j.1365-313x.2007.03145.x;
RA Dion E., Li L., Jean M., Belzile F.;
RT "An Arabidopsis MLH1 mutant exhibits reproductive defects and reveals a
RT dual role for this gene in mitotic recombination.";
RL Plant J. 51:431-440(2007).
RN [8]
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=18318687; DOI=10.1111/j.1365-313x.2008.03470.x;
RA Higgins J.D., Vignard J., Mercier R., Pugh A.G., Franklin F.C., Jones G.H.;
RT "AtMSH5 partners AtMSH4 in the class I meiotic crossover pathway in
RT Arabidopsis thaliana, but is not required for synapsis.";
RL Plant J. 55:28-39(2008).
RN [9]
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=20628250; DOI=10.1159/000314096;
RA Chelysheva L., Grandont L., Vrielynck N., le Guin S., Mercier R.,
RA Grelon M.;
RT "An easy protocol for studying chromatin and recombination protein dynamics
RT during Arabidopsis thaliana meiosis: immunodetection of cohesins, histones
RT and MLH1.";
RL Cytogenet. Genome Res. 129:143-153(2010).
RN [10]
RP FUNCTION.
RX PubMed=23184005; DOI=10.1007/s11033-012-2269-5;
RA Galles C., Spampinato C.P.;
RT "Yeast mutator phenotype enforced by Arabidopsis PMS1 expression.";
RL Mol. Biol. Rep. 40:2107-2114(2013).
RN [11]
RP DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=22844245; DOI=10.1371/journal.pgen.1002799;
RA Chelysheva L., Vezon D., Chambon A., Gendrot G., Pereira L., Lemhemdi A.,
RA Vrielynck N., Le Guin S., Novatchkova M., Grelon M.;
RT "The Arabidopsis HEI10 is a new ZMM protein related to Zip3.";
RL PLoS Genet. 8:E1002799-E1002799(2012).
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 downstream 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:16856855, ECO:0000269|PubMed:17559505,
CC ECO:0000269|PubMed:23184005}.
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. Heterodimer of MLH1 and MLH3, called MutLbeta, which is involved
CC in correction of a specific subset of IDLs when associated with
CC MutSbeta (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16467846,
CC ECO:0000269|PubMed:16856855, ECO:0000269|PubMed:18318687,
CC ECO:0000269|PubMed:20628250, ECO:0000269|PubMed:22844245}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:16467846}.
CC -!- DEVELOPMENTAL STAGE: Expressed during prophase I of meiosis: detected
CC from pachytene to diakinesis stages. {ECO:0000269|PubMed:16467846,
CC ECO:0000269|PubMed:16856855, ECO:0000269|PubMed:18318687,
CC ECO:0000269|PubMed:20628250, ECO:0000269|PubMed:22844245}.
CC -!- DISRUPTION PHENOTYPE: Reduced fertility and mitotic defects: 72 per
CC cent reduction in homologous somatic recombination.
CC {ECO:0000269|PubMed:17559505}.
CC -!- SIMILARITY: Belongs to the DNA mismatch repair MutL/HexB family.
CC {ECO:0000305}.
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DR EMBL; AJ012747; CAA10163.1; -; mRNA.
DR EMBL; AC005359; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF072897; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161514; CAB78038.1; -; Genomic_DNA.
DR EMBL; CP002687; AEE82726.1; -; Genomic_DNA.
DR EMBL; AF360278; AAK25988.1; -; mRNA.
DR PIR; F85092; F85092.
DR PIR; T51620; T51620.
DR RefSeq; NP_567345.2; NM_116983.3.
DR AlphaFoldDB; Q9ZRV4; -.
DR SMR; Q9ZRV4; -.
DR IntAct; Q9ZRV4; 1.
DR STRING; 3702.Q9ZRV4; -.
DR iPTMnet; Q9ZRV4; -.
DR PaxDb; 3702-AT4G09140-1; -.
DR ProteomicsDB; 238367; -.
DR EnsemblPlants; AT4G09140.1; AT4G09140.1; AT4G09140.
DR GeneID; 826493; -.
DR Gramene; AT4G09140.1; AT4G09140.1; AT4G09140.
DR KEGG; ath:AT4G09140; -.
DR Araport; AT4G09140; -.
DR TAIR; AT4G09140; MLH1.
DR eggNOG; KOG1979; Eukaryota.
DR HOGENOM; CLU_004131_2_0_1; -.
DR InParanoid; Q9ZRV4; -.
DR OMA; ANYHVKK; -.
DR OrthoDB; 5475669at2759; -.
DR PhylomeDB; Q9ZRV4; -.
DR PRO; PR:Q9ZRV4; -.
DR Proteomes; UP000006548; Chromosome 4.
DR ExpressionAtlas; Q9ZRV4; baseline and differential.
DR Genevisible; Q9ZRV4; AT.
DR GO; GO:0000785; C:chromatin; IDA:TAIR.
DR GO; GO:0032300; C:mismatch repair complex; IEA:InterPro.
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; IEA:InterPro.
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:0010154; P:fruit development; IMP:TAIR.
DR GO; GO:0006298; P:mismatch repair; IEA:InterPro.
DR GO; GO:0006312; P:mitotic recombination; IMP:TAIR.
DR GO; GO:0009555; P:pollen development; IMP:TAIR.
DR GO; GO:0048316; P:seed development; IMP:TAIR.
DR GO; GO:0009845; P:seed germination; IMP:TAIR.
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 2: Evidence at transcript level;
KW DNA damage; DNA repair; Nucleus; Reference proteome.
FT CHAIN 1..737
FT /note="DNA mismatch repair protein MLH1"
FT /id="PRO_0000421833"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 378..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..405
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 737 AA; 82365 MW; 0497793964CA3700 CRC64;
MIDDSSLTAE MEEEESPATT IVPREPPKIQ RLEESVVNRI AAGEVIQRPV SAVKELVENS
LDADSSSISV VVKDGGLKLI QVSDDGHGIR REDLPILCER HTTSKLTKFE DLFSLSSMGF
RGEALASMTY VAHVTVTTIT KGQIHGYRVS YRDGVMEHEP KACAAVKGTQ IMVENLFYNM
IARRKTLQNS ADDYGKIVDL LSRMAIHYNN VSFSCRKHGA VKADVHSVVS PSRLDSIRSV
YGVSVAKNLM KVEVSSCDSS GCTFDMEGFI SNSNYVAKKT ILVLFINDRL VECSALKRAI
EIVYAATLPK ASKPFVYMSI NLPREHVDIN IHPTKKEVSL LNQEIIIEMI QSEVEVKLRN
ANDTRTFQEQ KVEYIQSTLT SQKSDSPVSQ KPSGQKTQKV PVNKMVRTDS SDPAGRLHAF
LQPKPQSLPD KVSSLSVVRS SVRQRRNPKE TADLSSVQEL IAGVDSCCHP GMLETVRNCT
YVGMADDVFA LVQYNTHLYL ANVVNLSKEL MYQQTLRRFA HFNAIQLSDP APLSELILLA
LKEEDLDPGN DTKDDLKERI AEMNTELLKE KAEMLEEYFS VHIDSSANLS RLPVILDQYT
PDMDRVPEFL LCLGNDVEWE DEKSCFQGVS AAIGNFYAMH PPLLPNPSGD GIQFYSKRGE
SSQEKSDLEG NVDMEDNLDQ DLLSDAENAW AQREWSIQHV LFPSMRLFLK PPASMASNGT
FVKVASLEKL YKIFERC
//
