LEU33_ARATH
ID LEU33_ARATH Reviewed; 404 AA.
AC Q9SA14; Q1EBW0;
DT 11-JUL-2002, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=3-isopropylmalate dehydrogenase 3, chloroplastic {ECO:0000303|PubMed:15849421};
DE Short=3-IPM-DH 3 {ECO:0000303|PubMed:15849421};
DE Short=AtIMDH2 {ECO:0000303|PubMed:19674406};
DE Short=AtIMDH3 {ECO:0000303|PubMed:15849421};
DE Short=IMDH 3 {ECO:0000303|PubMed:15849421};
DE EC=1.1.1.85 {ECO:0000269|PubMed:15849421, ECO:0000269|PubMed:20840499};
DE AltName: Full=Beta-IPM dehydrogenase 3 {ECO:0000303|PubMed:15849421};
DE AltName: Full=Isopropylmalate dehydrogenase 3 {ECO:0000303|PubMed:19493961};
DE Short=AtIMD3 {ECO:0000303|PubMed:19493961};
DE Flags: Precursor;
GN Name=IMDH3 {ECO:0000303|PubMed:15849421};
GN Synonyms=IMD3 {ECO:0000303|PubMed:19493961},
GN IPMDH3 {ECO:0000303|PubMed:20840499};
GN OrderedLocusNames=At1g31180 {ECO:0000312|Araport:AT1G31180};
GN ORFNames=F28K20.14 {ECO:0000312|EMBL:AAD21684.1};
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], FUNCTION, CATALYTIC ACTIVITY, PATHWAY, TISSUE
RP SPECIFICITY, GENE FAMILY, AND NOMENCLATURE.
RC STRAIN=cv. Columbia;
RX PubMed=15849421; DOI=10.1271/bbb.69.806;
RA Nozawa A., Takano J., Miwa K., Nakagawa Y., Fujiwara T.;
RT "Cloning of cDNAs encoding isopropylmalate dehydrogenase from Arabidopsis
RT thaliana and accumulation patterns of their transcripts.";
RL Biosci. Biotechnol. Biochem. 69:806-810(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=cv. Columbia;
RX PubMed=11130712; DOI=10.1038/35048500;
RA Theologis A., Ecker J.R., Palm C.J., Federspiel N.A., Kaul S., White O.,
RA Alonso J., Altafi H., Araujo R., Bowman C.L., Brooks S.Y., Buehler E.,
RA Chan A., Chao Q., Chen H., Cheuk R.F., Chin C.W., Chung M.K., Conn L.,
RA Conway A.B., Conway A.R., Creasy T.H., Dewar K., Dunn P., Etgu P.,
RA Feldblyum T.V., Feng J.-D., Fong B., Fujii C.Y., Gill J.E., Goldsmith A.D.,
RA Haas B., Hansen N.F., Hughes B., Huizar L., Hunter J.L., Jenkins J.,
RA Johnson-Hopson C., Khan S., Khaykin E., Kim C.J., Koo H.L.,
RA Kremenetskaia I., Kurtz D.B., Kwan A., Lam B., Langin-Hooper S., Lee A.,
RA Lee J.M., Lenz C.A., Li J.H., Li Y.-P., Lin X., Liu S.X., Liu Z.A.,
RA Luros J.S., Maiti R., Marziali A., Militscher J., Miranda M., Nguyen M.,
RA Nierman W.C., Osborne B.I., Pai G., Peterson J., Pham P.K., Rizzo M.,
RA Rooney T., Rowley D., Sakano H., Salzberg S.L., Schwartz J.R., Shinn P.,
RA Southwick A.M., Sun H., Tallon L.J., Tambunga G., Toriumi M.J., Town C.D.,
RA Utterback T., Van Aken S., Vaysberg M., Vysotskaia V.S., Walker M., Wu D.,
RA Yu G., Fraser C.M., Venter J.C., Davis R.W.;
RT "Sequence and analysis of chromosome 1 of the plant Arabidopsis thaliana.";
RL Nature 408:816-820(2000).
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].
RC STRAIN=cv. Columbia;
RA Shinn P., Chen H., Kim C.J., Quinitio C., Ecker J.R.;
RT "Arabidopsis ORF clones.";
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION, AND INDUCTION BY MYB28.
RC STRAIN=cv. Columbia;
RX PubMed=19542295; DOI=10.1105/tpc.109.066399;
RA Gigolashvili T., Yatusevich R., Rollwitz I., Humphry M., Gershenzon J.,
RA Fluegge U.-I.;
RT "The plastidic bile acid transporter 5 is required for the biosynthesis of
RT methionine-derived glucosinolates in Arabidopsis thaliana.";
RL Plant Cell 21:1813-1829(2009).
RN [6]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=19493961; DOI=10.1093/pcp/pcp079;
RA Sawada Y., Kuwahara A., Nagano M., Narisawa T., Sakata A., Saito K.,
RA Hirai M.Y.;
RT "Omics-based approaches to methionine side chain elongation in Arabidopsis:
RT characterization of the genes encoding methylthioalkylmalate isomerase and
RT methylthioalkylmalate dehydrogenase.";
RL Plant Cell Physiol. 50:1181-1190(2009).
RN [7]
RP GENE FAMILY.
RX PubMed=19674406; DOI=10.1111/j.1365-313x.2009.03990.x;
RA He Y., Mawhinney T.P., Preuss M.L., Schroeder A.C., Chen B., Abraham L.,
RA Jez J.M., Chen S.;
RT "A redox-active isopropylmalate dehydrogenase functions in the biosynthesis
RT of glucosinolates and leucine in Arabidopsis.";
RL Plant J. 60:679-690(2009).
RN [8]
RP FUNCTION, MUTAGENESIS OF LEU-134, TISSUE SPECIFICITY, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=cv. Columbia;
RX PubMed=21697089; DOI=10.1074/jbc.m111.262519;
RA He Y., Galant A., Pang Q., Strul J.M., Balogun S.F., Jez J.M., Chen S.;
RT "Structural and functional evolution of isopropylmalate dehydrogenases in
RT the leucine and glucosinolate pathways of Arabidopsis thaliana.";
RL J. Biol. Chem. 286:28794-28801(2011).
RN [9]
RP FUNCTION, DISRUPTION PHENOTYPE, BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC
RP ACTIVITY, PATHWAY, AND TISSUE SPECIFICITY.
RC STRAIN=cv. Columbia;
RX PubMed=20840499; DOI=10.1111/j.1469-8137.2010.03460.x;
RA He Y., Chen L., Zhou Y., Mawhinney T.P., Chen B., Kang B.-H., Hauser B.A.,
RA Chen S.;
RT "Functional characterization of Arabidopsis thaliana isopropylmalate
RT dehydrogenases reveals their important roles in gametophyte development.";
RL New Phytol. 189:160-175(2011).
CC -!- FUNCTION: Involved in leucine biosynthesis; catalyzes the oxidative
CC decarboxylation step in leucine biosynthesis (primary metabolism)
CC (PubMed:21697089). Catalyzes the oxidation of 3-carboxy-2-hydroxy-4-
CC methylpentanoate (3-isopropylmalate, 3-IPM) to 3-carboxy-4-methyl-2-
CC oxopentanoate. The product decarboxylates to 4-methyl-2 oxopentanoate
CC (PubMed:15849421, PubMed:20840499). {ECO:0000269|PubMed:15849421,
CC ECO:0000269|PubMed:20840499, ECO:0000269|PubMed:21697089}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(2R,3S)-3-isopropylmalate + NAD(+) = 4-methyl-2-oxopentanoate
CC + CO2 + NADH; Xref=Rhea:RHEA:32271, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:17865, ChEBI:CHEBI:35121, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57945; EC=1.1.1.85;
CC Evidence={ECO:0000269|PubMed:15849421, ECO:0000269|PubMed:20840499};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P93832};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P50455};
CC Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit.
CC {ECO:0000250|UniProtKB:P50455};
CC -!- ACTIVITY REGULATION: Regulated by a thiol-based redox modification.
CC {ECO:0000250|UniProtKB:Q9FMT1}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=9.2 uM for 3-isopropylmalate {ECO:0000269|PubMed:20840499,
CC ECO:0000269|PubMed:21697089};
CC KM=502 uM for 3-(2'-methylthio)ethylmalate
CC {ECO:0000269|PubMed:21697089};
CC Vmax=4.98 umol/min/mg enzyme with 3-isopropylmalate as substrate
CC {ECO:0000269|PubMed:20840499};
CC Note=kcat is 543 min(-1) with 3-isopropylmalate as substrate
CC (PubMed:20840499, PubMed:21697089). kcat is 1 min(-1) with 3-(2'-
CC methylthio)ethylmalate as substrate (PubMed:21697089).
CC {ECO:0000269|PubMed:20840499, ECO:0000269|PubMed:21697089};
CC -!- PATHWAY: Amino-acid biosynthesis; L-leucine biosynthesis; L-leucine
CC from 3-methyl-2-oxobutanoate: step 3/4. {ECO:0000269|PubMed:15849421,
CC ECO:0000269|PubMed:20840499}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P12010}.
CC -!- SUBCELLULAR LOCATION: Plastid, chloroplast stroma
CC {ECO:0000269|PubMed:19542295}.
CC -!- TISSUE SPECIFICITY: Mostly expressed constitutively at high levels in
CC seedlings, cotyledons, hypocotyls, flowers, pollen and leaves and, to a
CC lower extent, in roots and stems. {ECO:0000269|PubMed:15849421,
CC ECO:0000269|PubMed:20840499, ECO:0000269|PubMed:21697089}.
CC -!- INDUCTION: Transactivated by MYB28. {ECO:0000269|PubMed:19542295}.
CC -!- DISRUPTION PHENOTYPE: No discernible vegetative or reproductive
CC phenotypes, but decreased leucine biosynthetic enzyme activities and
CC lower free leucine concentrations. {ECO:0000269|PubMed:20840499}.
CC -!- SIMILARITY: Belongs to the isocitrate and isopropylmalate
CC dehydrogenases family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD21684.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AC004793; AAD21684.1; ALT_SEQ; Genomic_DNA.
DR EMBL; CP002684; AEE31326.1; -; Genomic_DNA.
DR EMBL; BT025974; ABG25063.1; -; mRNA.
DR PIR; H86437; H86437.
DR RefSeq; NP_174403.1; NM_102856.3.
DR AlphaFoldDB; Q9SA14; -.
DR SMR; Q9SA14; -.
DR BioGRID; 25241; 21.
DR IntAct; Q9SA14; 1.
DR STRING; 3702.AT1G31180.1; -.
DR iPTMnet; Q9SA14; -.
DR MetOSite; Q9SA14; -.
DR PaxDb; Q9SA14; -.
DR PRIDE; Q9SA14; -.
DR EnsemblPlants; AT1G31180.1; AT1G31180.1; AT1G31180.
DR GeneID; 840006; -.
DR Gramene; AT1G31180.1; AT1G31180.1; AT1G31180.
DR KEGG; ath:AT1G31180; -.
DR Araport; AT1G31180; -.
DR TAIR; locus:2029519; AT1G31180.
DR eggNOG; KOG0786; Eukaryota.
DR HOGENOM; CLU_031953_0_3_1; -.
DR InParanoid; Q9SA14; -.
DR PhylomeDB; Q9SA14; -.
DR BRENDA; 1.1.1.85; 399.
DR UniPathway; UPA00048; UER00072.
DR PRO; PR:Q9SA14; -.
DR Proteomes; UP000006548; Chromosome 1.
DR ExpressionAtlas; Q9SA14; baseline and differential.
DR Genevisible; Q9SA14; AT.
DR GO; GO:0009507; C:chloroplast; HDA:TAIR.
DR GO; GO:0009570; C:chloroplast stroma; HDA:TAIR.
DR GO; GO:0005829; C:cytosol; HDA:TAIR.
DR GO; GO:0009536; C:plastid; IDA:TAIR.
DR GO; GO:0009579; C:thylakoid; HDA:TAIR.
DR GO; GO:0003862; F:3-isopropylmalate dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; IEA:InterPro.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0009098; P:leucine biosynthetic process; IDA:UniProtKB.
DR HAMAP; MF_01033; LeuB_type1; 1.
DR InterPro; IPR019818; IsoCit/isopropylmalate_DH_CS.
DR InterPro; IPR024084; IsoPropMal-DH-like_dom.
DR InterPro; IPR004429; Isopropylmalate_DH.
DR PANTHER; PTHR42979; PTHR42979; 1.
DR Pfam; PF00180; Iso_dh; 1.
DR SMART; SM01329; Iso_dh; 1.
DR TIGRFAMs; TIGR00169; leuB; 1.
DR PROSITE; PS00470; IDH_IMDH; 1.
PE 1: Evidence at protein level;
KW Amino-acid biosynthesis; Branched-chain amino acid biosynthesis;
KW Chloroplast; Leucine biosynthesis; Magnesium; Manganese; Metal-binding;
KW NAD; Oxidoreductase; Plastid; Reference proteome; Transit peptide.
FT TRANSIT 1..34
FT /note="Chloroplast"
FT /evidence="ECO:0000255"
FT CHAIN 35..404
FT /note="3-isopropylmalate dehydrogenase 3, chloroplastic"
FT /id="PRO_0000014453"
FT BINDING 115..130
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 137
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 147
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 175
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 235
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 265
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 265
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 266
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 289
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 293
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT BINDING 319..335
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT SITE 134
FT /note="Confers substrate specificity"
FT /evidence="ECO:0000269|PubMed:21697089"
FT SITE 182
FT /note="Important for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT SITE 229
FT /note="Essential for redox regulation"
FT /evidence="ECO:0000250|UniProtKB:Q9FMT1"
FT SITE 233
FT /note="Important for catalysis"
FT /evidence="ECO:0000250|UniProtKB:P93832"
FT SITE 387
FT /note="Essential for redox regulation"
FT /evidence="ECO:0000250|UniProtKB:Q9FMT1"
FT MUTAGEN 134
FT /note="L->F: Enhanced activity toward 3-(2'-methylthio)-
FT ethylmalate, but reduced catalytic efficiency with 3-
FT isopropylmalate."
FT /evidence="ECO:0000269|PubMed:21697089"
SQ SEQUENCE 404 AA; 43847 MW; D0A7E06E85AC40D0 CRC64;
MAAFLQTNIR LEIIPGRYSS LTDHKFRAPY RIRCAAASPV KKRYNITLLP GDGIGPEVIS
VAKNVLQKAG FLQGLEFDFQ EMPFGGAALD LVGVPLPEET STAAKQSDAI LLGAIGGYKW
DKNEKHLRPE MGLLNIRRDL NVFANLRPAT VLPQLVDAST LKKEVAQGVD MMIVRELTGG
IYFGEPRGIT INENGEEVGF NTEIYAAHEI DRIARVAFET ARKRRGKLCS VDKANVLDAS
ILWRKRVTAL ASEYPDVELS HMYVDNAAMQ LVRDPKQFDT IVTNNIFGDI LSDEASMITG
SIGMLPSASL GESGPGLFEP IHGSAPDIAG QDKANPLATI LSAAMLLKYG LGEEKAAKMI
EDAVVDALNK GFRTGDIYSP GNKLVGCKEM GEEVLKSVDS KVPV
