ID   MDHM2_ARATH             Reviewed;         341 AA.
AC   Q9LKA3;
DT   21-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2000, sequence version 1.
DT   27-MAR-2024, entry version 162.
DE   RecName: Full=Malate dehydrogenase 2, mitochondrial {ECO:0000305};
DE            EC=1.1.1.37 {ECO:0000269|PubMed:26203119};
DE   AltName: Full=Mitochondrial MDH2 {ECO:0000303|PubMed:20876337};
DE            Short=mMDH2 {ECO:0000303|PubMed:20876337};
DE   AltName: Full=Mitochondrial NAD-dependent malate dehydrogenase 2 {ECO:0000305};
DE            Short=mNAD-MDH 2 {ECO:0000305};
DE            Short=mtNAD-MDH2 {ECO:0000303|PubMed:20876337};
DE   Flags: Precursor;
GN   OrderedLocusNames=At3g15020; ORFNames=K15M2.16;
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=10907853; DOI=10.1093/dnares/7.3.217;
RA   Kaneko T., Katoh T., Sato S., Nakamura Y., Asamizu E., Tabata S.;
RT   "Structural analysis of Arabidopsis thaliana chromosome 3. II. Sequence
RT   features of the 4,251,695 bp regions covered by 90 P1, TAC and BAC
RT   clones.";
RL   DNA Res. 7:217-221(2000).
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   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR LOCATION [LARGE SCALE
RP   ANALYSIS].
RC   STRAIN=cv. Landsberg erecta;
RX   PubMed=14671022; DOI=10.1105/tpc.016055;
RA   Heazlewood J.L., Tonti-Filippini J.S., Gout A.M., Day D.A., Whelan J.,
RA   Millar A.H.;
RT   "Experimental analysis of the Arabidopsis mitochondrial proteome highlights
RT   signaling and regulatory components, provides assessment of targeting
RT   prediction programs, and indicates plant-specific mitochondrial proteins.";
RL   Plant Cell 16:241-256(2004).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, TISSUE SPECIFICITY, AND
RP   DISRUPTION PHENOTYPE.
RX   PubMed=20876337; DOI=10.1104/pp.110.161612;
RA   Tomaz T., Bagard M., Pracharoenwattana I., Linden P., Lee C.P.,
RA   Carroll A.J., Stroeher E., Smith S.M., Gardestroem P., Millar A.H.;
RT   "Mitochondrial malate dehydrogenase lowers leaf respiration and alters
RT   photorespiration and plant growth in Arabidopsis.";
RL   Plant Physiol. 154:1143-1157(2010).
RN   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY, AND CLEAVAGE OF TRANSIT PEPTIDE AFTER
RP   PHE-22.
RX   PubMed=25732537; DOI=10.1093/jxb/erv064;
RA   Carrie C., Venne A.S., Zahedi R.P., Soll J.;
RT   "Identification of cleavage sites and substrate proteins for two
RT   mitochondrial intermediate peptidases in Arabidopsis thaliana.";
RL   J. Exp. Bot. 66:2691-2708(2015).
RN   [7]
RP   FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=26203119; DOI=10.1093/pcp/pcv108;
RA   Huedig M., Maier A., Scherrers I., Seidel L., Jansen E.E.,
RA   Mettler-Altmann T., Engqvist M.K., Maurino V.G.;
RT   "Plants possess a cyclic mitochondrial metabolic pathway similar to the
RT   mammalian metabolic repair mechanism involving malate dehydrogenase and l-
RT   2-hydroxyglutarate dehydrogenase.";
RL   Plant Cell Physiol. 56:1820-1830(2015).
RN   [8]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=27208265; DOI=10.1104/pp.16.01654;
RA   Sew Y.S., Stroeher E., Fenske R., Millar A.H.;
RT   "Loss of mitochondrial malate dehydrogenase activity alters seed metabolism
RT   impairing seed maturation and post-germination growth in Arabidopsis.";
RL   Plant Physiol. 171:849-863(2016).
CC   -!- FUNCTION: Catalyzes a reversible NAD-dependent dehydrogenase reaction
CC       involved in central metabolism and redox homeostasis between organelle
CC       compartments (Probable). Required for carbon dioxide and energy
CC       partitioning in leaves. May limit photorespiration during the dark
CC       phase (PubMed:20876337, PubMed:27208265). Can convert 2-ketoglutarate
CC       to L-2-hydroxyglutarate in vitro (PubMed:26203119).
CC       {ECO:0000269|PubMed:20876337, ECO:0000269|PubMed:26203119,
CC       ECO:0000269|PubMed:27208265, ECO:0000305|PubMed:20876337}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-malate + NAD(+) = H(+) + NADH + oxaloacetate;
CC         Xref=Rhea:RHEA:21432, ChEBI:CHEBI:15378, ChEBI:CHEBI:15589,
CC         ChEBI:CHEBI:16452, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.37;
CC         Evidence={ECO:0000269|PubMed:26203119};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.02 mM for oxaloacetate {ECO:0000269|PubMed:26203119};
CC         KM=7 mM for 2-ketoglutarate {ECO:0000269|PubMed:26203119};
CC         Vmax=0.67 mmol/min/mg enzyme toward oxaloacetate (at pH 7.4)
CC         {ECO:0000269|PubMed:26203119};
CC         Vmax=0.02 mmol/min/mg enzyme toward malate (at pH 7.4)
CC         {ECO:0000269|PubMed:26203119};
CC         Vmax=0.08 mmol/min/mg enzyme toward 2-ketoglutarate (at pH 7.4)
CC         {ECO:0000269|PubMed:26203119};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000269|PubMed:14671022, ECO:0000305|PubMed:25732537}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=1;
CC         Comment=A number of isoforms are produced. According to EST
CC         sequences.;
CC       Name=1;
CC         IsoId=Q9LKA3-1; Sequence=Displayed;
CC   -!- TISSUE SPECIFICITY: Expressed in rosette leaves at low levels.
CC       {ECO:0000269|PubMed:20876337}.
CC   -!- DISRUPTION PHENOTYPE: No visible phenotype under normal growth
CC       conditions, but the double mutant plants mmdh1 and mmdh2 have decreased
CC       germination rate, grow slowly, are small, have increased
CC       photorespiration and die before producing seeds.
CC       {ECO:0000269|PubMed:20876337, ECO:0000269|PubMed:27208265}.
CC   -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
CC       {ECO:0000305}.
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DR   EMBL; AP000370; BAA97065.1; -; Genomic_DNA.
DR   EMBL; CP002686; AEE75604.1; -; Genomic_DNA.
DR   EMBL; AY045592; AAK73950.1; -; mRNA.
DR   EMBL; AY093788; AAM10404.1; -; mRNA.
DR   RefSeq; NP_188120.1; NM_112364.4. [Q9LKA3-1]
DR   AlphaFoldDB; Q9LKA3; -.
DR   SMR; Q9LKA3; -.
DR   BioGRID; 6065; 26.
DR   STRING; 3702.Q9LKA3; -.
DR   iPTMnet; Q9LKA3; -.
DR   PaxDb; 3702-AT3G15020-1; -.
DR   ProteomicsDB; 239048; -. [Q9LKA3-1]
DR   EnsemblPlants; AT3G15020.1; AT3G15020.1; AT3G15020. [Q9LKA3-1]
DR   GeneID; 820731; -.
DR   Gramene; AT3G15020.1; AT3G15020.1; AT3G15020. [Q9LKA3-1]
DR   KEGG; ath:AT3G15020; -.
DR   Araport; AT3G15020; -.
DR   TAIR; AT3G15020; MMDH2.
DR   eggNOG; KOG1494; Eukaryota.
DR   HOGENOM; CLU_047181_0_2_1; -.
DR   InParanoid; Q9LKA3; -.
DR   OMA; SHMDTPA; -.
DR   OrthoDB; 5059897at2759; -.
DR   PhylomeDB; Q9LKA3; -.
DR   BRENDA; 1.1.1.37; 399.
DR   PRO; PR:Q9LKA3; -.
DR   Proteomes; UP000006548; Chromosome 3.
DR   ExpressionAtlas; Q9LKA3; baseline and differential.
DR   GO; GO:0048046; C:apoplast; HDA:TAIR.
DR   GO; GO:0005829; C:cytosol; HDA:TAIR.
DR   GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0005739; C:mitochondrion; HDA:TAIR.
DR   GO; GO:0005507; F:copper ion binding; HDA:TAIR.
DR   GO; GO:0030060; F:L-malate dehydrogenase activity; IGI:TAIR.
DR   GO; GO:0006108; P:malate metabolic process; IEA:InterPro.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW.
DR   CDD; cd01337; MDH_glyoxysomal_mitochondrial; 1.
DR   Gene3D; 3.90.110.10; Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   InterPro; IPR001557; L-lactate/malate_DH.
DR   InterPro; IPR022383; Lactate/malate_DH_C.
DR   InterPro; IPR001236; Lactate/malate_DH_N.
DR   InterPro; IPR015955; Lactate_DH/Glyco_Ohase_4_C.
DR   InterPro; IPR001252; Malate_DH_AS.
DR   InterPro; IPR010097; Malate_DH_type1.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   NCBIfam; TIGR01772; MDH_euk_gproteo; 1.
DR   PANTHER; PTHR11540; MALATE AND LACTATE DEHYDROGENASE; 1.
DR   PANTHER; PTHR11540:SF58; MALATE DEHYDROGENASE 1, MITOCHONDRIAL-RELATED; 1.
DR   Pfam; PF02866; Ldh_1_C; 1.
DR   Pfam; PF00056; Ldh_1_N; 1.
DR   PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR   SUPFAM; SSF56327; LDH C-terminal domain-like; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   PROSITE; PS00068; MDH; 1.
DR   Genevisible; Q9LKA3; AT.
PE   1: Evidence at protein level;
KW   Alternative splicing; Mitochondrion; NAD; Oxidoreductase;
KW   Reference proteome; Transit peptide; Tricarboxylic acid cycle.
FT   TRANSIT         1..22
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:25732537"
FT   CHAIN           23..341
FT                   /note="Malate dehydrogenase 2, mitochondrial"
FT                   /id="PRO_0000224148"
FT   ACT_SITE        205
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P11708"
FT   BINDING         36..42
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         62
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         109
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11708"
FT   BINDING         115
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11708"
FT   BINDING         122
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         145..147
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         147
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11708"
FT   BINDING         181
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P11708"
FT   BINDING         256
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
SQ   SEQUENCE   341 AA;  35875 MW;  38364CAE36712AE1 CRC64;
     MFRSMIVRSA SPVKQGLLRR GFASESVPDR KVVILGAAGG IGQPLSLLMK LNPLVSSLSL
     YDIANTPGVA ADVGHINTRS QVSGYMGDDD LGKALEGADL VIIPAGVPRK PGMTRDDLFN
     INAGIVKNLS IAIAKYCPQA LVNMISNPVN STVPIAAEIF KKAGTYDEKK LFGVTTLDVV
     RARTFYAGKS DVNVAEVNVP VVGGHAGITI LPLFSQASPQ ANLSDDLIRA LTKRTQDGGT
     EVVEAKAGKG SATLSMAYAG ALFADACLKG LNGVPNVVEC SFVQSTITEL PFFASKVRLG
     KNGVEEVLDL GPLSDFEKEG LEALKAELKS SIEKGIKFAN Q
//