ID MDHM1_ARATH Reviewed; 341 AA. AC Q9ZP06; Q8LBB9; Q9MAH7; DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1999, sequence version 1. DT 27-MAR-2024, entry version 189. DE RecName: Full=Malate dehydrogenase 1, mitochondrial {ECO:0000305}; DE EC=1.1.1.37 {ECO:0000269|PubMed:26203119}; DE AltName: Full=Mitochondrial MDH1 {ECO:0000303|PubMed:20876337}; DE Short=mMDH1 {ECO:0000303|PubMed:20876337}; DE AltName: Full=Mitochondrial NAD-dependent malate dehydrogenase 1 {ECO:0000305}; DE Short=mNAD-MDH 1 {ECO:0000305}; DE Short=mtNAD-MDH1 {ECO:0000303|PubMed:20876337}; DE Flags: Precursor; GN OrderedLocusNames=At1g53240; ORFNames=F12M16.14; 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=9774405; DOI=10.1074/jbc.273.43.27927; RA Berkemeyer M., Scheibe R., Ocheretina O.; RT "A novel, non-redox-regulated NAD-dependent malate dehydrogenase from RT chloroplasts of Arabidopsis thaliana L."; RL J. Biol. Chem. 273:27927-27933(1998). 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; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Brover V.V., Troukhan M.E., Alexandrov N.A., Lu Y.-P., Flavell R.B., RA Feldmann K.A.; RT "Full-length cDNA from Arabidopsis thaliana."; RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases. RN [6] RP PROTEIN SEQUENCE OF 23-37, AND SUBCELLULAR LOCATION. RC TISSUE=Leaf, and Stem; RX PubMed=11743114; DOI=10.1104/pp.127.4.1694; RA Kruft V., Eubel H., Jaensch L., Werhahn W., Braun H.-P.; RT "Proteomic approach to identify novel mitochondrial proteins in RT Arabidopsis."; RL Plant Physiol. 127:1694-1710(2001). RN [7] 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 [8] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC STRAIN=cv. Landsberg erecta; RX PubMed=17272265; DOI=10.1074/mcp.m600408-mcp200; RA Maor R., Jones A., Nuehse T.S., Studholme D.J., Peck S.C., Shirasu K.; RT "Multidimensional protein identification technology (MudPIT) analysis of RT ubiquitinated proteins in plants."; RL Mol. Cell. Proteomics 6:601-610(2007). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19376835; DOI=10.1104/pp.109.138677; RA Reiland S., Messerli G., Baerenfaller K., Gerrits B., Endler A., RA Grossmann J., Gruissem W., Baginsky S.; RT "Large-scale Arabidopsis phosphoproteome profiling reveals novel RT chloroplast kinase substrates and phosphorylation networks."; RL Plant Physiol. 150:889-903(2009). RN [10] 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 [11] 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 [12] 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 [13] RP ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND DISULFIDE BOND. RX PubMed=26946085; DOI=10.1016/j.bbabio.2016.03.001; RA Yoshida K., Hisabori T.; RT "Adenine nucleotide-dependent and redox-independent control of RT mitochondrial malate dehydrogenase activity in Arabidopsis thaliana."; RL Biochim. Biophys. Acta 1857:810-818(2016). RN [14] RP FUNCTION, AND DISRUPTION PHENOTYPE. RX PubMed=26889011; DOI=10.1093/jxb/erw030; RA Linden P., Keech O., Stenlund H., Gardestroem P., Moritz T.; RT "Reduced mitochondrial malate dehydrogenase activity has a strong effect on RT photorespiratory metabolism as revealed by 13C labelling."; RL J. Exp. Bot. 67:3123-3135(2016). RN [15] 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). Its activity is essential to CC shuttle reductants out from the mitochondria to support the CC photorespiratory flux (PubMed:26889011). Can convert 2-oxoglutarate to CC (S)-2-hydroxyglutarate in vitro (PubMed:26203119). CC {ECO:0000269|PubMed:20876337, ECO:0000269|PubMed:26203119, CC ECO:0000269|PubMed:26889011, ECO:0000269|PubMed:27208265, CC 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 -!- ACTIVITY REGULATION: Negatively regulated by ATP. Not redox-regulated. CC The formation of intramolecular disulfide bonds does not alter CC enzymatic activity. {ECO:0000269|PubMed:26946085}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=0.8 mM for malate (at pH 7.5) {ECO:0000269|PubMed:26946085}; CC KM=0.11 mM for oxaloacetate (at pH 7.5) CC {ECO:0000269|PubMed:26946085}; CC KM=0.27 mM for oxaloacetate (at pH 7.4) CC {ECO:0000269|PubMed:26203119}; CC KM=0.6 mM for NAD(+) (at pH 7.5) {ECO:0000269|PubMed:26946085}; CC KM=0.23 mM for NADH (at pH 7.5) {ECO:0000269|PubMed:26946085}; CC KM=41 mM for 2-ketoglutarate (at pH 7.4) CC {ECO:0000269|PubMed:26203119}; CC Vmax=0.087 mmol/min/mg enzyme toward malate (at pH 7.5) CC {ECO:0000269|PubMed:26946085}; CC Vmax=0.03 mmol/min/mg enzyme toward malate (at pH 7.4) CC {ECO:0000269|PubMed:26203119}; CC Vmax=1.2 mmol/min/mg enzyme toward oxaloacetate (at pH 7.5) CC {ECO:0000269|PubMed:26946085}; CC Vmax=2.39 mmol/min/mg enzyme toward oxaloacetate (at pH 7.4) CC {ECO:0000269|PubMed:26203119}; CC Vmax=79 umol/min/mg enzyme toward NAD(+) (at pH 7.5) CC {ECO:0000269|PubMed:26946085}; CC Vmax=2732 umol/min/mg enzyme toward NADH (at pH 7.5) CC {ECO:0000269|PubMed:26946085}; CC Vmax=0.38 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:11743114, ECO:0000269|PubMed:14671022, CC ECO:0000305|PubMed:25732537}. CC -!- TISSUE SPECIFICITY: Expressed in rosette leaves. CC {ECO:0000269|PubMed:20876337}. CC -!- PTM: Forms intramolecular disulfide bonds. CC {ECO:0000269|PubMed:26946085}. CC -!- DISRUPTION PHENOTYPE: Slight reduction of rosette leaf size and CC reduction by 50 percents in fresh weight and seed production CC (PubMed:26889011). The double mutant plants mmdh1 and mmdh2 have CC decreased germination rate, grow slowly, are small, have increased CC photorespiration and die before producing seeds (PubMed:20876337). CC {ECO:0000269|PubMed:20876337, ECO:0000269|PubMed:26889011}. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAF69549.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AJ131205; CAA10320.1; -; mRNA. DR EMBL; AC008007; AAF69549.1; ALT_SEQ; Genomic_DNA. DR EMBL; CP002684; AEE32910.1; -; Genomic_DNA. DR EMBL; AF324670; AAG40021.1; -; mRNA. DR EMBL; AF339684; AAK00366.1; -; mRNA. DR EMBL; AY062580; AAL32658.1; -; mRNA. DR EMBL; AY128783; AAM91183.1; -; mRNA. DR EMBL; AY087304; AAM64855.1; -; mRNA. DR PIR; T51311; T51311. DR RefSeq; NP_564625.1; NM_104202.3. DR AlphaFoldDB; Q9ZP06; -. DR SMR; Q9ZP06; -. DR BioGRID; 26982; 25. DR IntAct; Q9ZP06; 1. DR STRING; 3702.Q9ZP06; -. DR iPTMnet; Q9ZP06; -. DR MetOSite; Q9ZP06; -. DR PaxDb; 3702-AT1G53240-1; -. DR ProteomicsDB; 238769; -. DR EnsemblPlants; AT1G53240.1; AT1G53240.1; AT1G53240. DR GeneID; 841757; -. DR Gramene; AT1G53240.1; AT1G53240.1; AT1G53240. DR KEGG; ath:AT1G53240; -. DR Araport; AT1G53240; -. DR TAIR; AT1G53240; MMDH1. DR eggNOG; KOG1494; Eukaryota. DR HOGENOM; CLU_047181_0_1_1; -. DR InParanoid; Q9ZP06; -. DR OMA; PSIVTGY; -. DR OrthoDB; 5059897at2759; -. DR PhylomeDB; Q9ZP06; -. DR BioCyc; ARA:AT1G53240-MONOMER; -. DR BioCyc; MetaCyc:AT1G53240-MONOMER; -. DR BRENDA; 1.1.1.37; 399. DR PRO; PR:Q9ZP06; -. DR Proteomes; UP000006548; Chromosome 1. DR ExpressionAtlas; Q9ZP06; baseline and differential. DR GO; GO:0009507; C:chloroplast; HDA:TAIR. DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IDA:TAIR. DR GO; GO:0005634; C:nucleus; HDA:TAIR. DR GO; GO:0009505; C:plant-type cell wall; HDA:TAIR. DR GO; GO:0005507; F:copper ion binding; HDA:TAIR. DR GO; GO:0030060; F:L-malate dehydrogenase activity; IMP:TAIR. DR GO; GO:0006108; P:malate metabolic process; IEA:InterPro. DR GO; GO:0009409; P:response to cold; IEP:TAIR. 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 SWISS-2DPAGE; Q9ZP06; -. DR Genevisible; Q9ZP06; AT. PE 1: Evidence at protein level; KW Direct protein sequencing; Disulfide bond; Mitochondrion; NAD; KW Oxidoreductase; Reference proteome; Transit peptide; KW Tricarboxylic acid cycle. FT TRANSIT 1..22 FT /note="Mitochondrion" FT /evidence="ECO:0000269|PubMed:11743114, FT ECO:0000269|PubMed:25732537" FT CHAIN 23..341 FT /note="Malate dehydrogenase 1, mitochondrial" FT /id="PRO_0000018622" 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" FT CONFLICT 17 FT /note="V -> A (in Ref. 5; AAM64855)" FT /evidence="ECO:0000305" SQ SEQUENCE 341 AA; 35804 MW; D035C4C38785BE57 CRC64; MFRSMLVRSS ASAKQAVIRR SFSSGSVPER KVAILGAAGG IGQPLALLMK LNPLVSSLSL YDIANTPGVA ADVGHINTRS EVVGYMGDDN LAKALEGADL VIIPAGVPRK PGMTRDDLFN INAGIVKNLC TAIAKYCPHA LINMISNPVN STVPIAAEIF KKAGMYDEKK LFGVTTLDVV RARTFYAGKA NVPVAEVNVP VIGGHAGVTI LPLFSQATPQ ANLSSDILTA LTKRTQDGGT EVVEAKAGKG SATLSMAYAG ALFADACLKG LNGVPDVIEC SYVQSTITEL PFFASKVRLG KNGVEEVLDL GPLSDFEKEG LEALKPELKS SIEKGVKFAN Q //