ID MDHC_BOVIN Reviewed; 334 AA. AC Q3T145; DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 27-MAR-2024, entry version 126. DE RecName: Full=Malate dehydrogenase, cytoplasmic; DE EC=1.1.1.37; DE AltName: Full=Aromatic alpha-keto acid reductase {ECO:0000305}; DE Short=KAR {ECO:0000305}; DE EC=1.1.1.96 {ECO:0000250|UniProtKB:P40925}; DE AltName: Full=Cytosolic malate dehydrogenase; GN Name=MDH1; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Crossbred X Angus; TISSUE=Ileum; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases. CC -!- FUNCTION: Catalyzes the reduction of aromatic alpha-keto acids in the CC presence of NADH. Plays essential roles in the malate-aspartate shuttle CC and the tricarboxylic acid cycle, important in mitochondrial NADH CC supply for oxidative phosphorylation. Catalyzes the reduction of 2- CC oxoglutarate to 2-hydroxyglutarate, leading to elevated reactive oxygen CC species (ROS). {ECO:0000250|UniProtKB:P40925}. 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:0000250|UniProtKB:P40925}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21433; CC Evidence={ECO:0000250|UniProtKB:P40925}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21434; CC Evidence={ECO:0000250|UniProtKB:P40925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2R)-2-hydroxy-3-(4-hydroxyphenyl)propanoate + NAD(+) = 3-(4- CC hydroxyphenyl)pyruvate + H(+) + NADH; Xref=Rhea:RHEA:10780, CC ChEBI:CHEBI:10980, ChEBI:CHEBI:15378, ChEBI:CHEBI:36242, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.96; CC Evidence={ECO:0000250|UniProtKB:P40925}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10782; CC Evidence={ECO:0000250|UniProtKB:P40925}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(S)-2-hydroxyglutarate + NAD(+) = 2-oxoglutarate + H(+) + CC NADH; Xref=Rhea:RHEA:57172, ChEBI:CHEBI:15378, ChEBI:CHEBI:16782, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; CC Evidence={ECO:0000250|UniProtKB:P40925}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:57174; CC Evidence={ECO:0000250|UniProtKB:P40925}; CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P11708}. CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P40925}. CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P40925}. CC -!- PTM: Acetylation at Lys-118 dramatically enhances enzymatic activity CC and promotes adipogenic differentiation. CC {ECO:0000250|UniProtKB:P40925}. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 family. CC {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; BC102133; AAI02134.1; -; mRNA. DR RefSeq; NP_001029800.1; NM_001034628.3. DR AlphaFoldDB; Q3T145; -. DR SMR; Q3T145; -. DR STRING; 9913.ENSBTAP00000069808; -. DR PaxDb; 9913-ENSBTAP00000025691; -. DR PeptideAtlas; Q3T145; -. DR Ensembl; ENSBTAT00000073367.1; ENSBTAP00000069808.1; ENSBTAG00000019295.6. DR GeneID; 535182; -. DR KEGG; bta:535182; -. DR CTD; 4190; -. DR VEuPathDB; HostDB:ENSBTAG00000019295; -. DR VGNC; VGNC:31333; MDH1. DR eggNOG; KOG1496; Eukaryota. DR GeneTree; ENSGT00530000063410; -. DR HOGENOM; CLU_040727_2_0_1; -. DR InParanoid; Q3T145; -. DR OMA; DHMRDWT; -. DR TreeFam; TF105826; -. DR Reactome; R-BTA-70263; Gluconeogenesis. DR Proteomes; UP000009136; Chromosome 11. DR Bgee; ENSBTAG00000019295; Expressed in cardiac ventricle and 103 other cell types or tissues. DR ExpressionAtlas; Q3T145; baseline and differential. DR GO; GO:0005813; C:centrosome; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IBA:GO_Central. DR GO; GO:0047995; F:hydroxyphenylpyruvate reductase activity; IEA:RHEA. DR GO; GO:0030060; F:L-malate dehydrogenase activity; IBA:GO_Central. DR GO; GO:0006108; P:malate metabolic process; IBA:GO_Central. DR GO; GO:0006734; P:NADH metabolic process; IBA:GO_Central. DR GO; GO:0006739; P:NADP metabolic process; IEA:Ensembl. DR GO; GO:0006107; P:oxaloacetate metabolic process; IBA:GO_Central. DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central. DR CDD; cd01336; MDH_cytoplasmic_cytosolic; 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 HAMAP; MF_01517; Malate_dehydrog_2; 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; IPR011274; Malate_DH_NAD-dep_euk. DR InterPro; IPR010945; Malate_DH_type2. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR NCBIfam; TIGR01759; MalateDH-SF1; 1. DR NCBIfam; TIGR01758; MDH_euk_cyt; 1. DR PANTHER; PTHR23382; MALATE DEHYDROGENASE; 1. DR PANTHER; PTHR23382:SF3; MALATE DEHYDROGENASE, CYTOPLASMIC; 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. PE 2: Evidence at transcript level; KW Acetylation; Cytoplasm; Methylation; NAD; Oxidoreductase; Phosphoprotein; KW Reference proteome; Tricarboxylic acid cycle; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000250|UniProtKB:P40925" FT CHAIN 2..334 FT /note="Malate dehydrogenase, cytoplasmic" FT /id="PRO_0000226735" FT ACT_SITE 187 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 11..17 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 42 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 92 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 98 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 105 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 112 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 129..131 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 131 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 162 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P11708" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000250|UniProtKB:P40925" FT MOD_RES 110 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P14152" FT MOD_RES 118 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P40925" FT MOD_RES 121 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P40925" FT MOD_RES 214 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P14152" FT MOD_RES 217 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P14152" FT MOD_RES 230 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:P14152" FT MOD_RES 241 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40925" FT MOD_RES 298 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40925" FT MOD_RES 298 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P14152" FT MOD_RES 309 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P14152" FT MOD_RES 318 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P14152" FT MOD_RES 333 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40925" SQ SEQUENCE 334 AA; 36438 MW; 72FA4DA47F46AB95 CRC64; MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC ALPLLKDVIA TDKEEIAFKD LDVAILVGSM PRRDGMERKD LLKANVKIFK CQGAALDKYA KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTSDDVKN VIIWGNHSST QYPDVNHAKV KLQGKEVGVY EALKDDSWLK GEFITTVQQR GAAVIKARKL SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG IISDGNSYGI PDDLLYSFPV TIKDKTWKVV EGLPINDFSR EKMDLTAKEL AEEKETAFEF LASA //