ID MDHC_XENTR Reviewed; 334 AA. AC Q6DIY9; Q28H34; DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot. DT 16-AUG-2004, sequence version 1. DT 27-MAR-2024, entry version 100. DE RecName: Full=Malate dehydrogenase, cytoplasmic; DE EC=1.1.1.37; DE AltName: Full=Cytosolic malate dehydrogenase; GN Name=mdh1; ORFNames=TEgg049g04.1; OS Xenopus tropicalis (Western clawed frog) (Silurana tropicalis). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia; OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana. OX NCBI_TaxID=8364; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Egg; RG Sanger Xenopus tropicalis EST/cDNA project; RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RG NIH - Xenopus Gene Collection (XGC) project; RL Submitted (JUN-2004) 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 -!- 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 -!- 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; CR761081; CAJ81507.1; -; mRNA. DR EMBL; BC075396; AAH75396.1; -; mRNA. DR RefSeq; NP_001006694.1; NM_001006693.2. DR RefSeq; NP_001303830.1; NM_001316901.1. DR AlphaFoldDB; Q6DIY9; -. DR SMR; Q6DIY9; -. DR STRING; 8364.ENSXETP00000009425; -. DR PaxDb; 8364-ENSXETP00000028522; -. DR DNASU; 448318; -. DR Ensembl; ENSXETT00000028520; ENSXETP00000028520; ENSXETG00000013016. DR Ensembl; ENSXETT00000101573; ENSXETP00000085091; ENSXETG00000013016. DR GeneID; 448318; -. DR KEGG; xtr:448318; -. DR AGR; Xenbase:XB-GENE-484872; -. DR CTD; 4190; -. DR Xenbase; XB-GENE-484872; mdh1. DR eggNOG; KOG1496; Eukaryota. DR InParanoid; Q6DIY9; -. DR OMA; TKGMERG; -. DR OrthoDB; 501358at2759; -. DR Reactome; R-XTR-70263; Gluconeogenesis. DR Proteomes; UP000008143; Chromosome 5. DR Bgee; ENSXETG00000013016; Expressed in skeletal muscle tissue and 20 other cell types or tissues. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0030060; F:L-malate dehydrogenase activity; IEA:UniProtKB-EC. DR GO; GO:0006108; P:malate metabolic process; IEA:InterPro. DR GO; GO:0006099; P:tricarboxylic acid cycle; IEA:UniProtKB-KW. 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 Cytoplasm; NAD; Oxidoreductase; Reference proteome; KW Tricarboxylic acid cycle. FT CHAIN 1..334 FT /note="Malate dehydrogenase, cytoplasmic" FT /id="PRO_0000226740" FT ACT_SITE 187 FT /note="Proton acceptor" FT /evidence="ECO:0000250" FT BINDING 11..17 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 92 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 98 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 105 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 112 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 129..131 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250" FT BINDING 131 FT /ligand="substrate" FT /evidence="ECO:0000250" FT BINDING 162 FT /ligand="substrate" FT /evidence="ECO:0000250" SQ SEQUENCE 334 AA; 36543 MW; 3771224ABFDCF324 CRC64; MPEPVKVLVT GAAGQIAYSL LYGIAKGDVF GKDQPLILVL LDITPMMTVL EGVVMELQDC ALPLLKEVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD LLKANVKIFK SQGAALNKYS KKSVKVIVVG NPANTNCLTA MKSAPSIPKE NFSCLTRLDH NRAKGQIALK LNVASDDVKN VIIWGNHSST QYPDASHATV NLQGKDVGAF EAVKNDDWLK GEFITTVQQR GAAVIKARKL SSAMSAAKAI CDHVRDIWFG TPDGQFVSMG VISDGNSYGI PEDLMYSFPL TIKNKTWKIV EGLPINDFSR EKMDLTAKEL HEEKETALEF LSCE //