ID   MDHC_XENLA              Reviewed;         334 AA.
AC   Q6PAB3;
DT   07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2004, sequence version 1.
DT   27-MAR-2024, entry version 98.
DE   RecName: Full=Malate dehydrogenase, cytoplasmic;
DE            EC=1.1.1.37;
DE   AltName: Full=Cytosolic malate dehydrogenase;
GN   Name=mdh1;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
RG   NIH - Xenopus Gene Collection (XGC) project;
RL   Submitted (OCT-2003) 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}.
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DR   EMBL; BC060386; AAH60386.1; -; mRNA.
DR   RefSeq; NP_001083335.1; NM_001089866.1.
DR   AlphaFoldDB; Q6PAB3; -.
DR   SMR; Q6PAB3; -.
DR   BioGRID; 100200; 1.
DR   MaxQB; Q6PAB3; -.
DR   DNASU; 398872; -.
DR   GeneID; 398872; -.
DR   KEGG; xla:398872; -.
DR   AGR; Xenbase:XB-GENE-865511; -.
DR   CTD; 398872; -.
DR   Xenbase; XB-GENE-865511; mdh1.S.
DR   OMA; TKGMERG; -.
DR   OrthoDB; 501358at2759; -.
DR   Proteomes; UP000186698; Chromosome 5S.
DR   Bgee; 398872; Expressed in kidney and 19 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_0000226739"
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;  36425 MW;  563293ACA427786A CRC64;
     MPEPVKVLVT GAAGQIAYSL LFGIAKGDVF GKDQPLILVL LDITPMMTVL EGVVMELQDC
     ALPLLKEVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD LLKANVKIFK SQGAALNKYS
     KKSVKVIVVG NPANTNCLTA LKSAPSIPKE NFSCLTRLDH NRAKAQIALK LNVASDDVKN
     VIIWGNHSST QYPDASHASV TLQGKDVGAF EAVKNDDWLK GGFITTVQQR GAAVIKARKL
     SSAMSAAKAI CDHVRDIWFG TPEGQFVSMG VISDGNSYGV PEDLMYSFPL TIKNKTWKIV
     EGLCINDFSR EKMDITAKEL QDEKETAFEF LSSE
//