ID MDHC_FELCA Reviewed; 334 AA.
AC Q7YRU4;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 27-MAR-2024, entry version 117.
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 Felis catus (Cat) (Felis silvestris catus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; Felinae; Felis.
OX NCBI_TaxID=9685;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Liver;
RA Nakamura M., Sasaki N., Arai T.;
RT "Cloning and characterization of feline cytosolic malate dehydrogenase.";
RL Submitted (JUN-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 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}.
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DR EMBL; AB113364; BAC78621.1; -; mRNA.
DR RefSeq; NP_001009329.1; NM_001009329.1.
DR AlphaFoldDB; Q7YRU4; -.
DR SMR; Q7YRU4; -.
DR STRING; 9685.ENSFCAP00000029433; -.
DR PaxDb; 9685-ENSFCAP00000017047; -.
DR Ensembl; ENSFCAT00000034057.3; ENSFCAP00000029433.1; ENSFCAG00000024183.4.
DR GeneID; 493924; -.
DR KEGG; fca:493924; -.
DR VGNC; VGNC:68220; MDH1.
DR eggNOG; KOG1496; Eukaryota.
DR GeneTree; ENSGT00530000063410; -.
DR HOGENOM; CLU_040727_2_0_1; -.
DR InParanoid; Q7YRU4; -.
DR OMA; TKGMERG; -.
DR OrthoDB; 501358at2759; -.
DR Proteomes; UP000011712; Chromosome A3.
DR Bgee; ENSFCAG00000024183; Expressed in brain and 10 other cell types or tissues.
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_0000226736"
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 332
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O88989"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P40925"
SQ SEQUENCE 334 AA; 36423 MW; 31FEB6E50FF5D946 CRC64;
MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC
ALPLLKDVIA TDKEDVAFKD LDVAILVGSM PRRDGMERKD LLKANVKIFK CQGAALEKYA
KKSVKVIVVG NPANTNCLTA CKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTSDDVKN
VIIWGNHSST QYPDVSHAKV KLHGKEVGVY DALKDDSWLK GEFITTVQQR GAAVIKARKL
SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG IISDGNPYGV PDDLLYSFPV TIKNKTWKVV
EGLTINDFSR EKMDLTAKEL AEEKETAFEF LSSA
//
