MDHC_RAT
ID MDHC_RAT Reviewed; 334 AA.
AC O88989; O88585; Q6PCV2;
DT 07-MAR-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Malate dehydrogenase, cytoplasmic;
DE EC=1.1.1.37;
DE AltName: Full=Cytosolic malate dehydrogenase;
GN Name=Mdh1; Synonyms=Mdh;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Achenbach P., Steinbrenner H., Reindl G., Seissler J.;
RT "Cloning of rat cytosolic malate dehydrogenase.";
RL Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pituitary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 7-32; 80-92; 126-157; 171-199; 206-230; 239-255;
RP 299-310 AND 319-334, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain, Hippocampus, and Spinal cord;
RA Lubec G., Afjehi-Sadat L., Diao W., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 251-284.
RA Earley S.;
RT "Partial sequence of rat malate dehydrogenase (MDH) mRNA.";
RL Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-217; SER-241; SER-332 AND
RP SER-333, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
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. {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 -!- SUBUNIT: Homodimer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
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; AF093773; AAC64180.1; -; mRNA.
DR EMBL; BC059124; AAH59124.1; -; mRNA.
DR EMBL; AF075574; AAC26799.1; -; mRNA.
DR RefSeq; NP_150238.1; NM_033235.2.
DR AlphaFoldDB; O88989; -.
DR SMR; O88989; -.
DR BioGRID; 246700; 5.
DR CORUM; O88989; -.
DR IntAct; O88989; 2.
DR STRING; 10116.ENSRNOP00000011429; -.
DR iPTMnet; O88989; -.
DR PhosphoSitePlus; O88989; -.
DR SwissPalm; O88989; -.
DR World-2DPAGE; 0004:O88989; -.
DR jPOST; O88989; -.
DR PaxDb; O88989; -.
DR PRIDE; O88989; -.
DR Ensembl; ENSRNOT00000011429; ENSRNOP00000011429; ENSRNOG00000008103.
DR GeneID; 24551; -.
DR KEGG; rno:24551; -.
DR UCSC; RGD:3072; rat.
DR CTD; 4190; -.
DR RGD; 3072; Mdh1.
DR eggNOG; KOG1496; Eukaryota.
DR GeneTree; ENSGT00530000063410; -.
DR HOGENOM; CLU_040727_2_0_1; -.
DR InParanoid; O88989; -.
DR OMA; TKGMERG; -.
DR OrthoDB; 1118998at2759; -.
DR PhylomeDB; O88989; -.
DR TreeFam; TF105826; -.
DR Reactome; R-RNO-70263; Gluconeogenesis.
DR PRO; PR:O88989; -.
DR Proteomes; UP000002494; Chromosome 14.
DR Bgee; ENSRNOG00000008103; Expressed in heart and 20 other tissues.
DR Genevisible; O88989; RN.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; IDA:RGD.
DR GO; GO:0016615; F:malate dehydrogenase activity; IDA:RGD.
DR GO; GO:0051287; F:NAD binding; IDA:RGD.
DR GO; GO:0006108; P:malate metabolic process; IDA:RGD.
DR GO; GO:0019674; P:NAD metabolic process; IDA:RGD.
DR GO; GO:0006734; P:NADH metabolic process; IDA:RGD.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IDA:RGD.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR CDD; cd01336; MDH_cytoplasmic_cytosolic; 1.
DR Gene3D; 3.90.110.10; -; 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 PANTHER; PTHR23382; PTHR23382; 1.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01759; MalateDH-SF1; 1.
DR TIGRFAMs; TIGR01758; MDH_euk_cyt; 1.
DR PROSITE; PS00068; MDH; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Methylation; NAD;
KW Oxidoreductase; Phosphoprotein; Reference proteome;
KW 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_0000226737"
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:0007744|PubMed:22673903"
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:0007744|PubMed:22673903"
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:0007744|PubMed:22673903"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT CONFLICT 251
FT /note="S -> A (in Ref. 4; AAC26799)"
FT /evidence="ECO:0000305"
FT CONFLICT 276
FT /note="N -> D (in Ref. 2; AAH59124)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 334 AA; 36483 MW; 8F6778722A607B3C CRC64;
MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC
ALPLLQDVIA TDKEEVAFKD LDVAVLVGSM PRREGMERKD LLKANVKIFK SQGAALEKYA
KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKSQIALK LGVTADDVKN
VIIWGNHSST QYPDVNHAKV KLQGKEVGVY EALKDDSWLK GEFITTVQQR GAAVIKARKL
SSAMSAAKAI SDHIRDIWFG TPEGEFVSMG VISDGNSYGV PDDLLYSFPV VIKNKTWKFV
EGLPINDFSR EKMDLTAKEL TEEKETAFEF LSSA
