ID MDHM_BOVIN Reviewed; 338 AA. AC Q32LG3; DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot. DT 06-DEC-2005, sequence version 1. DT 27-MAR-2024, entry version 115. DE RecName: Full=Malate dehydrogenase, mitochondrial; DE EC=1.1.1.37; DE Flags: Precursor; GN Name=MDH2; 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=Liver; RG NIH - Mammalian Gene Collection (MGC) project; RL Submitted (NOV-2005) to the EMBL/GenBank/DDBJ databases. RN [2] RP ACETYLATION AT LYS-185; LYS-307; LYS-314 AND LYS-328, MALONYLATION AT RP LYS-239 AND LYS-329, AND SUCCINYLATION AT LYS-239; LYS-301 AND LYS-328. RX PubMed=22076378; DOI=10.1126/science.1207861; RA Du J., Zhou Y., Su X., Yu J.J., Khan S., Jiang H., Kim J., Woo J., RA Kim J.H., Choi B.H., He B., Chen W., Zhang S., Cerione R.A., Auwerx J., RA Hao Q., Lin H.; RT "Sirt5 is a NAD-dependent protein lysine demalonylase and desuccinylase."; RL Science 334:806-809(2011). 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:0000255|PROSITE-ProRule:PRU10004}; CC -!- ACTIVITY REGULATION: Enzyme activity is enhanced by acetylation. CC {ECO:0000250|UniProtKB:P40926}. CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P00346}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000250|UniProtKB:P04636}. CC -!- PTM: Acetylation is enhanced after treatment either with trichostin A CC (TCA) or with nicotinamide (NAM) with the appearance of tri- and CC tetraacetylations. Glucose also increases acetylation. CC {ECO:0000250|UniProtKB:P40926}. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 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; BC109597; AAI09598.1; -; mRNA. DR RefSeq; XP_005225065.1; XM_005225008.2. DR AlphaFoldDB; Q32LG3; -. DR SMR; Q32LG3; -. DR IntAct; Q32LG3; 1. DR STRING; 9913.ENSBTAP00000012454; -. DR GlyCosmos; Q32LG3; 1 site, No reported glycans. DR iPTMnet; Q32LG3; -. DR PaxDb; 9913-ENSBTAP00000012454; -. DR PeptideAtlas; Q32LG3; -. DR Ensembl; ENSBTAT00000012454.5; ENSBTAP00000012454.5; ENSBTAG00000009462.6. DR CTD; 4191; -. DR VEuPathDB; HostDB:ENSBTAG00000009462; -. DR VGNC; VGNC:106817; MDH2. DR eggNOG; KOG1494; Eukaryota. DR GeneTree; ENSGT00390000016686; -. DR InParanoid; Q32LG3; -. DR OMA; SHMDTPA; -. DR OrthoDB; 5059897at2759; -. DR Reactome; R-BTA-70263; Gluconeogenesis. DR Reactome; R-BTA-71403; Citric acid cycle (TCA cycle). DR SABIO-RK; Q32LG3; -. DR Proteomes; UP000009136; Chromosome 25. DR Bgee; ENSBTAG00000009462; Expressed in cardiac ventricle and 104 other cell types or tissues. DR ExpressionAtlas; Q32LG3; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0016020; C:membrane; IEA:Ensembl. DR GO; GO:0005759; C:mitochondrial matrix; ISS:UniProtKB. DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central. DR GO; GO:0030060; F:L-malate dehydrogenase activity; ISS:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; ISS:UniProtKB. DR GO; GO:0006094; P:gluconeogenesis; IEA:Ensembl. DR GO; GO:0006108; P:malate metabolic process; IEA:Ensembl. DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central. DR CDD; cd01337; MDH_glyoxysomal_mitochondrial; 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 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; IPR010097; Malate_DH_type1. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR NCBIfam; TIGR01772; MDH_euk_gproteo; 1. DR PANTHER; PTHR11540; MALATE AND LACTATE DEHYDROGENASE; 1. DR PANTHER; PTHR11540:SF16; MALATE DEHYDROGENASE, MITOCHONDRIAL; 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 1: Evidence at protein level; KW Acetylation; Glycoprotein; Mitochondrion; NAD; Oxidoreductase; KW Phosphoprotein; Reference proteome; Transit peptide; KW Tricarboxylic acid cycle. FT TRANSIT 1..24 FT /note="Mitochondrion" FT /evidence="ECO:0000250|UniProtKB:P00346" FT CHAIN 25..338 FT /note="Malate dehydrogenase, mitochondrial" FT /id="PRO_0000260267" FT ACT_SITE 200 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P00346" FT BINDING 31..37 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P40926" FT BINDING 57 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P40926" FT BINDING 104 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004" FT BINDING 110 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004" FT BINDING 117 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P40926" FT BINDING 140..142 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P40926" FT BINDING 142 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004" FT BINDING 176 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004" FT BINDING 251 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 78 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 78 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 91 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 91 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 165 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 185 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 185 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 203 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 215 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 215 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 239 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 239 FT /note="N6-malonyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 239 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 246 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 269 FT /note="N6-succinyllysine" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 296 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 296 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 301 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 301 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 307 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 307 FT /note="N6-malonyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 307 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 314 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 314 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 324 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 324 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT MOD_RES 326 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 328 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 328 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 329 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 329 FT /note="N6-malonyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22076378" FT MOD_RES 335 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P40926" FT MOD_RES 335 FT /note="N6-succinyllysine; alternate" FT /evidence="ECO:0000250|UniProtKB:P08249" FT CARBOHYD 33 FT /note="O-linked (GlcNAc) serine" FT /evidence="ECO:0000250|UniProtKB:P04636" SQ SEQUENCE 338 AA; 35668 MW; 575B305752E11569 CRC64; MLSALARPAG AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH TPGVAADLSH IETRATVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI VATLTAACAQ HCPEAMICII SNPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANAF VAELKDLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVEFPQ DQLTTLTGRI QEAGTEVVKA KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETDCPYFST PLLLGKKGIE KNLGIGKVSP FEEKMIAEAI PELKASIKKG EEFVKNMK //