MDHM_PIG
ID MDHM_PIG Reviewed; 338 AA.
AC P00346; Q95308;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 2.
DT 03-AUG-2022, entry version 153.
DE RecName: Full=Malate dehydrogenase, mitochondrial;
DE EC=1.1.1.37;
DE Flags: Precursor;
GN Name=MDH2;
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-40.
RC TISSUE=Small intestine;
RX PubMed=8672129; DOI=10.1007/s003359900153;
RA Winteroe A.K., Fredholm M., Davies W.;
RT "Evaluation and characterization of a porcine small intestine cDNA library:
RT analysis of 839 clones.";
RL Mamm. Genome 7:509-517(1996).
RN [2]
RP PROTEIN SEQUENCE OF 25-338.
RX PubMed=6959107; DOI=10.1073/pnas.79.20.6166;
RA Birktoft J.J., Fernley R.T., Bradshaw R.A., Banaszak L.J.;
RT "Amino acid sequence homology among the 2-hydroxy acid dehydrogenases:
RT mitochondrial and cytoplasmic malate dehydrogenases form a homologous
RT system with lactate dehydrogenase.";
RL Proc. Natl. Acad. Sci. U.S.A. 79:6166-6170(1982).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 41-338.
RX PubMed=3038184; DOI=10.1021/bi00383a017;
RA Joh T., Takeshima H., Tsuzuki T., Shimada K., Tanase S., Morino Y.;
RT "Cloning and sequence analysis of cDNAs encoding mammalian mitochondrial
RT malate dehydrogenase.";
RL Biochemistry 26:2515-2520(1987).
RN [4] {ECO:0007744|PDB:1MLD}
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG,
RP SUBUNIT, AND ACTIVE SITE.
RC TISSUE=Heart;
RX PubMed=8117664; DOI=10.1021/bi00174a014;
RA Gleason W.B., Fu Z., Birktoft J.J., Banaszak L.J.;
RT "Refined crystal structure of mitochondrial malate dehydrogenase from
RT porcine heart and the consensus structure for dicarboxylic acid
RT oxidoreductases.";
RL Biochemistry 33:2078-2088(1994).
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:0000269|PubMed:8117664}.
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}.
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DR EMBL; Z81157; CAB03545.1; -; mRNA.
DR EMBL; M16427; AAA31071.1; -; mRNA.
DR PIR; A00355; DEPGMM.
DR PDB; 1MLD; X-ray; 1.83 A; A/B/C/D=25-338.
DR PDBsum; 1MLD; -.
DR SMR; P00346; -.
DR IntAct; P00346; 3.
DR MINT; P00346; -.
DR STRING; 9823.ENSSSCP00000025866; -.
DR BindingDB; P00346; -.
DR ChEMBL; CHEMBL3444; -.
DR DrugCentral; P00346; -.
DR iPTMnet; P00346; -.
DR PaxDb; P00346; -.
DR PeptideAtlas; P00346; -.
DR PRIDE; P00346; -.
DR eggNOG; KOG1494; Eukaryota.
DR InParanoid; P00346; -.
DR SABIO-RK; P00346; -.
DR EvolutionaryTrace; P00346; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; IPI:CAFA.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0009060; P:aerobic respiration; ISS:UniProtKB.
DR GO; GO:0006108; P:malate metabolic process; IEA:InterPro.
DR GO; GO:0006099; P:tricarboxylic acid cycle; IBA:GO_Central.
DR CDD; cd01337; MDH_glyoxysomal_mitochondrial; 1.
DR Gene3D; 3.90.110.10; -; 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 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; TIGR01772; MDH_euk_gproteo; 1.
DR PROSITE; PS00068; MDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Glycoprotein;
KW Mitochondrion; NAD; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transit peptide; Tricarboxylic acid cycle.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:6959107"
FT CHAIN 25..338
FT /note="Malate dehydrogenase, mitochondrial"
FT /id="PRO_0000018630"
FT ACT_SITE 200
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:8117664,
FT ECO:0007744|PDB:1MLD"
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:0000269|PubMed:8117664,
FT ECO:0007744|PDB:1MLD"
FT BINDING 110
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8117664,
FT ECO:0007744|PDB:1MLD"
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:0000269|PubMed:8117664,
FT ECO:0007744|PDB:1MLD"
FT BINDING 176
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:8117664,
FT ECO:0007744|PDB:1MLD"
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:0000250|UniProtKB:Q32LG3"
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:0000250|UniProtKB:Q32LG3"
FT MOD_RES 239
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
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:0000250|UniProtKB:Q32LG3"
FT MOD_RES 307
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
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:0000250|UniProtKB:Q32LG3"
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:0000250|UniProtKB:Q32LG3"
FT MOD_RES 328
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q32LG3"
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:0000250|UniProtKB:Q32LG3"
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"
FT CONFLICT 120
FT /note="I -> M (in Ref. 3; AAA31071)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="A -> V (in Ref. 3; AAA31071)"
FT /evidence="ECO:0000305"
FT CONFLICT 150
FT /note="I -> M (in Ref. 3; AAA31071)"
FT /evidence="ECO:0000305"
FT CONFLICT 304
FT /note="G -> R (in Ref. 3; AAA31071)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="M -> T (in Ref. 3; AAA31071)"
FT /evidence="ECO:0000305"
FT STRAND 26..31
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 37..45
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 51..60
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 61..68
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 71..74
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 86..90
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 94..98
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 114..131
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 135..139
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 144..157
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 165..168
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 171..184
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 189..191
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 202..204
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 205..207
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 220..241
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 249..267
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 273..279
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 282..295
FT /evidence="ECO:0007829|PDB:1MLD"
FT STRAND 298..302
FT /evidence="ECO:0007829|PDB:1MLD"
FT HELIX 310..334
FT /evidence="ECO:0007829|PDB:1MLD"
SQ SEQUENCE 338 AA; 35596 MW; B0435E87383D0B1E CRC64;
MLSALARPAG AALRRSFSTS XQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH
TPGVAADLSH IETRATVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI
VATLTAACAQ HCPDAMICII SNPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANAF
VAELKGLDPA RVSVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLSTLTGRI QEAGTEVVKA
KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETDCPYFST PLLLGKKGIE
KNLGIGKISP FEEKMIAEAI PELKASIKKG EEFVKNMK
