MDHC_PIG
ID MDHC_PIG Reviewed; 334 AA.
AC P11708; Q29560;
DT 01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Malate dehydrogenase, cytoplasmic;
DE EC=1.1.1.37;
DE AltName: Full=Cytosolic malate dehydrogenase;
GN Name=MDH1;
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 [MRNA].
RC TISSUE=Heart;
RX PubMed=8682322; DOI=10.1016/0378-1119(96)00178-3;
RA Trejo F., Costa M., Gelpi J.L., Busquets M., Clarke A.R., Holbrook J.J.,
RA Cortes A.;
RT "Cloning, sequencing and functional expression of a DNA encoding pig
RT cytosolic malate dehydrogenase: purification and characterization of the
RT recombinant enzyme.";
RL Gene 172:303-308(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 46-334.
RX PubMed=3312200; DOI=10.1016/s0021-9258(18)48147-1;
RA Joh T., Takeshima H., Tsuzuki T., Setoyama C., Shimada K., Tanase S.,
RA Kuramitsu S., Kagamiyama H., Morino Y.;
RT "Cloning and sequence analysis of cDNAs encoding mammalian cytosolic malate
RT dehydrogenase. Comparison of the amino acid sequences of mammalian and
RT bacterial malate dehydrogenase.";
RL J. Biol. Chem. 262:15127-15131(1987).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), PARTIAL PROTEIN SEQUENCE, AND
RP ACETYLATION AT SER-2.
RX PubMed=3606987; DOI=10.1021/bi00384a011;
RA Birktoft J.J., Bradshaw R.A., Banaszak L.J.;
RT "Structure of porcine heart cytoplasmic malate dehydrogenase: combining X-
RT ray diffraction and chemical sequence data in structural studies.";
RL Biochemistry 26:2722-2734(1987).
RN [4]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-334 IN COMPLEX WITH NAD, AND
RP ACTIVE SITE.
RX PubMed=2775751; DOI=10.1021/bi00440a051;
RA Birktoft J.J., Rhodes G., Banaszak L.J.;
RT "Refined crystal structure of cytoplasmic malate dehydrogenase at 2.5-A
RT resolution.";
RL Biochemistry 28:6065-6081(1989).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 2-334 IN COMPLEX WITH NAD AND
RP SUBSTRATE ANALOG, AND SUBUNIT.
RX PubMed=10075524; DOI=10.1006/jmbi.1998.2357;
RA Chapman A.D., Cortes A., Dafforn T.R., Clarke A.R., Brady R.L.;
RT "Structural basis of substrate specificity in malate dehydrogenases:
RT crystal structure of a ternary complex of porcine cytoplasmic malate
RT dehydrogenase, alpha-ketomalonate and tetrahydoNAD.";
RL J. Mol. Biol. 285:703-712(1999).
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:0000269|PubMed:10075524}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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}.
CC -!- WEB RESOURCE: Name=Worthington enzyme manual;
CC URL="https://www.worthington-biochem.com/MDH/";
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DR EMBL; U44846; AAC48610.1; -; mRNA.
DR EMBL; M29463; AAA31072.1; -; mRNA.
DR PIR; JC4876; A32472.
DR RefSeq; NP_999039.1; NM_213874.1.
DR RefSeq; XP_013851563.1; XM_013996109.1.
DR PDB; 4MDH; X-ray; 2.50 A; A/B=2-334.
DR PDB; 5MDH; X-ray; 2.40 A; A/B=2-334.
DR PDBsum; 4MDH; -.
DR PDBsum; 5MDH; -.
DR AlphaFoldDB; P11708; -.
DR SMR; P11708; -.
DR STRING; 9823.ENSSSCP00000021561; -.
DR BindingDB; P11708; -.
DR ChEMBL; CHEMBL4048; -.
DR DrugCentral; P11708; -.
DR iPTMnet; P11708; -.
DR PaxDb; P11708; -.
DR PeptideAtlas; P11708; -.
DR PRIDE; P11708; -.
DR Ensembl; ENSSSCT00000025091; ENSSSCP00000027164; ENSSSCG00000025751.
DR Ensembl; ENSSSCT00000084364; ENSSSCP00000062212; ENSSSCG00000025751.
DR Ensembl; ENSSSCT00005061167; ENSSSCP00005037807; ENSSSCG00005038108.
DR Ensembl; ENSSSCT00005061204; ENSSSCP00005037838; ENSSSCG00005038108.
DR Ensembl; ENSSSCT00015066598; ENSSSCP00015026700; ENSSSCG00015049456.
DR Ensembl; ENSSSCT00015066818; ENSSSCP00015026794; ENSSSCG00015049456.
DR Ensembl; ENSSSCT00025024872; ENSSSCP00025010511; ENSSSCG00025018263.
DR Ensembl; ENSSSCT00025024902; ENSSSCP00025010522; ENSSSCG00025018263.
DR Ensembl; ENSSSCT00030004373; ENSSSCP00030001739; ENSSSCG00030003287.
DR Ensembl; ENSSSCT00030004398; ENSSSCP00030001751; ENSSSCG00030003287.
DR Ensembl; ENSSSCT00035086982; ENSSSCP00035036265; ENSSSCG00035064600.
DR Ensembl; ENSSSCT00035086994; ENSSSCP00035036275; ENSSSCG00035064600.
DR Ensembl; ENSSSCT00045034851; ENSSSCP00045024175; ENSSSCG00045020269.
DR Ensembl; ENSSSCT00045034956; ENSSSCP00045024253; ENSSSCG00045020269.
DR Ensembl; ENSSSCT00055040807; ENSSSCP00055032460; ENSSSCG00055020633.
DR Ensembl; ENSSSCT00055040984; ENSSSCP00055032609; ENSSSCG00055020633.
DR Ensembl; ENSSSCT00060063466; ENSSSCP00060027214; ENSSSCG00060046704.
DR Ensembl; ENSSSCT00060063473; ENSSSCP00060027217; ENSSSCG00060046704.
DR Ensembl; ENSSSCT00065079812; ENSSSCP00065034720; ENSSSCG00065058308.
DR Ensembl; ENSSSCT00065079828; ENSSSCP00065034726; ENSSSCG00065058308.
DR Ensembl; ENSSSCT00070060652; ENSSSCP00070051692; ENSSSCG00070030148.
DR Ensembl; ENSSSCT00070060672; ENSSSCP00070051712; ENSSSCG00070030148.
DR GeneID; 396894; -.
DR KEGG; ssc:396894; -.
DR CTD; 4190; -.
DR VGNC; VGNC:109461; MDH1.
DR eggNOG; KOG1496; Eukaryota.
DR GeneTree; ENSGT00530000063410; -.
DR InParanoid; P11708; -.
DR OMA; TKGMERG; -.
DR OrthoDB; 1118998at2759; -.
DR BioCyc; MetaCyc:MON-13033; -.
DR SABIO-RK; P11708; -.
DR EvolutionaryTrace; P11708; -.
DR PRO; PR:P11708; -.
DR Proteomes; UP000008227; Chromosome 3.
DR Proteomes; UP000314985; Chromosome 3.
DR Bgee; ENSSSCG00000025751; Expressed in occipital cortex and 42 other tissues.
DR ExpressionAtlas; P11708; baseline and differential.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0030060; F:L-malate dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0051287; F:NAD binding; IDA:UniProtKB.
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: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; -; 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 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Methylation; NAD; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Tricarboxylic acid cycle; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT CHAIN 2..334
FT /note="Malate dehydrogenase, cytoplasmic"
FT /id="PRO_0000113411"
FT ACT_SITE 187
FT /note="Proton acceptor"
FT /evidence="ECO:0000305|PubMed:2775751"
FT BINDING 11..17
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10075524,
FT ECO:0000269|PubMed:2775751"
FT BINDING 42
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10075524,
FT ECO:0000269|PubMed:2775751"
FT BINDING 92
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10075524"
FT BINDING 98
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10075524"
FT BINDING 105
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10075524"
FT BINDING 112
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10075524"
FT BINDING 129..131
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10075524,
FT ECO:0000269|PubMed:2775751"
FT BINDING 131
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10075524"
FT BINDING 162
FT /ligand="substrate"
FT /evidence="ECO:0000305|PubMed:10075524"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000269|PubMed:3606987"
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"
FT CONFLICT 238
FT /note="R -> Q (in Ref. 2; AAA31072)"
FT /evidence="ECO:0000305"
FT STRAND 5..11
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 15..18
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 21..25
FT /evidence="ECO:0007829|PDB:5MDH"
FT TURN 26..30
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 36..41
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 47..59
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 65..72
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 74..77
FT /evidence="ECO:0007829|PDB:5MDH"
FT TURN 78..80
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 82..86
FT /evidence="ECO:0007829|PDB:5MDH"
FT TURN 98..101
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 102..119
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 125..128
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 130..132
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 133..142
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 149..151
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 152..154
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 157..171
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 175..177
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 182..185
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 192..194
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 199..201
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 206..208
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 209..213
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 216..220
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 222..238
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 244..259
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 285..293
FT /evidence="ECO:0007829|PDB:5MDH"
FT STRAND 296..299
FT /evidence="ECO:0007829|PDB:5MDH"
FT HELIX 307..333
FT /evidence="ECO:0007829|PDB:5MDH"
SQ SEQUENCE 334 AA; 36454 MW; 2574A8F3C2DD2C84 CRC64;
MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC
ALPLLKDVIA TDKEEIAFKD LDVAILVGSM PRRDGMERKD LLKANVKIFK CQGAALDKYA
KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTSDDVKN
VIIWGNHSST QYPDVNHAKV KLQAKEVGVY EAVKDDSWLK GEFITTVQQR GAAVIKARKL
SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG IISDGNSYGV PDDLLYSFPV TIKDKTWKIV
EGLPINDFSR EKMDLTAKEL AEEKETAFEF LSSA
