ID   MDHM_YEAST              Reviewed;         334 AA.
AC   P17505; D6VXK3; E9P8U0;
DT   01-AUG-1990, integrated into UniProtKB/Swiss-Prot.
DT   01-JUN-1994, sequence version 2.
DT   27-MAR-2024, entry version 209.
DE   RecName: Full=Malate dehydrogenase, mitochondrial;
DE            EC=1.1.1.37;
DE   Flags: Precursor;
GN   Name=MDH1; OrderedLocusNames=YKL085W;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PROTEIN SEQUENCE OF 18-33.
RC   STRAIN=S173-6B;
RX   PubMed=3072021; DOI=10.1021/bi00422a015;
RA   Thompson L.M., Sutherland P., Steffan J.S., McAlister-Henn L.;
RT   "Gene sequence and primary structure of mitochondrial malate dehydrogenase
RT   from Saccharomyces cerevisiae.";
RL   Biochemistry 27:8393-8400(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8196765; DOI=10.1038/369371a0;
RA   Dujon B., Alexandraki D., Andre B., Ansorge W., Baladron V.,
RA   Ballesta J.P.G., Banrevi A., Bolle P.-A., Bolotin-Fukuhara M., Bossier P.,
RA   Bou G., Boyer J., Buitrago M.J., Cheret G., Colleaux L.,
RA   Daignan-Fornier B., del Rey F., Dion C., Domdey H., Duesterhoeft A.,
RA   Duesterhus S., Entian K.-D., Erfle H., Esteban P.F., Feldmann H.,
RA   Fernandes L., Fobo G.M., Fritz C., Fukuhara H., Gabel C., Gaillon L.,
RA   Garcia-Cantalejo J.M., Garcia-Ramirez J.J., Gent M.E., Ghazvini M.,
RA   Goffeau A., Gonzalez A., Grothues D., Guerreiro P., Hegemann J.H.,
RA   Hewitt N., Hilger F., Hollenberg C.P., Horaitis O., Indge K.J.,
RA   Jacquier A., James C.M., Jauniaux J.-C., Jimenez A., Keuchel H.,
RA   Kirchrath L., Kleine K., Koetter P., Legrain P., Liebl S., Louis E.J.,
RA   Maia e Silva A., Marck C., Monnier A.-L., Moestl D., Mueller S.,
RA   Obermaier B., Oliver S.G., Pallier C., Pascolo S., Pfeiffer F.,
RA   Philippsen P., Planta R.J., Pohl F.M., Pohl T.M., Poehlmann R.,
RA   Portetelle D., Purnelle B., Puzos V., Ramezani Rad M., Rasmussen S.W.,
RA   Remacha M.A., Revuelta J.L., Richard G.-F., Rieger M.,
RA   Rodrigues-Pousada C., Rose M., Rupp T., Santos M.A., Schwager C.,
RA   Sensen C., Skala J., Soares H., Sor F., Stegemann J., Tettelin H.,
RA   Thierry A., Tzermia M., Urrestarazu L.A., van Dyck L.,
RA   van Vliet-Reedijk J.C., Valens M., Vandenbol M., Vilela C., Vissers S.,
RA   von Wettstein D., Voss H., Wiemann S., Xu G., Zimmermann J., Haasemann M.,
RA   Becker I., Mewes H.-W.;
RT   "Complete DNA sequence of yeast chromosome XI.";
RL   Nature 369:371-378(1994).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [5]
RP   PROTEIN SEQUENCE OF 18-73.
RX   PubMed=3552052; DOI=10.1016/0167-4838(87)90044-6;
RA   Kopetzki E., Entian K.-D., Lottspeich F., Mecke D.;
RT   "Purification procedure and N-terminal amino acid sequence of yeast malate
RT   dehydrogenase isoenzymes.";
RL   Biochim. Biophys. Acta 912:398-403(1987).
RN   [6]
RP   PROTEIN SEQUENCE OF 55-62, AND SUBCELLULAR LOCATION.
RC   STRAIN=ATCC 201238 / W303-1B;
RX   PubMed=11502169; DOI=10.1021/bi010277r;
RA   Grandier-Vazeille X., Bathany K., Chaignepain S., Camougrand N., Manon S.,
RA   Schmitter J.-M.;
RT   "Yeast mitochondrial dehydrogenases are associated in a supramolecular
RT   complex.";
RL   Biochemistry 40:9758-9769(2001).
RN   [7]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-177, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 76625 / YPH499;
RX   PubMed=17761666; DOI=10.1074/mcp.m700098-mcp200;
RA   Reinders J., Wagner K., Zahedi R.P., Stojanovski D., Eyrich B.,
RA   van der Laan M., Rehling P., Sickmann A., Pfanner N., Meisinger C.;
RT   "Profiling phosphoproteins of yeast mitochondria reveals a role of
RT   phosphorylation in assembly of the ATP synthase.";
RL   Mol. Cell. Proteomics 6:1896-1906(2007).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-199, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
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   -!- SUBUNIT: Homodimer.
CC   -!- INTERACTION:
CC       P17505; P10592: SSA2; NbExp=2; IntAct=EBI-10594, EBI-8603;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000269|PubMed:11502169}.
CC   -!- MISCELLANEOUS: Yeast contains at least 3 malate dehydrogenase
CC       isoenzymes: a mitochondrial (MDH1), a cytoplasmic (MDH2) and a
CC       peroxisomal (MDH3).
CC   -!- MISCELLANEOUS: Present with 28100 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family.
CC       {ECO:0000305}.
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DR   EMBL; J02841; AAA34759.1; -; Genomic_DNA.
DR   EMBL; Z28085; CAA81923.1; -; Genomic_DNA.
DR   EMBL; AY557914; AAS56240.1; -; Genomic_DNA.
DR   EMBL; BK006944; DAA09073.1; -; Genomic_DNA.
DR   PIR; A31945; DEBYMM.
DR   RefSeq; NP_012838.1; NM_001179651.1.
DR   PDB; 1HR9; X-ray; 3.01 A; O/P/Q/R=2-9.
DR   PDBsum; 1HR9; -.
DR   AlphaFoldDB; P17505; -.
DR   SMR; P17505; -.
DR   BioGRID; 34048; 165.
DR   DIP; DIP-5734N; -.
DR   IntAct; P17505; 31.
DR   STRING; 4932.YKL085W; -.
DR   iPTMnet; P17505; -.
DR   MaxQB; P17505; -.
DR   PaxDb; 4932-YKL085W; -.
DR   PeptideAtlas; P17505; -.
DR   TopDownProteomics; P17505; -.
DR   EnsemblFungi; YKL085W_mRNA; YKL085W; YKL085W.
DR   GeneID; 853777; -.
DR   KEGG; sce:YKL085W; -.
DR   AGR; SGD:S000001568; -.
DR   SGD; S000001568; MDH1.
DR   VEuPathDB; FungiDB:YKL085W; -.
DR   eggNOG; KOG1494; Eukaryota.
DR   GeneTree; ENSGT00940000176501; -.
DR   HOGENOM; CLU_047181_1_0_1; -.
DR   InParanoid; P17505; -.
DR   OMA; ASCAEYI; -.
DR   OrthoDB; 5059897at2759; -.
DR   BioCyc; YEAST:YKL085W-MONOMER; -.
DR   BioGRID-ORCS; 853777; 1 hit in 10 CRISPR screens.
DR   EvolutionaryTrace; P17505; -.
DR   PRO; PR:P17505; -.
DR   Proteomes; UP000002311; Chromosome XI.
DR   RNAct; P17505; Protein.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:SGD.
DR   GO; GO:0030060; F:L-malate dehydrogenase activity; IDA:SGD.
DR   GO; GO:0003729; F:mRNA binding; IDA:SGD.
DR   GO; GO:0009060; P:aerobic respiration; IMP:SGD.
DR   GO; GO:0006108; P:malate metabolic process; IEA:InterPro.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IMP:SGD.
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:SF73; MALATE DEHYDROGENASE, MITOCHONDRIAL-RELATED; 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.
DR   UCD-2DPAGE; P17505; -.
PE   1: Evidence at protein level;
KW   3D-structure; Direct protein sequencing; Mitochondrion; NAD;
KW   Oxidoreductase; Phosphoprotein; Reference proteome; Transit peptide;
KW   Tricarboxylic acid cycle.
FT   TRANSIT         1..17
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:3072021,
FT                   ECO:0000269|PubMed:3552052"
FT   CHAIN           18..334
FT                   /note="Malate dehydrogenase, mitochondrial"
FT                   /id="PRO_0000018633"
FT   ACT_SITE        195
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P00346"
FT   BINDING         24..30
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         50
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         99
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT   BINDING         105
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT   BINDING         112
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         135..137
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   BINDING         137
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT   BINDING         171
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10004"
FT   BINDING         245
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:P40926"
FT   MOD_RES         177
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:17761666"
FT   MOD_RES         199
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:19779198"
FT   CONFLICT        68
FT                   /note="S -> G (in Ref. 5; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        306
FT                   /note="S -> F (in Ref. 4; AAS56240)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   334 AA;  35650 MW;  8645C4CDFB9857C8 CRC64;
     MLSRVAKRAF SSTVANPYKV TVLGAGGGIG QPLSLLLKLN HKVTDLRLYD LKGAKGVATD
     LSHIPTNSVV KGFTPEEPDG LNNALKDTDM VLIPAGVPRK PGMTRDDLFA INASIVRDLA
     AATAESAPNA AILVISNPVN STVPIVAQVL KNKGVYNPKK LFGVTTLDSI RAARFISEVE
     NTDPTQERVN VIGGHSGITI IPLISQTNHK LMSDDKRHEL IHRIQFGGDE VVKAKNGAGS
     ATLSMAHAGA KFANAVLSGF KGERDVIEPS FVDSPLFKSE GIEFFASPVT LGPDGIEKIH
     PIGELSSEEE EMLQKCKETL KKNIEKGVNF VASK
//