ID MDHM_HUMAN Reviewed; 338 AA. AC P40926; A8K414; B2RE78; B4DE44; E9PDB2; O43682; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2008, sequence version 3. DT 27-MAR-2024, entry version 226. DE RecName: Full=Malate dehydrogenase, mitochondrial; DE EC=1.1.1.37 {ECO:0000269|PubMed:27989324}; DE Flags: Precursor; GN Name=MDH2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT VAL-9. RA Hu G.; RT "Human homolog of mouse and pig MDH mRNA."; RL Submitted (FEB-1998) to the EMBL/GenBank/DDBJ databases. RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Kidney, and Tongue; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT VAL-9. RC TISSUE=Lung; 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 [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=15592455; DOI=10.1038/nbt1046; RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., RA Zha X.-M., Polakiewicz R.D., Comb M.J.; RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."; RL Nat. Biotechnol. 23:94-101(2005). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [8] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-165; LYS-185; LYS-301; LYS-314; RP LYS-329 AND LYS-335, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). RN [9] RP ACETYLATION AT LYS-185; LYS-301; LYS-307 AND LYS-314, ACTIVITY REGULATION, RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF LYS-185; LYS-301; RP LYS-307 AND LYS-314. RX PubMed=20167786; DOI=10.1126/science.1179689; RA Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L., RA Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L., Chin J., RA Yang P., Chen X., Lei Q., Xiong Y., Guan K.L.; RT "Regulation of cellular metabolism by protein lysine acetylation."; RL Science 327:1000-1004(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP MALONYLATION AT LYS-307. RX PubMed=21908771; DOI=10.1074/mcp.m111.012658; RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y., He W., RA Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C., Dai J., RA Verdin E., Ye Y., Zhao Y.; RT "The first identification of lysine malonylation substrates and its RT regulatory enzyme."; RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-246 AND SER-326, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [15] RP INVOLVEMENT IN DEE51, VARIANTS DEE51 ARG-37; LEU-133 AND LEU-207, RP CHARACTERIZATION OF VARIANTS DEE51 LEU-133 AND LEU-207, AND CATALYTIC RP ACTIVITY. RX PubMed=27989324; DOI=10.1016/j.ajhg.2016.11.014; RA Ait-El-Mkadem S., Dayem-Quere M., Gusic M., Chaussenot A., Bannwarth S., RA Francois B., Genin E.C., Fragaki K., Volker-Touw C.L., Vasnier C., RA Serre V., van Gassen K.L., Lespinasse F., Richter S., Eisenhofer G., RA Rouzier C., Mochel F., De Saint-Martin A., Abi Warde M.T., RA de Sain-van der Velde M.G., Jans J.J., Amiel J., Avsec Z., Mertes C., RA Haack T.B., Strom T., Meitinger T., Bonnen P.E., Taylor R.W., Gagneur J., RA van Hasselt P.M., Roetig A., Delahodde A., Prokisch H., Fuchs S.A., RA Paquis-Flucklinger V.; RT "Mutations in MDH2, encoding a Krebs cycle enzyme, cause early-onset severe RT encephalopathy."; RL Am. J. Hum. Genet. 100:151-159(2017). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 20-338 IN COMPLEX WITH NAD AND RP SUBSTRATE, AND SUBUNIT. RG Structural genomics consortium (SGC); RT "Crystal structure of human malate dehydrogenase type 2."; RL Submitted (MAR-2006) to the PDB data bank. 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:0000269|PubMed:27989324}; CC -!- ACTIVITY REGULATION: Enzyme activity is enhanced by acetylation. CC {ECO:0000269|PubMed:20167786}. CC -!- SUBUNIT: Homodimer. {ECO:0000269|Ref.16}. CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix CC {ECO:0000250|UniProtKB:P04636}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P40926-1; Sequence=Displayed; CC Name=2; CC IsoId=P40926-2; Sequence=VSP_055312; CC -!- PTM: Acetylation is enhanced by up to 67% after treatment either with CC trichostin A (TSA) or with nicotinamide (NAM) with the appearance of CC tri- and tetraacetylations. Glucose also increases acetylation by about CC 60%. {ECO:0000269|PubMed:20167786}. CC -!- DISEASE: Developmental and epileptic encephalopathy 51 (DEE51) CC [MIM:617339]: A form of epileptic encephalopathy, a heterogeneous group CC of severe early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE51 is an autosomal recessive form characterized by CC onset of intractable seizures and hypotonia in the first days or weeks CC of life, and severely delayed psychomotor development. CC {ECO:0000269|PubMed:27989324}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 1 family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=Malate dehydrogenase entry; CC URL="https://en.wikipedia.org/wiki/Malate_dehydrogenase"; 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; AF047470; AAC03787.1; -; mRNA. DR EMBL; AK290779; BAF83468.1; -; mRNA. DR EMBL; AK293460; BAG56955.1; -; mRNA. DR EMBL; AK316587; BAG38175.1; -; mRNA. DR EMBL; AC005077; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC006330; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471220; EAW71796.1; -; Genomic_DNA. DR EMBL; BC001917; AAH01917.1; -; mRNA. DR CCDS; CCDS5581.1; -. [P40926-1] DR CCDS; CCDS64691.1; -. [P40926-2] DR RefSeq; NP_001269332.1; NM_001282403.1. [P40926-2] DR RefSeq; NP_001269333.1; NM_001282404.1. DR RefSeq; NP_005909.2; NM_005918.3. [P40926-1] DR PDB; 2DFD; X-ray; 1.90 A; A/B/C/D=20-338. DR PDB; 4WLE; X-ray; 1.90 A; A/B/C/D=20-338. DR PDB; 4WLF; X-ray; 2.20 A; A/B/C/D=20-338. DR PDB; 4WLN; X-ray; 2.28 A; A/B/C/D=20-338. DR PDB; 4WLO; X-ray; 2.50 A; A/B/C/D=20-338. DR PDB; 4WLU; X-ray; 2.14 A; A/B/C/D=20-338. DR PDB; 4WLV; X-ray; 2.40 A; A/B/C/D=20-338. DR PDBsum; 2DFD; -. DR PDBsum; 4WLE; -. DR PDBsum; 4WLF; -. DR PDBsum; 4WLN; -. DR PDBsum; 4WLO; -. DR PDBsum; 4WLU; -. DR PDBsum; 4WLV; -. DR AlphaFoldDB; P40926; -. DR SMR; P40926; -. DR BioGRID; 110356; 491. DR IntAct; P40926; 56. DR MINT; P40926; -. DR STRING; 9606.ENSP00000327070; -. DR BindingDB; P40926; -. DR ChEMBL; CHEMBL5917; -. DR DrugBank; DB04272; Citric acid. DR DrugBank; DB00157; NADH. DR DrugBank; DB09092; Xanthinol. DR GlyCosmos; P40926; 2 sites, 2 glycans. DR GlyGen; P40926; 2 sites, 2 O-linked glycans (1 site). DR iPTMnet; P40926; -. DR MetOSite; P40926; -. DR PhosphoSitePlus; P40926; -. DR SwissPalm; P40926; -. DR BioMuta; MDH2; -. DR DMDM; 215274114; -. DR DOSAC-COBS-2DPAGE; P40926; -. DR REPRODUCTION-2DPAGE; IPI00291006; -. DR REPRODUCTION-2DPAGE; P40926; -. DR CPTAC; CPTAC-2753; -. DR CPTAC; CPTAC-2754; -. DR CPTAC; CPTAC-2755; -. DR CPTAC; CPTAC-542; -. DR CPTAC; CPTAC-543; -. DR EPD; P40926; -. DR jPOST; P40926; -. DR MassIVE; P40926; -. DR MaxQB; P40926; -. DR PaxDb; 9606-ENSP00000327070; -. DR PeptideAtlas; P40926; -. DR PRIDE; P40926; -. DR ProteomicsDB; 19624; -. DR ProteomicsDB; 55386; -. [P40926-1] DR Pumba; P40926; -. DR TopDownProteomics; P40926-1; -. [P40926-1] DR Antibodypedia; 14905; 431 antibodies from 35 providers. DR DNASU; 4191; -. DR Ensembl; ENST00000315758.10; ENSP00000327070.5; ENSG00000146701.12. [P40926-1] DR Ensembl; ENST00000432020.2; ENSP00000408649.2; ENSG00000146701.12. [P40926-2] DR GeneID; 4191; -. DR KEGG; hsa:4191; -. DR MANE-Select; ENST00000315758.10; ENSP00000327070.5; NM_005918.4; NP_005909.2. DR UCSC; uc003ueo.5; human. [P40926-1] DR AGR; HGNC:6971; -. DR DisGeNET; 4191; -. DR GeneCards; MDH2; -. DR HGNC; HGNC:6971; MDH2. DR HPA; ENSG00000146701; Tissue enhanced (skeletal muscle, tongue). DR MalaCards; MDH2; -. DR MIM; 154100; gene. DR MIM; 617339; phenotype. DR neXtProt; NX_P40926; -. DR OpenTargets; ENSG00000146701; -. DR Orphanet; 29072; Hereditary pheochromocytoma-paraganglioma. DR PharmGKB; PA30716; -. DR VEuPathDB; HostDB:ENSG00000146701; -. DR eggNOG; KOG1494; Eukaryota. DR GeneTree; ENSGT00390000016686; -. DR HOGENOM; CLU_047181_0_1_1; -. DR InParanoid; P40926; -. DR OMA; SHMDTPA; -. DR OrthoDB; 5059897at2759; -. DR PhylomeDB; P40926; -. DR TreeFam; TF300834; -. DR BioCyc; MetaCyc:HS07366-MONOMER; -. DR BRENDA; 1.1.1.37; 2681. DR PathwayCommons; P40926; -. DR Reactome; R-HSA-70263; Gluconeogenesis. DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle). DR SignaLink; P40926; -. DR SIGNOR; P40926; -. DR BioGRID-ORCS; 4191; 54 hits in 1169 CRISPR screens. DR ChiTaRS; MDH2; human. DR EvolutionaryTrace; P40926; -. DR GeneWiki; Malate_dehydrogenase_2; -. DR GenomeRNAi; 4191; -. DR Pharos; P40926; Tchem. DR PRO; PR:P40926; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; P40926; Protein. DR Bgee; ENSG00000146701; Expressed in body of tongue and 208 other cell types or tissues. DR ExpressionAtlas; P40926; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0016020; C:membrane; IEA:Ensembl. DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005634; C:nucleus; HDA:UniProtKB. DR GO; GO:0030060; F:L-malate dehydrogenase activity; IDA:UniProtKB. DR GO; GO:0046554; F:malate dehydrogenase (NADP+) activity; IEA:Ensembl. DR GO; GO:0043621; F:protein self-association; IEA:Ensembl. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0009060; P:aerobic respiration; IDA:UniProtKB. DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome. DR GO; GO:0006108; P:malate metabolic process; IDA:UniProtKB. DR GO; GO:0006734; P:NADH metabolic process; IEA:Ensembl. DR GO; GO:0006107; P:oxaloacetate 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. DR UCD-2DPAGE; P40926; -. DR Genevisible; P40926; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Disease variant; Epilepsy; KW Glycoprotein; Mitochondrion; NAD; Oxidoreductase; Phosphoprotein; KW Reference proteome; Transit peptide; 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_0000018628" 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:0000269|Ref.16" FT BINDING 57 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|Ref.16" FT BINDING 104 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004, FT ECO:0000269|Ref.16" FT BINDING 110 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004, FT ECO:0000269|Ref.16" FT BINDING 117 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|Ref.16" FT BINDING 140..142 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|Ref.16" FT BINDING 142 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004, FT ECO:0000269|Ref.16" FT BINDING 176 FT /ligand="substrate" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10004, FT ECO:0000269|Ref.16" FT BINDING 251 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000269|Ref.16" 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:0007744|PubMed:19608861" FT MOD_RES 185 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:20167786, FT ECO:0007744|PubMed:19608861" 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:0007744|PubMed:23186163" 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:0000269|PubMed:20167786, FT ECO:0007744|PubMed:19608861" 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:0000269|PubMed:20167786" FT MOD_RES 307 FT /note="N6-malonyllysine; alternate" FT /evidence="ECO:0000269|PubMed:21908771" 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:20167786, FT ECO:0007744|PubMed:19608861" 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:0007744|PubMed:23186163" 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:0007744|PubMed:19608861" 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:0007744|PubMed:19608861" 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 VAR_SEQ 144..185 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055312" FT VARIANT 9 FT /note="A -> V (in dbSNP:rs6720)" FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.1" FT /id="VAR_047787" FT VARIANT 37 FT /note="G -> R (in DEE51; severe defects in aerobic FT respiration, when assayed in a heterologous system; FT dbSNP:rs782308462)" FT /evidence="ECO:0000269|PubMed:27989324" FT /id="VAR_078001" FT VARIANT 133 FT /note="P -> L (in DEE51; decreased protein abundance; FT strong decrease in malate dehydrogenase activity; severe FT defects in aerobic respiration, when assayed in a FT heterologous system; dbSNP:rs375002796)" FT /evidence="ECO:0000269|PubMed:27989324" FT /id="VAR_078002" FT VARIANT 207 FT /note="P -> L (in DEE51; decreased protein abundance; FT strong decrease in malate dehydrogenase activity; severe FT defects in aerobic respiration, when assayed in a FT heterologous system; dbSNP:rs1057519566)" FT /evidence="ECO:0000269|PubMed:27989324" FT /id="VAR_078003" FT MUTAGEN 185 FT /note="K->R: No activation of enzyme activity on treatment FT with TSA or NAM; when associated with R-301; R-307 and FT R-314." FT /evidence="ECO:0000269|PubMed:20167786" FT MUTAGEN 301 FT /note="K->R: No activation of enzyme activity on treatment FT with TSA or NAM; when associated with R-185; R-307 and FT R-314." FT /evidence="ECO:0000269|PubMed:20167786" FT MUTAGEN 307 FT /note="K->R: No activation of enzyme activity on treatment FT with TSA or NAM; when associated with R-185; R-301 and FT R-314." FT /evidence="ECO:0000269|PubMed:20167786" FT MUTAGEN 314 FT /note="K->R: No activation of enzyme activity on treatment FT with TSA or NAM; when associated with R-185; R-301 and FT R-307." FT /evidence="ECO:0000269|PubMed:20167786" FT CONFLICT 301 FT /note="K -> R (in Ref. 2; BAG56955)" FT /evidence="ECO:0000305" FT STRAND 25..30 FT /evidence="ECO:0007829|PDB:2DFD" FT TURN 31..33 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 37..45 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 50..60 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 61..69 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 71..74 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 76..82 FT /evidence="ECO:0007829|PDB:2DFD" FT TURN 83..85 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 86..90 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 94..98 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 110..113 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 114..131 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 135..139 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 144..157 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 165..168 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 171..185 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 189..191 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 202..204 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 205..207 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 209..211 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 220..241 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 249..266 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 273..279 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 282..295 FT /evidence="ECO:0007829|PDB:2DFD" FT STRAND 298..302 FT /evidence="ECO:0007829|PDB:2DFD" FT HELIX 310..335 FT /evidence="ECO:0007829|PDB:2DFD" SQ SEQUENCE 338 AA; 35503 MW; AAB9F5E5B2FBC8CA CRC64; MLSALARPAS AALRRSFSTS AQNNAKVAVL GASGGIGQPL SLLLKNSPLV SRLTLYDIAH TPGVAADLSH IETKAAVKGY LGPEQLPDCL KGCDVVVIPA GVPRKPGMTR DDLFNTNATI VATLTAACAQ HCPEAMICVI ANPVNSTIPI TAEVFKKHGV YNPNKIFGVT TLDIVRANTF VAELKGLDPA RVNVPVIGGH AGKTIIPLIS QCTPKVDFPQ DQLTALTGRI QEAGTEVVKA KAGAGSATLS MAYAGARFVF SLVDAMNGKE GVVECSFVKS QETECTYFST PLLLGKKGIE KNLGIGKVSS FEEKMISDAI PELKASIKKG EDFVKTLK //