MDHM_HUMAN
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 03-AUG-2022, entry version 217.
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";
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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; 447.
DR IntAct; P40926; 53.
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 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 UCD-2DPAGE; P40926; -.
DR CPTAC; CPTAC-542; -.
DR CPTAC; CPTAC-543; -.
DR EPD; P40926; -.
DR jPOST; P40926; -.
DR MassIVE; P40926; -.
DR MaxQB; P40926; -.
DR PaxDb; P40926; -.
DR PeptideAtlas; P40926; -.
DR PRIDE; P40926; -.
DR ProteomicsDB; 19624; -.
DR ProteomicsDB; 55386; -. [P40926-1]
DR TopDownProteomics; P40926-1; -. [P40926-1]
DR Antibodypedia; 14905; 377 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 CTD; 4191; -.
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; MGWTSQA; -.
DR PhylomeDB; P40926; -.
DR TreeFam; TF300834; -.
DR BioCyc; MetaCyc:HS07366-MON; -.
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; 53 hits in 1085 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 206 other tissues.
DR ExpressionAtlas; P40926; baseline and differential.
DR Genevisible; P40926; HS.
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:UniProtKB.
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; IEA:Ensembl.
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; -; 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; 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 R-
FT 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 R-
FT 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 R-
FT 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 R-
FT 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
