ID MDHC_HUMAN Reviewed; 334 AA. AC P40925; B2R5V5; B4DUN2; B7Z3I7; F5H098; Q6I9V0; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 4. DT 24-JAN-2024, entry version 222. DE RecName: Full=Malate dehydrogenase, cytoplasmic {ECO:0000305}; DE EC=1.1.1.37 {ECO:0000269|PubMed:3052244}; DE AltName: Full=Aromatic alpha-keto acid reductase {ECO:0000305}; DE Short=KAR {ECO:0000305}; DE EC=1.1.1.96 {ECO:0000269|PubMed:3052244}; DE AltName: Full=Cytosolic malate dehydrogenase; GN Name=MDH1 {ECO:0000303|PubMed:34012073, ECO:0000312|HGNC:HGNC:6970}; GN Synonyms=MDHA; 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 SUBCELLULAR LOCATION. RC TISSUE=Heart; RX PubMed=8786100; DOI=10.1006/geno.1996.0087; RA Tanaka T., Inazawa J., Nakamura Y.; RT "Molecular cloning and mapping of a human cDNA for cytosolic malate RT dehydrogenase (MDH1)."; RL Genomics 32:128-130(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Heart; RA Lo A.S.Y., Waye M.M.Y.; RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Cerebellum, and Substantia nigra; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Placenta; 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 [8] RP PROTEIN SEQUENCE OF 2-18; 205-213 AND 324-334, CLEAVAGE OF INITIATOR RP METHIONINE, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY. RC TISSUE=T-cell; RA Bienvenut W.V., Kanor S., Tissot J.-D., Quadroni M.; RL Submitted (MAY-2006) to UniProtKB. RN [9] RP PROTEIN SEQUENCE OF 168-181. RC TISSUE=Heart; RX PubMed=7895732; DOI=10.1002/elps.11501501209; RA Corbett J.M., Wheeler C.H., Baker C.S., Yacoub M.H., Dunn M.J.; RT "The human myocardial two-dimensional gel protein database: update 1994."; RL Electrophoresis 15:1459-1465(1994). RN [10] RP PROTEIN SEQUENCE OF 180-201 AND 299-310, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=Brain, and Cajal-Retzius cell; RA Lubec G., Vishwanath V.; RL Submitted (MAR-2007) to UniProtKB. RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=2449162; DOI=10.1007/bf00556210; RA Friedrich C.A., Morizot D.C., Siciliano M.J., Ferrell R.E.; RT "The reduction of aromatic alpha-keto acids by cytoplasmic malate RT dehydrogenase and lactate dehydrogenase."; RL Biochem. Genet. 25:657-669(1987). RN [12] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=3052244; DOI=10.1111/j.1469-1809.1988.tb01075.x; RA Friedrich C.A., Ferrell R.E., Siciliano M.J., Kitto G.B.; RT "Biochemical and genetic identity of alpha-keto acid reductase and RT cytoplasmic malate dehydrogenase from human erythrocytes."; RL Ann. Hum. Genet. 52:25-37(1988). RN [13] RP ISGYLATION. RX PubMed=16139798; DOI=10.1016/j.bbrc.2005.08.132; RA Giannakopoulos N.V., Luo J.K., Papov V., Zou W., Lenschow D.J., RA Jacobs B.S., Borden E.C., Li J., Virgin H.W., Zhang D.E.; RT "Proteomic identification of proteins conjugated to ISG15 in mouse and RT human cells."; RL Biochem. Biophys. Res. Commun. 336:496-506(2005). RN [14] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-118 AND LYS-298, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [16] 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 [17] RP ACETYLATION AT LYS-118; LYS-121 AND LYS-298. RX PubMed=22693256; DOI=10.1194/jlr.m026567; RA Kim E.Y., Kim W.K., Kang H.J., Kim J.H., Chung S.J., Seo Y.S., Park S.G., RA Lee S.C., Bae K.H.; RT "Acetylation of malate dehydrogenase 1 promotes adipogenic differentiation RT via activating its enzymatic activity."; RL J. Lipid Res. 53:1864-1876(2012). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22905912; DOI=10.1021/pr300539b; RA Rosenow A., Noben J.P., Jocken J., Kallendrusch S., Fischer-Posovszky P., RA Mariman E.C., Renes J.; RT "Resveratrol-induced changes of the human adipocyte secretion profile."; RL J. Proteome Res. 11:4733-4743(2012). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-241, AND IDENTIFICATION BY RP 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 [20] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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 [21] RP INVOLVEMENT IN DEE88, VARIANT DEE88 VAL-120, FUNCTION, AND RP CHARACTERIZATIONC OF VARIANT DEE88 VAL-120. RX PubMed=31538237; DOI=10.1007/s00439-019-02063-z; RA Broeks M.H., Shamseldin H.E., Alhashem A., Hashem M., Abdulwahab F., RA Alshedi T., Alobaid I., Zwartkruis F., Westland D., Fuchs S., RA Verhoeven-Duif N.M., Jans J.J.M., Alkuraya F.S.; RT "MDH1 deficiency is a metabolic disorder of the malate-aspartate shuttle RT associated with early onset severe encephalopathy."; RL Hum. Genet. 138:1247-1257(2019). RN [22] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=34012073; DOI=10.1038/s41422-021-00506-9; RA Zhang J.Y., Zhou B., Sun R.Y., Ai Y.L., Cheng K., Li F.N., Wang B.R., RA Liu F.J., Jiang Z.H., Wang W.J., Zhou D., Chen H.Z., Wu Q.; RT "The metabolite alpha-KG induces GSDMC-dependent pyroptosis through death RT receptor 6-activated caspase-8."; RL Cell Res. 31:980-997(2021). CC -!- FUNCTION: Catalyzes the reduction of aromatic alpha-keto acids in the CC presence of NADH (PubMed:2449162, PubMed:3052244). Plays essential CC roles in the malate-aspartate shuttle and the tricarboxylic acid cycle, CC important in mitochondrial NADH supply for oxidative phosphorylation CC (PubMed:31538237). Catalyzes the reduction of 2-oxoglutarate to 2- CC hydroxyglutarate, leading to elevated reactive oxygen species (ROS) CC (PubMed:34012073). {ECO:0000269|PubMed:2449162, CC ECO:0000269|PubMed:3052244, ECO:0000269|PubMed:31538237}. 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:2449162, ECO:0000269|PubMed:3052244}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21433; CC Evidence={ECO:0000269|PubMed:2449162, ECO:0000269|PubMed:3052244}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:21434; CC Evidence={ECO:0000269|PubMed:2449162, ECO:0000269|PubMed:3052244}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(2R)-2-hydroxy-3-(4-hydroxyphenyl)propanoate + NAD(+) = 3-(4- CC hydroxyphenyl)pyruvate + H(+) + NADH; Xref=Rhea:RHEA:10780, CC ChEBI:CHEBI:10980, ChEBI:CHEBI:15378, ChEBI:CHEBI:36242, CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.96; CC Evidence={ECO:0000269|PubMed:2449162, ECO:0000269|PubMed:3052244}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10782; CC Evidence={ECO:0000269|PubMed:2449162, ECO:0000269|PubMed:3052244}; CC -!- CATALYTIC ACTIVITY: CC Reaction=(S)-2-hydroxyglutarate + NAD(+) = 2-oxoglutarate + H(+) + CC NADH; Xref=Rhea:RHEA:57172, ChEBI:CHEBI:15378, ChEBI:CHEBI:16782, CC ChEBI:CHEBI:16810, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; CC Evidence={ECO:0000269|PubMed:34012073}; CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:57174; CC Evidence={ECO:0000269|PubMed:34012073}; CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:P11708}. CC -!- INTERACTION: CC P40925; P54274: TERF1; NbExp=2; IntAct=EBI-709625, EBI-710997; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:8786100}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=P40925-1; Sequence=Displayed; CC Name=2; CC IsoId=P40925-2; Sequence=VSP_042661; CC Name=3; CC IsoId=P40925-3; Sequence=VSP_045847; CC -!- PTM: ISGylated. {ECO:0000269|PubMed:16139798}. CC -!- PTM: Acetylation at Lys-118 dramatically enhances enzymatic activity CC and promotes adipogenic differentiation. {ECO:0000269|PubMed:22693256, CC ECO:0000269|Ref.8}. CC -!- DISEASE: Developmental and epileptic encephalopathy 88 (DEE88) CC [MIM:618959]: A form of epileptic encephalopathy, a heterogeneous group CC of 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. DEE88 is an autosomal recessive severe form CC characterized by global developmental delay, epilepsy, and progressive CC microcephaly. {ECO:0000269|PubMed:31538237}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. MDH type 2 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; D55654; BAA09513.1; -; mRNA. DR EMBL; U20352; AAC16436.1; -; mRNA. DR EMBL; CR457405; CAG33686.1; -; mRNA. DR EMBL; AK295931; BAH12223.1; -; mRNA. DR EMBL; AK300719; BAG62394.1; -; mRNA. DR EMBL; AK312331; BAG35252.1; -; mRNA. DR EMBL; AC016734; AAY14893.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99959.1; -; Genomic_DNA. DR EMBL; BC001484; AAH01484.1; -; mRNA. DR CCDS; CCDS1874.1; -. [P40925-1] DR CCDS; CCDS56121.1; -. [P40925-3] DR PIR; G01650; G01650. DR RefSeq; NP_001186040.1; NM_001199111.1. [P40925-3] DR RefSeq; NP_001186041.1; NM_001199112.1. [P40925-2] DR RefSeq; NP_001303303.1; NM_001316374.1. DR RefSeq; NP_005908.1; NM_005917.3. [P40925-1] DR PDB; 7RM9; X-ray; 1.65 A; A/B=1-334. DR PDB; 7RRL; X-ray; 2.05 A; A/B=1-334. DR PDBsum; 7RM9; -. DR PDBsum; 7RRL; -. DR AlphaFoldDB; P40925; -. DR SMR; P40925; -. DR BioGRID; 110355; 130. DR ComplexPortal; CPX-7142; Hydride transfer complex. DR IntAct; P40925; 32. DR MINT; P40925; -. DR BindingDB; P40925; -. DR ChEMBL; CHEMBL3560; -. DR DrugBank; DB11638; Artenimol. DR DrugBank; DB00157; NADH. DR DrugBank; DB03461; Nicotinamide adenine dinucleotide phosphate. DR DrugCentral; P40925; -. DR GlyGen; P40925; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P40925; -. DR MetOSite; P40925; -. DR PhosphoSitePlus; P40925; -. DR SwissPalm; P40925; -. DR BioMuta; MDH1; -. DR DMDM; 1708967; -. DR REPRODUCTION-2DPAGE; IPI00291005; -. DR CPTAC; CPTAC-236; -. DR CPTAC; CPTAC-237; -. DR CPTAC; CPTAC-2752; -. DR EPD; P40925; -. DR jPOST; P40925; -. DR MassIVE; P40925; -. DR MaxQB; P40925; -. DR PaxDb; 9606-ENSP00000438144; -. DR PeptideAtlas; P40925; -. DR ProteomicsDB; 25276; -. DR ProteomicsDB; 55384; -. [P40925-1] DR ProteomicsDB; 55385; -. [P40925-2] DR Pumba; P40925; -. DR TopDownProteomics; P40925-1; -. [P40925-1] DR Antibodypedia; 15986; 491 antibodies from 39 providers. DR CPTC; P40925; 3 antibodies. DR DNASU; 4190; -. DR Ensembl; ENST00000233114.13; ENSP00000233114.8; ENSG00000014641.21. [P40925-1] DR Ensembl; ENST00000432309.6; ENSP00000410073.2; ENSG00000014641.21. [P40925-3] DR Ensembl; ENST00000544381.4; ENSP00000446395.2; ENSG00000014641.21. [P40925-1] DR GeneID; 4190; -. DR KEGG; hsa:4190; -. DR MANE-Select; ENST00000233114.13; ENSP00000233114.8; NM_005917.4; NP_005908.1. DR UCSC; uc010ypv.3; human. [P40925-1] DR AGR; HGNC:6970; -. DR CTD; 4190; -. DR DisGeNET; 4190; -. DR GeneCards; MDH1; -. DR HGNC; HGNC:6970; MDH1. DR HPA; ENSG00000014641; Tissue enhanced (heart muscle, tongue). DR MalaCards; MDH1; -. DR MIM; 154200; gene. DR MIM; 618959; phenotype. DR neXtProt; NX_P40925; -. DR OpenTargets; ENSG00000014641; -. DR PharmGKB; PA30714; -. DR VEuPathDB; HostDB:ENSG00000014641; -. DR eggNOG; KOG1496; Eukaryota. DR GeneTree; ENSGT00530000063410; -. DR HOGENOM; CLU_040727_2_0_1; -. DR InParanoid; P40925; -. DR OMA; TKGMERG; -. DR OrthoDB; 501358at2759; -. DR PhylomeDB; P40925; -. DR TreeFam; TF105826; -. DR BioCyc; MetaCyc:HS00361-MONOMER; -. DR BRENDA; 1.1.1.37; 2681. DR PathwayCommons; P40925; -. DR Reactome; R-HSA-70263; Gluconeogenesis. DR SABIO-RK; P40925; -. DR SignaLink; P40925; -. DR SIGNOR; P40925; -. DR BioGRID-ORCS; 4190; 16 hits in 1166 CRISPR screens. DR ChiTaRS; MDH1; human. DR GenomeRNAi; 4190; -. DR Pharos; P40925; Tchem. DR PRO; PR:P40925; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P40925; Protein. DR Bgee; ENSG00000014641; Expressed in lateral nuclear group of thalamus and 214 other cell types or tissues. DR ExpressionAtlas; P40925; baseline and differential. DR GO; GO:0005813; C:centrosome; IDA:HPA. DR GO; GO:0005737; C:cytoplasm; IDA:ComplexPortal. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0047860; F:diiodophenylpyruvate reductase activity; IEA:UniProtKB-EC. DR GO; GO:0047995; F:hydroxyphenylpyruvate reductase activity; IEA:RHEA. DR GO; GO:0030060; F:L-malate dehydrogenase activity; EXP:Reactome. DR GO; GO:0004470; F:malic enzyme activity; TAS:ProtInc. DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome. DR GO; GO:0006108; P:malate metabolic process; IBA:GO_Central. DR GO; GO:0006734; P:NADH metabolic process; IDA:ComplexPortal. DR GO; GO:0006739; P:NADP metabolic process; IDA:ComplexPortal. 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; Lactate dehydrogenase/glycoside hydrolase, family 4, C-terminal; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 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 NCBIfam; TIGR01759; MalateDH-SF1; 1. DR NCBIfam; TIGR01758; MDH_euk_cyt; 1. DR PANTHER; PTHR23382; MALATE DEHYDROGENASE; 1. DR PANTHER; PTHR23382:SF3; MALATE DEHYDROGENASE, CYTOPLASMIC; 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; P40925; -. DR Genevisible; P40925; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Direct protein sequencing; Disease variant; Epilepsy; Methylation; NAD; KW Oxidoreductase; Phosphoprotein; Reference proteome; KW Tricarboxylic acid cycle; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712" FT CHAIN 2..334 FT /note="Malate dehydrogenase, cytoplasmic" FT /id="PRO_0000113409" FT ACT_SITE 187 FT /note="Proton acceptor" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 11..17 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 42 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 92 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 98 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 105 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 112 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 129..131 FT /ligand="NAD(+)" FT /ligand_id="ChEBI:CHEBI:57540" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 131 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:P11708" FT BINDING 162 FT /ligand="substrate" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|Ref.8, ECO:0007744|PubMed:25944712" 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:0000269|PubMed:22693256, FT ECO:0007744|PubMed:19608861" FT MOD_RES 121 FT /note="N6-acetyllysine" FT /evidence="ECO:0000269|PubMed:22693256" 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:0007744|PubMed:24275569" FT MOD_RES 298 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0000269|PubMed:22693256, FT ECO:0007744|PubMed:19608861" 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:0007744|PubMed:20068231" FT VAR_SEQ 1..89 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_042661" FT VAR_SEQ 1 FT /note="M -> MRRCSYFPKDVTVFDKDDK (in isoform 3)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_045847" FT VARIANT 120 FT /note="A -> V (in DEE88; decreased protein expression; FT increased levels of glutamate and glycerol-3-phosphate)" FT /evidence="ECO:0000269|PubMed:31538237" FT /id="VAR_083894" FT CONFLICT 15 FT /note="Q -> R (in Ref. 4; BAH12223)" FT /evidence="ECO:0000305" FT STRAND 5..11 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 15..25 FT /evidence="ECO:0007829|PDB:7RM9" FT TURN 26..30 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 36..41 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 44..46 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 47..59 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 65..72 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 74..77 FT /evidence="ECO:0007829|PDB:7RM9" FT TURN 78..80 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 82..86 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 98..101 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 102..119 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 125..128 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 133..142 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 149..151 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 152..154 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 157..171 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 175..177 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 192..194 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 199..202 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 205..208 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 209..213 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 216..220 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 222..238 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 243..259 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 267..272 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 277..279 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 285..293 FT /evidence="ECO:0007829|PDB:7RM9" FT STRAND 296..299 FT /evidence="ECO:0007829|PDB:7RM9" FT HELIX 307..332 FT /evidence="ECO:0007829|PDB:7RM9" SQ SEQUENCE 334 AA; 36426 MW; 5F7ED9789CA1DB55 CRC64; MSEPIRVLVT GAAGQIAYSL LYSIGNGSVF GKDQPIILVL LDITPMMGVL DGVLMELQDC ALPLLKDVIA TDKEDVAFKD LDVAILVGSM PRREGMERKD LLKANVKIFK SQGAALDKYA KKSVKVIVVG NPANTNCLTA SKSAPSIPKE NFSCLTRLDH NRAKAQIALK LGVTANDVKN VIIWGNHSST QYPDVNHAKV KLQGKEVGVY EALKDDSWLK GEFVTTVQQR GAAVIKARKL SSAMSAAKAI CDHVRDIWFG TPEGEFVSMG VISDGNSYGV PDDLLYSFPV VIKNKTWKFV EGLPINDFSR EKMDLTAKEL TEEKESAFEF LSSA //