MDHC_HUMAN
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 03-AUG-2022, entry version 214.
DE RecName: Full=Malate dehydrogenase, cytoplasmic {ECO:0000305};
DE EC=1.1.1.37 {ECO:0000269|PubMed:3052244};
DE AltName: Full=Cytosolic malate dehydrogenase;
DE AltName: Full=Diiodophenylpyruvate reductase;
DE EC=1.1.1.96 {ECO:0000269|PubMed:3052244};
GN Name=MDH1 {ECO:0000312|HGNC:HGNC:6970}; 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).
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 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 [12]
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 [13]
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 [14]
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 [15]
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 [16]
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 [17]
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 [18]
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 [19]
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 [20]
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).
CC -!- FUNCTION: Catalyzes the reduction of aromatic alpha-keto acids in the
CC presence of NADH (PubMed:3052244). Plays essential roles in the malate-
CC aspartate shuttle and the tricarboxylic acid cycle, important in
CC mitochondrial NADH supply for oxidative phosphorylation
CC (PubMed:31538237). {ECO:0000269|PubMed:3052244,
CC 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:3052244};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-(3,5-diiodo-4-hydroxyphenyl)lactate + NAD(+) = 3-(3,5-
CC diiodo-4-hydroxyphenyl)pyruvate + H(+) + NADH; Xref=Rhea:RHEA:20293,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57540, ChEBI:CHEBI:57647,
CC ChEBI:CHEBI:57945, ChEBI:CHEBI:58023; EC=1.1.1.96;
CC Evidence={ECO:0000269|PubMed:3052244};
CC -!- SUBUNIT: Homodimer.
CC -!- INTERACTION:
CC P40925; P54274: TERF1; NbExp=2; IntAct=EBI-709625, EBI-710997;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
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";
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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 CCDS; CCDS56122.1; -. [P40925-2]
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; 95.
DR ComplexPortal; CPX-7142; Hydride transfer complex.
DR IntAct; P40925; 29.
DR MINT; P40925; -.
DR STRING; 9606.ENSP00000438144; -.
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 UCD-2DPAGE; P40925; -.
DR CPTAC; CPTAC-236; -.
DR CPTAC; CPTAC-237; -.
DR EPD; P40925; -.
DR jPOST; P40925; -.
DR MassIVE; P40925; -.
DR MaxQB; P40925; -.
DR PaxDb; P40925; -.
DR PeptideAtlas; P40925; -.
DR PRIDE; P40925; -.
DR ProteomicsDB; 25276; -.
DR ProteomicsDB; 55384; -. [P40925-1]
DR ProteomicsDB; 55385; -. [P40925-2]
DR TopDownProteomics; P40925-1; -. [P40925-1]
DR Antibodypedia; 15986; 429 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 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; 1118998at2759; -.
DR PhylomeDB; P40925; -.
DR TreeFam; TF105826; -.
DR BioCyc; MetaCyc:HS00361-MON; -.
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; 12 hits in 1078 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 212 other tissues.
DR ExpressionAtlas; P40925; baseline and differential.
DR Genevisible; P40925; HS.
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:0030060; F:L-malate dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0004470; F:malic enzyme activity; TAS:ProtInc.
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; -; 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; 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
