MAOM_HUMAN
ID MAOM_HUMAN Reviewed; 584 AA.
AC P23368; B2R8J2; Q9BWL6; Q9BYG1; Q9H4B2;
DT 01-NOV-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1991, sequence version 1.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=NAD-dependent malic enzyme, mitochondrial;
DE Short=NAD-ME;
DE EC=1.1.1.38 {ECO:0000269|PubMed:1993674};
DE AltName: Full=Malic enzyme 2;
DE Flags: Precursor;
GN Name=ME2;
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), PARTIAL PROTEIN SEQUENCE, FUNCTION,
RP CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=1993674; DOI=10.1016/s0021-9258(18)49948-6;
RA Loeber G., Infante A.A., Maurer-Fogy I., Krystek E., Dworkin M.B.;
RT "Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary
RT structure, and expression in Escherichia coli.";
RL J. Biol. Chem. 266:3016-3021(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 37-80.
RX PubMed=11401430; DOI=10.1006/geno.2000.6454;
RA Yanaihara N., Kohno T., Takakura S., Takei K., Otsuka A., Sunaga N.,
RA Takahashi M., Yamazaki M., Tashiro H., Fukuzumi Y., Fujimori Y.,
RA Hagiwara K., Tanaka T., Yokota J.;
RT "Physical and transcriptional map of a 311-kb segment of chromosome 18q21,
RT a candidate lung tumor suppressor locus.";
RL Genomics 72:169-179(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Trachea;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 421-584 (ISOFORM 1).
RC TISSUE=B-cell;
RA Abts H.;
RL Thesis (1995), University of Cologne, Germany.
RN [8]
RP PROTEIN SEQUENCE OF 19-33.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-156; LYS-224; LYS-240; LYS-272
RP AND LYS-346, 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 [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 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 [12]
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 [13]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
RX PubMed=10467136; DOI=10.1016/s0969-2126(99)80115-4;
RA Xu Y., Bhargava G., Wu H., Loeber G., Tong L.;
RT "Crystal structure of human mitochondrial NAD(P)(+)-dependent malic enzyme:
RT a new class of oxidative decarboxylases.";
RL Structure 7:877-889(1999).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-584 IN COMPLEX WITH NAD;
RP DIVALENT METAL ION AND SUBSTRATE ANALOG, COFACTOR, AND HOMOTETRAMERIZATION.
RX PubMed=10700286; DOI=10.1038/73378;
RA Yang Z., Floyd D.L., Loeber G., Tong L.;
RT "Structure of a closed form of human malic enzyme and implications for
RT catalytic mechanism.";
RL Nat. Struct. Biol. 7:251-257(2000).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 20-573 IN COMPLEX WITH ATP;
RP MANGANESE; ALLOSTERIC ACTIVATOR AND SUBSTRATE ANALOG, MUTAGENESIS OF ARG-67
RP AND ARG-91, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, ACTIVITY REGULATION,
RP AND HOMOTETRAMERIZATION.
RX PubMed=12121650; DOI=10.1016/s0969-2126(02)00788-8;
RA Yang Z., Lanks C.W., Tong L.;
RT "Molecular mechanism for the regulation of human mitochondrial NAD(P)+-
RT dependent malic enzyme by ATP and fumarate.";
RL Structure 10:951-960(2002).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 21-584 IN COMPLEX WITH SUBSTRATE;
RP NAD; MANGANESE AND ALLOSTERIC ACTIVATOR, COFACTOR, ENZYME MECHANISM,
RP ACTIVITY REGULATION, AND ACTIVE SITES.
RX PubMed=12962632; DOI=10.1016/s0969-2126(03)00168-0;
RA Tao X., Yang Z., Tong L.;
RT "Crystal structures of substrate complexes of malic enzyme and insights
RT into the catalytic mechanism.";
RL Structure 11:1141-1150(2003).
CC -!- FUNCTION: NAD-dependent mitochondrial malic enzyme that catalyzes the
CC oxidative decarboxylation of malate to pyruvate.
CC {ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:1993674}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-malate + NAD(+) = CO2 + NADH + pyruvate;
CC Xref=Rhea:RHEA:12653, ChEBI:CHEBI:15361, ChEBI:CHEBI:15589,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.38;
CC Evidence={ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:1993674};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + oxaloacetate = CO2 + pyruvate; Xref=Rhea:RHEA:15641,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:16452,
CC ChEBI:CHEBI:16526; EC=1.1.1.38;
CC Evidence={ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:1993674};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10700286, ECO:0000269|PubMed:12121650,
CC ECO:0000269|PubMed:12962632};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:10700286, ECO:0000269|PubMed:12121650,
CC ECO:0000269|PubMed:12962632};
CC Note=Divalent metal cations. Prefers magnesium or manganese.
CC {ECO:0000269|PubMed:10700286, ECO:0000269|PubMed:12121650,
CC ECO:0000269|PubMed:12962632};
CC -!- ACTIVITY REGULATION: Subject to allosteric activation by fumarate.
CC {ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:12962632}.
CC -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:10700286,
CC ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:12962632}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:1993674}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P23368-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P23368-2; Sequence=VSP_042717;
CC -!- MISCELLANEOUS: This isoenzyme can also use NADP(+) but is more
CC effective with NAD(+). {ECO:0000269|PubMed:12121650,
CC ECO:0000269|PubMed:1993674}.
CC -!- SIMILARITY: Belongs to the malic enzymes family. {ECO:0000305}.
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DR EMBL; M55905; AAA36197.1; -; mRNA.
DR EMBL; AB045122; BAB40980.1; -; Genomic_DNA.
DR EMBL; AK313391; BAG36189.1; -; mRNA.
DR EMBL; AC015864; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC087687; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471096; EAW62980.1; -; Genomic_DNA.
DR EMBL; BC000147; AAH00147.1; -; mRNA.
DR EMBL; AJ294818; CAC14574.1; -; mRNA.
DR CCDS; CCDS11948.1; -. [P23368-1]
DR CCDS; CCDS54187.1; -. [P23368-2]
DR PIR; A39503; A39503.
DR RefSeq; NP_001161807.1; NM_001168335.1. [P23368-2]
DR RefSeq; NP_002387.1; NM_002396.4. [P23368-1]
DR PDB; 1DO8; X-ray; 2.20 A; A/B/C/D=21-584.
DR PDB; 1EFK; X-ray; 2.60 A; A/B/C/D=1-584.
DR PDB; 1EFL; X-ray; 2.60 A; A/B/C/D=1-584.
DR PDB; 1GZ3; X-ray; 2.30 A; A/B/C/D=20-573.
DR PDB; 1GZ4; X-ray; 2.20 A; A/B/C/D=23-573.
DR PDB; 1PJ2; X-ray; 2.30 A; A/B/C/D=21-584.
DR PDB; 1PJ3; X-ray; 2.10 A; A/B/C/D=21-584.
DR PDB; 1PJ4; X-ray; 2.30 A; A/B/C/D=21-584.
DR PDB; 1PJL; X-ray; 2.90 A; A/B/C/D/E/F/G/H=1-584.
DR PDB; 1QR6; X-ray; 2.10 A; A/B=1-584.
DR PDB; 7BSJ; X-ray; 2.48 A; A/B=19-584.
DR PDB; 7BSK; X-ray; 2.55 A; A/B=19-584.
DR PDB; 7BSL; X-ray; 2.55 A; A/B=19-584.
DR PDBsum; 1DO8; -.
DR PDBsum; 1EFK; -.
DR PDBsum; 1EFL; -.
DR PDBsum; 1GZ3; -.
DR PDBsum; 1GZ4; -.
DR PDBsum; 1PJ2; -.
DR PDBsum; 1PJ3; -.
DR PDBsum; 1PJ4; -.
DR PDBsum; 1PJL; -.
DR PDBsum; 1QR6; -.
DR PDBsum; 7BSJ; -.
DR PDBsum; 7BSK; -.
DR PDBsum; 7BSL; -.
DR AlphaFoldDB; P23368; -.
DR SMR; P23368; -.
DR BioGRID; 110364; 73.
DR IntAct; P23368; 12.
DR MINT; P23368; -.
DR STRING; 9606.ENSP00000321070; -.
DR DrugBank; DB03499; D-Malic acid.
DR DrugBank; DB01677; Fumaric acid.
DR DrugBank; DB03589; Mesoxalic acid.
DR DrugBank; DB00157; NADH.
DR DrugBank; DB03680; Tartronate.
DR CarbonylDB; P23368; -.
DR GlyGen; P23368; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P23368; -.
DR MetOSite; P23368; -.
DR PhosphoSitePlus; P23368; -.
DR SwissPalm; P23368; -.
DR BioMuta; ME2; -.
DR DMDM; 126733; -.
DR EPD; P23368; -.
DR jPOST; P23368; -.
DR MassIVE; P23368; -.
DR MaxQB; P23368; -.
DR PaxDb; P23368; -.
DR PeptideAtlas; P23368; -.
DR PRIDE; P23368; -.
DR ProteomicsDB; 54082; -. [P23368-1]
DR ProteomicsDB; 54083; -. [P23368-2]
DR Antibodypedia; 1636; 221 antibodies from 33 providers.
DR DNASU; 4200; -.
DR Ensembl; ENST00000321341.11; ENSP00000321070.5; ENSG00000082212.13. [P23368-1]
DR Ensembl; ENST00000382927.3; ENSP00000372384.2; ENSG00000082212.13. [P23368-2]
DR GeneID; 4200; -.
DR KEGG; hsa:4200; -.
DR MANE-Select; ENST00000321341.11; ENSP00000321070.5; NM_002396.5; NP_002387.1.
DR UCSC; uc002ley.4; human. [P23368-1]
DR CTD; 4200; -.
DR DisGeNET; 4200; -.
DR GeneCards; ME2; -.
DR HGNC; HGNC:6984; ME2.
DR HPA; ENSG00000082212; Low tissue specificity.
DR MIM; 154270; gene.
DR neXtProt; NX_P23368; -.
DR OpenTargets; ENSG00000082212; -.
DR PharmGKB; PA30724; -.
DR VEuPathDB; HostDB:ENSG00000082212; -.
DR eggNOG; KOG1257; Eukaryota.
DR GeneTree; ENSGT00950000183134; -.
DR HOGENOM; CLU_011405_5_0_1; -.
DR InParanoid; P23368; -.
DR OMA; QMWDPVY; -.
DR OrthoDB; 435571at2759; -.
DR PhylomeDB; P23368; -.
DR TreeFam; TF300537; -.
DR BRENDA; 1.1.1.38; 2681.
DR PathwayCommons; P23368; -.
DR Reactome; R-HSA-71403; Citric acid cycle (TCA cycle).
DR SABIO-RK; P23368; -.
DR SignaLink; P23368; -.
DR SIGNOR; P23368; -.
DR BioGRID-ORCS; 4200; 24 hits in 1078 CRISPR screens.
DR ChiTaRS; ME2; human.
DR EvolutionaryTrace; P23368; -.
DR GeneWiki; ME2; -.
DR GeneWiki; ME2_(gene); -.
DR GenomeRNAi; 4200; -.
DR Pharos; P23368; Tbio.
DR PRO; PR:P23368; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; P23368; protein.
DR Bgee; ENSG00000082212; Expressed in choroid plexus epithelium and 215 other tissues.
DR ExpressionAtlas; P23368; baseline and differential.
DR Genevisible; P23368; HS.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0009055; F:electron transfer activity; TAS:UniProtKB.
DR GO; GO:0004471; F:malate dehydrogenase (decarboxylating) (NAD+) activity; TAS:ProtInc.
DR GO; GO:0004473; F:malate dehydrogenase (decarboxylating) (NADP+) activity; IBA:GO_Central.
DR GO; GO:0004470; F:malic enzyme activity; IMP:CACAO.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051287; F:NAD binding; IEA:InterPro.
DR GO; GO:0008948; F:oxaloacetate decarboxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0006108; P:malate metabolic process; IBA:GO_Central.
DR GO; GO:0006090; P:pyruvate metabolic process; IBA:GO_Central.
DR GO; GO:1902031; P:regulation of NADP metabolic process; IMP:CACAO.
DR Gene3D; 3.40.50.10380; -; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR015884; Malic_enzyme_CS.
DR InterPro; IPR012301; Malic_N_dom.
DR InterPro; IPR037062; Malic_N_dom_sf.
DR InterPro; IPR012302; Malic_NAD-bd.
DR InterPro; IPR001891; Malic_OxRdtase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF00390; malic; 1.
DR Pfam; PF03949; Malic_M; 1.
DR PIRSF; PIRSF000106; ME; 1.
DR PRINTS; PR00072; MALOXRDTASE.
DR SMART; SM01274; malic; 1.
DR SMART; SM00919; Malic_M; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00331; MALIC_ENZYMES; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing;
KW Direct protein sequencing; Metal-binding; Mitochondrion; NAD;
KW Oxidoreductase; Reference proteome; Transit peptide.
FT TRANSIT 1..18
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:12665801"
FT CHAIN 19..584
FT /note="NAD-dependent malic enzyme, mitochondrial"
FT /id="PRO_0000018537"
FT ACT_SITE 112
FT /note="Proton donor"
FT /evidence="ECO:0000269|PubMed:12962632"
FT ACT_SITE 183
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:12962632"
FT BINDING 67
FT /ligand="fumarate"
FT /ligand_id="ChEBI:CHEBI:29806"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:12121650,
FT ECO:0000269|PubMed:12962632"
FT BINDING 91
FT /ligand="fumarate"
FT /ligand_id="ChEBI:CHEBI:29806"
FT /ligand_note="allosteric activator"
FT /evidence="ECO:0000269|PubMed:12121650,
FT ECO:0000269|PubMed:12962632"
FT BINDING 165..173
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10700286,
FT ECO:0000269|PubMed:12962632"
FT BINDING 165
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12962632"
FT BINDING 255
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:10700286,
FT ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:12962632"
FT BINDING 256
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:10700286,
FT ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:12962632"
FT BINDING 259
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10700286,
FT ECO:0000269|PubMed:12962632"
FT BINDING 279
FT /ligand="a divalent metal cation"
FT /ligand_id="ChEBI:CHEBI:60240"
FT /evidence="ECO:0000269|PubMed:10700286,
FT ECO:0000269|PubMed:12121650, ECO:0000269|PubMed:12962632"
FT BINDING 311..328
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:10700286,
FT ECO:0000269|PubMed:12962632"
FT BINDING 421
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12962632"
FT BINDING 466
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:12962632"
FT MOD_RES 156
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 240
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 272
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 346
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT VAR_SEQ 474..584
FT /note="VALAVILCNTRHISDSVFLEAAKALTSQLTDEELAQGRLYPPLANIQEVSIN
FT IAIKVTEYLYANKMAFRYPEPEDKAKYVKERTWRSEYDSLLPDVYEWPESASSPPVITE
FT -> YRIPIC (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_042717"
FT VARIANT 114
FT /note="P -> L (in dbSNP:rs16952692)"
FT /id="VAR_034104"
FT VARIANT 450
FT /note="G -> E (in dbSNP:rs649224)"
FT /id="VAR_050017"
FT MUTAGEN 67
FT /note="R->S: Abolishes activation by fumarate."
FT /evidence="ECO:0000269|PubMed:12121650"
FT MUTAGEN 91
FT /note="R->T: Abolishes activation by fumarate."
FT /evidence="ECO:0000269|PubMed:12121650"
FT CONFLICT 263
FT /note="F -> Y (in Ref. 3; BAG36189)"
FT /evidence="ECO:0000305"
FT HELIX 27..30
FT /evidence="ECO:0007829|PDB:1PJ3"
FT TURN 32..34
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 37..39
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 42..47
FT /evidence="ECO:0007829|PDB:1PJ3"
FT TURN 51..53
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 61..74
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 93..102
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 104..111
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 115..121
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 123..126
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 132..136
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 137..139
FT /evidence="ECO:0007829|PDB:1PJ3"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:1PJL"
FT HELIX 143..147
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 157..161
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 163..165
FT /evidence="ECO:0007829|PDB:1PJ3"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:1QR6"
FT HELIX 173..177
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 178..191
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 198..205
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 229..246
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 251..254
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 259..269
FT /evidence="ECO:0007829|PDB:1PJ3"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 273..277
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 278..298
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 307..310
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 314..329
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 334..339
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 341..345
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 351..353
FT /evidence="ECO:0007829|PDB:7BSJ"
FT TURN 360..362
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 377..384
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 387..391
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:1GZ3"
FT HELIX 401..410
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 415..418
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 423..425
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 426..428
FT /evidence="ECO:0007829|PDB:1QR6"
FT HELIX 430..436
FT /evidence="ECO:0007829|PDB:1PJ3"
FT TURN 437..439
FT /evidence="ECO:0007829|PDB:1PJ3"
FT STRAND 442..447
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 467..469
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 471..480
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 488..499
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 504..508
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 516..518
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 519..536
FT /evidence="ECO:0007829|PDB:1PJ3"
FT HELIX 549..555
FT /evidence="ECO:0007829|PDB:1PJ3"
SQ SEQUENCE 584 AA; 65444 MW; 4CEF9AF89B07D93D CRC64;
MLSRLRVVST TCTLACRHLH IKEKGKPLML NPRTNKGMAF TLQERQMLGL QGLLPPKIET
QDIQALRFHR NLKKMTSPLE KYIYIMGIQE RNEKLFYRIL QDDIESLMPI VYTPTVGLAC
SQYGHIFRRP KGLFISISDR GHVRSIVDNW PENHVKAVVV TDGERILGLG DLGVYGMGIP
VGKLCLYTAC AGIRPDRCLP VCIDVGTDNI ALLKDPFYMG LYQKRDRTQQ YDDLIDEFMK
AITDRYGRNT LIQFEDFGNH NAFRFLRKYR EKYCTFNDDI QGTAAVALAG LLAAQKVISK
PISEHKILFL GAGEAALGIA NLIVMSMVEN GLSEQEAQKK IWMFDKYGLL VKGRKAKIDS
YQEPFTHSAP ESIPDTFEDA VNILKPSTII GVAGAGRLFT PDVIRAMASI NERPVIFALS
NPTAQAECTA EEAYTLTEGR CLFASGSPFG PVKLTDGRVF TPGQGNNVYI FPGVALAVIL
CNTRHISDSV FLEAAKALTS QLTDEELAQG RLYPPLANIQ EVSINIAIKV TEYLYANKMA
FRYPEPEDKA KYVKERTWRS EYDSLLPDVY EWPESASSPP VITE
