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UniProtKB/Swiss-Prot entry P23368


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name MAOM_HUMAN
Primary accession number P23368
Secondary accession numbers Q9BYG1 Q9H4B2
Integrated into Swiss-Prot on November 1, 1991
Sequence was last modified on November 1, 1991 (Sequence version 1)
Annotations were last modified on    November 25, 2008 (Entry version 98)
Name and origin of the protein
Protein name NAD-dependent malic enzyme, mitochondrial [Precursor]
Synonyms NAD-ME
EC 1.1.1.38
Malic enzyme 2
Gene name
Name: ME2
From
Homo sapiens (Human) [TaxID: 9606] 
Taxonomy Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
PubMed=1993674 [NCBI, ExPASy, EBI, Israel, Japan]
Loeber G., Infante A.A., Maurer-Fogy I., Krystek E., Dworkin M.B.;
"Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary structure, and expression in Escherichia coli.";
J. Biol. Chem. 266:3016-3021(1991).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 37-80.
DOI=10.1006/geno.2000.6454; PubMed=11401430 [NCBI, ExPASy, EBI, Israel, Japan]
Yanaihara N., Kohno T., Takakura S., Takei K., Otsuka A., Sunaga N., Takahashi M., Yamazaki M., Tashiro H., Fukuzumi Y., Fujimori Y., Hagiwara K., Tanaka T., Yokota J.;
"Physical and transcriptional map of a 311-kb segment of chromosome 18q21, a candidate lung tumor suppressor locus.";
Genomics 72:169-179(2001).
[3]
NUCLEOTIDE SEQUENCE OF 421-584.
TISSUE=B-cell;
Abts H.;
Thesis (1995), University of Cologne, Germany.
[4]
PROTEIN SEQUENCE OF 19-33.
TISSUE=Platelet;
DOI=10.1038/nbt810; PubMed=12665801 [NCBI, ExPASy, EBI, Israel, Japan]
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.;
"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides.";
Nat. Biotechnol. 21:566-569(2003).
[5]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
DOI=10.1016/S0969-2126(99)80115-4; PubMed=10467136 [NCBI, ExPASy, EBI, Israel, Japan]
Xu Y., Bhargava G., Wu H., Loeber G., Tong L.;
"Crystal structure of human mitochondrial NAD(P)(+)-dependent malic enzyme: a new class of oxidative decarboxylases.";
Structure 7:877-889(1999).
[6]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-584 IN COMPLEX WITH NAD; DIVALENT METAL ION AND SUBSTRATE ANALOG, AND HOMOTETRAMERIZATION.
DOI=10.1038/73378; PubMed=10700286 [NCBI, ExPASy, EBI, Israel, Japan]
Yang Z., Floyd D.L., Loeber G., Tong L.;
"Structure of a closed form of human malic enzyme and implications for catalytic mechanism.";
Nat. Struct. Biol. 7:251-257(2000).
[7]
X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 20-573 IN COMPLEX WITH ATP; MANGANESE; ALLOSTERIC ACTIVATOR AND SUBSTRATE ANALOG, MUTAGENESIS OF ARG-67 AND ARG-91, AND HOMOTETRAMERIZATION.
DOI=10.1016/S0969-2126(02)00788-8; PubMed=12121650 [NCBI, ExPASy, EBI, Israel, Japan]
Yang Z., Lanks C.W., Tong L.;
"Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate.";
Structure 10:951-960(2002).
[8]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 21-584 IN COMPLEX WITH SUBSTRATE; NAD; MANGANESE AND ALLOSTERIC ACTIVATOR, AND MECHANISM.
DOI=10.1016/S0969-2126(03)00168-0; PubMed=12962632 [NCBI, ExPASy, EBI, Israel, Japan]
Tao X., Yang Z., Tong L.;
"Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism.";
Structure 11:1141-1150(2003).
Comments
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M55905; AAA36197.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AB045122; BAB40980.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AJ294818; CAC14574.1; -; mRNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR A39503; A39503.
RefSeq NP_002387.1; -.
UniGene Hs.699163
3D structure databases
PDB
1DO8; X-ray; 2.20 A; A/B/C/D=21-584.[ExPASy / RCSB / EBI]
1EFK; X-ray; 2.60 A; A/B/C/D=1-584.[ExPASy / RCSB / EBI]
1EFL; X-ray; 2.60 A; A/B/C/D=1-584.[ExPASy / RCSB / EBI]
1GZ3; X-ray; 2.30 A; A/B/C/D=20-573.[ExPASy / RCSB / EBI]
1GZ4; X-ray; 2.20 A; A/B/C/D=23-573.[ExPASy / RCSB / EBI]
1PJ2; X-ray; 2.30 A; A/B/C/D=21-584.[ExPASy / RCSB / EBI]
1PJ3; X-ray; 2.10 A; A/B/C/D=21-584.[ExPASy / RCSB / EBI]
1PJ4; X-ray; 2.30 A; A/B/C/D=21-584.[ExPASy / RCSB / EBI]
1PJL; X-ray; 2.90 A; A/B/C/D/E/F/G/H=1-584.[ExPASy / RCSB / EBI]
1QR6; X-ray; 2.10 A; A/B=1-584.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1DO8; -.
1EFK; -.
1EFL; -.
1GZ3; -.
1GZ4; -.
1PJ2; -.
1PJ3; -.
1PJ4; -.
1PJL; -.
1QR6; -.
ModBase P23368.
Protein-protein interaction databases
IntAct P23368; -.
PTM databases
PhosphoSite P23368; -.
Organism-specific databases
H-InvDB HIX0014451; -.
HGNC HGNC:6984; ME2.
GenAtlas ME2.
HPA HPA008247; -.
HPA008880; -.
MIM 154270; gene. [NCBI / EBI]
PharmGKB PA134863517; -.
GeneCards P23368.
Gene expression databases
ArrayExpress P23368; -.
CleanEx HS_ME2; -.
GermOnline ENSG00000082212; Homo sapiens.
Ontologies
GO
GO:0005759; Cellular component: mitochondrial matrix (inferred from electronic annotation from UniProtKB-SubCell).
GO:0009055; Molecular function: electron carrier activity (traceable author statement from UniProtKB).
GO:0004471; Molecular function: malate dehydrogenase (decarboxylating) activity (traceable author statement from ProtInc).
GO:0016619; Molecular function: malate dehydrogenase (oxaloacetate-decarboxylating) activity (inferred from electronic annotation from EC).
GO:0046872; Molecular function: metal ion binding (inferred from electronic annotation from UniProtKB-KW).
GO:0051287; Molecular function: NAD binding (inferred from electronic annotation from InterPro).
GO:0006108; Biological process: malate metabolic process (inferred from electronic annotation from InterPro).
GO:0055114; Biological process: oxidation reduction (inferred from electronic annotation from UniProtKB-KW).
QuickGo view.
Family and domain databases
InterPro IPR015884; Malic_enzyme_CS.
IPR012301; Malic_N.
IPR012302; Malic_NAD_bd.
IPR001891; Malic_OxRdtase.
IPR016040; NAD(P)-bd.
Graphical view of domain structure.
Gene3D G3DSA:3.40.50.720; NAD(P)-bd; 1.
Pfam PF00390; malic; 1.
PF03949; Malic_M; 1.
Pfam graphical view of domain structure.
PRINTS PR00072; MALOXRDTASE.
PROSITE PS00331; MALIC_ENZYMES; 1.
ProtoNet P23368.
Proteomic databases
PeptideAtlas P23368; -.
Genome annotation databases
Ensembl ENSG00000082212; Homo sapiens. [Contig view]
GeneID 4200; -.
KEGG hsa:4200; -.
Phylogenomic databases
HOGENOM P23368; -.
HOVERGEN P23368; -.
Other
DrugBank DB00157; NADH.
LinkHub P23368; -.
NextBio 16554; -.
SOURCE ME2; Homo sapiens.
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Allosteric enzyme; Direct protein sequencing; Metal-binding; Mitochondrion; NAD; Oxidoreductase; Polymorphism; Transit peptide.
Features
SEVIEWER logo Feature table viewer
KeyFrom   To Length Description FTId
TRANSIT   1    18  18     Mitochondrion. 
CHAIN   19   584  566     NAD-dependent malic enzyme, mitochondrial. PRO_0000018537
NP_BIND   165   173  9     NAD. 
NP_BIND   311   328  18     NAD. 
ACT_SITE   112   112        Proton donor. 
ACT_SITE   183   183        Proton acceptor. 
METAL   255   255        Divalent metal cation. 
METAL   256   256        Divalent metal cation. 
METAL   279   279        Divalent metal cation. 
BINDING   67    67        Allosteric activator. 
BINDING   91    91        Allosteric activator. 
BINDING   165   165        Substrate. 
BINDING   259   259        NAD. 
BINDING   421   421        Substrate. 
BINDING   466   466        Substrate. 
SITE   279   279  1     Important for activity (By similarity). 
VARIANT   114   114  1     P -> L (in dbSNP:rs16952692 [NCBI]). VAR_034104 [3D]
MUTAGEN   67    67        R->S: Abolishes activation by fumarate. 
MUTAGEN   91    91        R->T: Abolishes activation by fumarate. 
HELIX   27    30  4      
TURN   32    34  3      
HELIX   37    39  3      
HELIX   42    47  6      
TURN   51    53  3      
HELIX   61    72  12      
HELIX   78    88  11      
TURN   89    91  3      
HELIX   93   102  10      
HELIX   104   111  8      
HELIX   115   126  12      
STRAND   132   136  5      
HELIX   137   139  3      
HELIX   143   147  5      
STRAND   157   161  5      
STRAND   163   166  4      
TURN   167   169  3      
HELIX   173   177  5      
HELIX   178   191  14      
HELIX   195   197  3      
STRAND   198   205  8      
HELIX   210   213  4      
HELIX   229   246  18      
STRAND   251   254  4      
HELIX   259   269  11      
TURN   270   272  3      
STRAND   273   277  5      
HELIX   278   298  21      
HELIX   302   304  3      
STRAND   307   310  4      
HELIX   314   328  15      
TURN   329   331  3      
HELIX   334   338  5      
STRAND   341   345  5      
TURN   360   362  3      
HELIX   363   365  3      
HELIX   377   384  8      
STRAND   387   391  5      
HELIX   401   410  10      
STRAND   415   418  4      
HELIX   423   425  3      
HELIX   430   436  7      
TURN   437   439  3      
STRAND   442   447  6      
HELIX   467   469  3      
HELIX   471   480  10      
HELIX   488   499  12      
HELIX   504   508  5      
HELIX   516   518  3      
HELIX   519   536  18      
HELIX   549   555  7      
Sequence information
Length: 584 AA [This is the length of the unprocessed precursor] Molecular weight: 65444 Da [This is the MW of the unprocessed precursor] CRC64: 4CEF9AF89B07D93D [This is a checksum on the sequence]
        10         20         30         40         50         60 
MLSRLRVVST TCTLACRHLH IKEKGKPLML NPRTNKGMAF TLQERQMLGL QGLLPPKIET 

        70         80         90        100        110        120 
QDIQALRFHR NLKKMTSPLE KYIYIMGIQE RNEKLFYRIL QDDIESLMPI VYTPTVGLAC 

       130        140        150        160        170        180 
SQYGHIFRRP KGLFISISDR GHVRSIVDNW PENHVKAVVV TDGERILGLG DLGVYGMGIP 

       190        200        210        220        230        240 
VGKLCLYTAC AGIRPDRCLP VCIDVGTDNI ALLKDPFYMG LYQKRDRTQQ YDDLIDEFMK 

       250        260        270        280        290        300 
AITDRYGRNT LIQFEDFGNH NAFRFLRKYR EKYCTFNDDI QGTAAVALAG LLAAQKVISK 

       310        320        330        340        350        360 
PISEHKILFL GAGEAALGIA NLIVMSMVEN GLSEQEAQKK IWMFDKYGLL VKGRKAKIDS 

       370        380        390        400        410        420 
YQEPFTHSAP ESIPDTFEDA VNILKPSTII GVAGAGRLFT PDVIRAMASI NERPVIFALS 

       430        440        450        460        470        480 
NPTAQAECTA EEAYTLTEGR CLFASGSPFG PVKLTDGRVF TPGQGNNVYI FPGVALAVIL 

       490        500        510        520        530        540 
CNTRHISDSV FLEAAKALTS QLTDEELAQG RLYPPLANIQ EVSINIAIKV TEYLYANKMA 

       550        560        570        580 
FRYPEPEDKA KYVKERTWRS EYDSLLPDVY EWPESASSPP VITE 

P23368 in FASTA format

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