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Reviewed, UniProtKB/Swiss-Prot P23368 (MAOM_HUMAN)

Last modified June 16, 2009. Version 107. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    NAD-dependent malic enzyme, mitochondrial
      Short name=NAD-ME
    EC=1.1.1.38
Alternative name(s):
    Malic enzyme 2
Gene names
Name: ME2
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length584 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Catalytic activity

(S)-malate + NAD+ = pyruvate + CO2 + NADH.

Cofactor

Divalent metal cations. Prefers magnesium or manganese.

Enzyme regulation

Subject to allosteric activation by fumarate.

Subunit structure

Homotetramer. Ref.7 Ref.8

Subcellular location

Mitochondrion matrix.

Miscellaneous

This isoenzyme can also use NADP+ but is more effective with NAD+.

Sequence similarities

Belongs to the malic enzymes family.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 1818Mitochondrion Ref.4
Chain19 – 584566NAD-dependent malic enzyme, mitochondrial
PRO_0000018537

Regions

Nucleotide binding165 – 1739NAD
Nucleotide binding311 – 32818NAD

Sites

Active site1121Proton donor
Active site1831Proton acceptor
Metal binding2551Divalent metal cation
Metal binding2561Divalent metal cation
Metal binding2791Divalent metal cation
Binding site671Allosteric activator
Binding site911Allosteric activator
Binding site1651Substrate
Binding site2591NAD
Binding site4211Substrate
Binding site4661Substrate
Site2791Important for activity By similarity

Natural variations

Natural variant1141P → L: dbSNP rs16952692.
VAR_034104
Natural variant4501G → E: dbSNP rs649224.
VAR_050017

Experimental info

Mutagenesis671R → S: Abolishes activation by fumarate. Ref.8
Mutagenesis911R → T: Abolishes activation by fumarate. Ref.8

Secondary structure

1 ........................................................................................... 584
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P23368-1 [UniParc].

Last modified November 1, 1991. Version 1.
Checksum: 4CEF9AF89B07D93D

FASTA58465,444
        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

« Hide

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References

« Hide 'large scale' references
[1]"Human NAD(+)-dependent mitochondrial malic enzyme. cDNA cloning, primary structure, and expression in Escherichia coli."
Loeber G., Infante A.A., Maurer-Fogy I., Krystek E., Dworkin M.B.
J. Biol. Chem. 266:3016-3021(1991) [PubMed: 1993674] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]"Physical and transcriptional map of a 311-kb segment of chromosome 18q21, a candidate lung tumor suppressor locus."
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.
Genomics 72:169-179(2001) [PubMed: 11401430] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 37-80.
[3]Abts H.
Thesis (1995), University of Cologne, Germany
Cited for: NUCLEOTIDE SEQUENCE OF 421-584.
Tissue: B-cell.
[4]"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides."
Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J.
Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-33.
Tissue: Platelet.
[5]Colinge J., Superti-Furga G., Bennett K.L.
Submitted (OCT-2008) to UniProtKB
Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[6]"Crystal structure of human mitochondrial NAD(P)(+)-dependent malic enzyme: a new class of oxidative decarboxylases."
Xu Y., Bhargava G., Wu H., Loeber G., Tong L.
Structure 7:877-889(1999) [PubMed: 10467136] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[7]"Structure of a closed form of human malic enzyme and implications for catalytic mechanism."
Yang Z., Floyd D.L., Loeber G., Tong L.
Nat. Struct. Biol. 7:251-257(2000) [PubMed: 10700286] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-584 IN COMPLEX WITH NAD; DIVALENT METAL ION AND SUBSTRATE ANALOG, HOMOTETRAMERIZATION.
[8]"Molecular mechanism for the regulation of human mitochondrial NAD(P)+-dependent malic enzyme by ATP and fumarate."
Yang Z., Lanks C.W., Tong L.
Structure 10:951-960(2002) [PubMed: 12121650] [Abstract]
Cited for: 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, HOMOTETRAMERIZATION.
[9]"Crystal structures of substrate complexes of malic enzyme and insights into the catalytic mechanism."
Tao X., Yang Z., Tong L.
Structure 11:1141-1150(2003) [PubMed: 12962632] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 21-584 IN COMPLEX WITH SUBSTRATE; NAD; MANGANESE AND ALLOSTERIC ACTIVATOR, MECHANISM.
+Additional computationally mapped references.

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Cross-references

Sequence databases

M55905 mRNA. Translation: AAA36197.1.
AB045122 Genomic DNA. Translation: BAB40980.1.
AJ294818 mRNA. Translation: CAC14574.1.
IPIIPI00011201.
PIRA39503.
RefSeqNP_002387.1.
UniGeneHs.233119

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1DO8X-ray2.20A/B/C/D21-584[»]
1EFKX-ray2.60A/B/C/D1-584[»]
1EFLX-ray2.60A/B/C/D1-584[»]
1GZ3X-ray2.30A/B/C/D20-573[»]
1GZ4X-ray2.20A/B/C/D23-573[»]
1PJ2X-ray2.30A/B/C/D21-584[»]
1PJ3X-ray2.10A/B/C/D21-584[»]
1PJ4X-ray2.30A/B/C/D21-584[»]
1PJLX-ray2.90A/B/C/D/E/F/G/H1-584[»]
1QR6X-ray2.10A/B1-584[»]
ModBaseSearch...

Protein-protein interaction databases

IntActP23368. 4 interactions.

PTM databases

PhosphoSiteP23368.

Proteomic databases

PeptideAtlasP23368.
PRIDEP23368.

Genome annotation databases

EnsemblENSG00000082212. Homo sapiens. [Contig view]
GeneID4200.
KEGGhsa:4200.

Organism-specific databases

GeneCardsGC18P046659.
H-InvDBHIX0014451.
HGNCHGNC:6984. ME2.
HPAHPA008247.
HPA008880.
MIM154270. gene.
PharmGKBPA134863517.
GenAtlasSearch...

Phylogenomic databases

HOGENOMP23368.
HOVERGENP23368.
OMAP23368. QALRFHR.

Enzyme and pathway databases

BRENDA1.1.1.38. 247.

Gene expression databases

ArrayExpressP23368.
BgeeP23368.
CleanExHS_ME2.
GermOnlineENSG00000082212. Homo sapiens.

Family and domain databases

InterProIPR015884. Malic_enzyme_CS.
IPR012301. Malic_N.
IPR012302. Malic_NAD_bd.
IPR001891. Malic_OxRdtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
Gene3DG3DSA:3.40.50.720. NAD(P)-bd. 1 hit.
PfamPF00390. malic. 1 hit.
PF03949. Malic_M. 1 hit.
[Graphical view]
PRINTSPR00072. MALOXRDTASE.
PROSITEPS00331. MALIC_ENZYMES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00157. NADH.
NextBio16554.
SOURCESearch...

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Entry information

Entry nameMAOM_HUMAN
AccessionPrimary (citable) accession number: P23368
Secondary accession number(s): Q9BYG1, Q9H4B2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: June 16, 2009
This is version 107 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 18

Human chromosome 18: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents