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P23368 (MAOM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 159. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

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) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

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

General annotation (Comments)

Catalytic activity

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

Oxaloacetate = pyruvate + CO2.

Cofactor

Divalent metal cations. Prefers magnesium or manganese.

Enzyme regulation

Subject to allosteric activation by fumarate.

Subunit structure

Homotetramer. Ref.12 Ref.13

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.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P23368-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P23368-2)

The sequence of this isoform differs from the canonical sequence as follows:
     474-584: VALAVILCNT...SASSPPVITE → YRIPIC
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 1818Mitochondrion Ref.8
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

Amino acid modifications

Modified residue1561N6-acetyllysine Ref.9
Modified residue2241N6-acetyllysine Ref.9
Modified residue2401N6-acetyllysine Ref.9
Modified residue2721N6-acetyllysine Ref.9
Modified residue3461N6-acetyllysine Ref.9

Natural variations

Alternative sequence474 – 584111VALAV…PVITE → YRIPIC in isoform 2.
VSP_042717
Natural variant1141P → L.
Corresponds to variant rs16952692 [ dbSNP | Ensembl ].
VAR_034104
Natural variant4501G → E.
Corresponds to variant rs649224 [ dbSNP | Ensembl ].
VAR_050017

Experimental info

Mutagenesis671R → S: Abolishes activation by fumarate. Ref.13
Mutagenesis911R → T: Abolishes activation by fumarate. Ref.13
Sequence conflict2631F → Y in BAG36189. Ref.3

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 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

Isoform 2 [UniParc].

Checksum: 8F4D1C728EDD83E5
Show »

FASTA47953,586

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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 37-80.
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Trachea.
[4]"DNA sequence and analysis of human chromosome 18."
Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. expand/collapse author list , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.
Nature 437:551-555(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Placenta.
[7]Abts H.
Thesis (1995), University of Cologne, Germany
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 421-584 (ISOFORM 1).
Tissue: B-cell.
[8]"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] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 19-33.
Tissue: Platelet.
[9]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-156; LYS-224; LYS-240; LYS-272 AND LYS-346, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS).
[12]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 21-584 IN COMPLEX WITH NAD; DIVALENT METAL ION AND SUBSTRATE ANALOG, HOMOTETRAMERIZATION.
[13]"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] [Europe PMC] [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.
[14]"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] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 21-584 IN COMPLEX WITH SUBSTRATE; NAD; MANGANESE AND ALLOSTERIC ACTIVATOR, ENZYME MECHANISM.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M55905 mRNA. Translation: AAA36197.1.
AB045122 Genomic DNA. Translation: BAB40980.1.
AK313391 mRNA. Translation: BAG36189.1.
AC015864 Genomic DNA. No translation available.
AC087687 Genomic DNA. No translation available.
CH471096 Genomic DNA. Translation: EAW62980.1.
BC000147 mRNA. Translation: AAH00147.1.
AJ294818 mRNA. Translation: CAC14574.1.
CCDSCCDS11948.1. [P23368-1]
CCDS54187.1. [P23368-2]
PIRA39503.
RefSeqNP_001161807.1. NM_001168335.1. [P23368-2]
NP_002387.1. NM_002396.4. [P23368-1]
UniGeneHs.233119.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalP23368.
SMRP23368. Positions 21-573.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110364. 2 interactions.
IntActP23368. 1 interaction.
MINTMINT-4530114.
STRING9606.ENSP00000321070.

Chemistry

DrugBankDB00157. NADH.

PTM databases

PhosphoSiteP23368.

Polymorphism databases

DMDM126733.

Proteomic databases

MaxQBP23368.
PaxDbP23368.
PeptideAtlasP23368.
PRIDEP23368.

Protocols and materials databases

DNASU4200.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000321341; ENSP00000321070; ENSG00000082212. [P23368-1]
ENST00000382927; ENSP00000372384; ENSG00000082212. [P23368-2]
GeneID4200.
KEGGhsa:4200.
UCSCuc002ley.3. human. [P23368-1]
uc010dpd.3. human. [P23368-2]

Organism-specific databases

CTD4200.
GeneCardsGC18P048405.
HGNCHGNC:6984. ME2.
HPAHPA008247.
HPA008880.
MIM154270. gene.
neXtProtNX_P23368.
PharmGKBPA30724.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0281.
HOGENOMHOG000042486.
HOVERGENHBG000746.
InParanoidP23368.
KOK00027.
OMALPDMYEW.
OrthoDBEOG7G4QF0.
PhylomeDBP23368.
TreeFamTF300537.

Enzyme and pathway databases

SABIO-RKP23368.

Gene expression databases

BgeeP23368.
CleanExHS_ME2.
GenevestigatorP23368.

Family and domain databases

Gene3D3.40.50.10380. 1 hit.
3.40.50.720. 1 hit.
InterProIPR015884. Malic_enzyme_CS.
IPR012301. Malic_N_dom.
IPR012302. Malic_NAD-bd.
IPR001891. Malic_OxRdtase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PfamPF00390. malic. 1 hit.
PF03949. Malic_M. 1 hit.
[Graphical view]
PIRSFPIRSF000106. ME. 1 hit.
PRINTSPR00072. MALOXRDTASE.
SMARTSM00919. Malic_M. 1 hit.
[Graphical view]
PROSITEPS00331. MALIC_ENZYMES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP23368.
GeneWikiME2.
ME2_(gene).
GenomeRNAi4200.
NextBio16554.
PROP23368.
SOURCESearch...

Entry information

Entry nameMAOM_HUMAN
AccessionPrimary (citable) accession number: P23368
Secondary accession number(s): B2R8J2 expand/collapse secondary AC list , Q9BWL6, Q9BYG1, Q9H4B2
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: July 9, 2014
This is version 159 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 18

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