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Protein

NAD-dependent malic enzyme, mitochondrial

Gene

ME2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Miscellaneous

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

Catalytic activityi

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

Cofactori

Mg2+, Mn2+Note: Divalent metal cations. Prefers magnesium or manganese.

Enzyme regulationi

Subject to allosteric activation by fumarate.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei67Allosteric activator2 Publications1
Binding sitei91Allosteric activator2 Publications1
Active sitei112Proton donor1
Binding sitei165Substrate1 Publication1
Active sitei183Proton acceptor1
Metal bindingi255Divalent metal cation1
Metal bindingi256Divalent metal cation1
Binding sitei259NAD2 Publications1
Metal bindingi279Divalent metal cation1
Sitei279Important for activityBy similarity1
Binding sitei421Substrate1 Publication1
Binding sitei466Substrate1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi165 – 173NAD2 Publications9
Nucleotide bindingi311 – 328NAD2 PublicationsAdd BLAST18

GO - Molecular functioni

  • electron transfer activity Source: UniProtKB
  • malate dehydrogenase (decarboxylating) (NAD+) activity Source: Reactome
  • malate dehydrogenase (decarboxylating) (NADP+) activity Source: GO_Central
  • malic enzyme activity Source: CACAO
  • metal ion binding Source: UniProtKB-KW
  • NAD binding Source: InterPro
  • oxaloacetate decarboxylase activity Source: UniProtKB-EC

GO - Biological processi

  • malate metabolic process Source: GO_Central
  • pyruvate metabolic process Source: GO_Central
  • regulation of NADP metabolic process Source: CACAO
  • tricarboxylic acid cycle Source: Reactome

Keywordsi

Molecular functionAllosteric enzyme, Oxidoreductase
LigandMetal-binding, NAD

Enzyme and pathway databases

BRENDAi1.1.1.38 2681
ReactomeiR-HSA-71403 Citric acid cycle (TCA cycle)
SABIO-RKiP23368

Names & Taxonomyi

Protein namesi
Recommended name:
NAD-dependent malic enzyme, mitochondrial (EC:1.1.1.38)
Short name:
NAD-ME
Alternative name(s):
Malic enzyme 2
Gene namesi
Name:ME2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 18

Organism-specific databases

EuPathDBiHostDB:ENSG00000082212.11
HGNCiHGNC:6984 ME2
MIMi154270 gene
neXtProtiNX_P23368

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi67R → S: Abolishes activation by fumarate. 1 Publication1
Mutagenesisi91R → T: Abolishes activation by fumarate. 1 Publication1

Organism-specific databases

DisGeNETi4200
OpenTargetsiENSG00000082212
PharmGKBiPA30724

Chemistry databases

DrugBankiDB03589 Alpha-Ketomalonic Acid
DB01677 Fumarate
DB03499 Malate Ion
DB00157 NADH
DB03680 Tartronate

Polymorphism and mutation databases

BioMutaiME2
DMDMi126733

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 18Mitochondrion1 PublicationAdd BLAST18
ChainiPRO_000001853719 – 584NAD-dependent malic enzyme, mitochondrialAdd BLAST566

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei156N6-acetyllysineCombined sources1
Modified residuei224N6-acetyllysineCombined sources1
Modified residuei240N6-acetyllysineCombined sources1
Modified residuei272N6-acetyllysineCombined sources1
Modified residuei346N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP23368
MaxQBiP23368
PaxDbiP23368
PeptideAtlasiP23368
PRIDEiP23368
ProteomicsDBi54082
54083 [P23368-2]

PTM databases

CarbonylDBiP23368
iPTMnetiP23368
PhosphoSitePlusiP23368
SwissPalmiP23368

Expressioni

Gene expression databases

BgeeiENSG00000082212
CleanExiHS_ME2
ExpressionAtlasiP23368 baseline and differential
GenevisibleiP23368 HS

Organism-specific databases

HPAiHPA008247
HPA008880

Interactioni

Subunit structurei

Homotetramer.3 Publications

Protein-protein interaction databases

BioGridi110364, 6 interactors
IntActiP23368, 11 interactors
MINTiP23368
STRINGi9606.ENSP00000321070

Structurei

Secondary structure

1584
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi27 – 30Combined sources4
Turni32 – 34Combined sources3
Helixi37 – 39Combined sources3
Helixi42 – 47Combined sources6
Turni51 – 53Combined sources3
Helixi61 – 74Combined sources14
Helixi78 – 89Combined sources12
Helixi93 – 102Combined sources10
Helixi104 – 111Combined sources8
Helixi115 – 121Combined sources7
Helixi123 – 126Combined sources4
Beta strandi132 – 136Combined sources5
Helixi137 – 139Combined sources3
Turni140 – 142Combined sources3
Helixi143 – 147Combined sources5
Beta strandi157 – 161Combined sources5
Beta strandi163 – 165Combined sources3
Turni167 – 169Combined sources3
Helixi173 – 177Combined sources5
Helixi178 – 191Combined sources14
Helixi195 – 197Combined sources3
Beta strandi198 – 205Combined sources8
Helixi212 – 214Combined sources3
Helixi229 – 246Combined sources18
Beta strandi251 – 254Combined sources4
Helixi259 – 269Combined sources11
Turni270 – 272Combined sources3
Beta strandi273 – 277Combined sources5
Helixi278 – 298Combined sources21
Helixi302 – 304Combined sources3
Beta strandi307 – 310Combined sources4
Helixi314 – 329Combined sources16
Helixi334 – 339Combined sources6
Beta strandi341 – 345Combined sources5
Turni360 – 362Combined sources3
Helixi363 – 365Combined sources3
Helixi377 – 384Combined sources8
Beta strandi387 – 391Combined sources5
Beta strandi394 – 396Combined sources3
Helixi401 – 410Combined sources10
Beta strandi415 – 418Combined sources4
Helixi423 – 425Combined sources3
Beta strandi426 – 428Combined sources3
Helixi430 – 436Combined sources7
Turni437 – 439Combined sources3
Beta strandi442 – 447Combined sources6
Helixi467 – 469Combined sources3
Helixi471 – 480Combined sources10
Helixi488 – 499Combined sources12
Helixi504 – 508Combined sources5
Helixi516 – 518Combined sources3
Helixi519 – 536Combined sources18
Helixi549 – 555Combined sources7

3D structure databases

ProteinModelPortaliP23368
SMRiP23368
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP23368

Family & Domainsi

Sequence similaritiesi

Belongs to the malic enzymes family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG1257 Eukaryota
COG0281 LUCA
GeneTreeiENSGT00390000000754
HOGENOMiHOG000042486
HOVERGENiHBG000746
InParanoidiP23368
KOiK00027
OMAiFRYPEPE
OrthoDBiEOG091G04H9
PhylomeDBiP23368
TreeFamiTF300537

Family and domain databases

Gene3Di3.40.50.10380, 1 hit
InterProiView protein in InterPro
IPR015884 Malic_enzyme_CS
IPR012301 Malic_N_dom
IPR037062 Malic_N_dom_sf
IPR012302 Malic_NAD-bd
IPR001891 Malic_OxRdtase
IPR036291 NAD(P)-bd_dom_sf
PfamiView protein in Pfam
PF00390 malic, 1 hit
PF03949 Malic_M, 1 hit
PIRSFiPIRSF000106 ME, 1 hit
PRINTSiPR00072 MALOXRDTASE
SMARTiView protein in SMART
SM01274 malic, 1 hit
SM00919 Malic_M, 1 hit
SUPFAMiSSF51735 SSF51735, 1 hit
PROSITEiView protein in PROSITE
PS00331 MALIC_ENZYMES, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P23368-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLSRLRVVST TCTLACRHLH IKEKGKPLML NPRTNKGMAF TLQERQMLGL
60 70 80 90 100
QGLLPPKIET QDIQALRFHR NLKKMTSPLE KYIYIMGIQE RNEKLFYRIL
110 120 130 140 150
QDDIESLMPI VYTPTVGLAC SQYGHIFRRP KGLFISISDR GHVRSIVDNW
160 170 180 190 200
PENHVKAVVV TDGERILGLG DLGVYGMGIP VGKLCLYTAC AGIRPDRCLP
210 220 230 240 250
VCIDVGTDNI ALLKDPFYMG LYQKRDRTQQ YDDLIDEFMK AITDRYGRNT
260 270 280 290 300
LIQFEDFGNH NAFRFLRKYR EKYCTFNDDI QGTAAVALAG LLAAQKVISK
310 320 330 340 350
PISEHKILFL GAGEAALGIA NLIVMSMVEN GLSEQEAQKK IWMFDKYGLL
360 370 380 390 400
VKGRKAKIDS YQEPFTHSAP ESIPDTFEDA VNILKPSTII GVAGAGRLFT
410 420 430 440 450
PDVIRAMASI NERPVIFALS NPTAQAECTA EEAYTLTEGR CLFASGSPFG
460 470 480 490 500
PVKLTDGRVF TPGQGNNVYI FPGVALAVIL CNTRHISDSV FLEAAKALTS
510 520 530 540 550
QLTDEELAQG RLYPPLANIQ EVSINIAIKV TEYLYANKMA FRYPEPEDKA
560 570 580
KYVKERTWRS EYDSLLPDVY EWPESASSPP VITE
Length:584
Mass (Da):65,444
Last modified:November 1, 1991 - v1
Checksum:i4CEF9AF89B07D93D
GO
Isoform 2 (identifier: P23368-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     474-584: VALAVILCNT...SASSPPVITE → YRIPIC

Note: No experimental confirmation available.
Show »
Length:479
Mass (Da):53,586
Checksum:i8F4D1C728EDD83E5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti263F → Y in BAG36189 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_034104114P → L. Corresponds to variant dbSNP:rs16952692Ensembl.1
Natural variantiVAR_050017450G → E. Corresponds to variant dbSNP:rs649224Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_042717474 – 584VALAV…PVITE → YRIPIC in isoform 2. 1 PublicationAdd BLAST111

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS11948.1 [P23368-1]
CCDS54187.1 [P23368-2]
PIRiA39503
RefSeqiNP_001161807.1, NM_001168335.1 [P23368-2]
NP_002387.1, NM_002396.4 [P23368-1]
UniGeneiHs.233119

Genome annotation databases

EnsembliENST00000321341; ENSP00000321070; ENSG00000082212 [P23368-1]
ENST00000382927; ENSP00000372384; ENSG00000082212 [P23368-2]
GeneIDi4200
KEGGihsa:4200
UCSCiuc002ley.4 human [P23368-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiMAOM_HUMAN
AccessioniPrimary (citable) accession number: P23368
Secondary accession number(s): B2R8J2
, Q9BWL6, Q9BYG1, Q9H4B2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1991
Last sequence update: November 1, 1991
Last modified: July 18, 2018
This is version 193 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 18
    Human chromosome 18: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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