UniProtKB - P23368 (MAOM_HUMAN)
Protein
NAD-dependent malic enzyme, mitochondrial
Gene
ME2
Organism
Homo sapiens (Human)
Status
Functioni
Miscellaneous
This isoenzyme can also use NADP+ but is more effective with NAD+.
Catalytic activityi
Cofactori
Activity regulationi
Subject to allosteric activation by fumarate.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 67 | Allosteric activator2 Publications | 1 | |
Binding sitei | 91 | Allosteric activator2 Publications | 1 | |
Active sitei | 112 | Proton donor | 1 | |
Binding sitei | 165 | Substrate1 Publication | 1 | |
Active sitei | 183 | Proton acceptor | 1 | |
Metal bindingi | 255 | Divalent metal cation | 1 | |
Metal bindingi | 256 | Divalent metal cation | 1 | |
Binding sitei | 259 | NAD2 Publications | 1 | |
Metal bindingi | 279 | Divalent metal cation | 1 | |
Sitei | 279 | Important for activityBy similarity | 1 | |
Binding sitei | 421 | Substrate1 Publication | 1 | |
Binding sitei | 466 | Substrate1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 165 – 173 | NAD2 Publications | 9 | |
Nucleotide bindingi | 311 – 328 | NAD2 PublicationsAdd BLAST | 18 |
GO - Molecular functioni
- electron transfer activity Source: UniProtKB
- malate dehydrogenase (decarboxylating) (NAD+) activity Source: ProtInc
- 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 function | Allosteric enzyme, Oxidoreductase |
Ligand | Metal-binding, NAD |
Enzyme and pathway databases
BRENDAi | 1.1.1.38, 2681 |
PathwayCommonsi | P23368 |
Reactomei | R-HSA-71403, Citric acid cycle (TCA cycle) |
SABIO-RKi | P23368 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000082212.11 |
HGNCi | HGNC:6984, ME2 |
MIMi | 154270, gene |
neXtProti | NX_P23368 |
Subcellular locationi
Mitochondrion
Mitochondrion
- mitochondrial matrix Source: Reactome
- mitochondrion Source: HPA
Other locations
- intracellular membrane-bounded organelle Source: HPA
Keywords - Cellular componenti
MitochondrionPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 67 | R → S: Abolishes activation by fumarate. 1 Publication | 1 | |
Mutagenesisi | 91 | R → T: Abolishes activation by fumarate. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 4200 |
OpenTargetsi | ENSG00000082212 |
PharmGKBi | PA30724 |
Miscellaneous databases
Pharosi | P23368, Tbio |
Chemistry databases
DrugBanki | DB03499, D-Malic acid DB01677, Fumaric Acid DB03589, Mesoxalic acid DB00157, NADH DB03680, Tartronate |
Polymorphism and mutation databases
BioMutai | ME2 |
DMDMi | 126733 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transit peptidei | 1 – 18 | Mitochondrion1 PublicationAdd BLAST | 18 | |
ChainiPRO_0000018537 | 19 – 584 | NAD-dependent malic enzyme, mitochondrialAdd BLAST | 566 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 156 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 224 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 240 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 272 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 346 | N6-acetyllysineCombined sources | 1 |
Keywords - PTMi
AcetylationProteomic databases
EPDi | P23368 |
jPOSTi | P23368 |
MassIVEi | P23368 |
MaxQBi | P23368 |
PaxDbi | P23368 |
PeptideAtlasi | P23368 |
PRIDEi | P23368 |
ProteomicsDBi | 54082 [P23368-1] 54083 [P23368-2] |
PTM databases
CarbonylDBi | P23368 |
iPTMneti | P23368 |
MetOSitei | P23368 |
PhosphoSitePlusi | P23368 |
SwissPalmi | P23368 |
Expressioni
Gene expression databases
Bgeei | ENSG00000082212, Expressed in colon and 241 other tissues |
ExpressionAtlasi | P23368, baseline and differential |
Genevisiblei | P23368, HS |
Organism-specific databases
HPAi | ENSG00000082212, Low tissue specificity |
Interactioni
Subunit structurei
Homotetramer.
3 PublicationsProtein-protein interaction databases
BioGRIDi | 110364, 28 interactors |
IntActi | P23368, 9 interactors |
MINTi | P23368 |
STRINGi | 9606.ENSP00000321070 |
Miscellaneous databases
RNActi | P23368, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | P23368 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | P23368 |
Family & Domainsi
Sequence similaritiesi
Belongs to the malic enzymes family.Curated
Keywords - Domaini
Transit peptidePhylogenomic databases
eggNOGi | KOG1257, Eukaryota |
GeneTreei | ENSGT00950000183134 |
HOGENOMi | CLU_011405_5_0_1 |
InParanoidi | P23368 |
OMAi | GVNGMPI |
OrthoDBi | 435571at2759 |
PhylomeDBi | P23368 |
TreeFami | TF300537 |
Family and domain databases
Gene3Di | 3.40.50.10380, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00390, malic, 1 hit PF03949, Malic_M, 1 hit |
PIRSFi | PIRSF000106, ME, 1 hit |
PRINTSi | PR00072, MALOXRDTASE |
SMARTi | View protein in SMART SM01274, malic, 1 hit SM00919, Malic_M, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00331, MALIC_ENZYMES, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 12 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: P23368-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There are 12 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A1W2PQH3 | A0A1W2PQH3_HUMAN | Malic enzyme | ME2 | 547 | Annotation score: | ||
A0A1W2PQT3 | A0A1W2PQT3_HUMAN | Malic enzyme | ME2 | 536 | Annotation score: | ||
A0A1W2PQY8 | A0A1W2PQY8_HUMAN | Malic enzyme | ME2 | 565 | Annotation score: | ||
A0A1W2PR68 | A0A1W2PR68_HUMAN | Malic enzyme | ME2 | 530 | Annotation score: | ||
A0A1W2PPH1 | A0A1W2PPH1_HUMAN | Malic enzyme | ME2 | 546 | Annotation score: | ||
A0A1W2PQ37 | A0A1W2PQ37_HUMAN | Malic enzyme | ME2 | 443 | Annotation score: | ||
A0A1W2PQF8 | A0A1W2PQF8_HUMAN | Malic enzyme | ME2 | 480 | Annotation score: | ||
A0A1W2PPY2 | A0A1W2PPY2_HUMAN | NAD-dependent malic enzyme, mitocho... | ME2 | 55 | Annotation score: | ||
A0A1W2PQH4 | A0A1W2PQH4_HUMAN | NAD-dependent malic enzyme, mitocho... | ME2 | 133 | Annotation score: | ||
A0A1W2PRS2 | A0A1W2PRS2_HUMAN | NAD-dependent malic enzyme, mitocho... | ME2 | 132 | Annotation score: | ||
There are more potential isoformsShow all |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 263 | F → Y in BAG36189 (PubMed:14702039).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_034104 | 114 | P → L. Corresponds to variant dbSNP:rs16952692Ensembl. | 1 | |
Natural variantiVAR_050017 | 450 | G → E. Corresponds to variant dbSNP:rs649224Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_042717 | 474 – 584 | VALAV…PVITE → YRIPIC in isoform 2. 1 PublicationAdd BLAST | 111 |
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 |
CCDSi | CCDS11948.1 [P23368-1] CCDS54187.1 [P23368-2] |
PIRi | A39503 |
RefSeqi | NP_001161807.1, NM_001168335.1 [P23368-2] NP_002387.1, NM_002396.4 [P23368-1] |
Genome annotation databases
Ensembli | ENST00000321341; ENSP00000321070; ENSG00000082212 [P23368-1] ENST00000382927; ENSP00000372384; ENSG00000082212 [P23368-2] |
GeneIDi | 4200 |
KEGGi | hsa:4200 |
UCSCi | uc002ley.4, human [P23368-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
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 |
CCDSi | CCDS11948.1 [P23368-1] CCDS54187.1 [P23368-2] |
PIRi | A39503 |
RefSeqi | NP_001161807.1, NM_001168335.1 [P23368-2] NP_002387.1, NM_002396.4 [P23368-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
1DO8 | X-ray | 2.20 | A/B/C/D | 21-584 | [»] | |
1EFK | X-ray | 2.60 | A/B/C/D | 1-584 | [»] | |
1EFL | X-ray | 2.60 | A/B/C/D | 1-584 | [»] | |
1GZ3 | X-ray | 2.30 | A/B/C/D | 20-573 | [»] | |
1GZ4 | X-ray | 2.20 | A/B/C/D | 23-573 | [»] | |
1PJ2 | X-ray | 2.30 | A/B/C/D | 21-584 | [»] | |
1PJ3 | X-ray | 2.10 | A/B/C/D | 21-584 | [»] | |
1PJ4 | X-ray | 2.30 | A/B/C/D | 21-584 | [»] | |
1PJL | X-ray | 2.90 | A/B/C/D/E/F/G/H | 1-584 | [»] | |
1QR6 | X-ray | 2.10 | A/B | 1-584 | [»] | |
SMRi | P23368 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110364, 28 interactors |
IntActi | P23368, 9 interactors |
MINTi | P23368 |
STRINGi | 9606.ENSP00000321070 |
Chemistry databases
DrugBanki | DB03499, D-Malic acid DB01677, Fumaric Acid DB03589, Mesoxalic acid DB00157, NADH DB03680, Tartronate |
PTM databases
CarbonylDBi | P23368 |
iPTMneti | P23368 |
MetOSitei | P23368 |
PhosphoSitePlusi | P23368 |
SwissPalmi | P23368 |
Polymorphism and mutation databases
BioMutai | ME2 |
DMDMi | 126733 |
Proteomic databases
EPDi | P23368 |
jPOSTi | P23368 |
MassIVEi | P23368 |
MaxQBi | P23368 |
PaxDbi | P23368 |
PeptideAtlasi | P23368 |
PRIDEi | P23368 |
ProteomicsDBi | 54082 [P23368-1] 54083 [P23368-2] |
Protocols and materials databases
Antibodypediai | 1636, 200 antibodies |
DNASUi | 4200 |
Genome annotation databases
Ensembli | ENST00000321341; ENSP00000321070; ENSG00000082212 [P23368-1] ENST00000382927; ENSP00000372384; ENSG00000082212 [P23368-2] |
GeneIDi | 4200 |
KEGGi | hsa:4200 |
UCSCi | uc002ley.4, human [P23368-1] |
Organism-specific databases
CTDi | 4200 |
DisGeNETi | 4200 |
EuPathDBi | HostDB:ENSG00000082212.11 |
GeneCardsi | ME2 |
HGNCi | HGNC:6984, ME2 |
HPAi | ENSG00000082212, Low tissue specificity |
MIMi | 154270, gene |
neXtProti | NX_P23368 |
OpenTargetsi | ENSG00000082212 |
PharmGKBi | PA30724 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1257, Eukaryota |
GeneTreei | ENSGT00950000183134 |
HOGENOMi | CLU_011405_5_0_1 |
InParanoidi | P23368 |
OMAi | GVNGMPI |
OrthoDBi | 435571at2759 |
PhylomeDBi | P23368 |
TreeFami | TF300537 |
Enzyme and pathway databases
BRENDAi | 1.1.1.38, 2681 |
PathwayCommonsi | P23368 |
Reactomei | R-HSA-71403, Citric acid cycle (TCA cycle) |
SABIO-RKi | P23368 |
Miscellaneous databases
BioGRID-ORCSi | 4200, 15 hits in 843 CRISPR screens |
ChiTaRSi | ME2, human |
EvolutionaryTracei | P23368 |
GeneWikii | ME2 ME2_(gene) |
GenomeRNAii | 4200 |
Pharosi | P23368, Tbio |
PROi | PR:P23368 |
RNActi | P23368, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000082212, Expressed in colon and 241 other tissues |
ExpressionAtlasi | P23368, baseline and differential |
Genevisiblei | P23368, HS |
Family and domain databases
Gene3Di | 3.40.50.10380, 1 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00390, malic, 1 hit PF03949, Malic_M, 1 hit |
PIRSFi | PIRSF000106, ME, 1 hit |
PRINTSi | PR00072, MALOXRDTASE |
SMARTi | View protein in SMART SM01274, malic, 1 hit SM00919, Malic_M, 1 hit |
SUPFAMi | SSF51735, SSF51735, 1 hit |
PROSITEi | View protein in PROSITE PS00331, MALIC_ENZYMES, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | MAOM_HUMAN | |
Accessioni | P23368Primary (citable) accession number: P23368 Secondary accession number(s): B2R8J2 Q9H4B2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1991 |
Last sequence update: | November 1, 1991 | |
Last modified: | December 2, 2020 | |
This is version 211 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Direct protein sequencing, Reference proteomeDocuments
- 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 - 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