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ME2 malic enzyme 2 [ Homo sapiens (human) ]

Gene ID: 4200, updated on 3-Nov-2024

Summary

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Official Symbol
ME2provided by HGNC
Official Full Name
malic enzyme 2provided by HGNC
Primary source
HGNC:HGNC:6984
See related
Ensembl:ENSG00000082212 MIM:154270; AllianceGenome:HGNC:6984
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
ODS1
Summary
This gene encodes a mitochondrial NAD-dependent malic enzyme, a homotetrameric protein, that catalyzes the oxidative decarboxylation of malate to pyruvate. It had previously been weakly linked to a syndrome known as Friedreich ataxia that has since been shown to be the result of mutation in a completely different gene. Certain single-nucleotide polymorphism haplotypes of this gene have been shown to increase the risk for idiopathic generalized epilepsy. Alternatively spliced transcript variants encoding different isoforms found for this gene. [provided by RefSeq, Dec 2009]
Expression
Ubiquitous expression in duodenum (RPKM 15.0), colon (RPKM 14.1) and 25 other tissues See more
Orthologs
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Genomic context

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See ME2 in Genome Data Viewer
Location:
18q21.2
Exon count:
16
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 18 NC_000018.10 (50879118..50954257)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 18 NC_060942.1 (51080843..51155984)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 18 NC_000018.9 (48405488..48480627)

Chromosome 18 - NC_000018.10Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr18:48346071-48346704 Neighboring gene heterogeneous nuclear ribonucleoprotein A3 pseudogene 16 Neighboring gene maestro Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13322 Neighboring gene ribosomal protein L17 pseudogene 46 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:48405277-48405778 Neighboring gene MPRA-validated peak3150 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9459 Neighboring gene MPRA-validated peak3151 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid active region 13323 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 9460 Neighboring gene uncharacterized LOC107985152 Neighboring gene elaC ribonuclease Z 1 Neighboring gene H3K27ac hESC enhancer GRCh37_chr18:48518398-48518898 Neighboring gene Sharpr-MPRA regulatory region 8611 Neighboring gene Sharpr-MPRA regulatory region 5267 Neighboring gene uncharacterized LOC124904303

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Structure of a closed form of human malic enzyme and implications for catalytic mechanism. Yang Z, et al. Nat Struct Biol, 2000 Mar. PMID 10700286
  2. Induction of erythroid differentiation in human erythroleukemia cells by depletion of malic enzyme 2. Ren JG, et al. PLoS One, 2010 Sep 2. PMID 20824065, Free PMC Article
  3. Variation in the malic enzyme 2 gene: implications for the pharmacogenomics of psychotic disorders. Escamilla M. Pharmacogenomics, 2007 Jul. PMID 17638511
  4. Association analysis of malic enzyme 2 gene polymorphisms with idiopathic generalized epilepsy. Lenzen KP, et al. Epilepsia, 2005 Oct. PMID 16190936
  5. Functional roles of ATP-binding residues in the catalytic site of human mitochondrial NAD(P)+-dependent malic enzyme. Hung HC, et al. Biochemistry, 2005 Sep 27. PMID 16171388

See all (80) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration.
    Title: SIRT5-mediated ME2 desuccinylation promotes cancer growth by enhancing mitochondrial respiration.
  2. Malic enzyme 2 maintains protein stability of mutant p53 through 2-hydroxyglutarate.
    Title: Malic enzyme 2 maintains protein stability of mutant p53 through 2-hydroxyglutarate.
  3. Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma.
    Title: Expression levels of SIX1, ME2, and AP2M1 in adenoid cystic carcinoma and mucoepidermoid carcinoma.
  4. influences susceptibility to adolescent-onset genetic generalized epilepsy
    Title: Replication, reanalysis, and gene expression: ME2 and genetic generalized epilepsy.
  5. ME2 was involved in glioblastoma multiforme growth, invasion, migration, Reactive oxygen species and ATP production.
    Title: The mechanisms of malic enzyme 2 in the tumorigenesis of human gliomas.
  6. The chromosome 18q21 deletion in nearly one third of pancreatic adenocarcinomas eliminates not only the tumor suppressor SMAD4, but also neighboring genes with important cellular roles, such as ME2
    Title: Collateral Lethality in Pancreatic Cancer.
  7. deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer
    Title: Genomic deletion of malic enzyme 2 confers collateral lethality in pancreatic cancer.
  8. ME1/ME2 expression phenotype may have a potential to be a valuable marker for sebaceous differentiation in sebaceous lesions.
    Title: Expression of Malic Enzymes in Sebaceous Lesions.
  9. Data indicate that malic enzyme 2 knockdown impacts phosphatidylinositol 3-kinases/proto-oncogene protein akt (PI3K/AKT) signaling.
    Title: Knockdown of malic enzyme 2 suppresses lung tumor growth, induces differentiation and impacts PI3K/AKT signaling.
  10. ME2 might be an important factor in melanoma progression and a novel biomarker of invasion.
    Title: Human mitochondrial NAD(P)(+)-dependent malic enzyme participates in cutaneous melanoma progression and invasion.
Submit: New GeneRIF Correction See all GeneRIFs (20)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association with MRI atrophy measures as a quantitative trait locus for Alzheimer's disease.
EBI GWAS Catalog

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables NAD binding IEA
Inferred from Electronic Annotation
more info
  
enables electron transfer activity TAS
Traceable Author Statement
more info
 PubMed 
enables malate dehydrogenase (decarboxylating) (NAD+) activity IEA
Inferred from Electronic Annotation
more info
  
enables malate dehydrogenase (decarboxylating) (NADP+) activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables malic enzyme activity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
enables metal ion binding IEA
Inferred from Electronic Annotation
more info
  
enables oxaloacetate decarboxylase activity IEA
Inferred from Electronic Annotation
more info
  
Process Evidence Code Pubs
involved_in malate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in pyruvate metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of NADP metabolic process IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in mitochondrial matrix TAS
Traceable Author Statement
more info
  
located_in mitochondrion HTP PubMed 
is_active_in mitochondrion IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in mitochondrion IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
NAD-dependent malic enzyme, mitochondrial
Names
NAD-ME
malate dehydrogenase (oxaloacetate-decarboxylating)
malic enzyme 2, NAD(+)-dependent, mitochondrial
pyruvic-malic carboxylase
NP_001161807.1
NP_002387.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_016198.2 RefSeqGene

    Range
    5002..80141
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001168335.2 → NP_001161807.1  NAD-dependent malic enzyme, mitochondrial isoform 2 precursor

    See identical proteins and their annotated locations for NP_001161807.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks two alternate in-frame exons in the 3' coding region, compared to variant 1. The resulting protein (isoform 2) is shorter, compared to isoform 1.
    Source sequence(s)
    AC087687, BC000147, BI465083, CD370709
    Consensus CDS
    CCDS54187.1
    UniProtKB/TrEMBL
    A0A1W2PQF8
    Related
    ENSP00000372384.2, ENST00000382927.3
    Conserved Domains (1) summary
    PLN03129
    Location:28 → 473
    PLN03129; NADP-dependent malic enzyme; Provisional

  2. NM_002396.5 → NP_002387.1  NAD-dependent malic enzyme, mitochondrial isoform 1 precursor

    See identical proteins and their annotated locations for NP_002387.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).
    Source sequence(s)
    AC087687, AK313391, BI559761, CD370709, M55905
    Consensus CDS
    CCDS11948.1
    UniProtKB/Swiss-Prot
    B2R8J2, P23368, Q9BWL6, Q9BYG1, Q9H4B2
    UniProtKB/TrEMBL
    A0A1W2PQH3
    Related
    ENSP00000321070.5, ENST00000321341.11
    Conserved Domains (3) summary
    cd05312
    Location:280 → 558
    NAD_bind_1_malic_enz; NAD(P) binding domain of malic enzyme (ME), subgroup 1
    PLN03129
    Location:28 → 566
    PLN03129; NADP-dependent malic enzyme; Provisional
    pfam00390
    Location:89 → 270
    malic; Malic enzyme, N-terminal domain

RNA

  1. NR_174094.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC015864, AC087687

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000018.10 Reference GRCh38.p14 Primary Assembly

    Range
    50879118..50954257
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060942.1 Alternate T2T-CHM13v2.0

    Range
    51080843..51155984
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P23368.1 GenPept UniProtKB/Swiss-Prot:P23368

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