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    ME2 malic enzyme 2 [ Homo sapiens (human) ]

    Gene ID: 4200, updated on 27-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
    mouse all
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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
    • 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)

    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

    Gene LinkOut

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