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    ME3 malic enzyme 3 [ Homo sapiens (human) ]

    Gene ID: 10873, updated on 27-Nov-2024

    Summary

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    Official Symbol
    ME3provided by HGNC
    Official Full Name
    malic enzyme 3provided by HGNC
    Primary source
    HGNC:HGNC:6985
    See related
    Ensembl:ENSG00000151376 MIM:604626; AllianceGenome:HGNC:6985
    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
    NADP-ME
    Summary
    Malic enzyme catalyzes the oxidative decarboxylation of malate to pyruvate using either NAD+ or NADP+ as a cofactor. Mammalian tissues contain 3 distinct isoforms of malic enzyme: a cytosolic NADP(+)-dependent isoform, a mitochondrial NADP(+)-dependent isoform, and a mitochondrial NAD(+)-dependent isoform. This gene encodes a mitochondrial NADP(+)-dependent isoform. Multiple alternatively spliced transcript variants have been found for this gene, but the biological validity of some variants has not been determined. [provided by RefSeq, Jul 2008]
    Expression
    Ubiquitous expression in ovary (RPKM 4.2), fat (RPKM 4.1) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ME3 in Genome Data Viewer
    Location:
    11q14.2
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 11 NC_000011.10 (86434930..86672616, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 11 NC_060935.1 (86377442..86612763, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 11 NC_000011.9 (86145972..86383658, complement)

    Chromosome 11 - NC_000011.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105369421 Neighboring gene Sharpr-MPRA regulatory region 8024 Neighboring gene coiled-coil domain containing 81 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr11:86153050-86154249 Neighboring gene ReSE screen-validated silencer GRCh37_chr11:86158730-86158943 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr11:86171015-86171543 Neighboring gene PTP4A1 pseudogene 6 Neighboring gene Sharpr-MPRA regulatory region 11231 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:86208417-86209018 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr11:86209019-86209620 Neighboring gene MPRA-validated peak1375 silencer Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 3827 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr11:86234525-86235724 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:86270243-86270744 Neighboring gene MPRA-validated peak1376 silencer Neighboring gene Sharpr-MPRA regulatory region 6909 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_21738 Neighboring gene NANOG-H3K27ac hESC enhancer GRCh37_chr11:86451485-86452099 Neighboring gene H3K27ac hESC enhancer GRCh37_chr11:86452100-86452713 Neighboring gene uncharacterized LOC102724775 Neighboring gene Neanderthal introgressed variant-containing enhancer experimental_21766 Neighboring gene NANOG hESC enhancer GRCh37_chr11:86522581-86523167 Neighboring gene Sharpr-MPRA regulatory region 1521 Neighboring gene serine protease 23 Neighboring gene MOB4 pseudogene 2

    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. Influential factor contributing to the isoform-specific inhibition by ATP of human mitochondrial NAD(P)+-dependent malic enzyme: functional roles of the nucleotide binding site Lys346. Hsieh JY, et al. FEBS J, 2008 Nov. PMID 18959763
    2. Dual roles of Lys(57) at the dimer interface of human mitochondrial NAD(P)+-dependent malic enzyme. Hsieh JY, et al. Biochem J, 2009 May 13. PMID 19236308
    3. Effects of ME3 on the proliferation, invasion and metastasis of pancreatic cancer cells through epithelial-mesenchymal transition. Zhang Q, et al. Neoplasma, 2019 Nov. PMID 31607129
    4. State-of-the-art computational methods to predict protein-protein interactions with high accuracy and coverage. Kewalramani N, et al. Proteomics, 2023 Nov. PMID 37401192
    5. Mitochondrial malic enzyme (E.C.1.1.1.40) in human leukocytes: formal genetics and population genetics. Siebert G, et al. Hum Genet, 1979 Oct 2. PMID 511162

    See all (26) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Downregulation of malic enzyme 3 facilitates progression of gastric carcinoma via regulating intracellular oxidative stress and hypoxia-inducible factor-1alpha stabilization.
      Title: Downregulation of malic enzyme 3 facilitates progression of gastric carcinoma via regulating intracellular oxidative stress and hypoxia-inducible factor-1α stabilization.
    2. Adaptive and Constitutive Activations of Malic Enzymes Confer Liver Cancer Multilayered Protection Against Reactive Oxygen Species.
      Title: Adaptive and Constitutive Activations of Malic Enzymes Confer Liver Cancer Multilayered Protection Against Reactive Oxygen Species.
    3. ME3 is extensively involved in carcinogenesis of pancreatic cancer
      Title: Effects of ME3 on the proliferation, invasion and metastasis of pancreatic cancer cells through epithelial-mesenchymal transition.
    4. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    5. This protein has been found differentially expressed in thalami from patients with schizophrenia.
      Title: Proteome analysis of the thalamus and cerebrospinal fluid reveals glycolysis dysfunction and potential biomarkers candidates for schizophrenia.
    6. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
      Title: Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score.
    7. human c-NADP-ME exists mainly as a tetramer, whereas human m-NAD(P)-ME exists as a mixture of dimers and tetramers
      Title: Functional roles of the tetramer organization of malic enzyme.
    8. Studies demonstrate that the Lys57 residue plays dual functional roles in the structural integrity of the allosteric site and in the subunit-subunit interaction at the dimer interface of m-NAD(P)-ME.
      Title: Dual roles of Lys(57) at the dimer interface of human mitochondrial NAD(P)+-dependent malic enzyme.
    9. ATP inhibition is proposed to be determined by the electrostatic potential involving the positive charge on the side chain of Lys346
      Title: Influential factor contributing to the isoform-specific inhibition by ATP of human mitochondrial NAD(P)+-dependent malic enzyme: functional roles of the nucleotide binding site Lys346.
    Submit: New GeneRIF Correction

    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
    A genome-wide association study of chemotherapy-induced alopecia in breast cancer patients.
    EBI GWAS Catalog
    Genome-wide association study of chemotherapeutic agent-induced severe neutropenia/leucopenia for patients in Biobank Japan.
    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

    Clone Names

    • FLJ34862

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NAD binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables NADP+ binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables malate dehydrogenase (decarboxylating) (NADP+) activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables malate dehydrogenase (decarboxylating) (NADP+) activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables malic enzyme activity IDA
    Inferred from Direct Assay
    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 aerobic respiration TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in malate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in malate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in oxygen metabolic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in pyruvate metabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in pyruvate metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    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 TAS
    Traceable Author Statement
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    NADP-dependent malic enzyme, mitochondrial
    Names
    malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))
    malic enzyme 3, NADP(+)-dependent, mitochondrial
    malic enzyme, NADP+-dependent, mitochondrial
    mitochondrial NADP(+)-dependent malic enzyme 3
    pyruvic-malic carboxylase
    NP_001014811.1
    NP_001155058.1
    NP_001338863.1
    NP_001382797.1
    NP_006671.2
    XP_016872626.1
    XP_047282261.1
    XP_047282263.1
    XP_047282264.1
    XP_047282265.1
    XP_054223500.1
    XP_054223501.1
    XP_054223502.1
    XP_054223503.1
    XP_054223504.1
    XP_054223505.1
    XP_054223506.1

    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.

    mRNA and Protein(s)

    1. NM_001014811.2 → NP_001014811.1  NADP-dependent malic enzyme, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_001014811.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) has an alternate 5' UTR and encodes the same protein, as compared to variant 1. Variants 1-4 all encode the same protein.
      Source sequence(s)
      AA403046, AI198184, AI948779, AY424278, BC022472
      Consensus CDS
      CCDS8277.1
      UniProtKB/Swiss-Prot
      B7Z6V0, Q16798, Q8TBJ0
      UniProtKB/TrEMBL
      B2R995
      Related
      ENSP00000376998.2, ENST00000393324.7
      Conserved Domains (1) summary
      PLN03129
      Location:38 → 588
      PLN03129; NADP-dependent malic enzyme; Provisional

    2. NM_001161586.3 → NP_001155058.1  NADP-dependent malic enzyme, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_001155058.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) has an alternate 5' UTR and encodes the same protein, as compared to variant 1. Variants 1-4 all encode the same protein.
      Source sequence(s)
      AP001148, AP001831, AP002492
      Consensus CDS
      CCDS8277.1
      UniProtKB/Swiss-Prot
      B7Z6V0, Q16798, Q8TBJ0
      UniProtKB/TrEMBL
      B2R995
      Related
      ENSP00000440246.1, ENST00000543262.6
      Conserved Domains (1) summary
      PLN03129
      Location:38 → 588
      PLN03129; NADP-dependent malic enzyme; Provisional

    3. NM_001351934.2 → NP_001338863.1  NADP-dependent malic enzyme, mitochondrial isoform 1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) has an alternate 5' UTR and encodes the same protein, as compared to variant 1. Variants 1-4 all encode the same protein.
      Source sequence(s)
      AP001148, AP001831, AP002492
      Consensus CDS
      CCDS8277.1
      UniProtKB/Swiss-Prot
      B7Z6V0, Q16798, Q8TBJ0
      UniProtKB/TrEMBL
      B2R995
      Conserved Domains (1) summary
      PLN03129
      Location:38 → 588
      PLN03129; NADP-dependent malic enzyme; Provisional

    4. NM_001395868.1 → NP_001382797.1  NADP-dependent malic enzyme, mitochondrial isoform 2

      Status: REVIEWED

      Source sequence(s)
      AP001148, AP001831, AP002492
      UniProtKB/TrEMBL
      B2R995
      Conserved Domains (1) summary
      PLN03129
      Location:38 → 551
      PLN03129; NADP-dependent malic enzyme; Provisional

    5. NM_006680.3 → NP_006671.2  NADP-dependent malic enzyme, mitochondrial isoform 1

      See identical proteins and their annotated locations for NP_006671.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) and variants 2-4 all encode the same protein.
      Source sequence(s)
      AA449933, AI198184, AI948779, AP001831, AY424278, BC022472, BM906572, X79440
      Consensus CDS
      CCDS8277.1
      UniProtKB/Swiss-Prot
      B7Z6V0, Q16798, Q8TBJ0
      UniProtKB/TrEMBL
      B2R995
      Conserved Domains (1) summary
      PLN03129
      Location:38 → 588
      PLN03129; NADP-dependent malic enzyme; Provisional

    RNA

    1. NR_147828.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP001148, AP001831, AP002492

    2. NR_147829.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP001148, AP001831, AP002492

    3. NR_147830.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP001148, AP001831, AP002492

    4. NR_147831.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP001148, AP001831, AP002492

    5. NR_172888.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP001148, AP001831, AP002492

    6. NR_172889.1 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AP001148, AP001831, AP002492

    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_000011.10 Reference GRCh38.p14 Primary Assembly

      Range
      86434930..86672616 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047426309.1 → XP_047282265.1  NADP-dependent malic enzyme, mitochondrial isoform X5

    2. XM_017017137.2 → XP_016872626.1  NADP-dependent malic enzyme, mitochondrial isoform X2

    3. XM_047426305.1 → XP_047282261.1  NADP-dependent malic enzyme, mitochondrial isoform X1

    4. XM_047426307.1 → XP_047282263.1  NADP-dependent malic enzyme, mitochondrial isoform X3

      Related
      ENSP00000315255.6, ENST00000323418.10

    5. XM_047426308.1 → XP_047282264.1  NADP-dependent malic enzyme, mitochondrial isoform X4

      Related
      ENSP00000433636.1, ENST00000526504.5

    RNA

    1. XR_007062445.1 RNA Sequence

    2. XR_007062441.1 RNA Sequence

    3. XR_949761.4 RNA Sequence

    4. XR_007062446.1 RNA Sequence

    5. XR_007062443.1 RNA Sequence

    6. XR_007062444.1 RNA Sequence

    7. XR_007062442.1 RNA Sequence

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060935.1 Alternate T2T-CHM13v2.0

      Range
      86377442..86612763 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054367527.1 → XP_054223502.1  NADP-dependent malic enzyme, mitochondrial isoform X5

    2. XM_054367525.1 → XP_054223500.1  NADP-dependent malic enzyme, mitochondrial isoform X2

    3. XM_054367526.1 → XP_054223501.1  NADP-dependent malic enzyme, mitochondrial isoform X1

    4. XM_054367528.1 → XP_054223503.1  NADP-dependent malic enzyme, mitochondrial isoform X3

    5. XM_054367531.1 → XP_054223506.1  NADP-dependent malic enzyme, mitochondrial isoform X4

    6. XM_054367529.1 → XP_054223504.1  NADP-dependent malic enzyme, mitochondrial isoform X6

    7. XM_054367530.1 → XP_054223505.1  NADP-dependent malic enzyme, mitochondrial isoform X4

    RNA

    1. XR_008488332.1 RNA Sequence

    2. XR_008488329.1 RNA Sequence

    3. XR_008488328.1 RNA Sequence

    4. XR_008488330.1 RNA Sequence

    5. XR_008488331.1 RNA Sequence

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16798.2 GenPept UniProtKB/Swiss-Prot:Q16798

    Gene LinkOut

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