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    ME1 malic enzyme 1 [ Homo sapiens (human) ]

    Gene ID: 4199, updated on 10-Dec-2024

    Summary

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    Official Symbol
    ME1provided by HGNC
    Official Full Name
    malic enzyme 1provided by HGNC
    Primary source
    HGNC:HGNC:6983
    See related
    Ensembl:ENSG00000065833 MIM:154250; AllianceGenome:HGNC:6983
    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
    MES; HUMNDME
    Summary
    This gene encodes a cytosolic, NADP-dependent enzyme that generates NADPH for fatty acid biosynthesis. The activity of this enzyme, the reversible oxidative decarboxylation of malate, links the glycolytic and citric acid cycles. The regulation of expression for this gene is complex. Increased expression can result from elevated levels of thyroid hormones or by higher proportions of carbohydrates in the diet. [provided by RefSeq, Jul 2008]
    Expression
    Broad expression in fat (RPKM 29.4), adrenal (RPKM 23.1) and 21 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ME1 in Genome Data Viewer
    Location:
    6q14.2
    Exon count:
    14
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 6 NC_000006.12 (83210402..83431051, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 6 NC_060930.1 (84433644..84654257, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 6 NC_000006.11 (83920121..84140770, complement)

    Chromosome 6 - NC_000006.12Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17355 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24781 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24782 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24783 Neighboring gene NANOG hESC enhancer GRCh37_chr6:83821047-83821571 Neighboring gene DOP1 leucine zipper like protein A Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17356 Neighboring gene H3K27ac hESC enhancer GRCh37_chr6:83902947-83903446 Neighboring gene phosphoglucomutase 3 Neighboring gene RWD domain containing 2A Neighboring gene MPRA-validated peak5928 silencer Neighboring gene ReSE screen-validated silencer GRCh37_chr6:84004031-84004257 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 24784 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17358 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr6:84140986-84142185 Neighboring gene serine protease 35 Neighboring gene synaptosome associated protein 91 Neighboring gene Sharpr-MPRA regulatory region 13924 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17359 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 17360

    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. Sub-unit structure of soluble and mitochondrial malic enzyme: demonstration of human mitochondrial enzyme in human-mouse hybrids. Povey S, et al. Ann Hum Genet, 1975 Oct. PMID 1088824
    2. ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis. Lu YX, et al. Cancer Res, 2018 Apr 15. PMID 29654155
    3. ME1 promotes basal-like breast cancer progression and associates with poor prognosis. Liao R, et al. Sci Rep, 2018 Nov 13. PMID 30425310, Free PMC Article
    4. Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma. Nakashima C, et al. Cancer Sci, 2018 Jun. PMID 29601126, Free PMC Article
    5. Evidence for a direct cross-talk between malic enzyme and the pentose phosphate pathway via structural interactions. Yao P, et al. J Biol Chem, 2017 Oct 13. PMID 28848047, Free PMC Article

    See all (75) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Cytosolic malic enzyme and glucose-6-phosphate dehydrogenase modulate redox balance in NSCLC with acquired drug resistance.
      Title: Cytosolic malic enzyme and glucose-6-phosphate dehydrogenase modulate redox balance in NSCLC with acquired drug resistance.
    2. Targeting Ferroptosis Vulnerability in Synovial Sarcoma: Is It All About ME1?
      Title: Targeting Ferroptosis Vulnerability in Synovial Sarcoma: Is It All About ME1?
    3. 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.
    4. miR-885-5p Inhibits Invasion and Metastasis in Gastric Cancer by Targeting Malic Enzyme 1.
      Title: miR-885-5p Inhibits Invasion and Metastasis in Gastric Cancer by Targeting Malic Enzyme 1.
    5. Malic Enzyme 1 Is Associated with Tumor Budding in Oral Squamous Cell Carcinomas.
      Title: Malic Enzyme 1 Is Associated with Tumor Budding in Oral Squamous Cell Carcinomas.
    6. In which ME1 transcripts are upregulated.
      Title: Dynamic Regulation of ME1 Phosphorylation and Acetylation Affects Lipid Metabolism and Colorectal Tumorigenesis.
    7. A small molecule inhibitor of ME1 suppressed growth of human CRC cells in vitro, but had little effect on normal rat intestinal epithelial cells. Targeting of ME1 may add to the armentarium of therapies for cancers of the gastrointestinal tract.
      Title: Malic Enzyme 1 (ME1) is pro-oncogenic in Apc(Min/+) mice.
    8. ME1 promotes basal-like breast cancer progression and associates with poor prognosis
      Title: ME1 promotes basal-like breast cancer progression and associates with poor prognosis.
    9. results shed light on crucial roles of ME1-mediated production of NADPH in gastric cancer growth and metastasis
      Title: ME1 Regulates NADPH Homeostasis to Promote Gastric Cancer Growth and Metastasis.
    10. Bioinformatics analysis identified that miR612 targeted ME1, which expression was high and inversely associated with miR612 expression in bladder cancer tissues.
      Title: Tumor-suppressing effects of microRNA-612 in bladder cancer cells by targeting malic enzyme 1 expression.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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

    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 ADP binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables NAD binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables NADP binding TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables electron transfer activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables magnesium ion 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 malate dehydrogenase (decarboxylating) (NADP+) activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    enables malic enzyme activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables malic enzyme activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    enables manganese ion binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables oxaloacetate decarboxylase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in NADH metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in NADP metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in carbohydrate metabolic process NAS
    Non-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 nucleotide biosynthetic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in protein homotetramerization IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    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 
    involved_in response to carbohydrate TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in response to hormone ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in cytosol ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    NADP-dependent malic enzyme
    Names
    Malic enzyme, cytoplasmic
    NADP-ME
    malate dehydrogenase (oxaloacetate-decarboxylating) (NADP(+))
    malic enzyme 1, NADP(+)-dependent, cytosolic
    malic enzyme 1, soluble
    pyruvic-malic carboxylase
    NP_002386.1

    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_002395.6 → NP_002386.1  NADP-dependent malic enzyme

      See identical proteins and their annotated locations for NP_002386.1

      Status: REVIEWED

      Source sequence(s)
      AL049699, BC025246, DA520723, KF458214
      Consensus CDS
      CCDS34492.1
      UniProtKB/Swiss-Prot
      B4DZ70, P48163, Q16797, Q16855, Q53F72, Q5VWA2, Q9BWX8, Q9H1W3, Q9UIY4
      UniProtKB/TrEMBL
      A8K168
      Related
      ENSP00000358719.3, ENST00000369705.4
      Conserved Domains (3) summary
      cd05312
      Location:270 → 547
      NAD_bind_1_malic_enz; NAD(P) binding domain of malic enzyme (ME), subgroup 1
      PLN03129
      Location:11 → 551
      PLN03129; NADP-dependent malic enzyme; Provisional
      pfam00390
      Location:79 → 260
      malic; Malic enzyme, N-terminal domain

    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_000006.12 Reference GRCh38.p14 Primary Assembly

      Range
      83210402..83431051 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060930.1 Alternate T2T-CHM13v2.0

      Range
      84433644..84654257 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P48163.1 GenPept UniProtKB/Swiss-Prot:P48163

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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