FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Gene: Dmel\Mdh2
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General Information
Symbol
Dmel\Mdh2
Species
D. melanogaster
Name
Malate dehydrogenase 2
Annotation Symbol
CG7998
Feature Type
FlyBase ID
FBgn0262559
Gene Model Status
Stock Availability
Enzyme Name (EC)
(S)-malate dehydrogenase (NAD(+), oxaloacetate-forming) (1.1.1.37)
Gene Summary
Malate dehydrogenase 2 (Mdh2) encodes a mitochondrial enzyme that reversibly catalyzes the oxidation of S-malate to oxaloacetate using the reduction of NAD+ to NADH. It is involved in the tricarboxylic acid (TCA) cycle, gluconeogenesis and the malate-aspartate shuttle. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)
Also Known As

l(3)psg7, psg7, malate dehydrogenase

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-62
RefSeq locus
NT_033777 REGION:18226396..18228718
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (20 terms)
Molecular Function (5 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
inferred from direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (4 terms)
CV Term
Evidence
References
Biological Process (12 terms)
Terms Based on Experimental Evidence (8 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
involved_in pupal development
inferred from mutant phenotype
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
Terms Based on Predictions or Assertions (5 terms)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR001557
involved_in gluconeogenesis
inferred from sequence or structural similarity with UniProtKB:P08249
inferred from sequence or structural similarity with UniProtKB:Q9VKX2
inferred from sequence or structural similarity with UniProtKB:P40926
inferred from electronic annotation with InterPro:IPR010097
inferred from biological aspect of ancestor with PANTHER:PTN000899458
Cellular Component (3 terms)
Terms Based on Experimental Evidence (1 term)
CV Term
Evidence
References
located_in mitochondrion
inferred from high throughput direct assay
inferred from direct assay
Terms Based on Predictions or Assertions (3 terms)
CV Term
Evidence
References
is_active_in cytoplasm
inferred from biological aspect of ancestor with PANTHER:PTN000166149
inferred from sequence or structural similarity with UniProtKB:P08249
is_active_in mitochondrion
inferred from biological aspect of ancestor with PANTHER:PTN000899458
Gene Group (FlyBase)
Protein Family (UniProt)
-
Catalytic Activity (EC/Rhea)
oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor
L-malate dehydrogenase (NAD+) activity
(S)-malate + NAD(+) = oxaloacetate + NADH + H(+) (1.1.1.37)
RHEA 21432:
Summaries
Gene Snapshot
Malate dehydrogenase 2 (Mdh2) encodes a mitochondrial enzyme that reversibly catalyzes the oxidation of S-malate to oxaloacetate using the reduction of NAD+ to NADH. It is involved in the tricarboxylic acid (TCA) cycle, gluconeogenesis and the malate-aspartate shuttle. [Date last reviewed: 2019-03-14]
Gene Group (FlyBase)
L-MALATE DEHYDROGENASES -
L-malate dehydrogenases are NAD-dependent oxidoreductases that catalyze interconversion of the substrates malate and oxaloacetate. This reaction plays key role in the malate/aspartate shuttle across the mitochondrial membrane, and in the tricarboxylic acid cycle within the mitochondrial matrix. (Adapted from PMID:12537350.)
Pathway (FlyBase)
GLUCONEOGENESIS -
Gluconeogenesis converts non-carbohydrate precursors such as pyruvate, lactate, alanine, glutamine and glycerol into glucose 6-phosphate (Glc-6P) and plays a crucial role in maintaining sugar homeostasis when dietary carbohydrates are limited. The pathway starts in the mitochondrion with the production of oxaloacetate which, via a series of enzymatic reactions and transport, is converted to cytosolic oxaloacetate which in turn is decarboxylated and phosphorylated to form phosphoenolpyruvate. The subsequent steps involved in the production of Glc-6P are the reverse reactions of glycolysis, only the penultimate step, the dephosphorylation of fructose 1,6-phosphate, is carried out by a different enzyme Fbp. In D. melanogaster, Glc-6P is mainly converted into the disaccharide trehalose, the main hemolymph sugar. However, in a subset of neurons, Glc-6P is converted in the endoplasmic reticulum into glucose. (Adapted from FBrf0236342 and PMID:33397651.)
MALATE-ASPARTATE SHUTTLE -
The malate-aspartate shuttle is composed of two cytosolic enzymes, two mitochondrial enzymes and two transporters. It is used to transport reducing equivalents from the cytosol to the mitochondrion, since cytosolic NADH cannot cross the inner mitochondrial membrane directly. The shuttle regenerates cytosolic NAD(+) to sustain cytosolic oxidative pathways such as glycolysis and provides reducing equivalents in the form of NADH for mitochondrial oxidative phosphorylation. (Adapted from PMID:38945121.)
TRICARBOXYLIC ACID (TCA) CYCLE -
The tricarboxylic acid (TCA) cycle is a central metabolic process that occurs in mitochondria. It consists of a cyclic series of chemical reactions that harness high-energy electrons from nutrients to produce energy (ATP). Each turn of the TCA cycle oxidizes one acetyl-CoA to two CO2 molecules and yields one GTP or ATP and 6 electrons in the form of four reducing equivalents (three NADH and one FADH2). Then, these electron carriers transfer their electrons onto the electron transport chain (ETC) complexes to generate ATP in a process known as oxidative phosphorylation (OXPHOS). The TCA cycle intermediates can also be used as precursors for the biosynthesis of amino acids, fatty acids and porphyrins and for gluconeogenesis. (Adapted from PMID:36581208).
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
Mdh2
Structural gene for the mitochondrial NAD-dependent malate dehydrogenase = (S)-Malate: NAD+ oxidoreductase [MDH2 (EC 1.1.1.37)].
Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\Mdh2 for information on other features

To submit a correction to a gene model please use the Contact FlyBase form

Protein Domains (via Pfam)
Isoform displayed:
Pfam protein domains
InterPro name
classification
start
end
Protein Domains (via SMART)
Isoform displayed:
SMART protein domains
InterPro name
classification
start
end
Structure
Protein 3D structure   (Predicted by AlphaFold)   (AlphaFold entry Q9VEB1)

If you don't see a structure in the viewer, refresh your browser.
Model Confidence:
  • Very high (pLDDT > 90)
  • Confident (90 > pLDDT > 70)
  • Low (70 > pLDDT > 50)
  • Very low (pLDDT < 50)

AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Some regions with low pLDDT may be unstructured in isolation.

Experimentally Determined Structures
Crossreferences
Comments on Gene Model

Low-frequency RNA-Seq exon junction(s) not annotated.

Gene model reviewed during 5.47

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0083563
1335
336
Additional Transcript Data and Comments
Reported size (kB)
Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0082985
35.3
336
9.65
Polypeptides with Identical Sequences

There is only one protein coding transcript and one polypeptide associated with this gene

Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Linkouts
Sequences Consistent with the Gene Model
Mapped Features

Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\Mdh2 using the Feature Mapper tool.

External Data
Crossreferences
Linkouts
Expression Data
Testis-specificity index

The testis specificity index was calculated from modENCODE tissue expression data by Vedelek et al., 2018 to indicate the degree of testis enrichment compared to other tissues. Scores range from -2.52 (underrepresented) to 5.2 (very high testis bias).

-0.85

Transcript Expression
dissected tissue
Stage
Tissue/Position (including subcellular localization)
Reference
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
pole plasm

Comment: maternally deposited

organism

Comment: maternally deposited

northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

Mdh2 levels remain relatively flat in salivary glands as in whole animals throughout the period from -12 hr APF to +12 hr APF.

Mdh2 transcript is expressed more strongly at late larval stages than at early pupal stages.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in mitochondrion
inferred from high throughput direct assay
inferred from direct assay
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Mdh2 in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Reference
See Gelbart and Emmert, 2013 for analysis details and data files for all genes.
Developmental Proteome: Life Cycle
Developmental Proteome: Embryogenesis
External Data and Images
Linkouts
BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 13 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 7 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Mdh2
Transgenic constructs containing regulatory region of Mdh2
Aberrations (Deficiencies and Duplications) ( 4 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
For more details about a specific phenotype click on the relevant allele symbol.
Lethality
Allele
Sterility
Allele
Other Phenotypes
Allele
Phenotype manifest in
Allele
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (9)
14 of 14
Yes
Yes
2 of 14
No
No
1  
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2  
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (7)
14 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
Mus musculus (laboratory mouse) (8)
13 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (5)
8 of 13
Yes
Yes
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (7)
14 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
2 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (3)
14 of 14
Yes
Yes
2 of 14
No
No
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (3)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (11)
13 of 13
Yes
Yes
13 of 13
Yes
Yes
12 of 13
No
Yes
10 of 13
No
Yes
10 of 13
No
Yes
3 of 13
No
Yes
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
2 of 13
No
No
Saccharomyces cerevisiae (Brewer's yeast) (3)
12 of 13
Yes
Yes
5 of 13
No
Yes
5 of 13
No
Yes
Schizosaccharomyces pombe (Fission yeast) (2)
12 of 12
Yes
Yes
2 of 12
No
No
Escherichia coli (enterobacterium) (1)
8 of 11
Yes
Yes
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Mdh2. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (5)
11 of 13
10 of 13
3 of 13
3 of 13
2 of 13
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 1 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Interaction
    References
    Disease Associations of Human Orthologs (via DIOPT v9.1 and OMIM)
    Note that ortholog calls supported by only 1 or 2 algorithms (DIOPT score < 3) are not shown.
    Homo sapiens (Human)
    Gene name
    Score
    OMIM
    OMIM Phenotype
    DO term
    Complementation?
    Transgene?
    Functional Complementation Data
    Functional complementation data is computed by FlyBase using a combination of the orthology data obtained from DIOPT and OrthoDB and the allele-level genetic interaction data curated from the literature.
    Interactions
    Summary of Physical Interactions
    Interaction Browsers

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    Interaction Browsers
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Linkouts
    DroID - A comprehensive database of gene and protein interactions.
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    External Links
    KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.
    Reactome Metabolic Pathways - An open-source, open access, manually curated and peer-reviewed metabolic pathway database.
    External Data
    Linkouts
    KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
    Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
    Class of Gene
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    3R
    Recombination map
    3-62
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    90F8-90F9
    Limits computationally determined from genome sequence between P{EP}cpoEP3679 and P{EP}Dlc90FEP3634
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes

    Based on 21 recombinants between sr and gl.

    Stocks and Reagents
    Stocks (11)
    Genomic Clones (20)
    cDNA Clones (144)
     

    Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see JBrowse for alignment of the cDNAs and ESTs to the gene model.

    cDNA clones, fully sequenced
    BDGP DGC clones
    Other clones
      Drosophila Genomics Resource Center cDNA clones

      For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.

      cDNA Clones, End Sequenced (ESTs)
      RNAi and Array Information
      Linkouts
      DRSC - Results frm RNAi screens
      Antibody Information
      Laboratory Generated Antibodies
       
      Commercially Available Antibodies
       
      Cell Line Information
      Publicly Available Cell Lines
       
        Other Stable Cell Lines
         
          Other Comments

          No difference in allele fixed in lines selected over 700 generations for high (negative) and low (positive) geotaxis.

          The effect of dietary sucrose and ethanol on Mdh2 activity in the third larval instar has been studied.

          Structural gene for the mitochondrial NAD-dependent malate dehydrogenase = (S)-Malate: NAD+ oxidoreductase (MDH2).

          Relationship to Other Genes
          Source for database merge of

          Source for merge of: Mdh2 l(3)psg7

          Additional comments

          "Mdh2" is likely to correspond to "CG7998" based on map position and relevant GO annotations.

          "CG7998" is likely to correspond to "Mdh2" based on map position and relevant GO annotations.

          Nomenclature History
          Source for database identify of

          Source for identity of: l(3)psg7 CG7998

          Nomenclature comments
          Etymology
          Synonyms and Secondary IDs (20)
          Reported As
          Name Synonyms
          L-Malate dehydrogenase
          Malate dehydrogenase
          Malate dehydrogenase 2
          lethal (3) persistent salivary gland 7
          malate dehydrogenase (mitochondrial)
          mitochondrial malate dehydrogenase
          mitochondrial-Mdh
          Secondary FlyBase IDs
          • FBgn0002700
          • FBgn0038587
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          Study result (0)
          Result
          Result Type
          Title
          External Crossreferences and Linkouts ( 54 )
          Sequence Crossreferences
          NCBI Gene - Gene integrates information from a wide range of species. A record may include nomenclature, Reference Sequences (RefSeqs), maps, pathways, variations, phenotypes, and links to genome-, phenotype-, and locus-specific resources worldwide.
          GenBank Nucleotide - A collection of sequences from several sources, including GenBank, RefSeq, TPA, and PDB.
          GenBank Protein - A collection of sequences from several sources, including translations from annotated coding regions in GenBank, RefSeq and TPA, as well as records from SwissProt, PIR, PRF, and PDB.
          RefSeq - A comprehensive, integrated, non-redundant, well-annotated set of reference sequences including genomic, transcript, and protein.
          UniProt/GCRP - The gene-centric reference proteome (GCRP) provides a 1:1 mapping between genes and UniProt accessions in which a single 'canonical' isoform represents the product(s) of each protein-coding gene.
          UniProt/TrEMBL - Automatically annotated and unreviewed records of protein sequence and functional information
          Other crossreferences
          AlphaFold DB - AlphaFold provides open access to protein structure predictions for the human proteome and other key proteins of interest, to accelerate scientific research.
          BDGP expression data - Patterns of gene expression in Drosophila embryogenesis
          DRscDB - A single-cell RNA-seq resource for data mining and data comparison across species
          EMBL-EBI Single Cell Expression Atlas - Single cell expression across species
          FlyAtlas2 - A Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data
          KEGG Genes - Molecular building blocks of life in the genomic space.
          MARRVEL_MODEL - MARRVEL (model organism gene)
          Linkouts
          Drosophila Genomics Resource Center - Drosophila Genomics Resource Center (DGRC) cDNA clones
          DroID - A comprehensive database of gene and protein interactions.
          DRSC - Results frm RNAi screens
          FlyAtlas - Adult expression by tissue, using Affymetrix Dros2 array
          FlyCyc Genes - Genes from a BioCyc PGDB for Dmel
          Fly-FISH - A database of Drosophila embryo and larvae mRNA localization patterns
          FlyMet - A comprehensive tissue-specific metabolomics resource for Drosophila.
          iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
          KEGG Metabolic Pathways - A collection of manually drawn metabolic pathway maps representing knowledge of molecular interaction, reaction and relation networks.
          KEGG Pathways - A collection of manually drawn pathway maps representing knowledge of molecular interaction, reaction and relation networks.
          MIST (protein-protein) - An integrated Molecular Interaction Database
          Reactome - An open-source, open access, manually curated and peer-reviewed pathway database.
          Reactome Metabolic Pathways - An open-source, open access, manually curated and peer-reviewed metabolic pathway database.
          References (102)