FB2026_02 , released June 18, 2026
Gene: Dmel\LKRSDH
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General Information
Symbol
Dmel\LKRSDH
Species
D. melanogaster
Name
Lysine ketoglutarate reductase/saccharopine dehydrogenase
Annotation Symbol
CG7144
Feature Type
protein_coding_gene
FlyBase ID
FBgn0286198
Gene Model Status
Current
Stock Availability
14 publicly available
Enzyme Name (EC)
saccharopine dehydrogenase (NAD(+), L-lysine-forming) (1.5.1.7)
saccharopine dehydrogenase (NAD(+), L-glutamate-forming) (1.5.1.9)
Gene Summary
Lysine ketoglutarate reductase/saccharopine dehydrogenase (LKRSDH) encodes a bifunctional enzyme that catalyzes the first two steps in the lysine degradation pathway. Independently of its enzymatic activity, it also acts as a transcriptional corepressor in ecdysone signaling. [Date last reviewed: 2019-03-14] (FlyBase Gene Snapshot)
All Summaries
Also Known As

BEST:CK02318 , LKR, lysine, lys

Key Links
Genomic Location
Cytogenetic map
28C4-28C4
Sequence location
Recombination map
2-28
RefSeq locus
NT_033779 REGION:7791175..7795959
Sequence
Get Decorated FASTA
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
NCBI
UCSC
Ensembl
PopFly
Function
Gene Ontology (GO) Annotations (11 terms)
Molecular Function (5 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
enables histone binding
inferred from direct assay
(Cakouros et al., 2008)
enables nuclear receptor binding
inferred from physical interaction with FLYBASE:EcR; FB:FBgn0000546
(Cakouros et al., 2008)
enables saccharopine dehydrogenase (NAD+, L-lysine-forming) activity
inferred from direct assay
(Cakouros et al., 2008)
enables transcription corepressor activity
inferred from mutant phenotype
(Cakouros et al., 2008)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
enables saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity
inferred from sequence or structural similarity with UniProtKB:Q9UDR5
(Gene Ontology Curators, 2002-)
Biological Process (3 terms)
Terms Based on Experimental Evidence (3 terms)
CV Term
Evidence
References
involved_in L-lysine catabolic process
inferred from mutant phenotype
(St Clair et al., 2017)
inferred from direct assay
(Cakouros et al., 2008)
involved_in negative regulation of ecdysone receptor signaling pathway
inferred from direct assay
(Cakouros et al., 2008)
involved_in negative regulation of transcription by RNA polymerase II
inferred from direct assay
(Cakouros et al., 2008)
inferred from mutant phenotype
(Cakouros et al., 2008)
Terms Based on Predictions or Assertions (0 terms)
Cellular Component (3 terms)
Terms Based on Experimental Evidence (2 terms)
CV Term
Evidence
References
located_in cytosol
inferred from direct assay
(Cakouros et al., 2008)
located_in nucleus
inferred from direct assay
(Cakouros et al., 2008)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
located_in mitochondrion
inferred from sequence or structural similarity with UniProtKB:Q9UDR5
(Gene Ontology Curators, 2002-)
Gene Group (FlyBase)
Pathway (FlyBase)
Protein Family (UniProt)
-
Protein Signatures (InterPro)
Catalytic Activity (EC/Rhea)
saccharopine dehydrogenase (NAD+, L-glutamate-forming) activity
L-saccharopine + NAD(+) + H2O = (S)-2-amino-6-oxohexanoate + L-glutamate + NADH + H(+) (1.5.1.9)
RHEA 24520: saccharopine dehydrogenase (NAD+, L-lysine-forming) activity
L-saccharopine + NAD(+) + H2O = L-lysine + 2-oxoglutarate + NADH + H(+) (1.5.1.7)
RHEA 12440:
Summaries
Gene Snapshot
Lysine ketoglutarate reductase/saccharopine dehydrogenase (LKRSDH) encodes a bifunctional enzyme that catalyzes the first two steps in the lysine degradation pathway. Independently of its enzymatic activity, it also acts as a transcriptional corepressor in ecdysone signaling. [Date last reviewed: 2019-03-14]
Gene Group (FlyBase)
CH-NH OXIDOREDUCTASES, NAD OR NADP AS ACCEPTOR -
CH-NH oxidoreductases with NAD or NADP as acceptor, include dehydrogenases that oxidize a CH-NH with the reduction of NAD or NADP.
Pathway (FlyBase)
L-LYSINE CATABOLISM -
L-lysine is an essential amino acid acquired from the diet. The main catabolic route occurs in the mitochondria. It begins with the ε-deamination of L-lysine and proceeds via the intermediate metabolite L-saccharopine to produce acetyl-CoA. Acetyl-CoA can enter the tricarboxylic acid (TCA) cycle or be used for fatty acid biosynthesis. The pathway also produces the intermediates glutaryl-CoA and crotonyl-CoA which are the precursors for histone lysine glutarylation and crotonylation, respectively. (Adapted from PMID:28986444.)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
lys: lysine
Larvae, pupae, and adults contain a higher concentration of lysine than wild type. Accumulation of lysine is postulated to result from block in its degradation. Flies homozygous for lys occasionally have faintly reddish fat cells, especially in thorax. This effect enhanced by starvation, by combining lys with rc, rc2, or cho. RK3.
Gene Model and Products
Number of Transcripts
2
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\LKRSDH 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 Q9VLX0)

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 5.52

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
LKRSDH-RA
FBtr0079495
NM_135306
3264
928
LKRSDH-RB
FBtr0343404
NM_001298790
3495
928
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
LKRSDH-PA
FBpp0079118
103.1
928
6.78
Q9VLX0
NP_609150
AAF52559
LKRSDH-PB
FBpp0310050
103.1
928
6.78
Q9VLX0
NP_001285719
AHN54234
Polypeptides with Identical Sequences

The group(s) of polypeptides indicated below share identical sequence to each other.

928 aa isoforms: LKRSDH-PA, LKRSDH-PB
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Crossreferences
InterPro - A database of protein families, domains and functional sites
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\LKRSDH 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).

-0.61

Transcript Expression
northern blot
Stage
Tissue/Position (including subcellular localization)
Reference
pupal stage
salivary gland
(Lee et al., 2003)
Additional Descriptive Data

The expression of this gene along with several others is induced in salivary glands in pupae at the time of head eversion. This stage is characterized by an increase in the ecdysone titer as well as large amounts of cell death in this tissue.

(Lee et al., 2003)
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
adult stage
adult head
(Aradska et al., 2015)
day 7 of adulthood -- day 49 of adulthood
adult heart
(Cammarato et al., 2011)
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
located_in cytosol
inferred from direct assay
(Cakouros et al., 2008)
located_in nucleus
inferred from direct assay
(Cakouros et al., 2008)
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\LKRSDH in JBrowse
RNA-Seq by Region - Search RNA-Seq expression levels by exon or genomic region
Bulk Downloads
RNA-Seq RPKM values for all genes
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
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
FlyBase Wiki
Image Based Resources
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 8 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 10 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of LKRSDH
Transgenic constructs containing regulatory region of LKRSDH
Aberrations (Deficiencies and Duplications) ( 10 )
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
viable
viable, with Dcr-2UAS.cDa, Scer\GAL4elav.PLu
viable, with Scer\GAL4tin.CΔ4
Sterility
Allele
fertile
Other Phenotypes
Allele
abnormal circadian rhythm | adult stage | progressive
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4Ilp5.PU
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4LKRSDH-CR70173-TG4.0
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4LKRSDH-CR70173-TG4.0, Spyo\Cas9UAS.cUa
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4nSyb.PP
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4nSyb.PP, Spyo\Cas9UAS.cUa
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4repo.PU
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4repo.PU, Spyo\Cas9UAS.cUa
abnormal circadian rhythm | adult stage | progressive, with Scer\GAL4tim.PU
abnormal size | third instar larval stage, with Scer\GAL4Cg.PA
decreased cell number | embryonic stage, with Scer\GAL4srp.Hemo
decreased rate of movement | adult stage
short lived
Phenotype manifest in
Allele
embryonic/larval fat body | third instar larval stage, with Scer\GAL4Cg.PA
embryonic/larval plasmatocyte | embryonic stage, with Scer\GAL4srp.Hemo
fat body
germ band, with Scer\GAL4srp.Hemo
mitochondrion | third instar larval stage, with Scer\GAL4Cg.PA
wing, with Scer\GAL4e22c
yolk, with Scer\GAL4srp.Hemo
Orthologs
Downloads
Download All DIOPT Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (1)
Hsap\AASS
13 of 14
Yes
Yes
1  
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Source
Compara
Domainoid
eggNOG
Hieranoid
Homologene
Inparanoid
OMA
OrthoDB
OrthoFinder
OrthoInspector
orthoMCL
Panther
Phylome
SonicParanoid
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (1)
Rnor\Aass
14 of 14
Yes
Yes
Mus musculus (laboratory mouse) (1)
Mmus\Aass
13 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (1)
Xtro\aass
7 of 13
Yes
Yes
Danio rerio (Zebrafish) (1)
Drer\aass
14 of 14
Yes
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
Cele\aass-1
13 of 14
Yes
Yes
Anopheles gambiae (African malaria mosquito) (1)
Agam\AgaP_AGAP008632
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (2)
Atha\AT4G33150
13 of 13
Yes
Yes
Atha\AT1G50450
1 of 13
No
Yes
Saccharomyces cerevisiae (Brewer's yeast) (2)
Scer\LYS9
9 of 13
Yes
Yes
Scer\LYS1
3 of 13
No
Yes
Schizosaccharomyces pombe (Fission yeast) (2)
Spom\SPBC3B8.03
9 of 12
Yes
Yes
Spom\lys3
3 of 12
No
Yes
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:LKRSDH. Refer to their site for version information.
Paralogs
Downloads
Download All DIOPT Paralogs
Paralogs (via DIOPT v9.1)
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
    AASS; aminoadipate-semialdehyde synthase
    model of  hyperlysinemia
    IEA
    (FlyBase, 2019-)
    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?
    AASS; aminoadipate-semialdehyde synthase
    13 of 14
    605113
     
    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
    Summary of Genetic Interactions
    Interaction Browsers
    View in FlyBase Interactions Browser   View in MIST tool (external link)
    Please look at the allele data for full details of the genetic interactions
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    LKRSDH
    suppressible
    Art4
    (Lv et al., 2024)
    LKRSDH
    suppressible
    EcR
    (Cakouros et al., 2008)
    LKRSDH
    suppressible
    Ilp2
    (Lv et al., 2024)
    LKRSDH
    suppressible
    Ilp3
    (Lv et al., 2024)
    LKRSDH
    suppressible
    Ilp3|Ilp5
    (Lv et al., 2024)
    LKRSDH
    suppressible
    Ilp5
    (Lv et al., 2024)
    LKRSDH
    enhanceable
    rc
    LKRSDH
    enhanceable
    VhaAC39-1
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    atos
    suppressible
    LKRSDH
    (Emtenani et al., 2022)
    External Data
    Linkouts
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    FlyBase
    L-LYSINE CATABOLISM
    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)
    2L
    Recombination map
    2-28
    Cytogenetic map
    28C4-28C4
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    28C4-28C4
    Limits computationally determined from genome sequence between P{EP}EP2419EP2419&P{EP}EP575 and P{PZ}l(2)rL220rL220
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Experimentally Determined Recombination Data
    Location

    2-28

    (FlyBase, 2016)

    2-25.0

    (Comeron et al., 2012)

    2-22.9

    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (14)
    Genomic Clones (27)
    cDNA Clones (35)
     

    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)
      BDGP DGC clones
      Other clones
      RNAi and Array Information
      Linkouts
      Antibody Information
      Laboratory Generated Antibodies
       

      polyclonal

      (Cakouros et al., 2008)
      Commercially Available Antibodies
       
      Cell Line Information
      Publicly Available Cell Lines
       
        Other Stable Cell Lines
         
          Other Comments

          LKR binds directly to EcR in vitro, regardless of whether ecdysone is present.

          (Cakouros et al., 2008)

          LKR regulates hormone-mediated histone arginine methylation and transcription of cell death genes.

          (Cakouros et al., 2008)

          Identification: cDNA screen for secreted and transmembrane proteins expressed during embryogenesis.

          (Kopczynski et al., 1998)
          Relationship to Other Genes
          Source for database merge of

          Source for merge of: BEST:CK02318 CG7144

          (Bayraktaroglu, 2000.11.2)

          Source for merge of: CG7144 anon-WO0149856.1

          (FlyBase, 1996-)

          Source for merge of: LKRSDH lys

          (St Clair et al., 2017)
          Additional comments

          Source for merge of CG7144 anon-WO0149856.1 was sequence comparison ( date:051113 ).

          (FlyBase, 1996-)
          Nomenclature History
          Source for database identify of

          Source for identity of: LKR CG7144

          (Cakouros et al., 2008)

          Source for identity of: LKRSDH LKR

          (FlyBase, 2009-)
          Nomenclature comments

          Renamed from 'LKR' to 'LKRSDH' to minimise confusion with the 'Lkr' ('Leucokinin receptor') gene symbol, from which it differed only by case. Moreover, 'LKRSDH' better reflects the symbol used in the original paper ('dLKR/SDH') which initially characterised the gene (FBrf0205793).

          (FlyBase, 2009-)
          Etymology
          Synonyms and Secondary IDs (16)
          Datasets (0)
          Study focus (0)
          Experimental Role
          Project
          Project Type
          Title
          Study result (0)
          Result
          Result Type
          Title
          External Crossreferences and Linkouts ( 36 )
          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.
          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
          InterPro - A database of protein families, domains and functional sites
          KEGG Genes - Molecular building blocks of life in the genomic space.
          MARRVEL_MODEL - MARRVEL (model organism gene)
          Linkouts
          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
          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.
          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 (68)