FB2025_01 , released February 20, 2025
Gene: Dmel\Hmgcr
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General Information
Symbol
Dmel\Hmgcr
Species
D. melanogaster
Name
HMG Coenzyme A reductase
Annotation Symbol
CG10367
Feature Type
FlyBase ID
FBgn0263782
Gene Model Status
Stock Availability
Enzyme Name (EC)
hydroxymethylglutaryl-CoA reductase (NADPH) (1.1.1.34)
Gene Summary
HMG Coenzyme A reductase (Hmgcr) encodes the rate-controlling enzyme of the mevalonate pathway that produces isoprenoids. It is required during heart tube formation, molting regulation and primordial germ cell migration. [Date last reviewed: 2019-05-16] (FlyBase Gene Snapshot)
Also Known As

columbus, clb, l(3)01152, HMGR, HMG-CoA reductase

Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
3-80
RefSeq locus
NT_033777 REGION:23733324..23750992
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (14 terms)
Molecular Function (2 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
Biological Process (10 terms)
Terms Based on Experimental Evidence (6 terms)
CV Term
Evidence
References
inferred from mutant phenotype
inferred from mutant phenotype
inferred from direct assay
inferred from mutant phenotype
inferred from genetic interaction with FLYBASE:hh; FB:FBgn0004644
inferred from genetic interaction with FLYBASE:disp; FB:FBgn0029088
inferred from mutant phenotype
Terms Based on Predictions or Assertions (6 terms)
CV Term
Evidence
References
traceable author statement
traceable author statement
involved_in gonad development
traceable author statement
inferred from electronic annotation with InterPro:IPR004554, InterPro:IPR004816
inferred from biological aspect of ancestor with PANTHER:PTN000060346
traceable author statement
inferred from biological aspect of ancestor with PANTHER:PTN000060346
Cellular Component (2 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN000060347
inferred from electronic annotation with InterPro:IPR004816
inferred from biological aspect of ancestor with PANTHER:PTN000060347
inferred from sequence or structural similarity with HGNC:5006
Protein Family (UniProt)
Belongs to the HMG-CoA reductase family. (P14773)
Catalytic Activity (EC/Rhea)
hydroxymethylglutaryl-CoA reductase (NADPH) activity
(R)-mevalonate + 2 NADP(+) + CoA = (3S)-hydroxy-3-methylglutaryl-CoA + 2 NADPH + 2 H(+) (1.1.1.34)
RHEA 15989:
Summaries
Gene Snapshot
HMG Coenzyme A reductase (Hmgcr) encodes the rate-controlling enzyme of the mevalonate pathway that produces isoprenoids. It is required during heart tube formation, molting regulation and primordial germ cell migration. [Date last reviewed: 2019-05-16]
Gene Group (FlyBase)
UNCLASSIFIED CH-OH OXIDOREDUCTASES, NAD OR NADP AS ACCEPTOR -
This group comprises CH-OH oxidoreductases using NAD or NADP as acceptor that do not classify under other groups in FlyBase.
Protein Function (UniProtKB)
Synthesis of mevalonate for the production of non-sterol isoprenoids, which are essential for growth differentiation. Provides spatial information during embryogenesis to guide migrating primordial germ cells (the pole cells) from the ectoderm to the mesoderm. Also required for association of the pole cells with the gonadal mesoderm.
(UniProt, P14773)
Phenotypic Description (Red Book; Lindsley and Zimm 1992)
Hmg: Hmg-CoA-reductase
Encodes 3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-controlling enzyme for cholesterol synthesis in mammals. In Drosophila melanogaster, the enzyme is not regulated by sterols (Brown, Havel, and Watson, 1983, J. Biol. Chem. 258: 8512-15; Silberkang, Havel, Friend, McCarthy, and Watson, 1983, J. Biol. Chem. 258: 8503-11); it synthesizes mevalonate for the production of nonsterol isoprenoids which are needed for growth and differentiation. The enzyme is found in cultured Kc and Schneider cells.
Summary (Interactive Fly)

catalyzes the biosynthesis of a mevalonate precursor for isoprenoids - functions in the hedgehog signaling pathway, implicated in the production of a signal by the somatic gonadal precursor cells that attracts migrating germ cells

Gene Model and Products
Number of Transcripts
1
Number of Unique Polypeptides
1

Please see the JBrowse view of Dmel\Hmgcr 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 P14773)

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

Gene model reviewed during 5.47

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

Gene model reviewed during 6.02

Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0084450
3818
920
Additional Transcript Data and Comments
Reported size (kB)

4.0, 3.2 (northern blot)

Comments
External Data
Crossreferences
Polypeptide Data
Annotated Polypeptides
Name
FlyBase ID
Predicted MW (kDa)
Length (aa)
Theoretical pI
UniProt
RefSeq ID
GenBank
FBpp0083842
98.3
920
6.59
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)

916 (aa); 98 (kD predicted)

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\Hmgcr using the Feature Mapper tool.

External Data
Crossreferences
Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
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).

1.64

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
organism

Comment: maternally deposited

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

Hmgcr transcripts are expressed in a dynamic pattern in the embryo. They are expressed in the target tissue of the primordial germ cells (PGCs) which is the gonadal mesoderm. Expression in the mesoderm is initially broad and then is restricted to a segmental pattern. This occurs at the stage when the PGCs migrate from the endoderm to the mesoderm. Mesodermal expression of Hmgcr is limited to a cluster of cells in each of parasegments 10, 11, and 12 at the location of the gonadal mesoderm. The three clusters of Hmgcr-expressing cells join to form a continuous band, which is tightly associated with the PGCs. Expression is also observed in the dorsal vessel, in regions of the foregut, midgut, and hindgut, in clusters of cells along the ventral midline, and in the salivary gland.

The 4.0kb Hmgcr transcript is detected at all developmental stages with the highest levels in late embryos.

Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
immunolocalization
Stage
Tissue/Position (including subcellular localization)
Reference
mass spectroscopy
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data

Hmgcr is expressed in the fat body in flies younger than 4 days. In flies older than 5 days, no Hmgcr expression is detectable.

Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
Reporter: P{Hmgcr.A-Gal4}
Stage
Tissue/Position (including subcellular localization)
Reference
Reporter: P{Hmgcr.B-Gal4}
Stage
Tissue/Position (including subcellular localization)
Reference
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\Hmgcr 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 ( 26 )
For All Classical and Insertion Alleles Show
 
Other relevant insertions
Transgenic Constructs ( 9 )
For All Alleles Carried on Transgenic Constructs Show
Transgenic constructs containing/affecting coding region of Hmgcr
Transgenic constructs containing regulatory region of Hmgcr
Aberrations (Deficiencies and Duplications) ( 17 )
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
pole cell & embryonic nervous system, with Scer\GAL4elav-C155
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (1)
14 of 14
Yes
Yes
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (1)
14 of 14
Yes
Yes
Mus musculus (laboratory mouse) (1)
13 of 14
Yes
Yes
Xenopus tropicalis (Western clawed frog) (2)
8 of 13
Yes
Yes
1 of 13
No
Yes
Danio rerio (Zebrafish) (2)
14 of 14
Yes
Yes
12 of 14
No
Yes
Caenorhabditis elegans (Nematode, roundworm) (1)
11 of 14
Yes
Yes
Anopheles gambiae (African malaria mosquito) (1)
12 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (2)
11 of 13
Yes
Yes
11 of 13
Yes
Yes
Saccharomyces cerevisiae (Brewer's yeast) (2)
11 of 13
Yes
Yes
11 of 13
Yes
Yes
Schizosaccharomyces pombe (Fission yeast) (1)
10 of 12
Yes
Yes
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:Hmgcr. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Human Disease Associations
FlyBase Human Disease Model Reports
    Disease Ontology (DO) Annotations
    Models Based on Experimental Evidence ( 1 )
    Allele
    Disease
    Evidence
    References
    Potential Models Based on Orthology ( 0 )
    Human Ortholog
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 3 )
    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.
    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
    esyN Network Diagram
    Other Interaction Browsers
    Summary of Genetic Interactions
    esyN Network Diagram
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    esyN Network Key:
    Suppression
    Enhancement
    Other Interaction Browsers

    Please look at the allele data for full details of the genetic interactions
    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 (genetic) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Metabolic Pathways
    FlyBase
    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
    3-80
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    95B1-95B1
    Limits computationally determined from genome sequence between P{PZ}l(3)0690606906 and P{PZ}l(3)0468404684
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    95B1-95B6
    (determined by in situ hybridisation)
    95B5-95B6
    (determined by in situ hybridisation)
    95A-95A
    (determined by in situ hybridisation)
    Experimentally Determined Recombination Data
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (12)
    Genomic Clones (22)
    cDNA Clones (46)
     

    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
             
            Commercially Available Antibodies
             
            Cell Line Information
            Publicly Available Cell Lines
             
              Other Stable Cell Lines
               
                Other Comments

                Ortholog of B. mori juvenile-hormone-related gene (involved in JH biosynthesis, metabolism or signaling).

                Isolated in an EMS mutagenesis screen to identify zygotic mutations affecting germ cell migration at discrete points during embryogenesis.

                Mutants exhibit specific germ cell migration defects.

                The Hmgcr gene product has a critical developmental function in providing spatial information to guide migrating primordial germ cells.

                The autosomal "FLP-DFS" technique (using the P{ovoD1-18} P{FRT(whs)} P{hsFLP} chromosomes) has been used to identify the specific maternal effect phenotype for the zygotic lethal mutation.

                Encodes 3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-controlling enzyme for cholesterol synthesis in mammals. In D.melanogaster, the enzyme is not regulated by sterols (Brown et al., 1983; Silberkang et al., 1983); it synthesizes mevalonate for the production of nonsterol isoprenoids which are needed for growth and differentiation. The enzyme is found in cultured Kc and Schneider cells.

                Relationship to Other Genes
                Source for database merge of

                Source for merge of: Hmgcr l(3)01152

                Source for merge of: Hmgcr BcDNA:LD15354

                Source for merge of: Hmgcr l(3)04684

                Additional comments

                Source for merge of Hmgcr BcDNA:LD15354 was a shared cDNA ( date:030728 ).

                Nomenclature History
                Source for database identify of
                Nomenclature comments
                Etymology
                Synonyms and Secondary IDs (31)
                Reported As
                Symbol Synonym
                BcDNA:LD15354
                l(3)04684
                Secondary FlyBase IDs
                • FBgn0010845
                • FBgn0001205
                • FBgn0010738
                • FBgn0024247
                • FBgn0061415
                Datasets (0)
                Study focus (0)
                Experimental Role
                Project
                Project Type
                Title
                Study result (0)
                Result
                Result Type
                Title
                External Crossreferences and Linkouts ( 55 )
                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/Swiss-Prot - Manually annotated and reviewed 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.
                Eukaryotic Promoter Database - A collection of databases of experimentally validated promoters for selected model organisms.
                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)
                Interactive Fly - A cyberspace guide to Drosophila development and metazoan evolution
                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 (genetic) - 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 (160)