FB2024_03 , released June 25, 2024
Gene: Dmel\LUBEL
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General Information
Symbol
Dmel\LUBEL
Species
D. melanogaster
Name
Linear Ubiquitin E3 ligase
Annotation Symbol
CG11321
Feature Type
FlyBase ID
FBgn0031857
Gene Model Status
Stock Availability
Gene Summary
Linear Ubiquitin E3 ligase (LUBEL) encodes an E3 ligase belonging to the RBR (RING-in-between-RING)-type ubiquitin E3 ligase family. It specifically generates N-terminal methionine-linked ubiquitin chains, which are important for heat-tolerance in vivo. [Date last reviewed: 2018-11-15] (FlyBase Gene Snapshot)
Key Links
Genomic Location
Cytogenetic map
Sequence location
Recombination map
2-22
RefSeq locus
NT_033779 REGION:6759829..6772755
Sequence
Genomic Maps
Other Genome Views
The following external sites may use different assemblies or annotations than FlyBase.
Function
Gene Ontology (GO) Annotations (12 terms)
Molecular Function (6 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (6 terms)
CV Term
Evidence
References
Biological Process (5 terms)
Terms Based on Experimental Evidence (4 terms)
CV Term
Evidence
References
Terms Based on Predictions or Assertions (2 terms)
CV Term
Evidence
References
inferred from biological aspect of ancestor with PANTHER:PTN001041902
inferred from sequence or structural similarity with HGNC:16031
Cellular Component (2 terms)
Terms Based on Experimental Evidence (0 terms)
Terms Based on Predictions or Assertions (1 term)
CV Term
Evidence
References
inferred from electronic annotation with InterPro:IPR026254
Protein Family (UniProt)
Belongs to the RBR family. (Q8IPJ3)
Summaries
Gene Snapshot
Linear Ubiquitin E3 ligase (LUBEL) encodes an E3 ligase belonging to the RBR (RING-in-between-RING)-type ubiquitin E3 ligase family. It specifically generates N-terminal methionine-linked ubiquitin chains, which are important for heat-tolerance in vivo. [Date last reviewed: 2018-11-15]
Gene Group (FlyBase)
RING-BETWEEN-RING UBIQUITIN LIGASES -
E3 (ubiquitin) ligases interact with ubiquitin-E2 (ubiquitin-conjugating) enzymes and the target protein, transferring the ubiquitin from the E2 to the substrate. RING-between-RING (RBR) E3 ligases are characterised by three closely spaced domains: RING1 (a classical RING finger domain), a In-Betweeen-RING (IBR) domain and a RING2 domain. The mechanism of action is described as RING/HECT-like, with the RING1 domain facilitating E2-transfer (E3 RING-like) to form a thioester intermediate with a cysteine in RING2 which then modifies the substrate protein (HECT-like). (Adapted from PMID:24469331).
Pathway (FlyBase)
Positive Regulators of Imd Signaling Pathway -
Positive regulators of the immune deficiency (Imd) pathway result in the increased activity of the NFκB-like transcription factor Rel in the nucleus. (Adapted from FBrf0224587 and FBrf0238555.)
Protein Function (UniProtKB)
E3 ubiquitin-protein ligase which conjugates linear 'Met-1'- and 'Lys-63'-linked polyubiquitin chains to substrates and plays a crucial role in the NF-kappa-B intestinal inflammatory response to oral infection and in the heat stress response (PubMed:27702987, PubMed:30026495). Preferentially interacts with 'Lys-63'-linked, and to a lesser extent 'Lys-48'-linked, polyubiquitin chains (PubMed:27702987). Upon oral infection with a Gram-negative bacterium E.carotovora subsp. carotovora 15, functions with the E2 ubiquitin-conjugating enzyme Ubc10 to mediate the conjugation of 'Lys-63'- and linear 'Met-1'-linked polyubiquitin chains to the substrate key which is essential for activation of the NF-kappa-B signaling cascade in the adult intestinal epithelium (PubMed:27702987, PubMed:30026495). It is not required for systemic immune response to septic infection with either E.carotovora subsp. carotovora 15 or Gram-positive M.luteus bacteria (PubMed:30026495). Function in controlling linear ubiquitination is also essential for regulating the heat stress response in adults. This function may require the E2 ubiquitin-conjugating enzymes Ubc10 or eff (PubMed:27702987).
(UniProt, Q8IPJ3)
Gene Model and Products
Number of Transcripts
9
Number of Unique Polypeptides
7

Please see the JBrowse view of Dmel\LUBEL 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 Q8IPJ3)

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.

Annotated transcripts do not represent all possible combinations of alternative exons and/or alternative promoters.

Gene model reviewed during 5.44

Gene model reviewed during 5.56

Sequence Ontology: Class of Gene
Transcript Data
Annotated Transcripts
Name
FlyBase ID
RefSeq ID
Length (nt)
Assoc. CDS (aa)
FBtr0290295
2768
834
FBtr0301972
783
180
FBtr0331216
9188
2892
FBtr0331217
2882
834
FBtr0331218
9186
2851
FBtr0331219
2907
887
FBtr0331220
9009
2839
FBtr0331221
8906
2798
FBtr0331222
763
180
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
FBpp0288734
91.3
834
10.16
FBpp0291182
19.7
180
10.30
FBpp0303658
320.9
2892
4.84
FBpp0303659
91.3
834
10.16
FBpp0303660
316.4
2851
4.84
FBpp0303661
97.2
887
10.05
FBpp0303662
315.0
2839
4.82
FBpp0303663
310.5
2798
4.82
FBpp0303664
19.7
180
10.30
Polypeptides with Identical Sequences

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

180 aa isoforms: LUBEL-PD, LUBEL-PK
834 aa isoforms: LUBEL-PC, LUBEL-PF
Additional Polypeptide Data and Comments
Reported size (kDa)
Comments
External Data
Domain

UBA-like 2 (UBA2), but not UBA-like 1 (UBA1), domain interacts with tetra or longer polyubiquitin chains, and di-ubiquitin chains linked via 'lys-63', and to a lesser extent 'lys-48'. However, neither of the UBA1 or UBA2 domains interact with linear 'Met-1'-linked polyubiquitin chains.

(UniProt, Q8IPJ3)
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\LUBEL 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).

-0.84

Transcript Expression
in situ
Stage
Tissue/Position (including subcellular localization)
Reference
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Polypeptide Expression
Additional Descriptive Data
Marker for
 
Subcellular Localization
CV Term
Evidence
References
Expression Deduced from Reporters
High-Throughput Expression Data
Associated Tools

JBrowse - Visual display of RNA-Seq signals

View Dmel\LUBEL 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
Flygut - An atlas of the Drosophila adult midgut
Images
Alleles, Insertions, Transgenic Constructs, and Aberrations
Classical and Insertion Alleles ( 4 )
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 LUBEL
Transgenic constructs containing regulatory region of LUBEL
Aberrations (Deficiencies and Duplications) ( 1 )
Inferred from experimentation ( 1 )
Gene disrupted in
Inferred from location ( 0 )
Variants
Variant Molecular Consequences
Alleles Representing Disease-Implicated Variants
Phenotypes
Orthologs
Human Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Homo sapiens (Human) (15)
11 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
4  
1 of 14
No
No
1 of 14
No
No
12  
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
Model Organism Orthologs (via DIOPT v9.1)
Species\Gene Symbol
Score
Best Score
Best Reverse Score
Alignment
Complementation?
Transgene?
Rattus norvegicus (Norway rat) (13)
10 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Mus musculus (laboratory mouse) (13)
10 of 14
Yes
Yes
2 of 14
No
No
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Xenopus tropicalis (Western clawed frog) (8)
7 of 13
Yes
Yes
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
Danio rerio (Zebrafish) (22)
8 of 14
Yes
Yes
4 of 14
No
Yes
2 of 14
No
No
2 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
Yes
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
Caenorhabditis elegans (Nematode, roundworm) (12)
2 of 14
Yes
No
2 of 14
Yes
Yes
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
1 of 14
No
Yes
1 of 14
No
No
Anopheles gambiae (African malaria mosquito) (7)
9 of 12
Yes
Yes
Arabidopsis thaliana (thale-cress) (47)
3 of 13
Yes
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
No
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
2 of 13
No
Yes
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
No
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
Yes
1 of 13
No
No
Saccharomyces cerevisiae (Brewer's yeast) (2)
2 of 13
Yes
Yes
1 of 13
No
No
Schizosaccharomyces pombe (Fission yeast) (2)
1 of 12
Yes
Yes
1 of 12
Yes
No
Escherichia coli (enterobacterium) (0)
Other Organism Orthologs (via OrthoDB)
Data provided directly from OrthoDB:LUBEL. Refer to their site for version information.
Paralogs
Paralogs (via DIOPT v9.1)
Drosophila melanogaster (Fruit fly) (5)
2 of 13
1 of 13
1 of 13
1 of 13
1 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 ( 0 )
    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
    esyN Network Diagram
    Show neighbor-neighbor interactions:
    Show/hide secondary interactors 
    (data from AllianceMine provided by esyN)
    Select Layout:
    Legend:
    Protein
    RNA
    Selected Interactor(s)
    Other Interaction Browsers

    Please see the Physical Interaction reports below for full details
    protein-protein
    Physical Interaction
    Assay
    References
    Summary of Genetic Interactions
    esyN Network Diagram
    Other Interaction Browsers
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    Starting gene(s)
    Interaction type
    Interacting gene(s)
    Reference
    External Data
    Linkouts
    BioGRID - A database of protein and genetic interactions.
    DroID - A comprehensive database of gene and protein interactions.
    MIST (protein-protein) - An integrated Molecular Interaction Database
    Pathways
    Signaling Pathways (FlyBase)
    Positive Regulators of Imd Signaling Pathway -
    Positive regulators of the immune deficiency (Imd) pathway result in the increased activity of the NFκB-like transcription factor Rel in the nucleus. (Adapted from FBrf0224587 and FBrf0238555.)
    Metabolic Pathways
    External Data
    Linkouts
    Genomic Location and Detailed Mapping Data
    Chromosome (arm)
    2L
    Recombination map
    2-22
    Cytogenetic map
    Sequence location
    FlyBase Computed Cytological Location
    Cytogenetic map
    Evidence for location
    27B1-27B1
    Experimentally Determined Cytological Location
    Cytogenetic map
    Notes
    References
    Experimentally Determined Recombination Data
    Location
    Left of (cM)
    Right of (cM)
    Notes
    Stocks and Reagents
    Stocks (6)
    Genomic Clones (14)
     

    Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete

    cDNA Clones (16)
     

    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
        Relationship to Other Genes
        Source for database merge of
        Additional comments
        Nomenclature History
        Source for database identify of

        Source for identity of: LUBEL CG11321

        Nomenclature comments
        Etymology
        Synonyms and Secondary IDs (6)
        Datasets (0)
        Study focus (0)
        Experimental Role
        Project
        Project Type
        Title
        Study result (0)
        Result
        Result Type
        Title
        External Crossreferences and Linkouts ( 72 )
        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
        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
        FlyMine - An integrated database for Drosophila genomics
        KEGG Genes - Molecular building blocks of life in the genomic space.
        MARRVEL_MODEL - MARRVEL (model organism gene)
        Linkouts
        BioGRID - A database of protein and genetic interactions.
        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
        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
        Flygut - An atlas of the Drosophila adult midgut
        iBeetle-Base - RNAi phenotypes in the red flour beetle (Tribolium castaneum)
        MIST (protein-protein) - An integrated Molecular Interaction Database
        References (42)