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General Information
Name
neurodegenerative disease, UBQLN-related
FlyBase ID
FBhh0000824
Disease Ontology Term
Parent Disease
OMIM
Overview

This report describes neurodegenerative disease modeled by the Drosophila ubiquilin gene Ubqn. There are five ubiquilin genes in human, at least one of which (UBQLN2) is implicated in neurodegenerative disease. Ubiquilins are a family of ubiquitin-like proteins that play a role in the regulation of different protein degradation pathways and are thought to functionally link the ubiquitination machinery to the proteasome. In Drosophila, Ubqn is the highest-scoring ortholog of all five human genes; a less similar ubiquilin gene, CG31528, is also present in D. melanogaster. RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Ubqn.

Multiple UAS constructs of the human Hsap\UBQLN2 gene have been introduced into flies, including wild-type and variants associated with ALS15; see the human disease model report 'amyotrophic lateral sclerosis 15' (FBhh0000823).

Ubiquitous reduction in Dmel\Ubqn expression effected by RNAi results in lethality. Neuronal reduction effected by RNAi results in locomotor and neuranatomy defects; accumulation of polyubiquitinated proteins is observed. Physical and genetic interactions of Dmel\Ubqn have been described; see below and in the Ubqn gene report.

[updated Jun. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Disease Summary: neurodegenerative disease, UBQLN-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

Ubiquilins encode ubiquitin-like proteins that plays a role in the regulation of different protein degradation mechanisms and pathways including ubiquitin-proteasome system (UPS), autophagy and the endoplasmic reticulum-associated protein degradation (ERAD) pathway. They physically associate with both proteasomes and ubiquitin ligases, thus, are thought to functionally link the ubiquitination machinery to the proteasome. [Gene Cards, UBQLN1, UBQLN2; 2018.06.29]

External links
Disease synonyms
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 5 human genes to 2 Drosophila gene. Dmel\Ubqn is more closely related to all 5 human genes than is CG31528.

Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 5 human genes to 2 Drosophila genes. Dmel\Ubqn is more closely related to all 5 human genes than is CG31528.

Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 5 human genes to 2 Drosophila genes. Dmel\Ubqn is more closely related to all 5 human genes than is CG31528.

Human gene (HGNC)
Symbol / Name
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 5 human genes to 2 Drosophila genes. Dmel\Ubqn is more closely related to all 5 human genes than is CG31528.

Human gene (HGNC)
D. melanogaster ortholog (based on DIOPT)
Comments on ortholog(s)

Many to many: 5 human genes to 2 Drosophila genes. Dmel\Ubqn is more closely related to all 5 human genes than is CG31528.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Gene Snapshot
    Ubiquilin (Ubqn) encodes a protein containing an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. It binds and delivers ubiquitinated, misfolded or no longer functionally required proteins to the ubiquitin-proteasome system and/or autophagy. [Date last reviewed: 2018-10-04]
    Cellular component (GO)
    Gene Groups / Pathways
      Comments on ortholog(s)

      High-scoring ortholog of human UBQLN1, UBQLN2, UBQLN4; moderate-scoring ortholog of UBQLNL and UBQLN3 (2 Drosophila to 5 human). Dmel\Ubqn shares 46-50% identity and 63-67% similarity with UBQLN1, UBQLN2, UBQLN4; it shares 26-32% identity and 44-46% similarity with UBQLNL and UBQLN3.

      Orthologs and Alignments from DRSC
      DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
      Other Genes Used: Viral, Bacterial, Synthetic (0)
        Summary of Physical Interactions (25 groups)
        protein-protein
        Interacting group
        Assay
        References
        experimental knowledge based
        experimental knowledge based
        enzymatic study, western blot
        experimental knowledge based
        enzymatic study, western blot
        experimental knowledge based
        experimental knowledge based
        enzymatic study, western blot
        experimental knowledge based
        cosedimentation, western blot, anti bait coimmunoprecipitation
        anti bait coimmunoprecipitation, western blot, cosedimentation
        experimental knowledge based
        affinity chromatography technology, molecular sieving, western blot
        pull down, anti tag western blot
        experimental knowledge based
        anti bait coimmunoprecipitation, western blot, cosedimentation, experimental knowledge based
        affinity chromatography technology, molecular sieving, western blot
        affinity chromatography technology, molecular sieving, western blot
        affinity chromatography technology, molecular sieving, western blot, pull down, cosedimentation, anti tag western blot
        affinity chromatography technology, molecular sieving, western blot
        experimental knowledge based
        anti bait coimmunoprecipitation, western blot
        anti tag coimmunoprecipitation, western blot
        experimental knowledge based
        anti tag coimmunoprecipitation, western blot, anti bait coimmunoprecipitation, experimental knowledge based
        Alleles Reported to Model Human Disease (Disease Ontology) (7 alleles)
        Models Based on Experimental Evidence ( 3 )
        Modifiers Based on Experimental Evidence ( 4 )
        Models Based on Experimental Evidence ( 2 )
        Modifiers Based on Experimental Evidence ( 0 )
        Allele
        Disease
        Interaction
        References
        Alleles Representing Disease-Implicated Variants
        Genetic Tools, Stocks and Reagents
        Sources of Stocks
        Contact lab of origin for a reagent not available from a public stock center.
        Bloomington Stock Center Disease Page
        Selected mammalian transgenes
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila transgenes
        Allele
        Transgene
        Publicly Available Stocks
        RNAi constructs available
        Allele
        Transgene
        Publicly Available Stocks
        Selected Drosophila classical alleles
        Allele
        Allele class
        Mutagen
        Publicly Available Stocks
        amorphic allele - molecular evidence
        ethyl methanesulfonate
        References (14)