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General Information
Name
alcohol, response to, cathepsin-related
FlyBase ID
FBhh0001181
OMIM
Overview

This report describes characterization of the fly alcohol response using the Drosophila gene Cp1. Dmel\Cp1 encodes a member of the cysteine cathepsin protease family. There are multiple members of this family in both Drosophila and human; the mostly closed related human genes are CTSV and CTSL. RNAi targeting constructs and alleles caused by insertional mutagenesis have been generated for Dmel\Cp1.

A UAS construct of the human Hsap\CTSV gene has been introduced into flies, but has not been characterized.

Animals homozygous for loss-of-function mutations of Dmel\Cp1 are viable; in some cases, females are sterile. In adult flies, RNAi-effected knockdown of Dmel\Cp1 in glia increases alcohol sedation in response to acute administration of alcohol; this effect is specific to cortex glia and adulthood. Genetic and physical interactions of Dmel\Cp1 have been described; see below and in the Cp1 gene report.

[updated Feb. 2020 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: alcohol use disorder, susceptibility to (fly models overview)
Symptoms and phenotype

Alcoholism can be defined as persistence of excessive drinking over a long period of time despite adverse health effects and disruption of social relations (Morozova et al., 2014; pubmed:24395673).

The 2013 Diagnostic and Statistical Manual of Mental Disorders (DSM) combined the two former categorizations of abnormal alcohol use (alcohol abuse and alcohol dependence) into one diagnosis: alcohol use disorder. The severity of an individual's AUD is broken into classifications: mild, moderate, or severe. "Alcoholism" is a non-medical term often used to describe a severe form of alcohol use disorder. (https://www.therecoveryvillage.com/recovery-blog/alcoholism-alcohol-use-disorder-whats-difference/)

Excessive alcohol consumption is associated with increased risk of different types of cancer, higher cardiovascular disease mortality, birth defects, liver diseases, and neuropsychiatric disorders (Morozova et al., 2014; pubmed:24395673).

Alcoholism is a multifactorial, genetically influenced disorder. [from OMIM:103780; 2017.12.19]

Specific Disease Summary: alcohol, response to, cathepsin-related
OMIM report
Human gene(s) implicated
Symptoms and phenotype
Genetics
Cellular phenotype and pathology
Molecular information

Cathepsins comprise a highly conserved protease family distinguished by their structure, catalytic mechanism, and substrate specificities. Most members of this family function primarily in lysosomes, becoming activated at the low pH found in lysosomes (https://www.genenames.org/data/genegroup/#!/group/470).

Cysteine cathepsins are optimally active in a slightly acidic pH and are mostly unstable at neutral pH. The view of cysteine cathepsins as exclusively lysosomal proteases is changing as there is now clear evidence of their localization in other cellular compartments. (Turk et al., 2012; pubmed:22024571).

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: multiple related genes in both species.

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

Many to many: multiple related genes in both species.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate- to high-scoring ortholog of human CTSV and CTSL; multiple related genes in both species. Dmel\Cp1 shares 51-52% identity and 67% similarity with CTSV and CTSL.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    Synthetic Gene(s) Used (0)
    Summary of Physical Interactions (25 groups)
    protein-protein
    Interacting group
    Assay
    References
    experimental knowledge based
    experimental knowledge based
    enzymatic study, fluorescence technology
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting
    experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    experimental knowledge based
    anti tag coimmunoprecipitation, peptide massfingerprinting
    Alleles Reported to Model Human Disease (Disease Ontology) (2 alleles)
    Models Based on Experimental Evidence ( 0 )
    Allele
    Disease
    Evidence
    References
    Modifiers Based on Experimental Evidence ( 2 )
    Allele
    Disease
    Interaction
    References
    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
    References (3)