FB2026_01 , released March 12, 2026
FB2026_01 , released March 12, 2026
Human Disease Model Report: Parkinson disease 5, susceptibility to
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General Information
Name
Parkinson disease 5, susceptibility to
FlyBase ID
FBhh0000859
Disease Ontology Term
Parent Disease
OMIM
PARKINSON DISEASE 5, AUTOSOMAL DOMINANT, SUSCEPTIBILITY TO; PARK5
Overview

This report describes Parkinson disease 5 (PARK5, PD5), which is a subtype of Parkinson disease; PARK5 exhibits autosomal dominant inheritance. The human gene implicated in this disease is UCHL1, Ubiquitin carboxyl-terminal esterase L1, which is involved in the processing of ubiquitin precursors and of ubiquitinated proteins. UCHL1 is also implicated in a form of spastic paraplegia (SPG7; MIM:615491). There is a single orthologous gene in Drosophila, Uch, for which RNAi-targeting constructs and alleles caused by insertional mutagenesis have been generated. Dmel\Uch is also orthologous to the human gene UCHL3.

A UAS construct of a tagged human Hsap\UCHL1 gene has been introduced into flies, but has not been characterized in the context of this disease model.

RNAi-mediated knockdown of Dmel\Uch in dopaminergic neurons (DA neurons) results in the underdevelopment and/or progressive degeneration of the DA neurons; adult animals exhibit age-dependent locomotor defects. Many physical interactions have been described for Dmel\Uch; see below and in the Uch gene report.

[updated Nov. 2018 by FlyBase; FBrf0222196]

Disease Summary Information
Parent Disease Summary: Parkinson disease
Symptoms and phenotype

Parkinson disease (PD) is a neurodegenerative disease usually typified by slow onset in mid to late adulthood; there are also early-onset and juvenile forms of the disease. Symptoms worsen over time and include resting tremor, muscular rigidity, bradykinesia [abnormal slowness of movement], and postural instability [impaired balance and coordination]; additional symptoms may include postural abnormalities, dysautonomia [symptoms caused by malfunction of the autonomic nervous system], dystonic cramps, and dementia. Parkinson disease is the second-most common neurodegenerative disease (after Alzheimer disease), affecting approximately 1% of the population over 50 (Polymeropoulos et al., 1996, pubmed:8895469). [from MIM:168600; 2013.07.23]

(OMIM, 2013-)

Parkinson disease is described as early-onset disease if signs and symptoms begin before age 50. Early-onset cases that begin before age 20 may be referred to as juvenile-onset disease. [from Genetics Home Reference, GHR_condition:parkinson-disease, 2015.02.13]

(FlyBase Curators, 2013-)
Specific Disease Summary: Parkinson disease 5, susceptibility to
OMIM report

[PARKINSON DISEASE 5, AUTOSOMAL DOMINANT, SUSCEPTIBILITY TO; PARK5](https://omim.org/entry/613643)

Human gene(s) implicated

[UBIQUITIN CARBOXYL-TERMINAL ESTERASE L1; UCHL1](https://omim.org/entry/191342)

Symptoms and phenotype
Genetics

Susceptibility to autosomal dominant Parkinson disease-5 (PARK5) is conferred by heterozygous mutation in the UCHL1 gene; one such family has been reported. [from MIM:613643; 2018.07.24]

(OMIM, 2013-)
Cellular phenotype and pathology
Molecular information

UCHL1 encodes a ubiquitin-protein hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. [Gene Cards, UCHL1; 2018.07.24]

(FlyBase Curators, 2013-)

Ubiquitin carboxyl-terminal esterase L1 (UCHL1) is a member of a gene family whose products hydrolyze small C-terminal adducts of ubiquitin to generate the ubiquitin monomer. Expression of UCHL1 is highly specific to neurons and to cells of the diffuse neuroendocrine system. It is present in all neurons (Doran et al., 1983; pubmed:6343558). [from MIM:191342; 2018.07.24]

(OMIM, 2013-)
External links
Disease synonyms
PARK5
PD5
Ortholog Information
Human gene(s) in FlyBase
Human gene (HGNC)
Symbol / Name
UCHL1; ubiquitin C-terminal hydrolase L1
D. melanogaster ortholog (based on DIOPT)
Dmel\Uch
(DIOPT, 2013-)
Comments on ortholog(s)

Many to one (2 human to 1 Drosophila); the other human gene is UCHL3.

Other mammalian ortholog(s) used
    D. melanogaster Gene Information (1)
    Dmel\Uch
    Gene Snapshot
    Contributions welcome
    Molecular function (GO)
    Cellular component (GO)
    Gene Groups / Pathways
    Comments on ortholog(s)

    Moderate- to high-scoring ortholog of human UCHL3 and UCHL1 (1 Drosophila to 2 human). Dmel\Uch shares 40-46% identity and 54-67% similarity with the human genes.

    Orthologs and Alignments from DRSC
    DIOPT - DRSC Integrative Ortholog Prediction Tool - Click the link below to search for orthologs in Humans
    H. sapiens (Human)
    Other Genes Used: Viral, Bacterial, Synthetic (0)
      Summary of Physical Interactions (64 groups)
      Uch
      RNA-protein
      Interacting group
      Assay
      References
      Uch - orb2
      pull down, western blot
      (Mastushita-Sakai et al., 2010)
      protein-protein
      Interacting group
      Assay
      References
      Uch - Acaa
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Akap200
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Aldo
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - AnxB9
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - AnxB10
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Ar1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Ar2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Ar3
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - awd
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Calr
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - capt
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - CG2852
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - CG4598
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - CG5174
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - CG6180
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - CG13887
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - CG14715
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Chd64
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - chic
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - cib
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Df31
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Dld
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Eb1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - eEF1δ
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - EndoGI
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Eno
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - fabp
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - fax
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Fim
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Fkbp12
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Fkbp14
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Gdi
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Glo1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - GstE6
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - GstO3
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - GstT1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Gtpx
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - HINT1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Inos
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Mdh2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Moe
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Nacα
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Nlp
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Nph
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Ntan1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - PCNA
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Pdi
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Pgd
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Pgk
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Prosα1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Prx6c
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - regucalcin
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - RhoGDI
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - scf
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - scu
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - sel
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Sh3β
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Sod2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Stip1
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Sumo
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - TER94
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Tkt
      experimental knowledge based
      (Guruharsha et al., 2011)
      Uch - Trx2
      experimental knowledge based
      (Guruharsha et al., 2011)
      Alleles Reported to Model Human Disease (Disease Ontology) (6 alleles)
      Uch
      Models Based on Experimental Evidence ( 4 )
      Modifiers Based on Experimental Evidence ( 6 )
      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
      Related mammalian, viral, bacterial, or synthetic transgenes
      Allele
      Transgene
      Publicly Available Stocks
      Hsap\UCHL1UAS.Tag:HA
      PBac{UAS-hUCHL1.HA}
      y1 w*; PBac{UAS-hUCHL1.HA}VK00033/TM3, Sb1 Ser1
      Selected Drosophila transgenes
      Allele
      Transgene
      Publicly Available Stocks
      RNAi constructs available
      Allele
      Transgene
      Publicly Available Stocks
      UchHMC06627
      P{TRiP.HMC06627}
      y1 v1; P{TRiP.HMC06627}attP40
      UchGD11265
      P{GD11265}
      w1118; P{GD11265}v26468
      UchKK101723
      P{KK101723}
      P{KK101723}VIE-260B
      UchNIG.4265R
      P{NIG.4265R}
      P{NIG.4265R}1
      Selected Drosophila classical alleles
      Allele
      Allele class
      Mutagen
      Publicly Available Stocks
      UchKO
      amorphic allele - molecular evidence
      CRISPR/Cas9
      UchE8A
      CRISPR/Cas9
      UchV96M
      CRISPR/Cas9
      UchC93S
      CRISPR/Cas9
      References (20)