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FLASH GENE
Symbol USP1 contributors: mct/npt/pgu - updated : 27-12-2018
HGNC name ubiquitin specific peptidase 1
HGNC id 12607
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
9 - 3949 - 785 - 2005 USP1
9 - 3519 - 785 - 2005 USP1
9 - 3424 - 785 - 2005 USP1
EXPRESSION
Type ubiquitous
constitutive of
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Lymphoid/Immunelymph node   highly
Reproductivemale systemtestis  highly
Respiratoryrespiratory tracttrachea  highly
Urinarybladder   highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminus of USP1 is sufficient to engineer specificity in a more promiscuous USP, but is not required for direct PCNA or FANCI deubiquitination
  • two nuclear localization signals in USP1 mediate nuclear import of the USP1/WDR48 complex
  • HOMOLOGY
    intraspecies paralog to USP12
    Homologene
    FAMILY
  • ubiquitin specific processing family member
  • peptidase C19 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus
    basic FUNCTION
  • involved in cleavage beta galactosidase
  • cleaving the ubiquitin moiety from ubiquitin-fused precursors and ubiquitinylated proteins
  • protease that removes monoubiquitin from FANCD2 and PCNA, was thought to reverse the DNA damage response of these substrates
  • involved in deubiquitination of FANCD2
  • deubiquitinating enzyme for PCNA after DNA damage bypass, and reduces the accumulation of monoubiquitinated PCNA during normal cell division
  • participates in the maintenance of both total and phosphorylated levels of CHEK1 in response to genotoxic stress
  • USP1 deubiquitinase controls a feedback loop that limits CHEK1 activity to rescue DNA-damaged cells
  • regulates DNA repair and the Fanconi anemia pathway through its association with WDR48, and through its deubiquitination of two critical DNA repair proteins, FANCD2-Ub and PCNA-Ub
  • USP1/WDR48 complex promotes homologous recombination, at least in part by suppressing nonhomologous end-joining
  • plays important roles in cancer-related processes, such as the DNA damage response, and the maintenance of the undifferentiated state of osteosarcoma cells
  • is a key senescence regulator controlling genomic integrity and a promising target for anti-cancer therapy
  • novel function of USP1 in the control of beta-cell survival
  • novel function of the USP1-ULK1 axis as a modulator of the switch between canonical and unconventional autophagy
  • USP1 exhibits DNA-mediated activation at the replication fork, protects the fork, and promotes survival in BRCA1-deficient cells
  • CELLULAR PROCESS protein, degradation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
  • formation of a stable USP1/WDR48 protein complex, activating FANCD2 (Cohn 2009), and can deubiquitinate PCNA
  • USP1/WDR48 complex is a regulator of the cellular response to DNA damage
  • USP1-WDR48 complex is a potential target for the prevention of viral diseases
  • USP1/WDR48 complex promotes stem cell conservation and regulation of DNA damage repair
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • deubiquitinates FANCD2 when cells exit S phase or recommence cycling after a DNA damage insult and may play a critical role in the FA pathway by recycling FANCD2
  • ATAD5 specifically directs USP1-WDR48 complex for PCNA deubiquitination
  • important regulatory role of the USP1-WDR48 complex in HR (homologous recombination) repair through its regulation of the FANCD2-ubiquitinated (Ub) and PCNA-Ub cellular pools
  • USP1 amino acid motif 420-520 is necessary and sufficient for WDR48 binding
  • efficient USP1 activity requires binding to its cofactor USP1-associated factor 1 (WDR48), and the USP1-WDR48 deubiquitinase complex has important roles in regulating DNA damage-related processes
  • USP1-WDR48 complex promotes homologous recombination (HR) repair via multiple mechanisms: through FANCD2 deubiquitination, as well as by interacting with RAD51AP1
  • WDR48 is a WD40 repeat protein, which binds and activates three important deubiquitinating enzymes (DUBs), USP1, USP12 and USP46
  • mechanistically, USP1 and WDR48 bound to TBK1, removed its K48-linked polyubiquitination, and then reversed the degradation process of TBK1
  • N-terminus of USP1 harbours a FANCD2-specific binding sequence required for deubiquitination of K561 on FANCD2
  • cell & other
    REGULATION
    activated by activated upon forming a complex with the novel WD40-domain containing activator protein WDR48
    Other serine phosphorylation is critical for the activation of USP1 and its interaction with WDR48
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    Inhibition of USP1 may be a useful treatment for a subset of PARP-inhibitor-resistant BRCA1-deficient tumors with acquired replication fork stabilization
    diabete  
    USP1 inhibition may have a potential therapeutic relevance for the suppression of beta-cell death in diabetes
    ANIMAL & CELL MODELS
    mouse Usp1 functions downstream in the FA pathway