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FLASH GENE
Symbol USP9X contributors: mct - updated : 05-09-2019
HGNC name ubiquitin specific peptidase 9, X-linked
HGNC id 12632
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • five highly conserved domains, domains I, II and III containing the expected catalytic triad Cys, Asp, His which defines cysteine proteases
  • catalytic and ubiquitin-like domains
  • C terminus of USP9X binds the regulator of neuronal cell migration Doublecortin
    • HOMOLOGY
    interspecies homolog to murine Dres14
    homolog to Drosophila developmental gene fat facets related on the X
    Homologene
    FAMILY
  • deubiquitin family
  • peptidase C19 family
    • CATEGORY enzyme , tumor suppressor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm
    text
  • interacting with MARCH7 in the cytosol
  • mostly cytosolic, but is also found in the nucleoplasm
  • localizes along the length of the ciliary axoneme
    • basic FUNCTION
  • may function as a ubiquitin-protein or polyubiquitin hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins
  • may play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin
  • can stabilize MARCH7, and deubiquitylate MARCH7 in the cytosol
  • deubiquitinase acting as essential and evolutionarily conserved component in TGFbeta and bone morphogenetic protein signaling, opposing the activity of Ectodermin/Tif1gamma (Ecto, TRIM33)
  • enhances the polarity and self-renewal of embryonic stem cell-derived neural progenitors
  • stabilizes MCL1 and thereby promotes cell survival
  • controlling the level of PSD, mediating its deubuiquitination and protecting from proteasomal degradation, thus regulating de nov tight junction assembly
  • is an elongated monomeric protein with the capacity to hydrolyze thioester, isopeptide, and peptide bonds
  • implicated in the participation in the PEX5-mediated peroxisomal protein import pathway
  • acts as a negative regulator of MTOR activity and muscle differentiation
  • is a major tumour suppressor gene with prognostic and therapeutic relevance in pancreatic ductal adenocarcinoma
  • is a novel regulator of SMURF1 and is required for SMURF1-dependent cellular physiology
  • required for normal neuronal cell migration
  • substrate-specific deubiquitylating enzyme, and thus regulates the proteome
  • role in de-ubiquitination of ciliary proteins
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    TGFB pathway
    a component
  • component of the TGFB pathway
    • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with DCX to regulate cell adhesion
  • binding partner of ITCH (transient overexpression of FAM/USP9X resulted in the deubiquitylation of ITCH)
  • interacting with and deubiquitinating monoubiquitinated SMAD4, opposing the activity of Ectodermin/TIF1G (TRIM33), rather than stability
  • with TRIM33 act as antagonistic SMAD4 regulator during embryonic development
  • binding MCL1 and removing the Lys48-linked polyubiquitin chains
  • interacting with MCL1 (stabilizes MCL1 by reversing its polyubiquitination)
  • interacts with and deubiquitinates SNCA
  • involved in MCL1 protein turnover by preventing its degradation through the removal of conjugated ubiquitin
  • SMURF1 is known to bind the C terminus of USP9X and has established roles in cell migration
  • PMAIP1 over-expression caused a decrease in the USP9X/MCL1 interaction associated with an increase in the MCL1 polyubiquitinated forms
  • USP9X was found to be the most active deubiquitinase acting on ubiquitin-PEX5
  • novel MTOR and CRTC2 binding partner that negatively regulates MTOR activity and skeletal muscle differentiation
  • USP9X interacts with SMURF1 and stabilizes SMURF1 through deubiquitination
  • in B lymphocytes, USP9X is required for the induction of PRKCB activity after BCR-dependent activation
  • USP9X functions as a positive regulatory switch during T lymphocyte priming through removal of inhibitory monoubiquitination from ZAP70
  • USP9X is a novel regulator of the translation initiation process via deubiquitination of EIF4A1, which offers new insight in understanding the pivotal role of USP9X in malignancies and neurodevelopmental disorders
  • deubiquitinase, USP9X interacts with ZBTB38, deubiquitinates it, and stabilizes it
  • USP9X is a deubiquitinase of PBX1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) MRX99 , MRXS99F
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    increased expression in follicular lymphomas and diffuse large B-cell lymphomas correlates with increased MCL1 expression and poor prognosis
    tumoral       loss of function
    inactivated in over 50p100 of the pancreatic ductal adenocarcinoma (PDA)
    constitutional     --low  
    lower levels of cytosolic USP9X and deubiquitinase activity in alpha-synucleinopathies may contribute to the accumulation and aggregation SNCA in Lewy bodies
    constitutional       loss of function
    resulted in changes to the neuronal cytoskeleton
    constitutional germinal mutation      
    associated with nonsyndromic X-linked intellectual disability
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • marker prognostic in follicular lymphomas and diffuse large B-cell lymphomas
    • Therapy target
    SystemTypeDisorderPubmed
    cancerreproductiveprostate
    targeting the USP9X/PBX1 axis could be a potential therapeutic strategy for managing advanced prostate cancer
    cancerhemopathy 
    therapy target in follicular lymphomas and diffuse large B-cell lymphomas
    ANIMAL & CELL MODELS