Selected-GenAtlas references SOURCE GeneCards NCBI Gene Swiss-Prot Ensembl
HGNC UniGene Nucleotide OMIM UCSC
Home Page
FLASH GENE
Symbol USP8 contributors: mct/npt/pgu - updated : 28-04-2016
HGNC name ubiquitin specific protease 8
HGNC id 12631
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Digestivesalivary gland   highly
 stomach   highly
Hearing/Equilibriumearinnercochlea highly
Reproductivemale systemmale genital tractepididymis   Homo sapiens
cells
SystemCellPubmedSpeciesStageRna symbol
Reproductivespermatozoa Homo sapiens
cell lineage myeloid cell lines
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • a Microtubule Interacting and Transport (MIT) domain at the N terminus that constitutes an endosomal localization signal, dispensable for its catalytic activity but essential for its localization to endosomes
  • a CHMP binding (domain dispensable for its catalytic activity but is essential for its localization to endosomes)
  • a rhodanese domain
  • C-terminal catalytic domain of USP8 exhibits the conserved tripartite architecture but shows unique traits
  • HOMOLOGY
    intraspecies paralog to ubiquitin specific protein proteases UBP
    paralog to tre oncogene
    Homologene
    FAMILY
  • deubiquitin family
  • peptidase c19 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • ubiquitin specific protease, hydrolyzing isopeptide bonds between UB and folded protein domains such as additional UB mioetis or target proteins
  • its function is essential for growth factor receptor down-regulation, and regulation of endosomal ubiquitin dynamics is essential for receptor down-regulation
  • regulates the level of protein ubiquitination on endosomes, which is required for maintaining the morphology of the organelle
  • can remove conjugated ubiquitin from proteins and therefore plays an important regulatory role at the level of protein turnover by preventing degradation
  • regulating endosomal ubiquitin dynamics and essential for receptor down-regulation
  • playing central and nonredundant role in growth regulation, endosomal sorting, and the control of several growth factor receptor tyrosine kinases (RTKs)
  • regulates cargo sorting and membrane traffic at early endosomes
  • with STAMBP are essential for trafficking and down-regulation of F2RL1 but not for regulating F2RL1 dissociation from beta-arrestin2 or F2RL1-mediated ERK2 activation
  • regulator of HGS function with consequences for the stability of receptors subject to HGS-dependent endocytosis
  • deubiquitinating activity of USP8 is required for trafficking of CXCR4 between the early and late endosomal compartments
  • modulates HGS ubiquitination to regulate endosomal ubiquitin dynamics and trafficking through the ESCRT-0 checkpoint
  • implicated in control of a highly topical and medically relevant plasma membrane receptor
  • USP8 regulates the rate of KCNN4 degradation by deubiquitylating KCNN4 prior to lysosomal delivery
  • positive regulator in HH signaling by down-regulating SMO ubiquitination and thereby mediating SMO intracellular trafficking
  • role for USP8 in the control of SCNN1A ubiquitination and trafficking
  • controls the trafficking and sorting of lysosomal enzymes
  • is critical for parkin-mediated mitophagy
  • preferentially removes non-canonical K6-linked ubiquitin chains from parkin, a process required for the efficient recruitment of parkin to depolarized mitochondria and for their subsequent elimination by mitophagy
  • BIRC6 and USP8 are two hitherto uncharacterized critical DNA damage response (DDR) regulators
  • USP8-sorted cargo contributes early to acrosomogenesis and its trafficking is microtubule-mediated
  • CELLULAR PROCESS protein, ubiquitin dependent proteolysis
    PHYSIOLOGICAL PROCESS
    text the MIT domain is required for efficient epidermal growth factor receptor degradation
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacts with the SH3 domain of STAM2
  • interacts with RASGRF1
  • interacting with RNF41, specific target for the USP8 deubiquitinating enzyme and are consistent with a model where USP8 activate RNF41 activity by mediating its stabilization
  • interacting with CHMP1A, CHMP1B or CHMP7
  • can interact with CHMP proteins, which are known to regulate endosomal sorting of ubiquitinated receptors
  • interacting with RNF41 hthrough the rhodanese domain
  • associates with STAM to mediate direct deubiquitination of activated EGFR, thereby stabilizing the receptor against down-regulation by the lysosome
  • cooperation between USP8, ITCH, and the ESCRT-0 machinery in shaping receptor progression through the sorting endosome
  • positive regulator of CXCR4 trafficking for degradation
  • time-dependent association between KCNN4 and USP8 following endocytosis
  • interacting with SMO (overexpression of USP8 prevents SMO ubiquitination and elevates SMO accumulation, leading to increased HH signaling activity)
  • RNF41-interacting deubiquitylating enzyme (DUB) stabilizes RNF41 and is involved in trafficking of various transmembrane proteins
  • USP8/UBPY, a deubiquitinating enzyme not previously implicated in mitochondrial quality control, is critical for PARK2-mediated mitophagy
  • BIRC6 acts as a scaffold, bridging the ubiquitin-specific peptidase 8 (USP8) and MCPH1 in a complex to coordinate USP8-catalyzed deubiquitination of MCPH1
  • USP8 plays a key role in the trafficking and degradation of BACE1 by deubiquitinating lysine 501
  • USP8 interacts with and deubiquitinates SEC31A; the interaction was mediated by the adaptor protein STAM
  • cell & other
    REGULATION
    inhibited by YWHAE (catalytically inhibited in a phosphorylation-dependent manner by 14-3-3s during the interphase, and this regulation is cancelled in the M phase)
    Other is post-translationally modified by tyrosine and serine phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    leads to diminished CXCR4 turnover and induces receptor accumulation on enlarged HGS-positive early endosomes
    constitutional somatic mutation     gain of function
    contribute to ACTH overproduction in Cushing disease
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    tumor  
    inhibition of USP8 or EGFR is promising for treating USP8-mutated corticotrophin adenoma
    ANIMAL & CELL MODELS