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FLASH GENE
Symbol USP19 contributors: mct/pgu - updated : 28-01-2020
HGNC name ubiquitin specific protease 19
HGNC id 12617
DNA
TYPE functioning gene
SPECIAL FEATURE arranged in tandem
STRUCTURE 12.89 kb     26 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Map pter - D3S3582 - USP19 - D3S1578 - D3S1588 - cen
Authors Gene Map (98)
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
26 - 4401 145.6 1318 - 2019 30386869
26 - 4492 - 1268 - 2019 30386869
26 - 4498 - 1270 - 2019 30386869
27 - 4795 - 1369 - 2019 30386869
27 - 4820 - 1371 - 2019 30386869
27 - 4847 - 1372 - 2019 30386869
26 - 4537 - 1283 - 2019 30386869
26 - 4537 - 1283 - 2019 30386869
27 - 4878 - 1419 - 2019 30386869
27 - 4883 - 1384 - 2019 30386869
27 - 4831 - 1381 - 2019 30386869
27 - 4867 - 1420 - 2019 30386869
27 - 4840 - 1384 - 2019 30386869
26 - 4543 - 1285 - 2019 30386869
27 - 4714 - 1369 - 2019 30386869
EXPRESSION
Type ubiquitous
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Nervousnerve   highly
Skin/Tegumentskin   highly
tissue
SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
Connectivebone  highly
Muscularstriatumskeletal highly
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • only deubiquitinating enzyme containing a C-terminal transmembrane domain, that appears to be partially stabilized in the cytosol by an interaction with its own catalytic domain, resulting in auto-inhibition of its deubiquitinating activity
  • HOMOLOGY
    Homologene
    FAMILY
  • deubiquitin family
  • peptidase C19 family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic
    text
  • like RNF123, is localized to the cytosol
  • tail-anchored ubiquitin-specific protease localized to the ER
  • basic FUNCTION
  • involved in the ubiquitin-dependent proteolytic pathway in conjunction with the 26S proteasome
  • deubiquitinating enzyme that regulates the stability of a cyclin-dependent kinase inhibitor and demonstrate that progression through G1 to S phase is, like the metaphase-anaphase transition, controlled in a hierarchical, multilayered fashion
  • rescues the ER-associated-degradation (ERAD) substrates CFTRDelta508 and TCR-alpha from proteasomal degradation
  • function on specific ERAD substrates
  • modulates transcription of major myofibrillar proteins and the ubiquitin system not only mediates the increased protein breakdown but is also involved in the decreased protein synthesis in atrophying skeletal muscle
  • positively regulates proliferation in fibroblasts by stabilizing RNF123, a ubiquitin ligase for CDKN1B
  • regulates hypoxia-inducible factor 1A (HIF1A) during hypoxia
  • only the ER-localized isoform of USP19 (USP19-ER) modulated myoblast fusion as well as the expression of myogenin and myofibrillar proteins, and these effects were also dependent on USP19 catalytic activity
  • USP19 is involved in human muscle wasting
  • possible function of USP19 in quality control of misfolded proteins by regulating their protein levels
  • USP19 is involved in the regulation of ERAD by controlling the stability of MARCHF6 via deubiquitination
  • dual functions of the USP19-BECN1 axis by balancing autophagy and the production of type IIFNs
  • USP19 is a key factor in modulating DNA damage repair by targeting HDAC1/2 K63-linked ubiquitination
  • USP19 is an important regulator of fat development
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with and stabilizing RNF123
  • USP19, a deubiquitinating enzyme, interacts with cellular BIRC2, BIRC3
  • interacts with components of the hypoxia pathway including HIF1A and rescues it from degradation independent of its catalytic activity
  • SIAH1 and SIAH2 are binding partners of USP19, interaction mediated by a SIAH-consensus binding motif and promoting USP19 ubiquitylation and proteasome-dependent degradation
  • overexpressed USP19 interacts with DERL1 and other ERAD machinery factors in the membrane, but endogenous USP19 is mostly in the cytosol where it binds Hsp90
  • regulation of CORO2A through the deubiquitinating activity of USP19 affected the transcriptional repression activity of the retinoic acid receptor (RAR), suggesting that USP19 may be involved in the regulation of RAR-mediated adipogenesis
  • USP19 is the only deubiquitinase that directly binds to SIAHs(SIAH1, SIAH2) through the substrate binding pocket
  • USP19 regulates the stability of SYVN1 and provide insight into the regulatory mechanism of the ERAD ubiquitin ligases
  • DNAJC5 facilitates USP19-dependent unconventional secretion of misfolded cytosolic proteins
  • mechanistically, USP19 interacted with MAP3K7 in a TNF or IL1B-dependent manner
  • USP19 interacts with TICAM1 and catalyzes the removal of TICAM1 K27-linked polyubiquitin moieties, thereby impairing the recruitment of TICAM1 to TLR3/4
  • cell & other
    REGULATION
    induced by in skeletal muscle atrophying in response to numerous catabolic stimuli
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       loss of function
    its inactivation leads to protection from muscle loss induced by stimuli that are common in many illnesses causing cachexia
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    diabete  
    inhibition of USP19 could have therapeutic potential to protect from the deleterious consequences of obesity and diabetes
    neuromuscular  
    inhibition of USP19 may be a useful approach to the treatment of many muscle-wasting conditions
    ANIMAL & CELL MODELS