ubiquitin D; Diubiquitin; ubiquitin-like protein FAT10 (UBD, FAT10)
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Function
- ubiquitin-like protein modifier
- can be covalently attached to target protein & subsequently leads to their degradation by the 26S proteasome (NUB1L-dependent)
- probably functions as a survival factor
- conjugation ability activated by UBA6
- promotes expression of the proteasome subunit beta type-9 (PSMB9/LMP2)
- regulates TNF-alpha-induced & LPS-mediated activation of the central mediator of innate immunity NF-kappa-B by promoting TNF-alpha-mediated proteasomal degradation of ubiquitinated I-kappa-B-alpha
- required for TNF-alpha-induced NF-kappa-B p65 nuclear translocation in renal tubular epithelial cells
- may be involved in dendritic cell maturation
- mediates mitotic non-disjunction & chromosome instability, in long-term in vitro culture & cancers, by abbreviating mitotic phase & impairing the kinetochore localization of MAD2L1 during the prometaphase stage of the cell cycle
- may be involved in the formation of aggresomes when proteasome is saturated or impaired
- mediates apoptosis (caspase-dependent), especially in renal epithelium & renal tubular cells during renal disease such as polycystic kidney disease & HIV1-associated nephropathy
- can be acetylated
- interacts directly with the 26S proteasome
- interaction with NUB1L vie the N-terminal ubiquitin domain facilitates linking of UBD-conjugated target protein to the proteasome complex & accelerates its own degradation & that of its conjugates
- interacts with the spindle checkpoint protein MAD2L1 during mitosis
- present in aggresomes of proteasome inhibited cells
- interacts with HDAC6 under proteasome impairment conditions
- forms a thioester with UBA6 in cells stimulated with TNF-alpha & IFN-gamma
Structure
- contains 2 ubiquitin-like domains
Compartment
- nucleus, cytoplasm (putative)
- accumulates in aggresomes under proteasome inhibition conditions
Expression
- constitutively expressed in mature dendritic cells & B-cells
- mostly expressed in the reticuloendothelial system (e.g. thymus, spleen), the gastrointestinal system, kidney, lung & prostate
- rapidly degraded by the proteasome
- cell-cycle regulation
- highest expression during S-phase (at protein level)
- induced during dendritic cell maturation
- negatively regulated by p53/TP53
- repressed by NUB1L (at protein level)
Pathology
- high levels in various GI cancers & urogenital cancers
- induced in renal tubular epithelial cells in renal disease including
- FAT10 may mediate NF-kappa-B activation & may promote tubulointerstitial inflammation in chronic kidney diseases
- induced in hepatocellular carcinoma
- inducible by the proinflammatory cytokines IFNG/IFN-gamma & TNF in liver cancer & colorectal carcinoma