ubiquitin D; Diubiquitin; ubiquitin-like protein FAT10 (UBD, FAT10)

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 - diabetic nephropathy - IgA nephropathy, - hypertensive nephrosclerosis - HIV1-associated nephropathy - 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

General

nuclear protein phosphoprotein

Properties

SIZE: entity length = 165 aa MW = 18 kD COMPARTMENT: cytoplasm cell nucleus MOTIF: Ubiquitin 1 {6-81} Ubiquitin 2 {90-163} MOTIF: Ser phosphorylation site {S109} Ser phosphorylation site {S110} Ser phosphorylation site {S111} peptide motif {164-165}

Database Correlations

OMIM 606050 UniProt O15205 Pfam PF00240 Entrez Gene 10537 Kegg hsa:10537

References

UniProt :accession O15205