Ubiquitin-like protein modifier which can be covalently attached to target protein and subsequently leads to their degradation by the 26S proteasome, in a NUB1-dependent manner. Probably functions as a survival factor. Promotes the expression of the proteasome subunit beta type-9 (PSMB9/LMP2). Regulates TNF-alpha-induced and 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 p65 nuclear translocation in renal tubular epithelial cells (RTECs). May be involved in dendritic cell (DC) maturation, the process by which immature dendritic cells differentiate into fully competent antigen-presenting cells that initiate T-cell responses. Mediates mitotic non-disjunction and chromosome instability, in long-term in vitro culture and cancers, by abbreviating mitotic phase and 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 in a caspase-dependent manner, especially in renal epithelium and tubular cells during renal diseases. Interacts directly with the 26S proteasome. The interaction with NUB1 via the N-terminal ubiquitin domain facilitates the linking of UBD-conjugated target protein to the proteasome complex and accelerates its own degradation and that of its conjugates. Interacts (via ubiquitin-like 1 domain) with the spindle checkpoint protein MAD2L1 during mitosis. Present in aggresomes of proteasome inhibited cells. Interacts with HDAC6 under proteasome impairment conditions (By similarity). Forms a thioester with UBA6 in cells stimulated with tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg) (PubMed:17889673). Interacts with SQSTM1 and TP53/p53 (By similarity). Accumulates in aggresomes under proteasome inhibition conditions. Mostly expressed in thymus and intestine. Rapidly degraded by the proteasome. Cell-cycle regulation with highest expression during the S-phase (at protein level). Over expressed in hepatocytes by drug injury (e.g. DDC; diethyl 1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate). Inducible by the pro-inflammatory cytokines tumor necrosis factor-alpha (TNFa) and interferon-gamma (IFNg). Can be acetylated. Spontaneous sporadic apoptotic death. Higher sensitivity toward endotoxin challenge. Abrogated TNF-alpha-induced NF-kappa-B activation and reduced induction of NF-kappa-B-regulated genes. Impaired TNF-alpha-induced I-kappa-B-alpha degradation and nuclear translocation of p65 in RTECs. Reduced expression of LMP2.