Ubiquilin 1 (UBQLN1), also known as DA41, was isolated from an adult rat lung cDNA library, and encodes a cellular protein that associates with DAN.1 DAN expression is reduced in rat fibroblast 3Y1 cells transformed with mouse sarcoma virus and in rodent fibroblasts transformed with a variety of oncogenes. The DAN-DA41 interaction is mediated through the N-terminal domain and a cysteine-knot region of DAN. Human DA41 encodes a 589-amino acid protein with 86% amino acid sequence identity with rat protein.2 DA41 expression is regulated in a cell cycle-dependent manner. PLIC1 and PLIC2 (UBQLN2) are homologs of the mouse Plics (proteins linking integrin-associated protein (IAP) and cytoskeleton) and the yeast Dsk2 protein. PLIC1, also called UBQLN1, shares 72% amino acid identity with PLIC2,3 Two motifs are conserved in the mammalian PLICs and yeast Dsk2, an N-terminal ubiquitin-like (UBL) domain and a C-terminal ubiquitin-associated (UBA) domain. Unlike ubiquitin, the UBL domain of the PLICs does not have a diglycine motif in its C terminus. The UBA domain is present in multiple enzyme classes of the ubiquitination machinery. Human PLICs associate with both proteasomes and ubiquitin ligases in large complexes. Overexpression of PLICs impairs the in vivo degradation of 2 unrelated ubiquitin-dependent proteasome substrates, p53 and I-kappa-B-alpha (NFKBIA), but not a ubiquitin-independent substrate. PLICs may link the ubiquitination machinery to the proteasome to affect in vivo protein degradation. The DA41 gene maps to chromosome 9q21.2-q21.3, a position overlapping a candidate tumor suppressor locus for bladder cancer.2