Figure 1.

Topology of the human UNC93B1 protein. (A) UNC93B1 comprises 597 amino acids and contains 12 transmembrane domains. A segment of the C-terminal tail indicated in red is required for the interaction with SDCBP and subsequent dampening of TLR7 signaling [18]. (B) Amino acid sequence from position 521 to 553. Substitution of a highly conserved proline with threonine causes exfoliative cutaneous lupus erythematosus in dogs [22]. Targeted mutagenesis of the four underlined motifs disrupted SDCBP binding in mouse macrophages [18]. A targeted mouse mutant, Unc93b1^PKP/PKP, in which the residues corresponding to the human positions 530–532 were replaced by alanines, developed systemic inflammation and autoimmunity [18].