PROSITE documentation PDOC00719

Peripherin / rom-1 signature

Peripherin (or RDS) and rom-1 are related retinal-specific integral membrane proteins which are located at the rims of the photoreceptor disks, where they may act jointly in disk morphogenesis [1]. Both peripherin and rom-1 form disulfide-linked homodimers.

Defects in the peripherin gene (RDS) cause various Human diseases such as autosomal dominant retinitis pigmentosa, autosomal dominant punctata albescens and butterfly-shaped pigment dystrophy. In mice it causes retinopathy known as 'retinal degeneration slow' (rds).

These proteins contain about 350 amino acid residues. Structurally they consist of a short cytoplasmic N-terminal domain, followed by four transmembrane segments that delimit two lumenal and one cytoplasmic loops; the C-terminal domain is cytoplasmic. The second lumenal loop is very large (about 140 amino acid residues) and contains seven conserved cysteines. The schematic representation of this structure is shown below.

       NH2-***                   ************-COOH
             *      * * *        *
             *     *     *       *   Cytoplasmic
          ---* ----* ----*-------*----------------
             *     *     *       *   Membrane
             *     *     *       *
          ---* ----* ----*-------*----------------
             *     *     *       *   Lumenal
              * * *      *       *
                         *       *
                          *     *
                            * *
                             *

As a signature pattern we selected a region of 16 residues which is almost perfectly conserved. This region is located in the large lumenal loop and it contains three of the seven conserved cysteines.