Rab are small GTPases implicated in vesicle trafficking. Like the other small GTPases, Rab proteins act as molecular switches, with an active GTP-bound form that interacts with its target or effector protein and an inactive GDP-bound form. A subgroup of Rab effectors contain in their N-terminal part a conserved region of around 70 amino acid residues, the Rab-binding domain (RabBD) . In some Rab effector domains an atypical FYVE-type zinc finger is inserted in the central part [1].

The crystal structure of the Rab effector domain of Rabphilin-3A in complex with Rab3A has been solved [2] (see <PDB:1ZBD>). The structure consists of two long helices separated by an atypical FYVE-type zinc finger which adopts a conformation similar to classical ones (see <PDOC50178>). The central zinc finger does not directly interact with Rab3A. The amino acids important for this interaction are located around a short C-terminal motif (SGAWFF) and an acidic cluster in the N-terminal area.

Proteins known to contain a Rab-binding domain are listed below:

• Mammalian Synaptotagmin-like 1 (SYTL1) (exophilin 7). Its Rab-binding domain does not contain an inclusive FYVE-type like zinc finger.
• Mammalian Synaptotagmin-like 2 (SYTL2) (exophilin 4). Its Rab-binding domain does not contain an inclusive FYVE-type like zinc finger.
• Mammalian Synaptotagmin-like 3 (SYTL3) (exophilin 6).
• Mammalian Synaptotagmin-like 4 (SYTL4) (exophilin 2 or granuphilin).
• Mammalian Synaptotagmin-like 5 (SYTL5).
• Animal Rabphilin-3A (exophilin 1).
• Mammalian Noc2 protein, a rabphilin 3A-like protein without C2 domains.
• Mammalian Slp homolog lacking C2 domains-a (Slac2-a or exophilin 3 or melanophilin).
• Mammalian Slp homolog lacking C2 domains-b (Slac2-b or exophilin 5). Its Rab-binding domain does not contain an inclusive FYVE-type like zinc finger.
• Mammalian Slp homolog lacking C2 domains-c (Slac2-c or MyRIP or Exophilin 8).
• Mammalian Rim1.
• Animal Rim2, a family of neuronal Rab effectors.

The profile we developed covers the entire Rab-binding domain.