{PDOC50916} {PS50916; RABBD} {BEGIN} ****************************** * Rab-binding domain profile * ****************************** 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 ). The structure consists of two long helices separated by an atypical FYVE-type zinc finger which adopts a conformation similar to classical ones (see ). 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. -Sequences known to belong to this class detected by the profile: ALL. -Other sequence(s) detected in Swiss-Prot: NONE. -Last update: July 2003 / First entry. [ 1] Fukuda M. "Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2." J. Biol. Chem. 278:15373-15380(2003). PubMed=12578829; DOI=10.1074/jbc.M212341200 [ 2] Ostermeier C., Brunger A.T. "Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A." Cell 96:363-374(1999). PubMed=10025402 -------------------------------------------------------------------------------- PROSITE is copyrighted by the SIB Swiss Institute of Bioinformatics and distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND 4.0) License, see https://prosite.expasy.org/prosite_license.html -------------------------------------------------------------------------------- {END}