PROSITE documentation PDOC50916Rab-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 <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.
Last update:July 2003 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Fukuda M. |
| Title | Distinct Rab binding specificity of Rim1, Rim2, rabphilin, and Noc2. Identification of a critical determinant of Rab3A/Rab27A recognition by Rim2. | |
| Source | J. Biol. Chem. 278:15373-15380(2003). | |
| PubMed ID | 12578829 | |
| DOI | 10.1074/jbc.M212341200 |
| 2 | Authors | Ostermeier C. Brunger A.T. |
| Title | Structural basis of Rab effector specificity: crystal structure of the small G protein Rab3A complexed with the effector domain of rabphilin-3A. | |
| Source | Cell 96:363-374(1999). | |
| PubMed ID | 10025402 |
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