PROSITE documentation PDOC51511 [for PROSITE entry PS51511]

FIP-RBD domain profile

The Rab11 GTPase regulates recycling of internalized plasma membrane receptors and is essential for completion of cytokinesis. A family of Rab11 interacting proteins (FIPs) that conserve a C-terminal Rab-binding domain (RBD) selectively recognize the active form of Rab11. FIPs are diverse in sequence length and composition toward their N-termini, presumably a feature that underpins their specific roles in Rab11-mediated vesicle trafficking. They have been divided into three subfamilies (classe I, II, and III)on the basis of domain architecture. Class I FIPs comprises a subfamily of three proteins (Rip11/pp75/FIP5, Rab-coupling protein (RCP), and FIP2) that possess an N-terminal C2 domain (see <PDOC00380>), localize to recycling endosomes, and regulate plasma membrane recycling. The class II subfamily consists of two proteins (FIP3/eferin/arfophilin and FIP4) with tandem EF hands (see <PDOC00018>) and a proline-rich region. Class II FIPs localize to recycling endosomes, the trans-Golgi network, and have been implicated in the regulation of membrane trafficking during cytokinesis. The class III subfamily consists of a single protein, FIP1, which does not contain obvious homology domains or motifs other than the FIP-RBD [1,2,3,4].

The FIB-RBD domain consists of an N-terminal long α-helix, followed by a 90° bend at a conserved proline residue, a 3(10) helix and a C-terminal short β-strand, adopting an "L" shape (see <PDB:2D7C>). The long α-helix forms a parallel coiled-coil homodimer that symmetrically interacts with two Rab11 molecules on both sides, forming a quaternary Rab11-(FIP)2-Rab11 complex. The Rab11-interacting region of FIP-RBD is confined to the C-terminal 24 amino acids, which cover the C-terminal half of the long α-helix and the short β-strand [1,2,3,4].

The profile we developed covers the entire FIP-RBD domain.