|PROSITE documentation PDOC50178|
The FYVE domain has been named after the first letter of the first four proteins in which it was found (Fab1, YOTB/ZK632.12, Vac1, and EEA1). It is a cysteine-rich domain of about 70 amino acids that coordinates two Zn2+ ions. The FYVE domain is found in several eukaryotic non-nuclear proteins involved in distinct cellular functions, including vesicle transport, signal transduction and cytoskeletal regulation. FYVE domains are generally found in one copy but two copies can also be found. Positions of FYVE domains in different proteins vary from the extreme N-terminus to the extreme C-terminus. FYVE domains are found associated with other domains such as IQ (see <PDOC50096>), PH (see <PDOC50003>), VHS, RCC, SH2 (see <PDOC50001>), RING finger (see <PDOC00449>) or C2H2 zinc finger (see <PDOC00028>) [1,2,3]. The function of the FYVE domain is to target signal-transducing proteins to cell membranes through binding to the membrane lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) with high specificity [4,5].
The FYVE domain has eight conserved cysteines, which coordinate the two Zn2+ ions in a 'cross-braced' topology: the first Zn2+ ion is coordinated by the first and third pairs of cysteines, and the second ion is coordinated by the second and fourth pairs. In addition, the FYVE domain contains several other conserved residues, most prominently a basic R-[RK]-H-H-C-R-x-C-G motif surrounding the third and fourth cysteine residues. Several hydrophobic amino acid positions are also conserved among the FYVE fingers, as is an isolated arginine residue towards the C-terminus [2,6]. Resolution of the crystal and solution structures of the FYVE domain has shown that it consists of two double-stranded antiparallel β-sheets, which are stabilized by the two zinc ions and a C-terminal α-helix. The conserved R-[RK]-H-H-C-R-x-C-G motif and the conserved arginine residue form a basic pocket involved in the inositol head group binding [6,7].
The FYVE-related domain is found in several proteins involved in regulated secretion, such as Rabphilin-3A and Rim. Although the structure of the FYVE-related domain is closely related to the one of the genuine FYVE domain, the FYVE-related domain lacks several of the conserved feature of the FYVE domain, like the basic R-[RK]-H-H-C-R-x-C-G motif, and it does not bind to PtdIns(3)P [2,4,6].
Some proteins known to contain a FYVE or a FYVE-related domain are listed below:
The profile we developed covers the entire FYVE domain.Last update:
December 2001 / First entry.
PROSITE method (with tools and information) covered by this documentation:
|1||Authors||Stenmark H. Aasland R. Toh B.-H. D'Arrigo A.|
|Title||Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger.|
|Source||J. Biol. Chem. 271:24048-24054(1996).|
|2||Authors||Stenmark H. Aasland R.|
|Title||FYVE-finger proteins--effectors of an inositol lipid.|
|Source||J. Cell Sci. 112:4175-4183(1999).|
|3||Authors||Gillooly D.J. Simonsen A. Stenmark H.|
|Title||Cellular functions of phosphatidylinositol 3-phosphate and FYVE domain proteins.|
|Source||Biochem. J. 355:249-258(2001).|
|4||Authors||Gaullier J.-M. Simonsen A. D'Arrigo A. Bremnes B. Stenmark H. Aasland R.|
|Title||FYVE fingers bind PtdIns(3)P.|
|5||Authors||Patki V. Lawe D.C. Corvera S. Virbasius J.V. Chawla A.|
|Title||A functional PtdIns(3)P-binding motif.|
|6||Authors||Misra S. Hurley J.H.|
|Title||Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p.|
|7||Authors||Kutateladze T. Overduin M.|
|Title||Structural mechanism of endosome docking by the FYVE domain.|