FYVE domain explained

In molecular biology the FYVE zinc finger domain is named after the four cysteine-rich proteins: Fab 1 (yeast orthologue of PIKfyve), YOTB, Vac 1 (vesicle transport protein), and EEA1, in which it has been found. FYVE domains bind phosphatidylinositol 3-phosphate,^[1] in a way dependent on its metal ion coordination and basic amino acids. The FYVE domain inserts into cell membranes in a pH-dependent manner.^[2] The FYVE domain has been connected to vacuolar protein sorting and endosome function.^[3]

Structure

The FYVE domain is composed of two small beta hairpins (or zinc knuckles) followed by an alpha helix.^[4] The FYVE finger binds two zinc ions. The FYVE finger has eight potential zinc coordinating cysteine positions and is characterized by having basic amino acids around the cysteines. Many members of this family also include two histidines in a sequence motif:The FYVE finger is structurally similar to the RING domain and the PHD finger.

Examples

See also: FYVE, RhoGEF and PH domain containing. The following is a list of human proteins containing this domain:

• ANKFY1, EEA1, FGD1, FGD2, FGD3, FGD4, FGD5, FGD6, FYCO1, HGS, MTMR3, MTMR4, PIKFYVE, PLEKHF1, PLEKHF2
• RUFY1, RUFY2, RUFY3, RUFY4, WDFY1, WDFY2, WDFY3, ZFYVE1, ZFYVE9, ZFYVE16, ZFYVE19, ZFYVE20, ZFYVE21, ZFYVE26, ZFYVE27, ZFYVE28

Further reading

• Stenmark H, Aasland R, Toh BH, D'Arrigo A . Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger. J. Biol. Chem.. 271. 39. 24048–54. September 1996 . 8798641. 10.1074/jbc.271.39.24048. free.
• Stenmark H, Aasland R . FYVE-finger proteins--effectors of an inositol lipid. J. Cell Sci.. 112. Pt 23. 4175–83. December 1999 . 10564636.

Notes and References

1. Gaullier JM, Simonsen A, D'Arrigo A, Bremnes B, Stenmark H, Aasland R . FYVE fingers bind PtdIns(3)P . Nature . 394 . 6692 . 432–3 . July 1998 . 9697764 . 10.1038/28767 . 4385768 .
2. He J, Vora M, Haney RM . Membrane insertion of the FYVE domain is modulated by pH . Proteins . 76 . 4 . 852–60 . September 2009 . 19296456 . 2909462 . 10.1002/prot.22392 . etal.
3. Leevers SJ, Vanhaesebroeck B, Waterfield MD . Signalling through phosphoinositide 3-kinases: the lipids take centre stage . Curr. Opin. Cell Biol. . 11 . 2 . 219–25 . April 1999 . 10209156 . 10.1016/S0955-0674(99)80029-5.
4. Misra S, Hurley JH . Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p . Cell . 97 . 5 . 657–66 . May 1999 . 10367894 . 10.1016/S0092-8674(00)80776-X. 15448444 . free .