FYVE domain

FYVE zinc finger
Early endosome antigen 1 (EEA1) dimer with lipids. [1]
Identifiers
Symbol	FYVE
Pfam	PF01363
InterPro	IPR000306
PROSITE	PDOC50178
SCOP2	1vfy / SCOPe / SUPFAM
OPM superfamily	59
OPM protein	1vfy
CDD	cd00065
Available protein structures: Pfam   structures / ECOD   PDB RCSB PDB; PDBe; PDBj PDBsum structure summary

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, ^[2] 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. ^[3] The FYVE domain has been connected to vacuolar protein sorting and endosome function. ^[4]

The human genome encodes about 30 FYVE-domain proteins. ^[5]

Structure

The FYVE domain is composed of two small beta hairpins (or zinc knuckles) followed by an alpha helix. ^[6] 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:

R+HHC+XCG, where + represents a charged residue and X any residue

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

References

1. Dumas JJ, Merithew E, Sudharshan E, et al. (November 2001). "Multivalent endosome targeting by homodimeric EEA1". Mol. Cell. 8 (5): 947–58. doi: 10.1016/S1097-2765(01)00385-9 . PMID   11741531.
2. Gaullier JM, Simonsen A, D'Arrigo A, Bremnes B, Stenmark H, Aasland R (July 1998). "FYVE fingers bind PtdIns(3)P". Nature. 394 (6692): 432–3. doi:10.1038/28767. PMID   9697764. S2CID   4385768.
3. He J, Vora M, Haney RM, et al. (September 2009). "Membrane insertion of the FYVE domain is modulated by pH". Proteins. 76 (4): 852–60. doi:10.1002/prot.22392. PMC   2909462 . PMID   19296456.
4. Leevers SJ, Vanhaesebroeck B, Waterfield MD (April 1999). "Signalling through phosphoinositide 3-kinases: the lipids take centre stage". Curr. Opin. Cell Biol. 11 (2): 219–25. doi:10.1016/S0955-0674(99)80029-5. PMID   10209156.
5. Simonsen, A.; Stenmark, H. (August 2001). "PX domains: attracted by phosphoinositides". Nature Cell Biology. 3 (8): E179–182. doi:10.1038/35087112. ISSN   1465-7392. PMID   11483972.
6. Misra S, Hurley JH (May 1999). "Crystal structure of a phosphatidylinositol 3-phosphate-specific membrane-targeting motif, the FYVE domain of Vps27p". Cell. 97 (5): 657–66. doi: 10.1016/S0092-8674(00)80776-X . PMID   10367894. S2CID   15448444.

Further reading

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