Endosomal localization of the autoantigen EEA1 is mediated by a zinc-binding FYVE finger

J Biol Chem. 1996 Sep 27;271(39):24048-54. doi: 10.1074/jbc.271.39.24048.


EEA1, a 162-kDa autoantigen associated with subacute cutaneous systemic lupus erythematosus, is a coiled-coil protein localized to early endosomes and cytosol. At its C terminus, the protein contains a cysteine-rich motif, which is shared with Vps27, Fab1, and Vac1, yeast proteins implicated in membrane traffic (Mu, F. T., Callaghan, J. M., Steele-Mortimer, O., Stenmark, H., Parton, R. G., Campbell, P. L., McCluskey, J., Yeo, J. P., Tock, E. P., and Toh, B. H. (1995) J. Biol. Chem. 270, 13503-13511). Here we show that this motif constitutes a genuine zinc binding domain, which we term the FYVE finger (based on the first letters of four proteins containing this motif). Profile-based data base searches identified the FYVE finger in 11 distinct proteins. The FYVE finger-containing C terminus of EEA1 was found to bind 2 mol equivalents of Zn2+. Mutations of conserved histidine and cysteine residues in the FYVE motif independently reduced zinc binding to 1 mol equivalent. Confocal immunofluorescence microscopy of transfected HEp2 cells revealed that the C-terminal part (residues 1277-1411) of EEA1 colocalizes extensively with a GTPase-deficient mutant of the early endosomal GTPase Rab5, while deletion of the FYVE finger or mutations that interfere with zinc binding cause a cytosolic localization. These results implicate the FYVE finger in the specific localization of EEA1 to endosomes.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Autoantigens / chemistry
  • Autoantigens / metabolism*
  • Cell Compartmentation*
  • Cell Line
  • Endosomes / metabolism*
  • Fluorescent Antibody Technique, Indirect
  • Humans
  • Lupus Erythematosus, Systemic
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • Microscopy, Confocal
  • Molecular Sequence Data
  • Sequence Alignment
  • Vesicular Transport Proteins
  • Zinc / metabolism*
  • Zinc Fingers*


  • Autoantigens
  • Membrane Proteins
  • Vesicular Transport Proteins
  • early endosome antigen 1
  • Zinc