A bilirubin-inducible fluorescent protein from eel muscle

Cell. 2013 Jun 20;153(7):1602-11. doi: 10.1016/j.cell.2013.05.038. Epub 2013 Jun 13.


The fluorescent protein toolbox has revolutionized experimental biology. Despite this advance, no fluorescent proteins have been identified from vertebrates, nor has chromogenic ligand-inducible activation or clinical utility been demonstrated. Here, we report the cloning and characterization of UnaG, a fluorescent protein from Japanese eel. UnaG belongs to the fatty-acid-binding protein (FABP) family, and expression in eel is restricted to small-diameter muscle fibers. On heterologous expression in cell lines or mouse brain, UnaG produces oxygen-independent green fluorescence. Remarkably, UnaG fluorescence is triggered by an endogenous ligand, bilirubin, a membrane-permeable heme metabolite and clinical health biomarker. The holoUnaG structure at 1.2 Å revealed a biplanar coordination of bilirubin by reversible π-conjugation, and we used this high-affinity and high-specificity interaction to establish a fluorescence-based human bilirubin assay with promising clinical utility. UnaG will be the prototype for a versatile class of ligand-activated fluorescent proteins, with applications in research, medicine, and bioengineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bilirubin / metabolism
  • Cloning, Molecular
  • Eels / metabolism*
  • Fish Proteins / chemistry
  • Fish Proteins / genetics*
  • Fish Proteins / isolation & purification*
  • Fish Proteins / metabolism
  • Green Fluorescent Proteins / chemistry
  • Green Fluorescent Proteins / genetics
  • Green Fluorescent Proteins / isolation & purification*
  • Green Fluorescent Proteins / metabolism
  • Molecular Sequence Data
  • Muscles / metabolism
  • Sequence Alignment


  • Fish Proteins
  • Green Fluorescent Proteins
  • Bilirubin

Associated data

  • GENBANK/AB763906
  • PDB/4I3B
  • PDB/4I3C
  • PDB/4I3D