Implication of tubby proteins as transcription factors by structure-based functional analysis

Science. 1999 Dec 10;286(5447):2119-25. doi: 10.1126/science.286.5447.2119.


Tubby-like proteins (TULPs) are found in a broad range of multicellular organisms. In mammals, genetic mutation of tubby or other TULPs can result in one or more of three disease phenotypes: obesity (from which the name "tubby" is derived), retinal degeneration, and hearing loss. These disease phenotypes indicate a vital role for tubby proteins; however, no biochemical function has yet been ascribed to any member of this protein family. A structure-directed approach was employed to investigate the biological function of these proteins. The crystal structure of the core domain from mouse tubby was determined at a resolution of 1.9 angstroms. From primarily structural clues, experiments were devised, the results of which suggest that TULPs are a unique family of bipartite transcription factors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Alternative Splicing
  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Nucleus / chemistry
  • Crystallography, X-Ray
  • DNA / metabolism
  • Eye Proteins / chemistry*
  • Eye Proteins / genetics
  • Eye Proteins / metabolism*
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Proteins / chemistry*
  • Proteins / genetics
  • Proteins / metabolism*
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Transcription Factors / chemistry*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcriptional Activation


  • Adaptor Proteins, Signal Transducing
  • Eye Proteins
  • Intercellular Signaling Peptides and Proteins
  • Intracellular Signaling Peptides and Proteins
  • Proteins
  • Recombinant Proteins
  • TULP1 protein, human
  • TULP2 protein, human
  • TULP3 protein, human
  • Transcription Factors
  • Tub protein, mouse
  • Tulp1 protein, mouse
  • Tulp2 protein, mouse
  • Tulp3 protein, mouse
  • DNA

Associated data

  • PDB/1C8Z