Abstract
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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Adaptor Proteins, Signal Transducing
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Alternative Splicing
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Amino Acid Sequence
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Animals
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Cell Line
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Cell Nucleus / chemistry
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Crystallography, X-Ray
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DNA / metabolism
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Eye Proteins / chemistry*
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Eye Proteins / genetics
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Eye Proteins / metabolism*
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Humans
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Models, Molecular
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Molecular Sequence Data
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Protein Conformation
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proteins / chemistry*
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Proteins / genetics
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Proteins / metabolism*
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Recombinant Proteins / chemistry
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Recombinant Proteins / metabolism
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Sequence Alignment
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Transcription Factors / chemistry*
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptional Activation
Substances
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Adaptor Proteins, Signal Transducing
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Eye Proteins
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Intercellular Signaling Peptides and Proteins
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Intracellular Signaling Peptides and Proteins
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Proteins
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Recombinant Proteins
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TULP1 protein, human
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TULP2 protein, human
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TULP3 protein, human
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Transcription Factors
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Tub protein, mouse
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Tulp1 protein, mouse
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Tulp2 protein, mouse
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Tulp3 protein, mouse
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DNA