Tubby protein

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A tubby protein expressed in mouse brain
Identifiers
Symbol	Tub
Pfam	PF01167
InterPro	IPR000007
PROSITE	PDOC00923
SCOP	1c8z
OPM family	177
OPM protein	1i7e
Available PDB structures: 1s31A:258-500 1i7eA:257-499 1c8zA:257-499

The tubby protein is an upstream cell signaling protein common to multicellular eukaryotes. The original tubby gene was identified in mice, but proteins that are homologous to tubby are known as "tubby-like proteins" (TULPs) and share a common and characteristic tertiary structure that consists of a beta barrel packed around an alpha helix in the central pore. The protein derives its name from its role in metabolism; mice with mutated tubby genes suffer from obesity.

Contents 1 Structure 2 Function 3 Human proteins containing this domain 4 External links 5 References

[edit] Structure

Tubby proteins are classified as α+β proteins and have a 12-beta stranded barrel surrounding a central alpha helix. Tubby proteins can bind the small cell signaling molecule phosphatidylinositol, which is typically localized to the cell membrane.

[edit] Function

Tubby proteins have been implicated as transcription factors^[1] and as potential signaling factors coupled to G-protein activity.^[2] They are associated with neuronal differentiation and development, and in mammals are implicated in three disease processes when mutated: obesity, retinal degeneration, and hearing loss.^[1] In mice, mutations in tubby proteins are known to affect lifespan and fat storage^[3] as well as carbohydrate metabolism.^[4] Tubby domains associate with cytoplasmic side of cell membranes through binding of different phosphoinositides^[5]

[edit] Human proteins containing this domain

TUB; TULP1; TULP2; TULP3; TULP4;

[edit] External links

• SCOP tubby fold

[edit] References

1. ^ ^{a b} Boggon TJ, Shan WS, Santagata S, Myers SC, Shapiro L. (1999). Implication of tubby proteins as transcription factors by structure-based functional analysis. Science 286(5447):2119-25.
2. ^ Carroll K, Gomez C, Shapiro L. (2004). Tubby proteins: the plot thickens. Nat Rev Mol Cell Biol5(1):55-63.
3. ^ Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA. (2005). C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell Metab 2(1):35-42.
4. ^ Wang Y, Seburn K, Bechtel L, Lee BY, Szatkiewicz JP, Nishina PM, Naggert JK. (2006). Defective carbohydrate metabolism in mice homozygous for the tubby mutation. Physiol Genomics Epub.
5. ^ Cho, W. and Stahelin, R.V. (June 2005). "Membrane-protein interactions in cell signaling and membrane trafficking" (abstract page). Annual Review of Biophysics and Biomolecular Structure 34: 119–151. doi:10.1146/annurev.biophys.33.110502.133337.