Tubby protein

Pfam_box
Symbol = Tub
Name =

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width =220
caption =A tubby protein expressed in mouse brain
Pfam= PF01167
InterPro= IPR000007
SMART=
PROSITE = PDOC00923
SCOP = 1c8z
TCDB =
OPM family= 177
OPM protein= 1i7e
PDB=PDB3|1s31A:258-500 PDB3|1i7eA:257-499 PDB3|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.

tructure

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.

Function

Tubby proteins have been implicated as transcription factorsBoggon 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.] and as potential signaling factors coupled to G-protein activity.Carroll K, Gomez C, Shapiro L. (2004). Tubby proteins: the plot thickens. "Nat Rev Mol Cell Biol"5(1):55-63.] 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. In mice, mutations in tubby proteins are known to affect lifespan and fat storageMukhopadhyay 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.] as well as carbohydrate metabolism.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.] Tubby domains associate with cytoplasmic side of cell membranes through binding of different phosphoinositides cite journal|author= Cho, W. and Stahelin, R.V. |year=2005|title= Membrane-protein interactions in cell signaling and membrane trafficking|journal=Annual Review of Biophysics and Biomolecular Structure|volume= 34|pages= 119–151|month=June |doi=10.1146/annurev.biophys.33.110502.133337 |url= http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.biophys.33.110502.133337?cookieSet=1&journalCode=biophys |accessdate=2007-01-23|format= abstract page ]

Human proteins containing this domain

TUB; TULP1; TULP2; TULP3; TULP4;

External links

* [http://scop.mrc-lmb.cam.ac.uk/scop/data/scop.b.e.ec.A.A.A.html SCOP tubby fold]

References