Can Tubby Make You Tubby?

Thu, 01/12/2012 - 08:32

The TUB gene, which encodes for the protein Tubby, is evolutionarily conserved in human, chimpanzee, dog, cow, mouse, chicken, zebrafish, fruit fly, mosquito, C. elegans, and rice.

The gene derives its name from its role in metabolism; mice with a mutated tubby gene develop delayed-onset obesity, sensorineural hearing loss and retinal degeneration (a syndrome known as the autosomal recessive syndrome “Tubby”)

The first tubby gene was identified in mice, and proteins that are homologous to tubby are known as "tubby-like proteins" (TULPs).

The identification of a mutation at the tubby (Tub) locus in mice, led to the discovery of the homologous tubby-like proteins (TULPs). Tub and the genes that encode for TULPs (TULP1, TULP2, TULP3, and TULP4) form a novel, small gene family that plays an important role in maintenance and function of neuronal cells during development and post-differentiation.

Western Blot: Tubby Antibody

All TULPs including TUB are classified as alpha and beta proteins and they share a common and characteristic tertiary structure that consists of a 12-beta stranded barrel packed around an alpha helix in the central pore.

The tubby protein is an upstream cell signaling protein common to multicellular eukaryotes which can bind the small cell signaling molecule phosphatidylinositol, which is typically localized to the cell membrane.

So can Tubby really make you Tubby?

The tubby protein is highly expressed in brain, especially hypothalamus where body weight regulation is controlled. The sequence of normal tubby includes putative tyrosine phosphorylation sites for SH-2 protein binding and a nuclear localization signal, while mutant tubby contains a 24 intron amino-acid insert substituted for 44 C-terminal amino acids.  In PC12 cells, insulin induces tyrosine phosphorylation. In vitro, tubby is phosphorylated by insulin receptor kinase, Abl, JAK2; and upon phosphorylation, tubby associates with the SH2 domains of Abl, Lck, phospholipase Cγ. The C-term region of tubby binds to phosphatidylinositol 4,5-bis-phosphate, which facilitates localization to the plasma membrane.  Receptor-mediated activation of Gαq releases tubby from the plasma membrane through the action of phospholipase C-B. This allows translocation of tubby to the nucleus where it plays a role in regulating transcription. Tubby proteins are also associated with neuronal differentiation and development, and when mutated, in mammals we observe obesity, retinal degeneration, and hearing loss.  In mice, mutations in tubby proteins are also known to affect life span and fat storage as well as carbohydrate metabolism.

Novus Biologicals offers Tubby reagents for your research needs including:


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