TUB (gene)

The TUB gene encodes the tubby protein, a mammalian-specific, bipartite protein involved in various cellular processes, including signal transduction, neuronal development, and retinal function. Mutations in the TUB gene are associated with autosomal recessive obesity and progressive retinal degeneration in humans, known as tubby-related obesity (TULP1).

The tubby protein is a transcription factor that translocates to the nucleus upon activation of G protein-coupled receptors (GPCRs). Its N-terminal region interacts with phosphoinositides at the plasma membrane, anchoring the protein. Upon GPCR activation, tubby is released from the membrane and traffics to the nucleus, where it regulates the expression of genes involved in neuronal differentiation and metabolism. The C-terminal region of tubby contains a DNA-binding domain, enabling it to directly interact with DNA.

The TUB gene is highly expressed in the brain, particularly in the hypothalamus, which is involved in regulating appetite and energy expenditure. It is also expressed in the retina. Loss-of-function mutations in TUB disrupt these pathways, leading to obesity and retinal degeneration. Research suggests the tubby protein plays a role in ciliogenesis and intracellular trafficking, further contributing to its diverse cellular functions.