TUBB4

Overview

TUBB4 is a gene that encodes the protein tubulin beta-4 chain, which is a member of the tubulin family. Tubulins are globular proteins that polymerize to form microtubules, which are essential components of the cytoskeleton in eukaryotic cells. Microtubules play critical roles in maintaining cell shape, enabling intracellular transport, and facilitating cell division.

Structure

The TUBB4 gene is located on chromosome 19 in humans. The protein product, tubulin beta-4 chain, consists of approximately 444 amino acids and has a molecular weight of about 50 kDa. The structure of tubulin beta-4 is characterized by a highly conserved core that is shared among all tubulin proteins, which includes a GTP-binding domain and a C-terminal domain that interacts with microtubule-associated proteins (MAPs).

Function

Tubulin beta-4 chain is a component of microtubules, which are dynamic structures that undergo rapid cycles of polymerization and depolymerization. These cycles are crucial for the microtubule's role in:

• Cell Division: Microtubules form the mitotic spindle, which segregates chromosomes during cell division.
• Intracellular Transport: Microtubules serve as tracks for the movement of organelles and vesicles within cells, facilitated by motor proteins such as kinesin and dynein.
• Cell Shape and Motility: Microtubules contribute to the maintenance of cell shape and are involved in cell motility processes such as cilia and flagella movement.

Clinical Significance

Mutations in the TUBB4 gene have been associated with several neurological disorders, including:

• Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum (H-ABC): A rare neurodegenerative disorder characterized by progressive motor and cognitive decline, associated with mutations in TUBB4.
• Dystonia: Some forms of dystonia, a movement disorder, have been linked to mutations in the TUBB4 gene.

Research and Developments

Ongoing research is focused on understanding the precise mechanisms by which TUBB4 mutations lead to neurological disorders. Studies are also exploring potential therapeutic approaches to mitigate the effects of these mutations.

Also see

• Microtubule
• Tubulin
• Cytoskeleton
• Hypomyelination with Atrophy of the Basal Ganglia and Cerebellum
• Dystonia