TUBB3
This gene encodes a class III member of the beta tubulin protein family. Beta tubulins are one of two core protein families (alpha and beta tubulins) that heterodimerize and assemble to form microtubules. This protein is primarily expressed in neurons and may be involved in neurogenesis and axon guidance and maintenance. Mutations in this gene are the cause of congenital fibrosis of the extraocular muscles type 3. Alternate splicing results in multiple transcript variants. A pseudogene of this gene is found on chromosome 6. [provided by RefSeq, Oct 2010]
Full Name
TUBB3 Gene(Protein Coding) Tubulin Beta 3 Class III
Function
Tubulin is the major constituent of microtubules, a cylinder consisting of laterally associated linear protofilaments composed of alpha- and beta-tubulin heterodimers (PubMed:34996871).
Microtubules grow by the addition of GTP-tubulin dimers to the microtubule end, where a stabilizing cap forms (PubMed:34996871).
Below the cap, tubulin dimers are in GDP-bound state, owing to GTPase activity of alpha-tubulin (PubMed:34996871).
TUBB3 plays a critical role in proper axon guidance and maintenance (PubMed:20074521).
Binding of NTN1/Netrin-1 to its receptor UNC5C might cause dissociation of UNC5C from polymerized TUBB3 in microtubules and thereby lead to increased microtubule dynamics and axon repulsion (PubMed:28483977).
Plays a role in dorsal root ganglion axon projection towards the spinal cord (PubMed:28483977).
Biological Process
Biological Process axon guidance Source:UniProtKB1 Publication
Biological Process dorsal root ganglion development Source:UniProtKB1 Publication
Biological Process microtubule cytoskeleton organization Source:UniProtKB1 Publication
Biological Process mitotic cell cycle Source:GO_Central1 Publication
Cellular Location
Cytoplasm, cytoskeleton
Cell projection, growth cone
Cell projection, lamellipodium
Cell projection, filopodium
Involvement in disease
Fibrosis of extraocular muscles, congenital, 3A (CFEOM3A):
A congenital ocular motility disorder marked by restrictive ophthalmoplegia affecting extraocular muscles innervated by the oculomotor and/or trochlear nerves. It is clinically characterized by anchoring of the eyes in downward gaze, ptosis, and backward tilt of the head. Congenital fibrosis of extraocular muscles type 3 presents as a non-progressive, autosomal dominant disorder with variable expression. Patients may be bilaterally or unilaterally affected, and their oculo-motility defects range from complete ophthalmoplegia (with the eyes fixed in a hypo- and exotropic position), to mild asymptomatic restrictions of ocular movement. Ptosis, refractive error, amblyopia, and compensatory head positions are associated with the more severe forms of the disorder. In some cases, the ocular phenotype is accompanied by additional features including developmental delay, corpus callosum agenesis, basal ganglia dysmorphism, facial weakness, polyneuropathy.
Cortical dysplasia, complex, with other brain malformations 1 (CDCBM1):
A disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe intellectual disability, strabismus, axial hypotonia, and spasticity. Brain imaging shows variable malformations of cortical development, including polymicrogyria, gyral disorganization, and fusion of the basal ganglia, as well as thin corpus callosum, hypoplastic brainstem, and dysplastic cerebellar vermis. Extraocular muscles are not involved.
PTM
Some glutamate residues at the C-terminus are polyglutamylated, resulting in polyglutamate chains on the gamma-carboxyl group (PubMed:26875866).
Polyglutamylation plays a key role in microtubule severing by spastin (SPAST). SPAST preferentially recognizes and acts on microtubules decorated with short polyglutamate tails: severing activity by SPAST increases as the number of glutamates per tubulin rises from one to eight, but decreases beyond this glutamylation threshold (PubMed:26875866).
Glutamylation is also involved in cilia motility (By similarity).
Some glutamate residues at the C-terminus are monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into cilia and flagella axonemes, which is required for their stability and maintenance. Flagella glycylation controls sperm motility. Both polyglutamylation and monoglycylation can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally.
Phosphorylated on Ser-172 by CDK1 during the cell cycle, from metaphase to telophase, but not in interphase. This phosphorylation inhibits tubulin incorporation into microtubules.
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