Human Gene TUBB3 (uc002fpf.2) Description and Page Index
Description: Homo sapiens tubulin, beta 3 class III (TUBB3), transcript variant 1, mRNA. RefSeq Summary (NM_006086): 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]. Transcript (Including UTRs) Position: hg19 chr16:89,985,259-90,002,505 Size: 17,247 Total Exon Count: 5 Strand: + Coding Region Position: hg19 chr16:89,985,667-90,002,212 Size: 16,546 Coding Exon Count: 5
ID:TBB3_HUMAN DESCRIPTION: RecName: Full=Tubulin beta-3 chain; AltName: Full=Tubulin beta-4 chain; AltName: Full=Tubulin beta-III; FUNCTION: Tubulin is the major constituent of microtubules. It binds two moles of GTP, one at an exchangeable site on the beta chain and one at a non-exchangeable site on the alpha-chain. TUBB3 plays a critical role in proper axon guidance and mantainance. SUBUNIT: Dimer of alpha and beta chains. SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. TISSUE SPECIFICITY: Expression is primarily restricted to central and peripheral nervous system. Greatly increased expression in most cancerous tissues. DOMAIN: The highly acidic C-terminal region may bind cations such as calcium. PTM: Some glutamate residues at the C-terminus are polyglutamylated. This modification occurs exclusively on glutamate residues and results in polyglutamate chains on the gamma-carboxyl group. Also monoglycylated but not polyglycylated due to the absence of functional TTLL10 in human. Monoglycylation is mainly limited to tubulin incorporated into axonemes (cilia and flagella) whereas glutamylation is prevalent in neuronal cells, centrioles, axonemes, and the mitotic spindle. Both modifications can coexist on the same protein on adjacent residues, and lowering glycylation levels increases polyglutamylation, and reciprocally. The precise function of such modifications is still unclear but they regulate the assembly and dynamics of axonemal microtubules (Probable). PTM: 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. DISEASE: Defects in TUBB3 are the cause of congenital fibrosis of extraocular muscles type 3A (CFEOM3A) [MIM:600638]. 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. DISEASE: Defects in TUBB3 are the cause of cortical dysplasia complex with other brain malformations (CDCBM) [MIM:614039]. CDCBM is a disorder of aberrant neuronal migration and disturbed axonal guidance. Affected individuals have mild to severe mental retardation, 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. SIMILARITY: Belongs to the tubulin family.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
SCOP Domains: 52490 - Tubulin nucleotide-binding domain-like 55307 - Tubulin C-terminal domain-like 81321 - Family A G protein-coupled receptor-like
ModBase Predicted Comparative 3D Structure on Q13509
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
R-HSA-389980 unfolded actin/tubulin associates with prefoldin R-HSA-389970 Actin/tubulin:prefoldin complex associates with CCT/TriC R-HSA-389954 Hydrolysis of ATP and release of tubulin folding intermediate from CCT/TriC R-HSA-389961 ADP is exchanged for ATP in the (ADP:CCT/TriC):tubulin complex R-HSA-389956 Beta-tubulin:GTP + Cofactor A -> Beta-tubulin:GTP: Cofactor A R-HSA-389969 Beta-tubulin:GTP + Cofactor D -> Beta-tubulin:GTP: Cofactor D R-HSA-389974 Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E:Cofactor C-> Beta-tubulin:GDP :alpha-tubulin:GTP heterodimer +Cofactor E+ Cofactor D+ Cofactor C+ Pi R-HSA-8955706 TTL ligates L-Tyr to the carboxy terminus of alpha-tubulin R-HSA-8955712 TTCP hydrolyzes the terminal L-Tyr residue from alpha-tubulin R-HSA-389955 Beta-tubulin:GTP: Cofactor A+ Cofactor D -> Beta-tubulin:GTP:Cofactor D + Cofactor A R-HSA-389976 Beta-tubulin:GTP:Cofactor D+alpha-tubulin:GTP:Cofactor E-> Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E R-HSA-389964 Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E+ Cofactor C-> Beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E:Cofactor C R-HSA-389957 Prefoldin mediated transfer of substrate to CCT/TriC R-HSA-389958 Cooperation of Prefoldin and TriC/CCT in actin and tubulin folding R-HSA-389960 Formation of tubulin folding intermediates by CCT/TriC R-HSA-389977 Post-chaperonin tubulin folding pathway R-HSA-8955332 Carboxyterminal post-translational modifications of tubulin R-HSA-390466 Chaperonin-mediated protein folding R-HSA-391251 Protein folding R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins