Tubulin alpha-1A chain

TUBA1A
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3HKC, 4X20, 3HKE, 3N2G, 4X1Y, 3N2K, 4X1I, 4X1K, 3HKB, 3HKD, 5JCO
Identifiers
Aliases	TUBA1A, B-ALPHA-1, LIS3, TUBA3, tubulin alpha 1a
External IDs	OMIM: 602529; MGI: 98869; HomoloGene: 68498; GeneCards: TUBA1A; OMA:TUBA1A - orthologs
Gene location (Human) Chr. Chromosome 12 (human)[1] Band 12q13.12 Start 49,184,686 bp[1] End 49,189,080 bp[1]
Gene location (Mouse) Chr. Chromosome 15 (mouse)[2] Band 15 F1|15 55.29 cM Start 98,847,718 bp[2] End 98,851,584 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell ganglionic eminence inferior ganglion of vagus nerve superior vestibular nucleus spinal ganglia inferior olivary nucleus ventricular zone bronchial epithelial cell optic nerve subthalamic nucleus Top expressed in trigeminal ganglion mammillary body medial dorsal nucleus fossa condyle medial vestibular nucleus median eminence superior cervical ganglion medial geniculate nucleus paraventricular nucleus of hypothalamus More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding protein domain specific binding GTP binding structural molecule activity structural constituent of cytoskeleton protein binding GTPase activity Cellular component cytoplasm recycling endosome cytosol myelin sheath cytoplasmic microtubule cytoplasmic ribonucleoprotein granule microtubule extracellular exosome cytoskeleton nucleus microtubule cytoskeleton membrane raft neuromuscular junction Biological process cytoskeleton-dependent intracellular transport cell division G2/M transition of mitotic cell cycle microtubule-based process cytoskeleton organization ciliary basal body-plasma membrane docking regulation of G2/M transition of mitotic cell cycle microtubule cytoskeleton organization mitotic cell cycle regulation of synapse organization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7846 22142 Ensembl ENSG00000167552 ENSMUSG00000072235 UniProt Q71U36 P68369 RefSeq (mRNA) NM_006009 NM_001270399 NM_001270400 NM_011653 RefSeq (protein) NP_001257328 NP_001257329 NP_006000 NP_035783 Location (UCSC) Chr 12: 49.18 – 49.19 Mb Chr 15: 98.85 – 98.85 Mb PubMed search [3] [4]
Wikidata
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Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.^[5][6][7]

Background

Tubulin alpha-1A chain is an alpha-tubulin that participates in the formation of microtubules - structural proteins that participate in cytoskeletal structure. Specifically, microtubules are composed of a heterodimer of alpha and beta-tubulin molecules. Cowan et al. demonstrated that bα1 is a primary α-tubulin of the human fetal brain, and that it is expressed solely in that structure, by way of Northern blot.^[8] Miller et al. further elaborated on the role of α-tubulins and the process of neuronal development and maturation, comparing the expressions of rat α-tubulins Tα1 and T26. These two rat α-tubulins are homologs of bα1 and kα1 showing that a rat homolog of human TUBA1A (Tα1) had elevated expression during the extension of neuronal processes. Culturing of pheochromocytoma cells with Nerve Growth Factor (NGF) induced differentiation and the development of neuronal processes. Northern blot assay showed markedly elevated levels of Tα1 mRNA expression; T26 mRNA expression increased minimally with exposure to NGF.^[9] These data suggest that TUBA1A models the brain by participating in the directing of neuronal migration through the ability of microtubules to readily form and break polymers to extend and retract processes to induce nucleokinesis.^[10] Poirier et al. used RNA in situ hybridization to show TUBA1A expression in mice embryo; embryo sections from embryonic day 16.5 “showed a strong labeling in the telencephalon, diencephalon, and mesencephalon, the developing cerebellum, the brainstem, the spinal cord, and the dorsal root ganglia”.^[11]

Function

Microtubules of the eukaryotic cytoskeleton perform essential and diverse functions and are composed of a heterodimer of alpha and beta tubulins. The genes encoding these microtubule constituents belong to the tubulin superfamily, which is composed of six distinct families. Genes from the alpha, beta and gamma tubulin families are found in all eukaryotes. The alpha and beta tubulins represent the major components of microtubules, while gamma tubulin plays a critical role in the nucleation of microtubule assembly. There are multiple alpha and beta tubulin genes, which are highly conserved among species. This gene encodes alpha tubulin and is highly similar to mouse and rat Tuba1 gene. Northern blotting studies have shown that the gene expression is predominantly found in morphologically differentiated neurologic cells. This gene is one of three alpha-tubulin genes in a cluster on chromosome 12q.^[7]

Interactions

TUBA1A has been shown to interact with PAFAH1B1.^[12]

Disease

Mutations to the TUBA1A gene manifest clinically as Type 3 Lissencephaly. In general, lissencephaly is characterized by agyria (lacking of gyri and sulci to the brain – a smooth brain), seizure activity, failure to thrive, as well as intellectual disability and psychomotor retardation, often to a profound degree.^[11] The symptoms of Lis3 Lissencephaly are not especially different from generalized lissencephaly (Lis1, related to PAFAH1B1). Diagnosis of lissencephaly generally is made from the symptom profile, while attribution to a specific type is obtained by microarray. Treatment is symptomatic; anti-convulsive drugs for seizure activity, g-button gastrostomy to feed the child, physical therapy for muscle disorders. TUBA1A mutation is common in microlissencephaly

Animal model

Keays et al. describe a mouse with a mutation of the TUBA1A gene induced by N-ethyl-N-nitrosourea. The relevant point mutation resulted in S140G;^[13] the site of the mutation participates in the N-site of the formed α-tubulin, and participates in stabilizing the α-β tubulin polymer by binding GTP at this site.^[14] The S140G mutation resulted in the formation of a “compromised GTP binding pocket”. Authors note defects associated with cortical layers II/III and IV, especially in cortical neuronal migration (with respect to wild-type counterparts), showing that the S140G mutation has value as a model for detailing disease associated with the Human TUBA homolog.^[13]

References

Further reading

External links

• Overview of all the structural information available in the PDB for UniProt: Q71U36 (Human Tubulin alpha-1A chain) at the PDBe-KB.
• Overview of all the structural information available in the PDB for UniProt: P68369 (Mouse Tubulin alpha-1A chain) at the PDBe-KB.