Tubulin alpha-1A chain

Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.^[5][6][7]

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
View/Edit Human View/Edit Mouse

Tubulin alpha-1A chain is a type of alpha-tubulin involved in the formation of microtubules, which are structural proteins that play a role in the cytoskeletal structure. Microtubules are composed of heterodimers of alpha- and beta-tubulin molecules. Tubulin alpha-1A (TUBA1A) is a primary alpha-tubulin expressed in the human fetal brain, specifically found in that structure.^[8]

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]

Alpha-tubulins, including TUBA1A, are involved in neuronal development and maturation. Studies have shown that the rat homologs of human TUBA1A, such as Tα1, exhibit elevated expression during the extension of neuronal processes. In experiments where pheochromocytoma cells were cultured with Nerve Growth Factor (NGF), differentiation and the development of neuronal processes were observed, accompanied by a significant increase in Tα1 mRNA expression, while T26 mRNA expression showed minimal change.^[9]

TUBA1A is believed to play a role in neuronal migration by regulating microtubule dynamics, enabling the rapid formation and disassembly of polymers, which allows for the extension and retraction of processes necessary for nucleokinesis.^[10]

RNA in situ hybridization studies demonstrated the expression of TUBA1A in mouse embryos. Embryonic day 16.5 sections showed strong labeling in the telencephalon, diencephalon, mesencephalon, developing cerebellum, brainstem, spinal cord, and dorsal root ganglia.^[11]

Interactions

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

Animal models

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]

Clinical significance

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