UniProt record for mouse Tuba1a (P68369)
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Tuba1a is tubulin alpha-1A, a major constituent of microtubules that forms alpha/beta-tubulin heterodimers and is present in sperm flagellar doublet microtubules.
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UniProt records GTP-tubulin dimers, Mg2+ cofactor use, and extensive alpha-tubulin post-translational modifications including acetylation, polyglutamylation, polyglycylation, and tyrosination/detyrosination.
Falcon deep research report for mouse Tuba1a
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Falcon verifies the target as mouse Tuba1a/P68369 and summarizes TUBA1A as a neuronal alpha-tubulin isotype that heterodimerizes with beta-tubulin and incorporates into microtubules.
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Falcon supports TUBA1A as the predominant developmental neuronal alpha-tubulin, with Tuba1a-rich microtubules required for neurite extension, neuronal migration, axonal transport, and commissure formation.
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Falcon summarizes mouse Tuba1a mutant evidence, including Tuba1aND dosage-sensitive commissural defects and S140G effects on microtubule straightness and neuronal saltatory migration.
InterPro2GO electronic annotation
Phylogenetic-based annotations by GO_Central (IBA)
UniProtKB-SubCell-based electronic annotation
ISO annotation from human ortholog via UniProt
ISO annotation from human ortholog
ISO annotation from human ortholog via GO_Central
UniProt Annotation Extension electronic annotation
Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans.
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S140G mutation in Tuba1a GTP binding pocket reduces GTP binding 5-fold and heterodimer formation
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Impaired radial migration at E14.5 and E16.5 demonstrated by BrdU labeling
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Fractured pyramidal cell layer in hippocampus and cortical wave-like perturbations
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Hyperactivity, impaired spatial working memory, and reduced anxiety
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BAC transgene rescue confirms all phenotypes are due to Tuba1a mutation
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No cerebellar abnormalities
Proteolipid protein is required for transport of sirtuin 2 into CNS myelin.
The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskeleton through activation of the ephrin pathway.
Alpha/beta-tubulin are A kinase anchor proteins for type I PKA in neurons.
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Alpha/beta-tubulin forms complex with PKA RI subunit serving as AKAP
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Complex is produced in cytosol and transported to synapses
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PKA RI co-localizes with tubulin in neuropils and at cell membrane
Inhibition of microtubule assembly in osteoblasts stimulates bone morphogenetic protein 2 expression and bone formation through transcription factor Gli2.
CYLD negatively regulates cell-cycle progression by inactivating HDAC6 and increasing the levels of acetylated tubulin.
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CYLD interacts with alpha-tubulin via CAP-Gly domains 1 and 2
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CYLD inhibits HDAC6-mediated tubulin deacetylation
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CYLD increases acetylated alpha-tubulin levels
HDAC1 nuclear export induced by pathological conditions is essential for the onset of axonal damage.
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HDAC1 nuclear export in neurons exposed to glutamate and TNF-alpha
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HDAC1 interacts with kinesin motor proteins impairing mitochondrial transport
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Axonal damage involves cytoskeletal disruption including tubulin
Disease-associated mutations in TUBA1A result in a spectrum of defects in the tubulin folding and heterodimer assembly pathway.
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Nine disease-causing TUBA1A mutations examined
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Defects in chaperone interactions (prefoldin, CCT, TBCB)
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Reduced heterodimer formation in varying yields
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Suppressed microtubule growth rate in neurites
The role of Tuba1a in adult hippocampal neurogenesis and the formation of the dentate gyrus.
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Normal neurogenic potential but ectopic neurogenesis in S140G mutant
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Disorganized subgranular zone and dispersed granule cell layer
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Defective migration of neurons and progenitors during development
Cytoarchitectural disruption of the superior colliculus and an enlarged acoustic startle response in the Tuba1a mutant mouse.
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Superior colliculus thinning with apparent fusion of deep layers
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Impaired radial migration in SC demonstrated by birthdate labeling
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Massive neuronal loss attributed to increased apoptotic cell death
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Exaggerated acoustic startle response
Behavioral and neuromorphological characterization of a novel Tuba1 mutant mouse.
TFIIB co-localizes and interacts with α-tubulin during oocyte meiosis in the mouse and depletion of TFIIB causes arrest of subsequent embryo development.
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TFIIB and alpha-tubulin co-localize during meiosis
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Direct interaction confirmed by BiFC
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TFIIB associates with spindle microtubules from GVBD to MII
Novel α-tubulin mutation disrupts neural development and tubulin proteostasis.
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Tuba1a ND mutation causes cortical dysgenesis and motor neuron defects
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Motor neurons fail to innervate limb muscles with synapse defects at NMJ
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Mutant alpha-tubulin depleted from cell lysate and microtubules
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Tubulin-binding cofactors suppress mutation effects
Ciliary smoothened-mediated noncanonical hedgehog signaling promotes tubulin acetylation.
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Hh pathway increases microtubule acetylation via Smo
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Dependent on Smo but not Sufu or Gli
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Requires primary cilia and intracellular calcium increase
Acetylated tubulin is essential for touch sensation in mice.
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Atat1 knockout mice lose mechanosensitivity
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All cutaneous afferent subtypes have reduced mechanosensitivity
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Acetylation maintains cellular elasticity required for mechanotransduction
Mutation of the α-tubulin Tuba1a leads to straighter microtubules and perturbs neuronal migration.
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S140G mutation causes increased microtubule straightness
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Slowed neuronal migration with increased branching
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Perturbed nucleus-centrosome coupling
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Glial cells dispersed along RMS
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Tuba1a plays essential non-compensated role in saltatory migration
Differential requirements of tubulin genes in mammalian forebrain development.
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Tuba1a null is perinatal lethal with significant forebrain dysmorphology
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Tubb2a and Tubb2b nulls survive with mild phenotypes
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Demonstrates non-redundant role of Tuba1a
Reduced TUBA1A Tubulin Causes Defects in Trafficking and Impaired Adult Motor Behavior.
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Tuba1a ND heterozygotes have reduced microtubule tracks in axons
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Increased organelle trafficking pausing
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Adult-onset ataxia
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Age-related NMJ synapse size reduction without neuronal death
De novo protein identification in mammalian sperm using in situ cryoelectron tomography and AlphaFold2 docking.