Tuba1a encodes tubulin alpha-1A, a major neuronal alpha-tubulin isotype that is especially abundant during mouse brain development. It heterodimerizes with beta-tubulin to form GTP-bound alpha/beta-tubulin dimers that polymerize into microtubules; GTP binding at the alpha-tubulin N-site stabilizes the heterodimer, while the tubulin polymer cycle drives microtubule dynamics. Tuba1a-rich microtubules are required for neuronal migration, neurite extension, axon pathfinding, and axonal transport. Direct structural evidence also places Tuba1a in sperm flagellar doublet microtubules. The protein undergoes extensive post-translational modifications including acetylation, detyrosination, glutamylation, and glycylation that tune microtubule stability and motor-protein interactions.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000226 microtubule cytoskeleton organization | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha-tubulin is a core structural component of microtubules, and its role in microtubule cytoskeleton organization is well established across the tubulin family. Tuba1a S140G mutant mice show disrupted microtubule organization in the brain (PMID:17218254, PMID:28687665). Reason: Core function of alpha-tubulin. Mutations in Tuba1a directly impair microtubule cytoskeleton organization as demonstrated in multiple ENU mutant mouse studies. Supporting Evidence: PMID:17218254 the causative mutation lies in the guanosine triphosphate (GTP) binding pocket of alpha-1 tubulin (Tuba1) and affects tubulin heterodimer formation PMID:28687665 Tuba1a mutation led to increased straightness of newly polymerized MTs file:mouse/Tuba1a/Tuba1a-deep-research-falcon.md Mouse Tuba1a encodes a neuronal alpha-tubulin isotype that heterodimerizes with beta-tubulin and incorporates into microtubule polymers; it is required for neurite extension, neuronal migration, and intracellular transport. |
| GO:0005737 cytoplasm | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha-tubulin is a cytoplasmic protein that forms microtubules in the cytoplasm. This is a fundamental localization for all tubulins. Reason: Core localization for alpha-tubulin. Well established across all tubulin family members. |
| GO:0005874 microtubule | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha-tubulin is a structural component of microtubules, forming alpha/beta heterodimers that polymerize into the microtubule lattice. This is a core localization for Tuba1a. Reason: Core localization. Alpha-tubulin is literally a building block of microtubules. UniProt confirms this is a major constituent of microtubules. Supporting Evidence: PMID:17218254 a FLAG-tagged mutant Tuba1 incorporated into the normal interphase microtubule network upon overexperession in cultured cells |
| GO:0000278 mitotic cell cycle | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Alpha-tubulin is required for mitotic spindle formation during cell division. This is a conserved function across the tubulin family. Reason: While microtubules are essential for mitotic spindle function, Tuba1a is primarily expressed in post-mitotic neurons (PMID:26658218). Other alpha-tubulin isotypes (e.g. Tuba1b, Tuba1c) are more likely the primary contributors to the mitotic spindle in dividing cells. Valid IBA annotation but not a core function of Tuba1a specifically. |
| GO:0005200 structural constituent of cytoskeleton | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha-tubulin is a core structural constituent of the microtubule cytoskeleton. This is the primary molecular function of alpha-tubulin. Reason: This is the defining molecular function of alpha-tubulin. UniProt annotates it with EC 3.6.5.- and describes it as "the major constituent of microtubules" Supporting Evidence: file:mouse/Tuba1a/Tuba1a-uniprot.txt Tubulin is the major constituent of microtubules |
| GO:0030182 neuron differentiation | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Tuba1a plays a key role in neuron differentiation through its requirement for neuronal migration and morphogenesis. Multiple Tuba1a mutant mice show defects in neuronal development (PMID:17218254, PMID:28687665, PMID:26658218). Reason: Tuba1a is the predominant alpha-tubulin in post-mitotic neurons and is essential for neuronal morphogenesis, but the direct supported process is neuronal migration and microtubule-dependent neurite extension rather than differentiation fate specification. Supporting Evidence: PMID:26658218 Tuba1a is highly expressed in the brain during late embryonic development, and specifically enriched in post-mitotic neurons that extend long processes |
| GO:0005525 GTP binding | IBA GO_REF:0000033 | ACCEPT | Summary: Alpha-tubulin binds GTP at the non-exchangeable N-site, which acts as a structural cofactor stabilizing the alpha/beta heterodimer. This is a fundamental property of all alpha-tubulins. Reason: Core molecular function. GTP binding is essential for tubulin heterodimer stability and microtubule polymerization. The Jenna (S140G) mutation directly affects GTP binding at the N-site (PMID:17218254). Supporting Evidence: PMID:17218254 The mutation causes an amino acid change from serine to glycine at residue 140 (S140G) |
| GO:0005200 structural constituent of cytoskeleton | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation consistent with IBA annotation for the same term. Structural constituent of cytoskeleton is the core molecular function of alpha-tubulin. Reason: Redundant with IBA annotation but correctly assigned. Core function. |
| GO:0005525 GTP binding | IEA GO_REF:0000002 | ACCEPT | Summary: IEA annotation consistent with IBA annotation for the same term. GTP binding is essential for tubulin function. Reason: Redundant with IBA annotation but correctly assigned. Core function. |
| GO:0005856 cytoskeleton | IEA GO_REF:0000044 | MARK AS OVER ANNOTATED | Summary: Tubulin is a component of the cytoskeleton. This is a broader parent term of microtubule cytoskeleton. Reason: Correct but less specific than microtubule cytoskeleton (GO:0015630), and subsumed by the more specific terms the gene already carries. [2026-08 SL project re-review] Uninformative parent from the UniProt subcellular-location pipeline. The sole source for this annotation is GO_REF:0000044 (UniProtKB-SubCell), and the gene already carries strictly more specific term(s) from independent evidence, namely GO:0035371 microtubule plus-end (IMP) and GO:0005881 cytoplasmic microtubule (IDA). The term is not false; it is an under-specified location that adds no information over what is already annotated, which is the dominant failure mode of the SL pipeline (see projects/SL.md). Marked over-annotated rather than MODIFY because the more precise term is already present, so there is nothing to replace it with. |
| GO:0005874 microtubule | IEA GO_REF:0000120 | ACCEPT | Summary: IEA annotation consistent with IBA annotation. Alpha-tubulin is a component of microtubules. Reason: Redundant with IBA annotation but correctly assigned. Core localization. |
| GO:0007017 microtubule-based process | IEA GO_REF:0000002 | ACCEPT | Summary: Alpha-tubulin is involved in microtubule-based processes. This is a broad parent term. Reason: Correct but very broad. Acceptable as an IEA annotation since more specific terms are also present. |
| GO:0005515 protein binding | IPI PMID:19893491 CYLD negatively regulates cell-cycle progression by inactiva... | MARK AS OVER ANNOTATED | Summary: PMID:19893491 demonstrates that CYLD interacts with alpha-tubulin through its CAP-Gly domains. The interaction was shown by co-immunoprecipitation in keratinocytes and melanocytes. However, "protein binding" is uninformative. Reason: The CYLD-alpha-tubulin interaction is experimentally supported, but GO:0005515 is an uninformative generic binding term and does not capture a core Tuba1a activity. The functional direction in the paper is CYLD binding polymerized tubulin and regulating HDAC6-mediated tubulin acetylation, not a specific binding activity that should define Tuba1a function. Supporting Evidence: PMID:19893491 Immunoprecipitation of endogenous CYLD in melanocytes revealed an interaction with alpha-tubulin |
| GO:0005879 axonemal microtubule | IEA GO_REF:0000107 | ACCEPT | Summary: Tuba1a has been directly identified as a component of sperm flagellar doublet microtubules by cryo-ET (PMID:37865089). Axonemal microtubules are the doublet microtubules found in cilia and flagella. Reason: Directly supported by structural evidence from cryo-ET of mouse sperm flagella (PMID:37865089). Also consistent with UniProt subcellular location annotation. Supporting Evidence: PMID:37865089 in situ cryoET and subtomogram averaging has achieved up to 6.0 Γ
reconstructions of native microtubule structures in mouse and human sperm samples |
| GO:0005929 cilium | IEA GO_REF:0000107 | ACCEPT | Summary: Alpha-tubulin is a component of ciliary microtubules. Consistent with the UniProt annotation showing flagellum axoneme localization and Reactome pathways for cilium assembly. Reason: Supported by the broader literature on tubulin in cilia and flagella, and by Reactome pathways (R-MMU-5617833 Cilium Assembly). |
| GO:0015630 microtubule cytoskeleton | IEA GO_REF:0000107 | ACCEPT | Summary: Alpha-tubulin is a fundamental component of the microtubule cytoskeleton. Reason: Core localization. Well established for all alpha-tubulins. |
| GO:0036464 cytoplasmic ribonucleoprotein granule | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This annotation suggests Tuba1a localizes to cytoplasmic ribonucleoprotein granules. While microtubules are involved in transport and localization of RNP granules, the evidence for Tuba1a being a resident component of these granules is not strong. Reason: This is likely a high-throughput proteomics-based annotation transferred from the human ortholog. While microtubules transport RNP granules, tubulin itself is not a functional component of RNP granules; it is a component of the microtubule tracks these granules travel on. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Alpha-tubulin can form lateral contacts with other alpha-tubulin subunits within the microtubule lattice. This is a consequence of its role in microtubule polymerization. Reason: While alpha-tubulin does make lateral contacts with itself in the microtubule lattice, the primary functional interaction is heterodimer formation with beta-tubulin (protein heterodimerization activity). Identical protein binding is a secondary consequence of microtubule structure, not a primary function. |
| GO:0055037 recycling endosome | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: This annotation suggests Tuba1a localizes to recycling endosomes. This is likely from proteomics experiments where tubulin was detected in endosome-enriched fractions. Reason: Tubulin is highly abundant and can be detected in many subcellular fractions. Microtubules provide tracks for recycling endosome transport, but tubulin is not a bona fide component of the recycling endosome itself. This is a common over-annotation for abundant cytoskeletal proteins. |
| GO:0035371 microtubule plus-end | IMP PMID:20603323 Disease-associated mutations in TUBA1A result in a spectrum ... | ACCEPT | Summary: PMID:20603323 examined disease-associated TUBA1A mutations and showed suppression of microtubule growth rate in neurites. Newly incorporated tubulin dimers are added at the plus-end of microtubules. Reason: Alpha-tubulin is incorporated at the microtubule plus-end during polymerization. This is a well-established localization for newly assembled tubulin. Supporting Evidence: PMID:20603323 a suppression of microtubule growth rate in the neurites (but not the soma) of cultured neurons |
| GO:0005874 microtubule | ISO GO_REF:0000119 | ACCEPT | Summary: ISO annotation for microtubule localization, consistent with IBA annotation. Core localization. Reason: Redundant with IBA but correct. Core localization. |
| GO:0005879 axonemal microtubule | ISO GO_REF:0000119 | ACCEPT | Summary: ISO annotation for axonemal microtubule localization. Directly supported by cryo-ET of mouse sperm flagella (PMID:37865089). Reason: Correct. Directly confirmed by PMID:37865089. |
| GO:0005929 cilium | ISO GO_REF:0000119 | ACCEPT | Summary: ISO annotation for cilium localization. Consistent with the known role of alpha-tubulin in cilia and flagella. Reason: Correct. Consistent with flagellum localization shown in PMID:37865089. |
| GO:0015630 microtubule cytoskeleton | ISO GO_REF:0000119 | ACCEPT | Summary: ISO annotation for microtubule cytoskeleton. Core localization. Reason: Correct. Redundant with IEA but well established. |
| GO:0036464 cytoplasmic ribonucleoprotein granule | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: ISO annotation for RNP granule localization. Same concern as the IEA annotation. Reason: Same issue as the IEA annotation. Tubulin is not a bona fide component of RNP granules. Likely an artifact of proteomic co-purification due to tubulin abundance. |
| GO:0042802 identical protein binding | ISO GO_REF:0000119 | KEEP AS NON CORE | Summary: ISO annotation for identical protein binding. Same assessment as the IEA annotation. Reason: Technically true due to lateral contacts in the microtubule lattice, but not a primary functional activity. The core interaction is heterodimerization with beta-tubulin. |
| GO:0055037 recycling endosome | ISO GO_REF:0000119 | MARK AS OVER ANNOTATED | Summary: ISO annotation for recycling endosome localization. Same concern as the IEA annotation. Reason: Tubulin is not a resident component of recycling endosomes. Likely over-annotation from proteomics data. |
| GO:0019904 protein domain specific binding | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: This annotation suggests Tuba1a has protein domain specific binding activity. Alpha-tubulin interacts with various MAPs and motors through specific domain interactions. Reason: Alpha-tubulin does interact with specific protein domains (e.g., CAP-Gly domains of CYLD, CLIP proteins), but this is a generic term. Not a core molecular function annotation. |
| GO:0043209 myelin sheath | ISO GO_REF:0000096 | KEEP AS NON CORE | Summary: ISO annotation for myelin sheath localization. Consistent with the HDA annotation from PMID:17634366 showing tubulin in purified myelin membranes. Reason: Tubulin has been detected in myelin proteomics studies (PMID:17634366), but this likely reflects cytoskeletal contamination of myelin preparations or microtubule tracks within myelin-forming oligodendrocyte processes. Not a core localization. |
| GO:0045121 membrane raft | ISO GO_REF:0000096 | MARK AS OVER ANNOTATED | Summary: This annotation suggests Tuba1a localizes to membrane rafts. Tubulin has been detected in detergent-resistant membrane fractions in some proteomics studies. Reason: Tubulin is one of the most abundant cellular proteins and is frequently detected in membrane raft preparations. This likely represents non-specific association or contamination rather than bona fide localization to membrane rafts. |
| GO:0030317 flagellated sperm motility | IDA PMID:37865089 De novo protein identification in mammalian sperm using in s... | KEEP AS NON CORE | Summary: PMID:37865089 identified Tuba1a as a component of sperm flagellar doublet microtubules using cryo-ET and AlphaFold2 docking. Tubulin is essential for flagellar assembly and motility. Reason: Tuba1a is a component of sperm flagellar microtubules, but its role in sperm motility is as a structural component rather than a regulatory one. This is a non-core function compared to its primary neuronal roles. The annotation is valid but represents a secondary tissue-specific function. Supporting Evidence: PMID:37865089 in situ cryoET and subtomogram averaging has achieved up to 6.0 Γ
reconstructions of native microtubule structures in mouse and human sperm samples |
| GO:0036126 sperm flagellum | IDA PMID:37865089 De novo protein identification in mammalian sperm using in s... | ACCEPT | Summary: PMID:37865089 directly identified Tuba1a in sperm flagellar doublet microtubules by cryo-ET structure determination at 7.7 angstrom resolution. Reason: Directly demonstrated by structural biology (cryo-ET). Tuba1a is a component of sperm flagellar doublet microtubules. Supporting Evidence: PMID:37865089 in situ cryoET and subtomogram averaging has achieved up to 6.0 Γ
reconstructions of native microtubule structures in mouse and human sperm samples |
| GO:0031594 neuromuscular junction | IMP PMID:26658218 Novel Ξ±-tubulin mutation disrupts neural development and tub... | KEEP AS NON CORE | Summary: PMID:26658218 showed that Tuba1a mutant mice (ND allele) have motor neuron synapse defects at the neuromuscular junction. Homozygous mutants showed failure of motor neurons to innervate target muscles. Reason: Tuba1a is localized to the NMJ as part of the microtubule cytoskeleton in motor neuron axon terminals. The defects in NMJ are secondary to its role in microtubule-based transport and synapse maintenance. Supporting Evidence: PMID:26658218 Motor neurons fail to innervate target muscles in the limbs and show synapse defects at proximal targets |
| GO:0031594 neuromuscular junction | IDA PMID:26658218 Novel Ξ±-tubulin mutation disrupts neural development and tub... | KEEP AS NON CORE | Summary: IDA annotation indicating Tuba1a is detected at the neuromuscular junction. This is consistent with the IMP annotation from the same paper. Reason: Tuba1a is present at the NMJ as part of the microtubule cytoskeleton but this is a secondary localization. Supporting Evidence: PMID:26658218 Motor neurons fail to innervate target muscles in the limbs and show synapse defects at proximal targets |
| GO:0050807 regulation of synapse organization | IMP PMID:26658218 Novel Ξ±-tubulin mutation disrupts neural development and tub... | KEEP AS NON CORE | Summary: PMID:26658218 demonstrated that Tuba1a ND mutation leads to synapse defects at the NMJ. The study also showed NMJ size reduction over time in heterozygous mutants (PMID:32184299). Reason: Tuba1a contributes to synapse organization through its role in microtubule-based transport and cytoskeletal integrity, but this is a downstream consequence rather than a direct regulatory function. The synapse defects are secondary to general microtubule dysfunction. Supporting Evidence: PMID:26658218 Motor neurons fail to innervate target muscles in the limbs and show synapse defects at proximal targets |
| GO:0050807 regulation of synapse organization | IDA PMID:26658218 Novel Ξ±-tubulin mutation disrupts neural development and tub... | KEEP AS NON CORE | Summary: IDA annotation for regulation of synapse organization from the same paper as the IMP annotation. Reason: Same rationale as the IMP annotation. Synapse organization effects are secondary to microtubule dysfunction. |
| GO:0000226 microtubule cytoskeleton organization | IMP PMID:22101068 Behavioral and neuromorphological characterization of a nove... | ACCEPT | Summary: PMID:22101068 describes a novel ENU-induced Tuba1a mutant (D263G) with abnormal brain morphology indicating disrupted microtubule organization during development. Reason: Core function. The D263G mutation in Tuba1a disrupts microtubule cytoskeleton organization, consistent with the S140G allele (PMID:17218254). Supporting Evidence: PMID:22101068 We identified a missense mutation in the Tuba1 gene, which encodes the TUBA1 protein, and designated the mutant gene Tuba1(Rgsc1736). This mutation results in an aspartic acid to glycine substitution in the TUBA1 protein. |
| GO:0007626 locomotory behavior | IMP PMID:22101068 Behavioral and neuromorphological characterization of a nove... | KEEP AS NON CORE | Summary: PMID:22101068 showed the Tuba1a Rgsc1736 mutant has significantly increased spontaneous locomotor activity, consistent with the hyperactive Jenna mutant (PMID:17218254). Reason: Locomotory behavior defects are downstream consequences of impaired neuronal migration and brain malformation, not a direct function of Tuba1a. This is a phenotypic readout of Tuba1a mutation rather than a function. Supporting Evidence: PMID:22101068 exhibited a significant increase in spontaneous locomotor activity |
| GO:0021859 pyramidal neuron differentiation | IMP PMID:22101068 Behavioral and neuromorphological characterization of a nove... | KEEP AS NON CORE | Summary: PMID:22101068 and PMID:17218254 both show disrupted pyramidal cell layers in the hippocampus of Tuba1a mutant mice, indicating a role in pyramidal neuron differentiation. Reason: The pyramidal neuron phenotype is a consequence of impaired neuronal migration rather than a specific role in pyramidal neuron differentiation per se. The defect is in migration not differentiation fate determination. Supporting Evidence: PMID:17218254 Staining with cresyl violet and with the neuronal marker NeuN showed hippocampal disorganization with an additional layer of pyramidal cells in the stratum oriens |
| GO:0021987 cerebral cortex development | IMP PMID:22101068 Behavioral and neuromorphological characterization of a nove... | KEEP AS NON CORE | Summary: PMID:22101068 showed cortical abnormalities in the Tuba1a Rgsc1736 mutant. PMID:17218254 showed wave-like perturbations in cortical layers II/III and IV in the Jenna mutant. Reason: Cerebral cortex development is affected by Tuba1a mutations, but this is a downstream phenotypic consequence of impaired neuronal migration. The core function is microtubule-based neuronal migration, which then impacts cortical development. Supporting Evidence: PMID:17218254 closer examination of NeuN, Cux-1, and Nissl stains revealed wave-like perturbations in layer IV |
| GO:0035641 locomotory exploration behavior | IMP PMID:22101068 Behavioral and neuromorphological characterization of a nove... | KEEP AS NON CORE | Summary: PMID:22101068 showed the mutant exhibited abnormal open-field behavior and inattention to novel objects, which relates to locomotory exploration. Reason: Behavioral phenotype is a distal consequence of brain malformation caused by Tuba1a mutation. Not a direct function. Supporting Evidence: PMID:22101068 Tuba1(Rgsc1736) heterozygotes exhibited inattention to novel objects and aberrant patterns of home-cage activity |
| GO:0006886 intracellular protein transport | IMP PMID:32184299 Reduced TUBA1A Tubulin Causes Defects in Trafficking and Imp... | KEEP AS NON CORE | Summary: PMID:32184299 showed that reduced TUBA1A results in fewer microtubule tracks in axons, leading to more pausing during organelle trafficking. Trafficking defects impair synaptic maintenance. Reason: Tuba1a contributes to intracellular transport by providing microtubule tracks for motor protein-based transport. The trafficking defect is secondary to reduced microtubule assembly. This is a downstream consequence of Tuba1a's structural role. Supporting Evidence: PMID:32184299 reduced TUBA1A allows for assembly of less microtubules in axons resulting in more pausing during organelle trafficking |
| GO:0046785 microtubule polymerization | IMP PMID:32184299 Reduced TUBA1A Tubulin Causes Defects in Trafficking and Imp... | ACCEPT | Summary: PMID:32184299 showed reduced microtubule assembly in axons of Tuba1a ND mutant neurons. Alpha-tubulin is the building block for microtubule polymerization. Reason: Core function. Alpha-tubulin heterodimers are the direct subunits that polymerize to form microtubules. Reduced Tuba1a leads directly to fewer microtubules. Supporting Evidence: PMID:32184299 reduced TUBA1A allows for assembly of less microtubules in axons |
| GO:0050808 synapse organization | IMP PMID:32184299 Reduced TUBA1A Tubulin Causes Defects in Trafficking and Imp... | KEEP AS NON CORE | Summary: PMID:32184299 showed Tuba1a ND heterozygous mice develop age-related NMJ synapse size reduction, demonstrating a role in synapse maintenance/organization. Reason: Synapse organization defects are downstream of microtubule-based transport deficits. The NMJ synapse deterioration is secondary to reduced microtubule tracks for trafficking. Supporting Evidence: PMID:32184299 However, NMJ synapse morphology and animal behavior deteriorate in an age-related manner in Tuba1aND/+animals, without evidence of neuronal cell death or degeneration |
| GO:0061744 motor behavior | IMP PMID:32184299 Reduced TUBA1A Tubulin Causes Defects in Trafficking and Imp... | KEEP AS NON CORE | Summary: PMID:32184299 showed Tuba1a ND heterozygous mice develop adult-onset ataxia. Motor behavior deficits are a phenotypic consequence of synaptic and trafficking defects. Reason: Motor behavior deficits are a distal phenotypic consequence of Tuba1a mutation, not a direct function. Behavioral phenotypes should be kept as non-core. Supporting Evidence: PMID:32184299 Tuba1aND/+ mice develop adult-onset ataxia |
| GO:0072384 organelle transport along microtubule | IMP PMID:32184299 Reduced TUBA1A Tubulin Causes Defects in Trafficking and Imp... | KEEP AS NON CORE | Summary: PMID:32184299 showed trafficking defects with more pausing during organelle transport in Tuba1a ND neurons due to insufficient microtubule tracks. Reason: Tuba1a provides the microtubule tracks for organelle transport. The transport defects are secondary to reduced microtubule assembly. Not a direct function of Tuba1a but a consequence of its structural role. Supporting Evidence: PMID:32184299 reduced TUBA1A allows for assembly of less microtubules in axons resulting in more pausing during organelle trafficking |
| GO:0000226 microtubule cytoskeleton organization | IMP PMID:28687665 Mutation of the Ξ±-tubulin Tuba1a leads to straighter microtu... | ACCEPT | Summary: PMID:28687665 showed the S140G mutation leads to increased straightness of newly polymerized microtubules and altered conformational properties of the alpha/beta heterodimer. Reason: Core function. Directly demonstrates the role of Tuba1a in microtubule cytoskeleton organization through its effect on microtubule geometry and dynamics. Supporting Evidence: PMID:28687665 Tuba1a mutation led to increased straightness of newly polymerized MTs, and structural modeling data suggest a conformational change in the alpha/beta-tubulin heterodimer |
| GO:0001764 neuron migration | IMP PMID:28687665 Mutation of the Ξ±-tubulin Tuba1a leads to straighter microtu... | ACCEPT | Summary: PMID:28687665 showed slowed neuronal migration and increased branching in Tuba1a S140G mutant neurons by live imaging. Neurons accumulated along the rostral migratory stream. Reason: Core function. Neuron migration is the most well-established and specific phenotype of Tuba1a mutations across multiple independent alleles and studies. This is the defining function of Tuba1a in brain development. Supporting Evidence: PMID:28687665 Live imaging of Tuba1a-mutant neurons revealed slowed migration and increased neuronal branching, which correlated with directionality alterations and perturbed nucleus-centrosome (N-C) coupling |
| GO:0001764 neuron migration | IMP PMID:31386652 Differential requirements of tubulin genes in mammalian fore... | ACCEPT | Summary: PMID:31386652 generated Tuba1a knockout mice and showed perinatal lethality with significant forebrain dysmorphology due to migration defects. Reason: Core function. The null allele confirms the essential, non-redundant role of Tuba1a in neuronal migration. Supporting Evidence: PMID:31386652 loss of Tuba1a is perinatal lethal and leads to significant forebrain dysmorphology |
| GO:0007098 centrosome cycle | IMP PMID:28687665 Mutation of the Ξ±-tubulin Tuba1a leads to straighter microtu... | KEEP AS NON CORE | Summary: PMID:28687665 showed perturbed nucleus-centrosome coupling in Tuba1a S140G mutant neurons, which is relevant to the centrosome cycle during neuronal migration. Reason: The centrosome coupling defect is a consequence of altered microtubule properties rather than a direct role in centrosome cycle regulation. The annotation is somewhat overspecific. Supporting Evidence: PMID:28687665 perturbed nucleus-centrosome (N-C) coupling |
| GO:0010001 glial cell differentiation | IMP PMID:28687665 Mutation of the Ξ±-tubulin Tuba1a leads to straighter microtu... | KEEP AS NON CORE | Summary: PMID:28687665 showed that glial cells are dispersed along the rostral migratory stream in Tuba1a S140G mutants. Reason: The glial cell dispersion is likely secondary to disrupted migration rather than a specific role in glial cell differentiation. Microtubules are broadly required in all cell types. Supporting Evidence: PMID:28687665 glial cells are dispersed along the rostral migratory stream in postnatal and adult brains |
| GO:0010467 gene expression | IMP PMID:31386652 Differential requirements of tubulin genes in mammalian fore... | MARK AS OVER ANNOTATED | Summary: PMID:31386652 examined differential requirements of tubulin genes in forebrain development. The annotation to gene expression is very broad and likely relates to indirect effects of Tuba1a loss on downstream gene expression patterns. Reason: Gene expression is an extremely broad term. Tuba1a is not a transcription factor or transcriptional regulator. Any effects on gene expression are indirect, downstream consequences of disrupted microtubule-dependent signaling or altered cellular state due to loss of Tuba1a. This is over-annotation. |
| GO:0021987 cerebral cortex development | IMP PMID:31386652 Differential requirements of tubulin genes in mammalian fore... | KEEP AS NON CORE | Summary: PMID:31386652 showed Tuba1a null mice have significant forebrain dysmorphology. Also shown in multiple other Tuba1a mutant studies. Reason: Valid phenotype but cerebral cortex development is a downstream consequence of Tuba1a's role in neuronal migration. Keep as non-core. Supporting Evidence: PMID:31386652 loss of Tuba1a is perinatal lethal and leads to significant forebrain dysmorphology |
| GO:0022008 neurogenesis | IMP PMID:31386652 Differential requirements of tubulin genes in mammalian fore... | KEEP AS NON CORE | Summary: PMID:31386652 showed defects in forebrain neurogenesis in Tuba1a null mice. Consistent with the essential role in neuronal development. Reason: Neurogenesis is a broad parent term. The specific function of Tuba1a is in neuron migration rather than neurogenesis per se. The neurogenesis annotation from PMID:21041996 showed normal neurogenic potential but ectopic positioning, confirming that the problem is migration, not generation of neurons. Supporting Evidence: PMID:21041996 mice harbouring an S140G mutation in Tuba1a present with normal neurogenic potential, but that this neurogenesis is often ectopic |
| GO:0030182 neuron differentiation | IMP PMID:28687665 Mutation of the Ξ±-tubulin Tuba1a leads to straighter microtu... | KEEP AS NON CORE | Summary: PMID:28687665 showed defects in neuronal migration and branching in Tuba1a S140G mutant, which affects neuron differentiation. Reason: The evidence supports altered migration and branching in mutant neurons. This is consistent with neuronal morphogenesis but is broader than the most precise supported process, neuron migration, so it should be retained as non-core. Supporting Evidence: PMID:28687665 our work shows that Tuba1a plays an essential, noncompensated role in neuronal saltatory migration in vivo |
| GO:0046785 microtubule polymerization | IMP PMID:28687665 Mutation of the Ξ±-tubulin Tuba1a leads to straighter microtu... | ACCEPT | Summary: PMID:28687665 showed altered microtubule polymerization properties (increased straightness) in Tuba1a S140G mutant neurons. Reason: Core function. Tuba1a heterodimers are the building blocks for microtubule polymerization. The S140G mutation directly alters polymerization properties. Supporting Evidence: PMID:28687665 Tuba1a mutation led to increased straightness of newly polymerized MTs |
| GO:0048853 forebrain morphogenesis | IMP PMID:31386652 Differential requirements of tubulin genes in mammalian fore... | KEEP AS NON CORE | Summary: PMID:31386652 showed Tuba1a null mice have significant forebrain dysmorphology with perinatal lethality. Reason: Forebrain morphogenesis defects are a downstream consequence of impaired neuronal migration. Keep as non-core. Supporting Evidence: PMID:31386652 loss of Tuba1a is perinatal lethal and leads to significant forebrain dysmorphology |
| GO:0140058 neuron projection arborization | IMP PMID:28687665 Mutation of the Ξ±-tubulin Tuba1a leads to straighter microtu... | KEEP AS NON CORE | Summary: PMID:28687665 showed increased neuronal branching in Tuba1a S140G mutant neurons during migration by live imaging. Reason: Increased branching is observed in Tuba1a mutant neurons but this reflects altered microtubule dynamics rather than a direct role in arborization regulation. Keep as non-core. Supporting Evidence: PMID:28687665 Live imaging of Tuba1a-mutant neurons revealed slowed migration and increased neuronal branching |
| GO:0001764 neuron migration | IMP PMID:21041996 The role of Tuba1a in adult hippocampal neurogenesis and the... | ACCEPT | Summary: PMID:21041996 showed that S140G mutant mice have defective migration of neurons in the dentate gyrus, with normal neurogenic potential but ectopic positioning. Reason: Core function. This study specifically demonstrated that the neurogenesis is normal but migration is defective in Tuba1a mutant hippocampus. Supporting Evidence: PMID:21041996 mice harbouring an S140G mutation in Tuba1a present with normal neurogenic potential, but that this neurogenesis is often ectopic. Morphological analysis of the dentate gyrus in adulthood revealed a disorganised subgranular zone and a dispersed granule cell layer. |
| GO:0007224 smoothened signaling pathway | IDA PMID:27793670 Ciliary smoothened-mediated noncanonical hedgehog signaling ... | MARK AS OVER ANNOTATED | Summary: PMID:27793670 showed that Hh pathway activation increases microtubule acetylation via Smoothened in MEFs. Tubulin acetylation is a downstream readout, not an active participant in Smo signaling. Reason: Tuba1a is a substrate of acetylation downstream of Smo signaling, not an active participant in the smoothened signaling pathway. The study shows that Smo promotes tubulin acetylation, meaning tubulin is a downstream target/substrate, not a signaling component. This is over-annotation. Supporting Evidence: PMID:27793670 Hh pathway activation in mouse embryonic fibroblast cells (MEFs) increases microtubule acetylation via smoothened (Smo) |
| GO:0071277 cellular response to calcium ion | IDA PMID:27793670 Ciliary smoothened-mediated noncanonical hedgehog signaling ... | MARK AS OVER ANNOTATED | Summary: PMID:27793670 showed that intracellular calcium increase is important for Hh-dependent tubulin acetylation downstream of Smo. Again, tubulin is a downstream substrate modified in response to calcium. Reason: Tubulin acetylation occurs in response to calcium signaling downstream of Smo, but tubulin itself is not responding to calcium in any direct sense. It is a substrate that gets modified. This is over-annotation of a passive substrate. Supporting Evidence: PMID:27793670 an increase in intracellular calcium is important for Hh-dependent tubulin acetylation at the downstream of Smo |
| GO:0009612 response to mechanical stimulus | IMP PMID:27976998 Acetylated tubulin is essential for touch sensation in mice. | KEEP AS NON CORE | Summary: PMID:27976998 showed that mice lacking Atat1 (the alpha-tubulin acetyltransferase) in sensory neurons have profound deficits in mechanosensitivity. Acetylated tubulin at K40 is essential for touch sensation by maintaining cellular stiffness. Reason: The study demonstrates that tubulin acetylation (which occurs on alpha-tubulin K40) is essential for mechanosensitivity. However, the annotation is to Tuba1a specifically when the study used Atat1 knockout mice. The mechanosensitivity role is for acetylated alpha-tubulin generally, not Tuba1a specifically. Keep as non-core since alpha-tubulin acetylation is important for touch but may involve multiple alpha-tubulin isotypes. Supporting Evidence: PMID:27976998 mice lacking the alpha-tubulin acetyltransferase Atat1 in sensory neurons display profound deficits in their ability to detect mechanical stimuli |
| GO:0021542 dentate gyrus development | IMP PMID:21041996 The role of Tuba1a in adult hippocampal neurogenesis and the... | KEEP AS NON CORE | Summary: PMID:21041996 showed the Tuba1a S140G mutant has a disorganized subgranular zone and dispersed granule cell layer in the dentate gyrus due to defective migration. Reason: Dentate gyrus development defects are a downstream consequence of impaired neuronal migration in the hippocampus. Keep as non-core. Supporting Evidence: PMID:21041996 Morphological analysis of the dentate gyrus in adulthood revealed a disorganised subgranular zone and a dispersed granule cell layer |
| GO:0022008 neurogenesis | IMP PMID:21041996 The role of Tuba1a in adult hippocampal neurogenesis and the... | KEEP AS NON CORE | Summary: PMID:21041996 explicitly showed normal neurogenic potential but ectopic neurogenesis in Tuba1a mutant mice. Reason: The study showed neurogenic potential is normal but positioning is ectopic. The core function is migration, not neurogenesis. This annotation should be kept as non-core since the defect is in migration of newly generated neurons, not in neurogenesis itself. Supporting Evidence: PMID:21041996 mice harbouring an S140G mutation in Tuba1a present with normal neurogenic potential, but that this neurogenesis is often ectopic |
| GO:0000226 microtubule cytoskeleton organization | IMP PMID:21875651 Cytoarchitectural disruption of the superior colliculus and ... | ACCEPT | Summary: PMID:21875651 showed that the S140G mutation impairs radial migration of neurons in the superior colliculus, leading to thinning and apparent layer fusion due to microtubule dysfunction. Reason: Core function. Consistent with the IBA and other IMP annotations for microtubule cytoskeleton organization. Supporting Evidence: PMID:21875651 The Jenna mutant mouse harbours an S140G mutation in Tuba1a that impairs tubulin heterodimer formation resulting in defective neuronal migration during development |
| GO:0000793 condensed chromosome | IDA PMID:24244602 TFIIB co-localizes and interacts with Ξ±-tubulin during oocyt... | KEEP AS NON CORE | Summary: PMID:24244602 showed TFIIB co-localizes with alpha-tubulin on condensed chromosomes during oocyte meiosis. Alpha-tubulin is part of the spindle that interacts with condensed chromosomes. Reason: The study primarily concerns TFIIB localization. Alpha-tubulin is present at the spindle near condensed chromosomes during meiosis, but is not a component of the condensed chromosome itself. The annotation may be slightly misleading but reflects the mitotic spindle-chromosome interface. Keep as non-core. Supporting Evidence: PMID:24244602 After progression to GV breakdown (GVBD), TFIIB and alpha-tubulin co-localize and accumulate in the vicinity of the condensed chromosomes |
| GO:0001764 neuron migration | IMP PMID:21875651 Cytoarchitectural disruption of the superior colliculus and ... | ACCEPT | Summary: PMID:21875651 showed impaired radial migration of neurons in the superior colliculus of S140G mutant mice using birthdate labeling at E12.5 and E13.5. Reason: Core function. Neuron migration defects in the superior colliculus add to the body of evidence across cortex, hippocampus, and RMS that Tuba1a is essential for neuronal migration. Supporting Evidence: PMID:21875651 the S140G mutation impairs the radial migration of neurons in the SC |
| GO:0001964 startle response | IMP PMID:21875651 Cytoarchitectural disruption of the superior colliculus and ... | KEEP AS NON CORE | Summary: PMID:21875651 showed Tuba1a S140G mutant mice have an exaggerated acoustic startle response, consistent with disrupted superior colliculus cytoarchitecture. Reason: The startle response phenotype is a distal behavioral consequence of disrupted brain cytoarchitecture due to impaired neuronal migration. Not a direct function. Supporting Evidence: PMID:21875651 we find that Jenna mutants exhibit an exaggerated acoustic startle response |
| GO:0005515 protein binding | IPI PMID:24244602 TFIIB co-localizes and interacts with Ξ±-tubulin during oocyt... | MARK AS OVER ANNOTATED | Summary: PMID:24244602 showed TFIIB interacts with alpha-tubulin by BiFC and co-localization during oocyte meiosis. Reason: The TFIIB-alpha-tubulin interaction is supported, but GO:0005515 is too generic to be informative for Tuba1a. The paper primarily supports TFIIB association with spindle microtubules during oocyte meiosis; it does not establish a distinct Tuba1a binding function beyond its microtubule structural role. Supporting Evidence: PMID:24244602 co-transfection of BiFC plasmids pHA-Tf2b and pFlag-Tuba1alpha further confirms a direct interaction between TFIIB and alpha-tubulins |
| GO:0048873 homeostasis of number of cells within a tissue | IMP PMID:21875651 Cytoarchitectural disruption of the superior colliculus and ... | KEEP AS NON CORE | Summary: PMID:21875651 showed a massive reduction in postmitotic neurons in the superior colliculus of Tuba1a mutant mice in adulthood, attributed to increased apoptotic cell death. Reason: The neuronal cell number reduction is a downstream consequence of impaired migration and subsequent apoptosis. Tuba1a does not directly regulate cell number homeostasis. Supporting Evidence: PMID:21875651 A quantitative assessment of neuronal number in adulthood reveals a massive reduction in postmitotic neurons in mutant animals, which we attribute to increased apoptotic cell death |
| GO:0051402 neuron apoptotic process | IMP PMID:21875651 Cytoarchitectural disruption of the superior colliculus and ... | KEEP AS NON CORE | Summary: PMID:21875651 showed increased apoptotic cell death in the superior colliculus of Tuba1a S140G mutant mice leading to neuronal loss. Reason: Neuronal apoptosis is a secondary consequence of impaired migration and mispositioning, not a direct function of Tuba1a. The apoptosis likely results from failure of migrating neurons to reach proper targets. Supporting Evidence: PMID:21875651 an elevated rate of cell death leads to a significant loss of neurons in the SC of the Jna/+ mouse between postnatal day 21 (P21) and 12 weeks of age |
| GO:0005515 protein binding | IPI PMID:20603323 Disease-associated mutations in TUBA1A result in a spectrum ... | MODIFY | Summary: PMID:20603323 examined disease-associated TUBA1A mutations and their effects on protein interactions in the tubulin folding pathway, including interactions with prefoldin, CCT, and TBCB. Reason: Protein binding is uninformative. The specific interactions described are with chaperones (prefoldin, CCT) and tubulin-specific cofactors (TBCB) in the folding pathway. A more specific term would be protein-folding chaperone binding, which is already annotated. Proposed replacements: protein-folding chaperone binding Supporting Evidence: PMID:20603323 These include a defective interaction with the chaperone prefoldin, a reduced efficiency in the generation of productive folding intermediates as a result of inefficient interaction with the cytosolic chaperonin, CCT |
| GO:0006458 'de novo' protein folding | IMP PMID:20603323 Disease-associated mutations in TUBA1A result in a spectrum ... | KEEP AS NON CORE | Summary: PMID:20603323 showed that TUBA1A mutations affect the de novo tubulin folding and heterodimer assembly pathway involving CCT, prefoldin, and tubulin-specific chaperones TBCA-TBCE. Reason: Tuba1a is a substrate of the de novo folding pathway, not an active participant in the folding process. The folding is performed by chaperones (CCT, prefoldin) and tubulin cofactors (TBCA-TBCE). This annotation describes the folding of Tuba1a, not a folding activity by Tuba1a. Supporting Evidence: PMID:20603323 We show that the expression of all the mutant proteins in vitro results in the generation of tubulin heterodimers in varying yield |
| GO:0008017 microtubule binding | IMP PMID:20603323 Disease-associated mutations in TUBA1A result in a spectrum ... | ACCEPT | Summary: PMID:20603323 showed that once folded, mutant tubulin heterodimers can co-polymerize with microtubules in vitro, demonstrating microtubule binding activity. Reason: Alpha-tubulin heterodimers bind to existing microtubules during polymerization. This is a core molecular function. Supporting Evidence: PMID:20603323 the expression of all the mutant proteins in vitro results in the generation of tubulin heterodimers in varying yield and that these can co-polymerize with microtubules in vitro |
| GO:0046982 protein heterodimerization activity | IMP PMID:20603323 Disease-associated mutations in TUBA1A result in a spectrum ... | ACCEPT | Summary: PMID:20603323 directly examined tubulin heterodimer formation and showed disease mutations affect the yield of alpha/beta heterodimers through the chaperone-dependent folding pathway. Reason: Core molecular function. Alpha-tubulin heterodimerizes with beta-tubulin to form the fundamental building block of microtubules. This is a defining activity of alpha-tubulin. Supporting Evidence: PMID:20603323 We show that the expression of all the mutant proteins in vitro results in the generation of tubulin heterodimers in varying yield |
| GO:0050821 protein stabilization | IMP PMID:20603323 Disease-associated mutations in TUBA1A result in a spectrum ... | KEEP AS NON CORE | Summary: PMID:20603323 showed that some mutations cause structural instability in vitro and diminished stability in vivo. Tuba1a contributes to the stability of the tubulin heterodimer. Reason: The protein stabilization annotation likely refers to the role of GTP binding in stabilizing the heterodimer. This is not an active stabilization activity but rather a consequence of heterodimer formation. Keep as non-core. Supporting Evidence: PMID:20603323 Other defects include structural instability in vitro, diminished stability in vivo |
| GO:0051087 protein-folding chaperone binding | IDA PMID:20603323 Disease-associated mutations in TUBA1A result in a spectrum ... | KEEP AS NON CORE | Summary: PMID:20603323 showed direct interactions between TUBA1A and chaperones (prefoldin, CCT) and tubulin cofactors (TBCB) using in vitro folding assays. Reason: Tuba1a interacts with prefoldin, CCT, and tubulin-specific cofactors during maturation, and the annotation is valid. It is a biogenesis interaction required to produce folded alpha/beta heterodimers rather than the core activity of the mature gene product. Supporting Evidence: PMID:20603323 These include a defective interaction with the chaperone prefoldin, a reduced efficiency in the generation of productive folding intermediates as a result of inefficient interaction with the cytosolic chaperonin, CCT, and, in several cases, a failure to stably interact with TBCB |
| GO:0001764 neuron migration | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | ACCEPT | Summary: The foundational paper demonstrating that the Tuba1a S140G mutation causes impaired neuronal migration in mice and lissencephaly in humans. BrdU labeling showed defective radial migration at E14.5 and E16.5. Reason: Core function. This is the seminal paper establishing that Tuba1a is essential for neuronal migration. The migration defect was directly demonstrated by BrdU birth-dating experiments and confirmed by BAC transgene rescue. Supporting Evidence: PMID:17218254 There was no significant difference between littermate controls and Jna/+ mutants when BrdU was injected at E12.5 (F[9,189] < 1; P > 0.05), however there was a highly significant difference when injected at E14.5 (F[9,198] = 4.75; P < 0.0001), and at E16.5 (F[9,270] = 13.3; P < 0.0001) |
| GO:0005515 protein binding | IPI PMID:20037577 HDAC1 nuclear export induced by pathological conditions is e... | MARK AS OVER ANNOTATED | Summary: PMID:20037577 showed that HDAC1 nuclear export leads to interaction with motor proteins and impaired mitochondrial transport. The connection to alpha-tubulin is indirect -- HDAC1 interacts with tubulin-dependent motor proteins. Reason: The study identifies alpha-tubulin in pathological HDAC1/motor-protein complexes during axonal damage, but GO:0005515 is too generic and the finding is context-dependent rather than a core Tuba1a activity. The more informative biology is impaired microtubule-based mitochondrial transport under injury conditions. Supporting Evidence: PMID:20037577 The formation of complexes between exported HDAC1 and members of the kinesin family of motor proteins hindered the interaction with cargo molecules |
| GO:0005525 GTP binding | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | ACCEPT | Summary: PMID:17218254 directly demonstrated that the S140G mutation in the GTP binding pocket reduces GTP incorporation by approximately 5-fold using in vitro folding assays with alpha-32P-GTP. Reason: Core molecular function. Directly demonstrated by biochemical assays showing the S140G mutation in the GTP binding N-site reduces GTP binding. Supporting Evidence: PMID:17218254 We found that the S140G mutation decreased the ability of CCT bound quasi-native alpha-tubulin folding intermediates to incorporate GTP by approximately 5-fold |
| GO:0005829 cytosol | IDA PMID:19056362 Alpha/beta-tubulin are A kinase anchor proteins for type I P... | ACCEPT | Summary: PMID:19056362 showed tubulin forms a high molecular weight complex with PKA RI subunit mainly in the cytosol, then transported to synapses. Reason: Correct localization. Tubulin heterodimers are present in the cytosol before assembly into microtubules. Consistent with general tubulin biology. Supporting Evidence: PMID:19056362 The enrichment of the endogenous HMWC by subcellular fractionation and its synthesis in vitro indicate that it is mainly produced in the cytosol, and then transported to the synapses |
| GO:0005886 plasma membrane | IDA PMID:19056362 Alpha/beta-tubulin are A kinase anchor proteins for type I P... | KEEP AS NON CORE | Summary: PMID:19056362 showed PKA RI co-localized with tubulin discretely at the cell membrane in COS-7 cells. Reason: Microtubules extend to the cell periphery and interact with the plasma membrane. The plasma membrane localization detected in this study likely reflects microtubules near the membrane or tubulin-PKA complexes at the membrane. Keep as non-core since this is not the primary localization. Supporting Evidence: PMID:19056362 In mouse brain RI co-localized with tubulin in neuropils and in COS-7 cells discretely at the cell membrane |
| GO:0007613 memory | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | KEEP AS NON CORE | Summary: PMID:17218254 showed Tuba1a S140G mutant mice have impaired spatial working memory assessed by T-maze spontaneous and rewarded alternation. Reason: Memory deficits are a behavioral consequence of disrupted hippocampal architecture due to impaired neuronal migration. Not a direct function of Tuba1a. Supporting Evidence: PMID:17218254 Jna/+ mice performed significantly worse than littermate controls (F[1,12] = 34.1; P < 0.0001) (Figure 5A), alternating just above chance |
| GO:0008344 adult locomotory behavior | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | KEEP AS NON CORE | Summary: PMID:17218254 showed Tuba1a S140G mutant mice are hyperactive. BAC transgene rescue normalized locomotor behavior. Reason: Locomotor hyperactivity is a behavioral phenotype resulting from disrupted brain cytoarchitecture. Not a direct function. The rescue by BAC transgene confirms the phenotype is due to Tuba1a mutation but the behavior is a downstream readout. Supporting Evidence: PMID:17218254 A single line that we named Jenna (Jna) was identified with a semidominant hyperactive phenotype |
| GO:0008542 visual learning | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | REMOVE | Summary: PMID:17218254 tested visual learning-dependent reference memory. However, the Tuba1a mutant mice performed well on the visual discrimination task (tactile reference memory), showing no deficit in this hippocampal-independent task. Reason: The study actually showed that Tuba1a S140G mutants can learn a hippocampal-independent reference memory task normally. The annotation to "visual learning" appears to be an error or over-annotation, as the mutant mice showed NO deficit in this task. Supporting Evidence: PMID:17218254 Both mutant and control mice were able to learn this task (Figure 5C) (F < 1; P > 0.5) |
| GO:0021696 cerebellar cortex morphogenesis | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | REMOVE | Summary: PMID:17218254 stated no anatomical abnormalities were seen in the cerebellum of Jna/+ mice. Reason: The paper explicitly states no cerebellar abnormalities were seen in Jna/+ mice. This annotation appears to be an error. Supporting Evidence: PMID:17218254 No anatomical abnormalities were seen in the cerebellum or amygdala |
| GO:0021766 hippocampus development | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | KEEP AS NON CORE | Summary: PMID:17218254 showed extensive hippocampal disorganization in Tuba1a S140G mutant mice, including a fractured pyramidal cell layer and disorganized mossy fiber tract. Reason: Hippocampus development defects are a consequence of impaired neuronal migration. The core function is neuron migration. Keep as non-core. Supporting Evidence: PMID:17218254 hippocampal disorganization with an additional layer of pyramidal cells in the stratum oriens that extended throughout the pyramidal cell subfields into the subiculum |
| GO:0030534 adult behavior | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | KEEP AS NON CORE | Summary: PMID:17218254 showed multiple behavioral abnormalities including hyperactivity, impaired memory, and reduced anxiety in Tuba1a S140G mutant mice. Reason: Adult behavior is a very broad term. The behavioral phenotypes are downstream consequences of brain malformation. Keep as non-core. |
| GO:0034612 response to tumor necrosis factor | IDA PMID:20037577 HDAC1 nuclear export induced by pathological conditions is e... | MARK AS OVER ANNOTATED | Summary: PMID:20037577 showed that TNF-alpha treatment of neurons induces HDAC1 nuclear export and axonal damage. The study examined the effect on neurons generally, and tubulin is a component of the damaged axonal cytoskeleton. Reason: Tuba1a is not specifically responding to TNF. The study examined the effect of TNF on neurons and found HDAC1 export-dependent axonal damage. Tubulin is part of the damaged cytoskeleton but is not an active responder to TNF. This is over-annotation of a passive substrate. Supporting Evidence: PMID:20037577 cultured neurons exposed to glutamate and tumor necrosis factor-alpha |
| GO:0044877 protein-containing complex binding | IDA PMID:19056362 Alpha/beta-tubulin are A kinase anchor proteins for type I P... | KEEP AS NON CORE | Summary: PMID:19056362 showed alpha/beta-tubulin forms a complex with PKA RI subunit, acting as an A kinase anchor protein. This represents binding to a protein-containing complex (PKA holoenzyme). Reason: The study demonstrated that alpha/beta-tubulin can form a complex with PKA type I, serving an AKAP-like role. This is a valid but specialized signaling-complex interaction and should not be treated as the core function of Tuba1a. Supporting Evidence: PMID:19056362 we have determined that the 105 kDa band is a high molecular weight complex (HMWC) containing alpha/beta-tubulin and PKA RI |
| GO:0045202 synapse | IDA PMID:19056362 Alpha/beta-tubulin are A kinase anchor proteins for type I P... | KEEP AS NON CORE | Summary: PMID:19056362 showed the tubulin-PKA complex is transported to synapses, and PKA RI co-localized with tubulin in neuropils. Reason: Microtubules extend into synaptic regions and tubulin-PKA complexes are transported to synapses. This is a valid but non-core localization for Tuba1a. Supporting Evidence: PMID:19056362 it is mainly produced in the cytosol, and then transported to the synapses |
| GO:0046982 protein heterodimerization activity | IMP PMID:17218254 Mutations in alpha-tubulin cause abnormal neuronal migration... | ACCEPT | Summary: PMID:17218254 directly demonstrated that the S140G mutation reduces heterodimer formation using in vitro folding assays with 35S-labeled Tuba1a. Reason: Core molecular function. Heterodimer formation with beta-tubulin is the primary functional activity of alpha-tubulin. Directly demonstrated by biochemical assays. Supporting Evidence: PMID:17218254 Consistent with the data obtained in our GTP labeling experiments, we found that the S140G mutation reduced the efficiency of de novo heterodimer formation |
| GO:1902065 response to L-glutamate | IDA PMID:20037577 HDAC1 nuclear export induced by pathological conditions is e... | MARK AS OVER ANNOTATED | Summary: PMID:20037577 showed that glutamate exposure of neurons induces HDAC1 nuclear export and impaired mitochondrial transport in axons. Tubulin is part of the affected cytoskeleton. Reason: Same as the TNF response annotation. Tuba1a is not actively responding to glutamate; it is part of the cytoskeleton that is damaged by excitotoxic conditions. The response is mediated by HDAC1, not by tubulin. Supporting Evidence: PMID:20037577 cultured neurons exposed to glutamate and tumor necrosis factor-alpha |
| GO:0043209 myelin sheath | HDA PMID:17634366 Proteolipid protein is required for transport of sirtuin 2 i... | KEEP AS NON CORE | Summary: PMID:17634366 identified alpha-tubulin in purified myelin membranes by proteomics. The study identified >160 proteins in purified myelin membranes. Reason: Tubulin was detected in myelin proteomics as it is an extremely abundant cytoplasmic protein present in oligodendrocyte processes. This is not a primary localization for Tuba1a. Supporting Evidence: PMID:17634366 By gel-based proteome analysis, we identified >160 proteins in purified myelin membranes |
| GO:0005881 cytoplasmic microtubule | IDA PMID:19103752 Inhibition of microtubule assembly in osteoblasts stimulates... | ACCEPT | Summary: PMID:19103752 showed that inhibition of microtubule assembly in osteoblasts stimulates BMP-2 expression through Gli2. Alpha-tubulin is a component of cytoplasmic microtubules that were disrupted in this study. Reason: Correct localization. Tuba1a is a component of cytoplasmic microtubules. Consistent with the core function of alpha-tubulin. |
| GO:0005881 cytoplasmic microtubule | IDA PMID:17686994 The synovial sarcoma SYT-SSX2 oncogene remodels the cytoskel... | ACCEPT | Summary: PMID:17686994 studied SYT-SSX2 oncogene remodeling of the cytoskeleton. The study detected alpha-tubulin in cytoplasmic microtubules as part of the investigation. Reason: Correct localization. Alpha-tubulin is a fundamental component of cytoplasmic microtubules. |
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