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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) Band 12q13.12 Start 49,184,686 bp End 49,189,080 bp
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15 F1|15 55.29 cM Start 98,847,718 bp End 98,851,584 bp
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
Wikidata
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Tubulin alpha-1A chain is a protein that in humans is encoded by the TUBA1A gene.

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.

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.

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.

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.

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.

Interactions

TUBA1A has been shown to interact with PAFAH1B1.

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; 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. 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.

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. 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

References

1. ^ GRCh38: Ensembl release 89: ENSG00000167552 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000072235 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Crabtree DV, Ojima I, Geng X, Adler AJ (August 2001). "Tubulins in the primate retina: evidence that xanthophylls may be endogenous ligands for the paclitaxel-binding site". Bioorganic & Medicinal Chemistry. 9 (8): 1967–1976. doi:10.1016/S0968-0896(01)00103-1. PMID 11504633.
6. Hall JL, Cowan NJ (January 1985). "Structural features and restricted expression of a human alpha-tubulin gene". Nucleic Acids Research. 13 (1): 207–223. doi:10.1093/nar/13.1.207. PMC 340985. PMID 3839072.
7. ^ "Entrez Gene: TUBA1A tubulin, alpha 1a".
8. Cowan NJ, Dobner PR, Fuchs EV, Cleveland DW (October 1983). "Expression of human alpha-tubulin genes: interspecies conservation of 3' untranslated regions". Molecular and Cellular Biology. 3 (10): 1738–1745. doi:10.1128/mcb.3.10.1738. PMC 370035. PMID 6646120.
9. Miller FD, Naus CC, Durand M, Bloom FE, Milner RJ (December 1987). "Isotypes of alpha-tubulin are differentially regulated during neuronal maturation". The Journal of Cell Biology. 105 (6 Pt 2): 3065–3073. doi:10.1083/jcb.105.6.3065. PMC 2114727. PMID 3693406.
10. Sakakibara A, Ando R, Sapir T, Tanaka T (July 2013). "Microtubule dynamics in neuronal morphogenesis". Open Biology. 3 (7): 130061. doi:10.1098/rsob.130061. PMC 3728923. PMID 23864552.
11. ^ Poirier K, Keays DA, Francis F, Saillour Y, Bahi N, Manouvrier S, et al. (November 2007). "Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A)". Human Mutation. 28 (11): 1055–1064. doi:10.1002/humu.20572. PMID 17584854. S2CID 22681290.
12. Sapir T, Elbaum M, Reiner O (December 1997). "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit". The EMBO Journal. 16 (23): 6977–6984. doi:10.1093/emboj/16.23.6977. PMC 1170301. PMID 9384577.
13. ^ Keays DA, Tian G, Poirier K, Huang GJ, Siebold C, Cleak J, et al. (January 2007). "Mutations in alpha-tubulin cause abnormal neuronal migration in mice and lissencephaly in humans". Cell. 128 (1): 45–57. doi:10.1016/j.cell.2006.12.017. PMC 1885944. PMID 17218254.
14. Löwe J, Li H, Downing KH, Nogales E (November 2001). "Refined structure of alpha beta-tubulin at 3.5 A resolution". Journal of Molecular Biology. 313 (5): 1045–1057. doi:10.1006/jmbi.2001.5077. PMID 11700061.

Further reading

• Desai A, Mitchison TJ (July 1998). "Tubulin and FtsZ structures: functional and therapeutic implications". BioEssays. 20 (7): 523–527. doi:10.1002/(SICI)1521-1878(199807)20:7<523::AID-BIES1>3.0.CO;2-L. PMID 9722999.
• Oakley BR (December 2000). "An abundance of tubulins". Trends in Cell Biology. 10 (12): 537–542. doi:10.1016/S0962-8924(00)01857-2. PMID 11121746.
• Dutcher SK (February 2001). "The tubulin fraternity: alpha to eta". Current Opinion in Cell Biology. 13 (1): 49–54. doi:10.1016/S0955-0674(00)00173-3. PMID 11163133.
• Miller FD, Naus CC, Durand M, Bloom FE, Milner RJ (December 1987). "Isotypes of alpha-tubulin are differentially regulated during neuronal maturation". The Journal of Cell Biology. 105 (6 Pt 2): 3065–3073. doi:10.1083/jcb.105.6.3065. PMC 2114727. PMID 3693406.
• Cowan NJ, Dobner PR, Fuchs EV, Cleveland DW (October 1983). "Expression of human alpha-tubulin genes: interspecies conservation of 3' untranslated regions". Molecular and Cellular Biology. 3 (10): 1738–1745. doi:10.1128/mcb.3.10.1738. PMC 370035. PMID 6646120.
• Alexandrova N, Niklinski J, Bliskovsky V, Otterson GA, Blake M, Kaye FJ, et al. (September 1995). "The N-terminal domain of c-Myc associates with alpha-tubulin and microtubules in vivo and in vitro". Molecular and Cellular Biology. 15 (9): 5188–5195. doi:10.1128/MCB.15.9.5188. PMC 230766. PMID 7651436.
• Sapir T, Elbaum M, Reiner O (December 1997). "Reduction of microtubule catastrophe events by LIS1, platelet-activating factor acetylhydrolase subunit". The EMBO Journal. 16 (23): 6977–6984. doi:10.1093/emboj/16.23.6977. PMC 1170301. PMID 9384577.
• Kinnunen T, Kaksonen M, Saarinen J, Kalkkinen N, Peng HB, Rauvala H (April 1998). "Cortactin-Src kinase signaling pathway is involved in N-syndecan-dependent neurite outgrowth". The Journal of Biological Chemistry. 273 (17): 10702–10708. doi:10.1074/jbc.273.17.10702. PMID 9553134.
• Faruki S, Geahlen RL, Asai DJ (July 2000). "Syk-dependent phosphorylation of microtubules in activated B-lymphocytes". Journal of Cell Science. 113 (14): 2557–2565. doi:10.1242/jcs.113.14.2557. PMID 10862713.
• Watts NR, Sackett DL, Ward RD, Miller MW, Wingfield PT, Stahl SS, et al. (July 2000). "HIV-1 rev depolymerizes microtubules to form stable bilayered rings". The Journal of Cell Biology. 150 (2): 349–360. doi:10.1083/jcb.150.2.349. PMC 2180222. PMID 10908577.
• Germani A, Bruzzoni-Giovanelli H, Fellous A, Gisselbrecht S, Varin-Blank N, Calvo F (December 2000). "SIAH-1 interacts with alpha-tubulin and degrades the kinesin Kid by the proteasome pathway during mitosis". Oncogene. 19 (52): 5997–6006. doi:10.1038/sj.onc.1204002. PMID 11146551. S2CID 41279377.
• Payton JE, Perrin RJ, Clayton DF, George JM (November 2001). "Protein-protein interactions of alpha-synuclein in brain homogenates and transfected cells". Brain Research. Molecular Brain Research. 95 (1–2): 138–145. doi:10.1016/S0169-328X(01)00257-1. PMID 11687285.
• Bifulco M, Laezza C, Stingo S, Wolff J (February 2002). "2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". Proceedings of the National Academy of Sciences of the United States of America. 99 (4): 1807–1812. Bibcode:2002PNAS...99.1807B. doi:10.1073/pnas.042678799. PMC 122275. PMID 11842207.
• Saugstad JA, Yang S, Pohl J, Hall RA, Conn PJ (March 2002). "Interaction between metabotropic glutamate receptor 7 and alpha tubulin". Journal of Neurochemistry. 80 (6): 980–988. doi:10.1046/j.0022-3042.2002.00778.x. PMC 2925652. PMID 11953448.
• Ivings L, Pennington SR, Jenkins R, Weiss JL, Burgoyne RD (May 2002). "Identification of Ca2+-dependent binding partners for the neuronal calcium sensor protein neurocalcin delta: interaction with actin, clathrin and tubulin". The Biochemical Journal. 363 (Pt 3): 599–608. doi:10.1042/0264-6021:3630599. PMC 1222513. PMID 11964161.

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.

• Genes on human chromosome 12