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Gene Review

TUBA4A  -  tubulin, alpha 4a

Homo sapiens

Synonyms: Alpha-tubulin 1, FLJ30169, H2-ALPHA, TUBA1, Testis-specific alpha-tubulin, ...
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Disease relevance of TUBA4A


Psychiatry related information on TUBA4A


High impact information on TUBA4A

  • There is an increasing awareness that genetic polymorphisms may have an important role in the susceptibility for NTDs (ref. 6). Here we identify five different haplotypes in the human PDGFRA promoter, of which the two most abundant ones, designated H1 and H2 alpha, differ in at least six polymorphic sites [4].
  • When testing for haplotype combinations, H1 homozygotes were fully absent from the group of sporadic patients, whereas H1/H2 alpha heterozygotes were over-represented in the groups of both sporadic and familial spina bifida patients, but strongly under-represented in unrelated controls [4].
  • The exchangeable nucleotide in beta-tubulin is exposed at the plus end of the microtubule, while the proposed catalytic residue in alpha-tubulin is exposed at the minus end [7].
  • Degradation of U2, U4, or U6 snRNA by site-directed cleavage with complementary deoxyoligonucleotides and RNAase H inhibits trans splicing of the spliced leader (SL) RNA and newly synthesized alpha-tubulin pre-mRNAs [8].
  • We have been able to use immunogold labeling with monoclonal antibodies specific for tyrosinated alpha-tubulin to define new microtubule assembly within the T. brucei pellicular cytoskeleton [9].

Chemical compound and disease context of TUBA4A

  • TECHNIQUE: Two formalin-fixed cadavers were dissected to demonstrate the relationship between the foramen ovale and the tuba auditiva and the mechanism of rhinorrhea [10].

Biological context of TUBA4A


Anatomical context of TUBA4A


Associations of TUBA4A with chemical compounds

  • A second alpha-tubulin gene, M alpha 6, is expressed ubiquitously at a low level, whereas a third gene, M alpha 4, is unique in that it does not encode a carboxy-terminal tyrosine residue [17].
  • The association of PSK with microtubules results in the production of stabilized perinuclear microtubule cables that are nocodazole-resistant and contain increased levels of acetylated alpha-tubulin [18].
  • The remaining modified peptides have undergone a combination of numerous posttranslational modifications generating significant heterogeneity of sperm tubulin. alpha-Tubulin is modified by detyrosylation, release of the penultimate glutamate, polyglutamylation, and polyglycylation [19].
  • Inclusion of 3-nitro-l-tyrosine (NO(2)Tyr) in the culture medium resulted in the selective nitrotyrosination of alpha-tubulin, that was paralleled by decreased elaboration of Glu-tubulin, decreased expression of cyclins A and E, decreased association of the microtubule plus-end binding protein EB1, and inhibited cell proliferation [20].
  • Immunoglobulin E binding reactivity of a recombinant allergen homologous to alpha-Tubulin from Tyrophagus putrescentiae [21].

Physical interactions of TUBA4A


Regulatory relationships of TUBA4A


Other interactions of TUBA4A

  • Sequence characterization of a newly identified human alpha-tubulin gene (TUBA2) [24].
  • NF1 protein did not display colocalization with alpha-tubulin or actin of the cytoskeleton, or with adherens junction proteins [25].
  • Maximum-parsimony trees were constructed from published data for four of the most broadly sequenced of the 25 proteins, actin, alpha-tubulin, beta-tubulin, and elongation factor 1 alpha, with the latter supplemented by three new outgroup sequences [26].
  • In addition, we show that wild-type c-Myc-alpha-tubulin interactions are also disrupted during a transient mitosis-specific hyperphosphorylation of c-Myc, which resembles the constitutive hyperphosphorylation pattern of Thr-58 in BL cells [27].
  • No mutation was found in three plausibly candidate genes: the KCNE4 gene, the TUBA1 gene and a predicted gene located in genomic contig NT_005403 [28].

Analytical, diagnostic and therapeutic context of TUBA4A

  • In situ hybridization and Northern blot analysis were used to characterize the mRNA expression of alpha-tubulin, a neuroprotein crucial for neuronal structural and functional restoration, in comparison to that of the stress inducible heat shock protein-70 (HSP-70), in the same gerbil brain following 10 min of forebrain ischemia [2].
  • Molecular cloning and characterization of a metal responsive Chironomus tentans alpha-tubulin cDNA [29].
  • We have studied, by immunolocalization and immunoblotting, the localization of alpha-tubulin and its acetylated form in different follicle cells and in the oocyte during the main steps of ovarian follicle differentiation [30].
  • The absence of acetylated tubulin form in the cytoplasm of intermediate and pyriform cells can be related to the colocalization of alpha-tubulin with the keratin cytoskeleton in these cells, as detected by confocal microscopy [30].
  • An alpha-tubulin gene fragment amplified by PCR from the hypotrichous ciliate Histriculus cavicola has been sequenced [31].


  1. Tubulin nitration in human gliomas. Fiore, G., Di Cristo, C., Monti, G., Amoresano, A., Columbano, L., Pucci, P., Cioffi, F.A., Di Cosmo, A., Palumbo, A., d'Ischia, M. Neurosci. Lett. (2006) [Pubmed]
  2. Comparison of alpha-tubulin mRNA and heat shock protein-70 mRNA in gerbil brain following 10 min of ischemia. Kumar, K., Savithiry, S., Madhukar, B.V. Brain Res. Mol. Brain Res. (1993) [Pubmed]
  3. Photodamage induced by Zinc(II)-phthalocyanine to microtubules, actin, alpha-actinin and keratin of HeLa cells. Juarranz, A., Espada, J., Stockert, J.C., Villanueva, A., Polo, S., Domínguez, V., Cañete, M. Photochem. Photobiol. (2001) [Pubmed]
  4. Promoter haplotype combinations of the platelet-derived growth factor alpha-receptor gene predispose to human neural tube defects. Joosten, P.H., Toepoel, M., Mariman, E.C., Van Zoelen, E.J. Nat. Genet. (2001) [Pubmed]
  5. Antitumor effect of 2-methoxyestradiol in a rat orthotopic brain tumor model. Kang, S.H., Cho, H.T., Devi, S., Zhang, Z., Escuin, D., Liang, Z., Mao, H., Brat, D.J., Olson, J.J., Simons, J.W., Lavallee, T.M., Giannakakou, P., Van Meir, E.G., Shim, H. Cancer Res. (2006) [Pubmed]
  6. Isolation rearing induces recognition memory deficits accompanied by cytoskeletal alterations in rat hippocampus. Bianchi, M., Fone, K.F., Azmi, N., Heidbreder, C.A., Hagan, J.J., Marsden, C.A. Eur. J. Neurosci. (2006) [Pubmed]
  7. High-resolution model of the microtubule. Nogales, E., Whittaker, M., Milligan, R.A., Downing, K.H. Cell (1999) [Pubmed]
  8. Destruction of U2, U4, or U6 small nuclear RNA blocks trans splicing in trypanosome cells. Tschudi, C., Ullu, E. Cell (1990) [Pubmed]
  9. Visualization of detyrosination along single microtubules reveals novel mechanisms of assembly during cytoskeletal duplication in trypanosomes. Sherwin, T., Gull, K. Cell (1989) [Pubmed]
  10. Unanticipated complication of percutaneous radiofrequency trigeminal rhizotomy: rhinorrhea: report of three cases and a cadaver study. Ugur, H.C., Savas, A., Elhan, A., Kanpolat, Y. Neurosurgery (2004) [Pubmed]
  11. The N-terminal domain of c-Myc associates with alpha-tubulin and microtubules in vivo and in vitro. Alexandrova, N., Niklinski, J., Bliskovsky, V., Otterson, G.A., Blake, M., Kaye, F.J., Zajac-Kaye, M. Mol. Cell. Biol. (1995) [Pubmed]
  12. Structural features and restricted expression of a human alpha-tubulin gene. Hall, J.L., Cowan, N.J. Nucleic Acids Res. (1985) [Pubmed]
  13. Alternative 5' exons either provide or deny an initiator methionine codon to the same alpha-tubulin coding region. Dobner, P.R., Kislauskis, E., Wentworth, B.M., Villa-Komaroff, L. Nucleic Acids Res. (1987) [Pubmed]
  14. Human T lymphocyte activation induces tyrosine phosphorylation of alpha-tubulin and its association with the SH2 domain of the p59fyn protein tyrosine kinase. Marie-Cardine, A., Kirchgessner, H., Eckerskorn, C., Meuer, S.C., Schraven, B. Eur. J. Immunol. (1995) [Pubmed]
  15. Syk, activated by cross-linking the B-cell antigen receptor, localizes to the cytosol where it interacts with and phosphorylates alpha-tubulin on tyrosine. Peters, J.D., Furlong, M.T., Asai, D.J., Harrison, M.L., Geahlen, R.L. J. Biol. Chem. (1996) [Pubmed]
  16. Inhibitory effect of HIV-1 Tat protein on the sodium-D-glucose symporter of human intestinal epithelial cells. Canani, R.B., De Marco, G., Passariello, A., Buccigrossi, V., Ruotolo, S., Bracale, I., Porcaro, F., Bifulco, G., Guarino, A. AIDS (2006) [Pubmed]
  17. Six mouse alpha-tubulin mRNAs encode five distinct isotypes: testis-specific expression of two sister genes. Villasante, A., Wang, D., Dobner, P., Dolph, P., Lewis, S.A., Cowan, N.J. Mol. Cell. Biol. (1986) [Pubmed]
  18. The prostate-derived sterile 20-like kinase (PSK) regulates microtubule organization and stability. Mitsopoulos, C., Zihni, C., Garg, R., Ridley, A.J., Morris, J.D. J. Biol. Chem. (2003) [Pubmed]
  19. Posttranslational modifications in the C-terminal tail of axonemal tubulin from sea urchin sperm. Mary, J., Redeker, V., Le Caer, J.P., Rossier, J., Schmitter, J.M. J. Biol. Chem. (1996) [Pubmed]
  20. Posttranslational nitrotyrosination of alpha-tubulin induces cell cycle arrest and inhibits proliferation of vascular smooth muscle cells. Phung, A.D., Soucek, K., Kubala, L., Harper, R.W., Chlo?? Bulinski, J., Eiserich, J.P. Eur. J. Cell Biol. (2006) [Pubmed]
  21. Immunoglobulin E binding reactivity of a recombinant allergen homologous to alpha-Tubulin from Tyrophagus putrescentiae. Jeong, K.Y., Lee, H., Lee, J.S., Lee, J., Lee, I.Y., Ree, H.I., Hong, C.S., Park, J.W., Yong, T.S. Clin. Diagn. Lab. Immunol. (2005) [Pubmed]
  22. Connexin-43 interactions with ZO-1 and alpha- and beta-tubulin. Giepmans, B.N., Verlaan, I., Moolenaar, W.H. Cell Commun. Adhes. (2001) [Pubmed]
  23. IFN-gamma-induced change in microtubule organization and alpha-tubulin expression during growth inhibition of lung squamous carcinoma cells. Everding, B., Wilhelm, S., Averesch, S., Scherdin, U., Hölzel, F., Steffen, M. J. Interferon Cytokine Res. (2000) [Pubmed]
  24. Sequence characterization of a newly identified human alpha-tubulin gene (TUBA2). Dodé, C., Weil, D., Levilliers, J., Crozet, F., Chaïb, H., Levi-Acobas, F., Guilford, P., Petit, C. Genomics (1998) [Pubmed]
  25. Functional expression of NF1 tumor suppressor protein: association with keratin intermediate filaments during the early development of human epidermis. Malminen, M., Peltonen, S., Koivunen, J., Peltonen, J. BMC Dermatol. (2002) [Pubmed]
  26. Animals and fungi are each other's closest relatives: congruent evidence from multiple proteins. Baldauf, S.L., Palmer, J.D. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  27. Disruption of Myc-tubulin interaction by hyperphosphorylation of c-Myc during mitosis or by constitutive hyperphosphorylation of mutant c-Myc in Burkitt's lymphoma. Niklinski, J., Claassen, G., Meyers, C., Gregory, M.A., Allegra, C.J., Kaye, F.J., Hann, S.R., Zajac-Kaye, M. Mol. Cell. Biol. (2000) [Pubmed]
  28. A second locus mapping to 2q35-36 for familial pseudohyperkalaemia. Carella, M., d'Adamo, A.P., Grootenboer-Mignot, S., Vantyghem, M.C., Esposito, L., D'Eustacchio, A., Ficarella, R., Stewart, G.W., Gasparini, P., Delaunay, J., Iolascon, A. Eur. J. Hum. Genet. (2004) [Pubmed]
  29. Molecular cloning and characterization of a metal responsive Chironomus tentans alpha-tubulin cDNA. Mattingly, K.S., Beaty, B.J., Mackie, R.S., McGaw, M., Carlson, J.O., Rayms-Keller, A. Aquat. Toxicol. (2001) [Pubmed]
  30. alpha-Tubulin and acetylated alpha-tubulin during ovarian follicle differentiation in the lizard Podarcis sicula Raf. Maurizii, M.G., Alibardi, L., Taddei, C. J. Exp. Zoolog. Part A Comp. Exp. Biol. (2004) [Pubmed]
  31. alpha-Tubulin of Histriculus cavicola (Ciliophora; Hypotrichea). Pérez-Romero, P., Villalobo, E., Díaz-Ramos, C., Calvo, P., Santos-Rosa, F., Torres, A. Microbiologia (1997) [Pubmed]
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