Tubulin beta-4A chain

Tubulin beta-4A chain is a protein that in humans is encoded by the TUBB4A gene. Two tubulin beta-4 chain proteins are encoded in the human genome by the genes TUBB4A (this entry) and TUBB4B.[5][6][7] Tubulin is the major constituent of microtubules, a key components of the cytoskeleton. It binds two molecules of GTP, one at an exchangeable site on the beta-chain and one at a non-exchangeable site on the alpha-chain. TUBB4A is preferentially and highly expressed in the central nervous system.[8]

TUBB4A
Identifiers
Aliases	TUBB4A, DYT4, TUBB4, TUBB5, beta-5, tubulin beta 4A class IVa
External IDs	OMIM: 602662 MGI: 107848 HomoloGene: 55952 GeneCards: TUBB4A
Gene location (Human) Chr. Chromosome 19 (human)[1] Band 19p13.3 Start 6,494,319 bp[1] End 6,502,848 bp[1]
Gene location (Mouse) Chr. Chromosome 17 (mouse)[2] Band 17 D|17 29.66 cM Start 57,080,066 bp[2] End 57,087,782 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • nucleotide binding • GTP binding • structural constituent of cytoskeleton • GO:0001948 protein binding • GTPase activity • calcium ion binding Cellular component • cytoplasm • cytosol • cell projection • myelin • internode region of axon • cilium • neuronal cell body • microtubule • extracellular exosome • cytoskeleton • cell nucleus • microtubule cytoskeleton • GO:0035085 axoneme Biological process • G2/M transition of mitotic cell cycle • microtubule-based process • cytoskeleton organization • ciliary basal body docking • negative regulation of microtubule polymerization • regulation of G2/M transition of mitotic cell cycle • microtubule cytoskeleton organization • GO:0007067 mitotic cell cycle Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	10382	22153
Ensembl	ENSG00000104833	ENSMUSG00000062591
UniProt	P04350	Q9D6F9
RefSeq (mRNA)	NM_006087 NM_001289123 NM_001289127 NM_001289129 NM_001289130 NM_001289131	NM_009451
RefSeq (protein)	NP_001276052 NP_001276056 NP_001276058 NP_001276059 NP_001276060 NP_006078	NP_033477
Location (UCSC)	Chr 19: 6.49 – 6.5 Mb	Chr 17: 57.08 – 57.09 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Clinical significance

Mutations in TUBB4A have been associated with two neurological disorders.

An R2G substitution in the autoregulatory MREI domain of TUBB4A has been identified as the cause of 'hereditary whispering dysphonia' or DYT4.[9][10]

A de novo D249N mutation has been identified as the cause of a rare leukoencephalopathy, hypomyelination with atrophy of basal ganglia and cerebellum (H-ABC).[11][12]

Mutations in TUBB4A are associated with Pelizaeus–Merzbacher disease.[13]

References

1. GRCh38: Ensembl release 89: ENSG00000104833 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000062591 - 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. Hall JL, Dudley L, Dobner PR, Lewis SA, Cowan NJ (Aug 1983). "Identification of two human beta-tubulin isotypes". Molecular and Cellular Biology. 3 (5): 854–862. doi:10.1128/mcb.3.5.854. PMC 368608. PMID 6865944.
6. Lee MG, Loomis C, Cowan NJ (Sep 1984). "Sequence of an expressed human beta-tubulin gene containing ten Alu family members". Nucleic Acids Research. 12 (14): 5823–5836. doi:10.1093/nar/12.14.5823. PMC 320034. PMID 6462917.
7. "Entrez Gene: TUBB4 tubulin, beta 4".
8. "UCSC Genome Browser: TUBB4A microarray expression".
9. Hersheson J, Mencacci NE, Davis M, Macdonald N, Trabzuni D, Ryten M, Pittman A, Paudel R, Kara E, Fawcett K, Plagnol V, Bhatia KP, Medlar AJ, Stanescu HC, Hardy J, Kleta R, Wood NW, Houlden H (December 2012). "Mutations in the autoregulatory domain of β-tubulin 4a cause hereditary dystonia". Annals of Neurology. 73 (4): 546–553. doi:10.1002/ana.23832. PMC 3698699. PMID 23424103.
10. Online Mendelian Inheritance in Man (OMIM): Dystonia 4, torsion, autosomal dominant; DYT4 - 128101
11. Simons C, Wolf NI, McNeil N, Caldovic L, Devaney JM, Takanohashi A, Crawford J, Ru K, Grimmond SM, Miller D, Tonduti D, Schmidt JL, Chudnow RS, van Coster R, Lagae L, Kisler J, Sperner J, van der Knaap MS, Schiffmann R, Taft RJ, Vanderver A (May 2013). "A de novo mutation in the β-tubulin gene TUBB4A results in the leukoencephalopathy hypomyelination with atrophy of the basal ganglia and cerebellum". American Journal of Human Genetics. 92 (5): 767–773. doi:10.1016/j.ajhg.2013.03.018. PMC 3644625. PMID 23582646.
12. Online Mendelian Inheritance in Man (OMIM): Leukodystrophy, hypomyelinating, with atrophy of the basal ganglia and cerebellum; HABC - 128101
13. Shimojima, K; Okumura, A; Ikeno, M; Nishimura, A; Saito, A; Saitsu, H; Matsumoto, N; Yamamoto, T (2014). "A de novo TUBB4A mutation in a patient with hypomyelination mimicking Pelizaeus-Merzbacher disease". Brain & Development. 37 (3): 281–285. doi:10.1016/j.braindev.2014.05.004. PMID 24974158.

Further reading

• Wang D, Villasante A, Lewis SA, Cowan NJ (1987). "The mammalian beta-tubulin repertoire: hematopoietic expression of a novel, heterologous beta-tubulin isotype". Journal of Cell Biology. 103 (5): 1903–1910. doi:10.1083/jcb.103.5.1903. PMC 2114403. PMID 3782288.
• Baumann MH, Wisniewski T, Levy E, et al. (1996). "C-terminal fragments of alpha- and beta-tubulin form amyloid fibrils in vitro and associate with amyloid deposits of familial cerebral amyloid angiopathy, British type". Biochem. Biophys. Res. Commun. 219 (1): 238–242. doi:10.1006/bbrc.1996.0211. PMID 8619814.
• Watts NR, Sackett DL, Ward RD, et al. (2000). "HIV-1 rev depolymerizes microtubules to form stable bilayered rings". Journal of Cell Biology. 150 (2): 349–360. doi:10.1083/jcb.150.2.349. PMC 2180222. PMID 10908577.
• Tarazona R, López-Lluch G, Galiani MD, et al. (2001). "HLA-B2702 (77-83/83-77) peptide binds to beta-tubulin on human NK cells and blocks their cytotoxic capacity". Journal of Immunology. 165 (12): 6776–6782. doi:10.4049/jimmunol.165.12.6776. PMID 11120798.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–16903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Chen D, Wang M, Zhou S, Zhou Q (2004). "HIV-1 Tat targets microtubules to induce apoptosis, a process promoted by the pro-apoptotic Bcl-2 relative Bim". EMBO Journal. 21 (24): 6801–6810. doi:10.1093/emboj/cdf683. PMC 139103. PMID 12486001.
• Zhang C, Dowd DR, Staal A, et al. (2003). "Nuclear coactivator-62 kDa/Ski-interacting protein is a nuclear matrix-associated coactivator that may couple vitamin D receptor-mediated transcription and RNA splicing". Journal of Biological Chemistry. 278 (37): 35325–35336. doi:10.1074/jbc.M305191200. PMID 12840015.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nature Genetics. 36 (1): 40–45. doi:10.1038/ng1285. PMID 14702039.
• Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.
• Villacé P, Marión RM, Ortín J (2004). "The composition of Staufen-containing RNA granules from human cells indicates their role in the regulated transport and translation of messenger RNAs". Nucleic Acids Research. 32 (8): 2411–2420. doi:10.1093/nar/gkh552. PMC 419443. PMID 15121898.
• Hassel S, Eichner A, Yakymovych M, et al. (2004). "Proteins associated with type II bone morphogenetic protein receptor (BMPR-II) and identified by two-dimensional gel electrophoresis and mass spectrometry". Proteomics. 4 (5): 1346–1358. doi:10.1002/pmic.200300770. PMID 15188402.
• Jin J, Smith FD, Stark C, et al. (2004). "Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization". Curr. Biol. 14 (16): 1436–1450. doi:10.1016/j.cub.2004.07.051. PMID 15324660.
• Campbell GR, Pasquier E, Watkins J, et al. (2005). "The glutamine-rich region of the HIV-1 Tat protein is involved in T-cell apoptosis". Journal of Biological Chemistry. 279 (46): 48197–48204. doi:10.1074/jbc.M406195200. PMID 15331610.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Research. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• de Mareuil J, Carre M, Barbier P, et al. (2006). "HIV-1 Tat protein enhances microtubule polymerization". Retrovirology. 2: 5. doi:10.1186/1742-4690-2-5. PMC 549075. PMID 15691386.
• Giacca M (2006). "HIV-1 Tat, apoptosis and the mitochondria: a tubulin link?". Retrovirology. 2: 7. doi:10.1186/1742-4690-2-7. PMC 549042. PMID 15698476.
• Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–126. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Coiras M, Camafeita E, Ureña T, et al. (2006). "Modifications in the human T cell proteome induced by intracellular HIV-1 Tat protein expression". Proteomics. 6 Suppl 1: S63–7S3. doi:10.1002/pmic.200500437. PMID 16526095.

External links

• TUBB4A human gene location in the UCSC Genome Browser.
• TUBB4A human gene details in the UCSC Genome Browser.