Tubulin beta-4A chain

TUBB4A
Identifiers
AliasesTUBB4A, DYT4, TUBB4, TUBB5, beta-5, tubulin beta 4A class IVa
External IDsOMIM: 602662; MGI: 107848; GeneCards: TUBB4A
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

10382

22153

Ensembl

ENSG00000104833

ENSMUSG00000062591

UniProt

P04350

Q9D6F9

RefSeq (mRNA)

NM_009451

RefSeq (protein)

NP_033477

Location (UCSC)Chr 19: 6.49 – 6.5 MbChr 17: 57.39 – 57.39 Mb
PubMed search
Wikidata
View/Edit HumanView/Edit Mouse

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. 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.

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.

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).

Mutations in TUBB4A are associated with Pelizaeus–Merzbacher disease.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000104833 – Ensembl, May 2017
  2. 1 2 3 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 (August 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 (September 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, et al. (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, et al. (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, et al. (March 2015). "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