DST
Available structures
PDBHuman UniProt search: PDBe RCSB
Identifiers
AliasesDST, BPA, BPAG1, CATX-15, CATX15, D6S1101, DMH, DT, EBSB2, HSAN6, MACF2, dystonin, BP230, BP240, EBS3
External IDsOMIM: 113810 HomoloGene: 134369 GeneCards: DST
Orthologs
SpeciesHumanMouse
Entrez

667

n/a

Ensembl

ENSG00000151914

n/a

UniProt

Q03001

n/a

RefSeq (mRNA)

n/a

RefSeq (protein)

n/a

Location (UCSC)Chr 6: 56.46 – 56.95 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Dystonin (DST), also known as bullous pemphigoid antigen 1 (BPAG1), isoforms 1/2/3/4/5/8, is a protein that in humans is encoded by the DST gene.[3][4][5]

This gene encodes a member of the plakin protein family of adhesion junction plaque proteins. Multiple alternatively spliced transcript variants encoding distinct isoforms have been found for this gene, but the full-length nature of some variants has not been defined. It has been known that some isoforms are expressed in neural and muscle tissue, anchoring neural intermediate filaments to the actin cytoskeleton, and some isoforms are expressed in epithelial tissue, anchoring keratin-containing intermediate filaments to hemidesmosomes. Consistent with the expression, mice defective for this gene show skin blistering and neurodegeneration.[5]

Interactions

Dystonin has been shown to interact with collagen, type XVII, alpha 1,[6][7] DCTN1,[8] MAP1B[9] and erbin.[10]

Loss of function in neurological disease

Several Dst mutant mouse lines have been described which share the common feature of having sensory neuron degeneration.[11][12] In humans, loss of dystonin function can cause hereditary sensory and autonomic neuropathy type VI[13] and axonal Charcot-Marie-Tooth disease.[14] In both human diseases, pathology is likely attributable to the loss of the dystonin-a2 protein isoform, which plays a role in neuronal autophagy.[15]

See also

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000151914 - Ensembl, May 2017
  2. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ↑ Stanley JR, Tanaka T, Mueller S, Klaus-Kovtun V, Roop D (December 1988). "Isolation of complementary DNA for bullous pemphigoid antigen by use of patients' autoantibodies". The Journal of Clinical Investigation. 82 (6): 1864–70. doi:10.1172/JCI113803. PMC 442765. PMID 2461961.
  4. ↑ Sawamura D, Nomura K, Sugita Y, Mattei MG, Chu ML, Knowlton R, Uitto J (December 1990). "Bullous pemphigoid antigen (BPAG1): cDNA cloning and mapping of the gene to the short arm of human chromosome 6". Genomics. 8 (4): 722–6. doi:10.1016/0888-7543(90)90261-R. PMID 2276744.
  5. 1 2 "Entrez Gene: DST dystonin".
  6. ↑ Koster J, Geerts D, Favre B, Borradori L, Sonnenberg A (January 2003). "Analysis of the interactions between BP180, BP230, plectin and the integrin alpha6beta4 important for hemidesmosome assembly". Journal of Cell Science. 116 (Pt 2): 387–99. doi:10.1242/jcs.00241. PMID 12482924. S2CID 16745491.
  7. ↑ Hopkinson SB, Jones JC (January 2000). "The N terminus of the transmembrane protein BP180 interacts with the N-terminal domain of BP230, thereby mediating keratin cytoskeleton anchorage to the cell surface at the site of the hemidesmosome". Molecular Biology of the Cell. 11 (1): 277–86. doi:10.1091/mbc.11.1.277. PMC 14774. PMID 10637308.
  8. ↑ Liu JJ, Ding J, Kowal AS, Nardine T, Allen E, Delcroix JD, et al. (October 2003). "BPAG1n4 is essential for retrograde axonal transport in sensory neurons". The Journal of Cell Biology. 163 (2): 223–9. doi:10.1083/jcb.200306075. PMC 2173519. PMID 14581450.
  9. ↑ Bhanot K, Young KG, Kothary R (November 2011). "MAP1B and clathrin are novel interacting partners of the giant cyto-linker dystonin". Journal of Proteome Research. 10 (11): 5118–27. doi:10.1021/pr200564g. PMID 21936565.
  10. ↑ Favre B, Fontao L, Koster J, Shafaatian R, Jaunin F, Saurat JH, et al. (August 2001). "The hemidesmosomal protein bullous pemphigoid antigen 1 and the integrin beta 4 subunit bind to ERBIN. Molecular cloning of multiple alternative splice variants of ERBIN and analysis of their tissue expression". The Journal of Biological Chemistry. 276 (35): 32427–36. doi:10.1074/jbc.M011005200. PMID 11375975.
  11. ↑ Pool M, Boudreau Larivière C, Bernier G, Young KG, Kothary R (December 2005). "Genetic alterations at the Bpag1 locus in dt mice and their impact on transcript expression". Mammalian Genome. 16 (12): 909–17. doi:10.1007/s00335-005-0073-4. PMID 16341670. S2CID 20415295.
  12. ↑ Young KG, Kothary R (December 2007). "Dystonin/Bpag1--a link to what?". Cell Motility and the Cytoskeleton. 64 (12): 897–905. doi:10.1002/cm.20235. PMID 17849487.
  13. ↑ Lynch-Godrei A, Kothary R (February 2020). "HSAN-VI: A spectrum disorder based on dystonin isoform expression". Neurology. Genetics. 6 (1): e389. doi:10.1212/NXG.0000000000000389. PMC 6975176. PMID 32042917.
  14. ↑ Motley WW, Züchner S, Scherer SS (October 2020). "Isoform-specific loss of dystonin causes hereditary motor and sensory neuropathy". Neurology. Genetics. 6 (5): e496. doi:10.1212/NXG.0000000000000496. PMC 7413632. PMID 32802955.
  15. ↑ Ferrier A, De Repentigny Y, Lynch-Godrei A, Gibeault S, Eid W, Kuo D, Zha X, Kothary R (2015). "Disruption in the autophagic process underlies the sensory neuropathy in dystonia musculorum mice". Autophagy. 11 (7): 1025–36. doi:10.1080/15548627.2015.1052207. PMC 4590603. PMID 26043942.

Further reading

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