Ataxin 3
Ataxin-3 is a protein that in humans is encoded by the ATXN3 gene.[1][2]
Clinical significance
Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by the ATXN3 gene contains (CAG)n repeats in the coding region, and the expansion of these repeats from the normal 13-36 to 68-79 is the cause of Machado-Joseph disease. There is an inverse correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[2]
Interactions
Ataxin 3 has been shown to interact with:
References
- ↑ Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H, Karube Y, Shimazaki H, Soutome M, Endo K, Ohta S et al. (September 1993). "The gene for Machado-Joseph disease maps to human chromosome 14q". Nat Genet 4 (3): 300–4. doi:10.1038/ng0793-300. PMID 8358439.
- ↑ 2.0 2.1 "Entrez Gene: ATXN3 ataxin 3".
- ↑ 3.0 3.1 Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (July 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Hum. Mol. Genet. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.
- ↑ Doss-Pepe EW, Stenroos ES, Johnson WG, Madura K (September 2003). "Ataxin-3 interactions with rad23 and valosin-containing protein and its associations with ubiquitin chains and the proteasome are consistent with a role in ubiquitin-mediated proteolysis". Mol. Cell. Biol. 23 (18): 6469–83. doi:10.1128/MCB.23.18.6469-6483.2003. PMC 193705. PMID 12944474.
- ↑ Wang Q, Li L, Ye Y (March 2008). "Inhibition of p97-dependent protein degradation by Eeyarestatin I". J. Biol. Chem. 283 (12): 7445–54. doi:10.1074/jbc.M708347200. PMC 2276333. PMID 18199748.
Further reading
- Goto J, Watanabe M, Ichikawa Y et al. (1997). "Machado-Joseph disease gene products carrying different carboxyl termini.". Neurosci. Res. 28 (4): 373–7. doi:10.1016/S0168-0102(97)00056-4. PMID 9274833.
- Schöls L, Vieira-Saecker AM, Schöls S et al. (1995). "Trinucleotide expansion within the MJD1 gene presents clinically as spinocerebellar ataxia and occurs most frequently in German SCA patients.". Hum. Mol. Genet. 4 (6): 1001–5. doi:10.1093/hmg/4.6.1001. PMID 7655453.
- Stevanin G, Cancel G, Dürr A et al. (1995). "The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of approximately 3 cM on chromosome 14q24.3-q32.2.". Am. J. Hum. Genet. 56 (1): 193–201. PMC 1801316. PMID 7825578.
- Kawaguchi Y, Okamoto T, Taniwaki M et al. (1995). "CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1.". Nat. Genet. 8 (3): 221–8. doi:10.1038/ng1194-221. PMID 7874163.
- Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.
- Ikeda H, Yamaguchi M, Sugai S et al. (1996). "Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo.". Nat. Genet. 13 (2): 196–202. doi:10.1038/ng0696-196. PMID 8640226.
- Paulson HL, Das SS, Crino PB et al. (1997). "Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain.". Ann. Neurol. 41 (4): 453–62. doi:10.1002/ana.410410408. PMID 9124802.
- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.
- Wellington CL, Ellerby LM, Hackam AS et al. (1998). "Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract.". J. Biol. Chem. 273 (15): 9158–67. doi:10.1074/jbc.273.15.9158. PMID 9535906.
- Tait D, Riccio M, Sittler A et al. (1998). "Ataxin-3 is transported into the nucleus and associates with the nuclear matrix.". Hum. Mol. Genet. 7 (6): 991–7. doi:10.1093/hmg/7.6.991. PMID 9580663.
- Wang G, Sawai N, Kotliarova S et al. (2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B.". Hum. Mol. Genet. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.
- Ichikawa Y, Goto J, Hattori M et al. (2001). "The genomic structure and expression of MJD, the Machado-Joseph disease gene.". J. Hum. Genet. 46 (7): 413–22. doi:10.1007/s100380170060. PMID 11450850.
- Chai Y, Shao J, Miller VM et al. (2002). "Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis.". Proc. Natl. Acad. Sci. U.S.A. 99 (14): 9310–5. doi:10.1073/pnas.152101299. PMC 123137. PMID 12084819.
- Yoshida H, Yoshizawa T, Shibasaki F et al. (2002). "Chemical chaperones reduce aggregate formation and cell death caused by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch.". Neurobiol. Dis. 10 (2): 88–99. doi:10.1006/nbdi.2002.0502. PMID 12127147.
- Li F, Macfarlan T, Pittman RN, Chakravarti D (2003). "Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities.". J. Biol. Chem. 277 (47): 45004–12. doi:10.1074/jbc.M205259200. PMID 12297501.
- 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.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Albrecht M, Hoffmann D, Evert BO et al. (2003). "Structural modeling of ataxin-3 reveals distant homology to adaptins.". Proteins 50 (2): 355–70. doi:10.1002/prot.10280. PMID 12486728.
- Marchal S, Shehi E, Harricane MC et al. (2003). "Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature.". J. Biol. Chem. 278 (34): 31554–63. doi:10.1074/jbc.M304205200. PMID 12766160.
External links
PDB gallery |
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| | 1yzb: Solution structure of the Josephin domain of Ataxin-3 |
| 2aga: De-ubiquitinating function of ataxin-3: insights from the solution structure of the Josephin domain |
| 2dos: Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme |
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| | Description |
- Gene expression
- DNA
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- binding proteins
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- ribonucleoproteins
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| | Disease |
- Replication and repair
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