Ataxin 3

Protein-coding gene in the species Homo sapiens
ATXN3
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

1YZB, 2AGA, 2DOS, 2JRI, 2KLZ, 4WTH, 4YS9

Identifiers
AliasesATXN3, AT3, ATX3, JOS, MJD, MJD1, SCA3, Ataxin 3
External IDsOMIM: 607047; MGI: 1099442; HomoloGene: 3658; GeneCards: ATXN3; OMA:ATXN3 - orthologs
Gene location (Human)
Chromosome 14 (human)
Chr.Chromosome 14 (human)[1]
Chromosome 14 (human)
Genomic location for ATXN3
Genomic location for ATXN3
Band14q32.12Start92,044,496 bp[1]
End92,106,621 bp[1]
Gene location (Mouse)
Chromosome 12 (mouse)
Chr.Chromosome 12 (mouse)[2]
Chromosome 12 (mouse)
Genomic location for ATXN3
Genomic location for ATXN3
Band12|12 EStart101,918,901 bp[2]
End101,958,246 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • Achilles tendon

  • endothelial cell

  • sural nerve

  • monocyte

  • pericardium

  • right uterine tube

  • Brodmann area 23

  • saphenous vein

  • skin of abdomen

  • corpus callosum
Top expressed in
  • spermatid

  • morula

  • superior cervical ganglion

  • aortic valve

  • ascending aorta

  • interventricular septum

  • cumulus cell

  • spermatocyte

  • hand

  • pineal gland
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • Lys63-specific deubiquitinase activity
  • cysteine-type peptidase activity
  • ATPase binding
  • Lys48-specific deubiquitinase activity
  • peptidase activity
  • protein binding
  • identical protein binding
  • hydrolase activity
  • thiol-dependent deubiquitinase
  • ubiquitin protein ligase binding
  • histone deacetylase activity
Cellular component
  • endoplasmic reticulum membrane
  • nuclear matrix
  • nucleoplasm
  • nucleus
  • nucleolus
  • cytosol
  • plasma membrane
  • cytoplasm
  • mitochondrial matrix
  • mitochondrial membranes
  • nuclear inclusion body
Biological process
  • nucleotide-excision repair
  • regulation of transcription, DNA-templated
  • protein K48-linked deubiquitination
  • positive regulation of ERAD pathway
  • transcription, DNA-templated
  • nervous system development
  • proteolysis
  • protein K63-linked deubiquitination
  • intermediate filament cytoskeleton organization
  • protein localization to cytosolic proteasome complex involved in ERAD pathway
  • microtubule cytoskeleton organization
  • actin cytoskeleton organization
  • chemical synaptic transmission
  • protein deubiquitination
  • ubiquitin-dependent protein catabolic process
  • protein quality control for misfolded or incompletely synthesized proteins
  • regulation of cell-substrate adhesion
  • cellular response to heat
  • monoubiquitinated protein deubiquitination
  • proteasome-mediated ubiquitin-dependent protein catabolic process
  • cellular response to misfolded protein
  • exploration behavior
  • histone H3 deacetylation
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
Entrez

4287

110616

Ensembl

ENSG00000066427

ENSMUSG00000021189

UniProt

P54252
Q4VBR4

Q9CVD2

RefSeq (mRNA)
NM_001024631
NM_001127696
NM_001127697
NM_001164774
NM_001164776

NM_001164777
NM_001164778
NM_001164779
NM_001164780
NM_001164781
NM_001164782
NM_004993
NM_030660

NM_001167914
NM_029705

RefSeq (protein)
NP_001121168
NP_001121169
NP_001158246
NP_001158248
NP_001158249

NP_001158250
NP_001158251
NP_001158252
NP_001158253
NP_001158254
NP_004984
NP_109376

NP_001161386
NP_083981

Location (UCSC)Chr 14: 92.04 – 92.11 MbChr 12: 101.92 – 101.96 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Ataxin-3 is a protein that in humans is encoded by the ATXN3 gene.[5][6]

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 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. This disorder is thus a trinucleotide repeat disorder type I known as a polyglutamine (PolyQ) 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.[6]

Interactions

Ataxin 3 has been shown to interact with:

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000066427 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000021189 – 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. ^ Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H, Karube Y, Shimazaki H, Soutome M, Endo K, Ohta S (Jul 1993). "The gene for Machado-Joseph disease maps to human chromosome 14q". Nature Genetics. 4 (3): 300–4. doi:10.1038/ng0793-300. PMID 8358439. S2CID 27424416.
  6. ^ a b "Entrez Gene: ATXN3 ataxin 3".
  7. ^ a b Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.
  8. ^ Doss-Pepe EW, Stenroos ES, Johnson WG, Madura K (Sep 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". Molecular and Cellular Biology. 23 (18): 6469–83. doi:10.1128/MCB.23.18.6469-6483.2003. PMC 193705. PMID 12944474.
  9. ^ Wang Q, Li L, Ye Y (Mar 2008). "Inhibition of p97-dependent protein degradation by Eeyarestatin I". The Journal of Biological Chemistry. 283 (12): 7445–54. doi:10.1074/jbc.M708347200. PMC 2276333. PMID 18199748.

Further reading

  • Goto J, Watanabe M, Ichikawa Y, Yee SB, Ihara N, Endo K, Igarashi S, Takiyama Y, Gaspar C, Maciel P, Tsuji S, Rouleau GA, Kanazawa I (Aug 1997). "Machado-Joseph disease gene products carrying different carboxyl termini". Neuroscience Research. 28 (4): 373–7. doi:10.1016/S0168-0102(97)00056-4. PMID 9274833. S2CID 27241785.
  • Schöls L, Vieira-Saecker AM, Schöls S, Przuntek H, Epplen JT, Riess O (Jun 1995). "Trinucleotide expansion within the MJD1 gene presents clinically as spinocerebellar ataxia and occurs most frequently in German SCA patients". Human Molecular Genetics. 4 (6): 1001–5. doi:10.1093/hmg/4.6.1001. PMID 7655453.
  • Stevanin G, Cancel G, Dürr A, Chneiweiss H, Dubourg O, Weissenbach J, Cann HM, Agid Y, Brice A (Jan 1995). "The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of approximately 3 cM on chromosome 14q24.3-q32.2". American Journal of Human Genetics. 56 (1): 193–201. PMC 1801316. PMID 7825578.
  • Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I (Nov 1994). "CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1". Nature Genetics. 8 (3): 221–8. doi:10.1038/ng1194-221. PMID 7874163. S2CID 29188685.
  • Maruyama K, Sugano S (Jan 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, Aze Y, Narumiya S, Kakizuka A (Jun 1996). "Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo". Nature Genetics. 13 (2): 196–202. doi:10.1038/ng0696-196. PMID 8640226. S2CID 21966287.
  • Paulson HL, Das SS, Crino PB, Perez MK, Patel SC, Gotsdiner D, Fischbeck KH, Pittman RN (Apr 1997). "Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain". Annals of Neurology. 41 (4): 453–62. doi:10.1002/ana.410410408. PMID 9124802. S2CID 43460483.
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 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, Margolis RL, Trifiro MA, Singaraja R, McCutcheon K, Salvesen GS, Propp SS, Bromm M, Rowland KJ, Zhang T, Rasper D, Roy S, Thornberry N, Pinsky L, Kakizuka A, Ross CA, Nicholson DW, Bredesen DE, Hayden MR (Apr 1998). "Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract". The Journal of Biological Chemistry. 273 (15): 9158–67. doi:10.1074/jbc.273.15.9158. PMID 9535906.
  • Tait D, Riccio M, Sittler A, Scherzinger E, Santi S, Ognibene A, Maraldi NM, Lehrach H, Wanker EE (Jun 1998). "Ataxin-3 is transported into the nucleus and associates with the nuclear matrix". Human Molecular Genetics. 7 (6): 991–7. CiteSeerX 10.1.1.588.3970. doi:10.1093/hmg/7.6.991. PMID 9580663.
  • Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N (Jul 2000). "Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B". Human Molecular Genetics. 9 (12): 1795–803. doi:10.1093/hmg/9.12.1795. PMID 10915768.
  • Ichikawa Y, Goto J, Hattori M, Toyoda A, Ishii K, Jeong SY, Hashida H, Masuda N, Ogata K, Kasai F, Hirai M, Maciel P, Rouleau GA, Sakaki Y, Kanazawa I (2001). "The genomic structure and expression of MJD, the Machado-Joseph disease gene". Journal of Human Genetics. 46 (7): 413–22. doi:10.1007/s100380170060. PMID 11450850.
  • Chai Y, Shao J, Miller VM, Williams A, Paulson HL (Jul 2002). "Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis". Proceedings of the National Academy of Sciences of the United States of America. 99 (14): 9310–5. Bibcode:2002PNAS...99.9310C. doi:10.1073/pnas.152101299. PMC 123137. PMID 12084819.
  • Yoshida H, Yoshizawa T, Shibasaki F, Shoji S, Kanazawa I (Jul 2002). "Chemical chaperones reduce aggregate formation and cell death caused by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch". Neurobiology of Disease. 10 (2): 88–99. doi:10.1006/nbdi.2002.0502. PMID 12127147. S2CID 25183307.
  • Li F, Macfarlan T, Pittman RN, Chakravarti D (Nov 2002). "Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities". The Journal of Biological Chemistry. 277 (47): 45004–12. doi:10.1074/jbc.M205259200. PMID 12297501.
  • Albrecht M, Hoffmann D, Evert BO, Schmitt I, Wüllner U, Lengauer T (Feb 2003). "Structural modeling of ataxin-3 reveals distant homology to adaptins". Proteins. 50 (2): 355–70. doi:10.1002/prot.10280. PMID 12486728. S2CID 25660172.
  • Marchal S, Shehi E, Harricane MC, Fusi P, Heitz F, Tortora P, Lange R (Aug 2003). "Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature". The Journal of Biological Chemistry. 278 (34): 31554–63. doi:10.1074/jbc.M304205200. PMID 12766160.

External links

  • GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 3
  • Human ATXN3 genome location and ATXN3 gene details page in the UCSC Genome Browser.
  • v
  • t
  • e
  • 1yzb: Solution structure of the Josephin domain of Ataxin-3
    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
    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
    2dos: Structural basis for the recognition of Lys48-linked polyubiquitin chain by the Josephin domain of ataxin-3, a putative deubiquitinating enzyme
  • v
  • t
  • e
Chaperones/
protein folding
Heat shock proteins/
Chaperonins
Other
Protein targeting
Ubiquitin
(ubiquitylation)
Ubiquitin-like proteins
(UBL)
SUMO protein
(SUMOylation)
  • E1 SUMO-activating enzyme
  • E2 SUMO-conjugating enzyme
Other