Ataxin 3: Difference between revisions

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{{Infobox_gene}}
{{PBB_Controls
'''Ataxin-3''' is a [[protein]] that in humans is encoded by the ''ATXN3'' [[gene]].<ref name="pmid8358439">{{cite journal | vauthors = Takiyama Y, Nishizawa M, Tanaka H, Kawashima S, Sakamoto H, Karube Y, Shimazaki H, Soutome M, Endo K, Ohta S | title = The gene for Machado-Joseph disease maps to human chromosome 14q | journal = Nature Genetics | volume = 4 | issue = 3 | pages = 300–4 | date = Jul 1993 | pmid = 8358439 | pmc =  | doi = 10.1038/ng0793-300 }}</ref><ref name="EntrezGene">{{cite web | title = Entrez Gene: ATXN3 ataxin 3| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4287| accessdate = }}</ref>
| update_page = yes
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| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Clinical significance ==
{{GNF_Protein_box
| image = PBB_Protein_ATXN3_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1yzb.
| PDB = {{PDB2|1yzb}}, {{PDB2|2aga}}, {{PDB2|2dos}}
| Name = Ataxin 3
| HGNCid = 7106
| Symbol = ATXN3
| AltSymbols =; AT3; ATX3; JOS; MJD; MJD1; SCA3
| OMIM = 607047
| ECnumber = 
| Homologene = 3658
| MGIid = 1099442
| GeneAtlas_image1 = PBB_GE_ATXN3_205415_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_ATXN3_205416_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0016787 |text = hydrolase activity}}
| Component = {{GNF_GO|id=GO:0005634 |text = nucleus}} {{GNF_GO|id=GO:0005654 |text = nucleoplasm}} {{GNF_GO|id=GO:0005737 |text = cytoplasm}}
| Process = {{GNF_GO|id=GO:0006289 |text = nucleotide-excision repair}} {{GNF_GO|id=GO:0006350 |text = transcription}} {{GNF_GO|id=GO:0006355 |text = regulation of transcription, DNA-dependent}} {{GNF_GO|id=GO:0007268 |text = synaptic transmission}} {{GNF_GO|id=GO:0007399 |text = nervous system development}} {{GNF_GO|id=GO:0008219 |text = cell death}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4287
    | Hs_Ensembl = ENSG00000066427
    | Hs_RefseqProtein = NP_001019802
    | Hs_RefseqmRNA = NM_001024631
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 14
    | Hs_GenLoc_start = 91598887
    | Hs_GenLoc_end = 91642707
    | Hs_Uniprot = 
    | Mm_EntrezGene = 110616
    | Mm_Ensembl = ENSMUSG00000021189
    | Mm_RefseqmRNA = NM_029705
    | Mm_RefseqProtein = NP_083981
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 12
    | Mm_GenLoc_start = 102320604
    | Mm_GenLoc_end = 102359232
    | Mm_Uniprot = Q546X9
  }}
}}
'''Ataxin 3''', also known as '''ATXN3''', is a human [[gene]].<ref>{{cite web | title = Entrez Gene: ATXN3 ataxin 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4287| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
[[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.<ref name="EntrezGene" />
{{PBB_Summary
 
| section_title =
== Interactions ==
| summary_text = Machado-Joseph disease, also known as spinocerebellar ataxia-3, is an autosomal dominant neurologic disorder. The protein encoded by this 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 a negative correlation between the age of onset and CAG repeat numbers. Alternatively spliced transcript variants encoding different isoforms have been described for this gene.<ref name="entrez">{{cite web | title = Entrez Gene: ATXN3 ataxin 3| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4287| accessdate = }}</ref>
 
}}
Ataxin 3 has been shown to [[Protein-protein interaction|interact]] with:
* [[RAD23A]],<ref name = pmid10915768>{{cite journal | vauthors = Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N | title = Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B | journal = Human Molecular Genetics | volume = 9 | issue = 12 | pages = 1795–803 | date = Jul 2000 | pmid = 10915768 | doi = 10.1093/hmg/9.12.1795 }}</ref>
* [[RAD23B]],<ref name = pmid10915768/> and
* [[Valosin-containing protein|VCP]].<ref name = pmid12944474>{{cite journal | vauthors = Doss-Pepe EW, Stenroos ES, Johnson WG, Madura K | title = 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 | journal = Molecular and Cellular Biology | volume = 23 | issue = 18 | pages = 6469–83 | date = Sep 2003 | pmid = 12944474 | pmc = 193705 | doi = 10.1128/MCB.23.18.6469-6483.2003 }}</ref><ref name = pmid18199748>{{cite journal | vauthors = Wang Q, Li L, Ye Y | title = Inhibition of p97-dependent protein degradation by Eeyarestatin I | journal = The Journal of Biological Chemistry | volume = 283 | issue = 12 | pages = 7445–54 | date = Mar 2008 | pmid = 18199748 | pmc = 2276333 | doi = 10.1074/jbc.M708347200 }}</ref>
 
==Model organisms==
[[Model organism]]s have been used in the study of ATXN3 function. A conditional [[knockout mouse]] line called ''Atxn3<sup>tm1a(KOMP)Wtsi</sup>'' was generated at the [[Wellcome Trust Sanger Institute]].<ref name="mgp_reference">{{cite journal |title=The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice |author=Gerdin AK |year=2010 |journal=Acta Ophthalmologica|volume=88 |pages=925–7|doi=10.1111/j.1755-3768.2010.4142.x }}</ref> Male and female animals underwent a standardized [[phenotypic screen]]<ref name="IMPCsearch_ref">{{cite web |url=http://www.mousephenotype.org/data/search?q=Atxn3#fq=*:*&facet=gene |title=International Mouse Phenotyping Consortium}}</ref> to determine the effects of deletion.<ref name="pmid21677750">{{cite journal | vauthors = Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A | title = A conditional knockout resource for the genome-wide study of mouse gene function | journal = Nature | volume = 474 | issue = 7351 | pages = 337–42 | date = Jun 2011 | pmid = 21677750 | pmc = 3572410 | doi = 10.1038/nature10163 }}</ref><ref name="mouse_library">{{cite journal | vauthors = Dolgin E | title = Mouse library set to be knockout | journal = Nature | volume = 474 | issue = 7351 | pages = 262–3 | date = Jun 2011 | pmid = 21677718 | doi = 10.1038/474262a }}</ref><ref name="mouse_for_all_reasons">{{cite journal | vauthors = Collins FS, Rossant J, Wurst W | title = A mouse for all reasons | journal = Cell | volume = 128 | issue = 1 | pages = 9–13 | date = Jan 2007 | pmid = 17218247 | doi = 10.1016/j.cell.2006.12.018 }}</ref><ref name="pmid23870131">{{cite journal | vauthors = White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, ((Sanger Institute Mouse Genetics Project)), Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP | title = Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes | journal = Cell | volume = 154 | issue = 2 | pages = 452–64 | year = 2013 | pmid = 23870131 | doi = 10.1016/j.cell.2013.06.022 | pmc=3717207}}</ref> Additional screens performed:  - In-depth immunological phenotyping<ref name="iii_ref">{{cite web |url= http://www.immunophenotyping.org/data/search?keys=Atxn3&field_gene_construct_tid=All |title=Infection and Immunity Immunophenotyping (3i) Consortium}}</ref> - in-depth bone and cartilage phenotyping<ref name="obcd_ref">{{cite web |url=http://www.boneandcartilage.com/ |title=OBCD Consortium}}</ref>  
{| class="wikitable sortable collapsible collapsed" border="1" cellpadding="2" style="float: left;" |
|+ ''Atxn3'' knockout mouse phenotype
|-
! Characteristic!! Phenotype
|-
| colspan=2; style="text-align: center;" | All data available at.<ref name="IMPCsearch_ref"/><ref name="iii_ref" /><ref name="obcd_ref"/>
 
|-
| Peripheral blood leukocytes 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Insulin || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 6 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Homozygous viability at P14 || bgcolor="#488ED3"|Normal
 
|-
| Homozygous Fertility || bgcolor="#488ED3"|Normal
 
|-
| Body weight || bgcolor="#488ED3"|Normal
 
|-
| Neurological assessment || bgcolor="#488ED3"|Normal
 
|-
| Grip strength || bgcolor="#488ED3"|Normal
 
|-
| [[Dysmorphology]] || bgcolor="#488ED3"|Normal
 
|-
| [[Indirect calorimetry]] || bgcolor="#488ED3"|Normal
 
|-
| [[Glucose tolerance test]] || bgcolor="#488ED3"|Normal
 
|-
| [[Auditory brainstem response]] || bgcolor="#488ED3"|Normal
 
|-
| [[Dual-energy X-ray absorptiometry|DEXA]] || bgcolor="#488ED3"|Normal
 
|-
| [[Radiography]] || bgcolor="#488ED3"|Normal
 
|-
| Eye morphology || bgcolor="#488ED3"|Normal
 
|-
| [[Clinical chemistry]] || bgcolor="#488ED3"|Normal
 
|-
| ''[[Haematology]]'' 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Peripheral blood leukocytes 16 Weeks || bgcolor="#488ED3"|Normal
 
|-
| Heart weight || bgcolor="#488ED3"|Normal
 
|-
| ''[[Salmonella]]'' infection || bgcolor="#488ED3"|Normal
 
|-
| Cytotoxic T Cell Function || bgcolor="#488ED3"|Normal
 
|-
| Spleen Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Mesenteric Lymph Node Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Bone Marrow Immunophenotyping || bgcolor="#488ED3"|Normal
 
|-
| Epidermal Immune Composition || bgcolor="#488ED3"|Normal
 
|-
| Influenza Challenge || bgcolor="#488ED3"|Normal
 
|-
|}


==References==
==References==
{{reflist|2}}
{{reflist|33em}}
==Further reading==
 
{{refbegin | 2}}
== Further reading ==
{{PBB_Further_reading
{{refbegin|33em}}
| citations =
* {{cite journal | vauthors = 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 | title = Machado-Joseph disease gene products carrying different carboxyl termini | journal = Neuroscience Research | volume = 28 | issue = 4 | pages = 373–7 | date = Aug 1997 | pmid = 9274833 | doi = 10.1016/S0168-0102(97)00056-4 }}
*{{cite journal | author=Goto J, Watanabe M, Ichikawa Y, ''et al.'' |title=Machado-Joseph disease gene products carrying different carboxyl termini. |journal=Neurosci. Res. |volume=28 |issue= 4 |pages= 373-7 |year= 1997 |pmid= 9274833 |doi= }}
* {{cite journal | vauthors = Schöls L, Vieira-Saecker AM, Schöls S, Przuntek H, Epplen JT, Riess O | title = Trinucleotide expansion within the MJD1 gene presents clinically as spinocerebellar ataxia and occurs most frequently in German SCA patients | journal = Human Molecular Genetics | volume = 4 | issue = 6 | pages = 1001–5 | date = Jun 1995 | pmid = 7655453 | doi = 10.1093/hmg/4.6.1001 }}
*{{cite journal | author=Schöls L, Vieira-Saecker AM, Schöls S, ''et al.'' |title=Trinucleotide expansion within the MJD1 gene presents clinically as spinocerebellar ataxia and occurs most frequently in German SCA patients. |journal=Hum. Mol. Genet. |volume=4 |issue= 6 |pages= 1001-5 |year= 1995 |pmid= 7655453 |doi= }}
* {{cite journal | vauthors = Stevanin G, Cancel G, Dürr A, Chneiweiss H, Dubourg O, Weissenbach J, Cann HM, Agid Y, Brice A | title = The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of approximately 3 cM on chromosome 14q24.3-q32.2 | journal = American Journal of Human Genetics | volume = 56 | issue = 1 | pages = 193–201 | date = Jan 1995 | pmid = 7825578 | pmc = 1801316 | doi =  }}
*{{cite journal | author=Stevanin G, Cancel G, Dürr A, ''et al.'' |title=The gene for spinal cerebellar ataxia 3 (SCA3) is located in a region of approximately 3 cM on chromosome 14q24.3-q32.2. |journal=Am. J. Hum. Genet. |volume=56 |issue= 1 |pages= 193-201 |year= 1995 |pmid= 7825578 |doi=  }}
* {{cite journal | vauthors = Kawaguchi Y, Okamoto T, Taniwaki M, Aizawa M, Inoue M, Katayama S, Kawakami H, Nakamura S, Nishimura M, Akiguchi I | title = CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1 | journal = Nature Genetics | volume = 8 | issue = 3 | pages = 221–8 | date = Nov 1994 | pmid = 7874163 | doi = 10.1038/ng1194-221 }}
*{{cite journal | author=Kawaguchi Y, Okamoto T, Taniwaki M, ''et al.'' |title=CAG expansions in a novel gene for Machado-Joseph disease at chromosome 14q32.1. |journal=Nat. Genet. |volume=8 |issue= 3 |pages= 221-8 |year= 1995 |pmid= 7874163 |doi= 10.1038/ng1194-221 }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Ikeda H, Yamaguchi M, Sugai S, Aze Y, Narumiya S, Kakizuka A | title = Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo | journal = Nature Genetics | volume = 13 | issue = 2 | pages = 196–202 | date = Jun 1996 | pmid = 8640226 | doi = 10.1038/ng0696-196 }}
*{{cite journal | author=Takiyama Y, Nishizawa M, Tanaka H, ''et al.'' |title=The gene for Machado-Joseph disease maps to human chromosome 14q. |journal=Nat. Genet. |volume=4 |issue= 3 |pages= 300-4 |year= 1993 |pmid= 8358439 |doi= 10.1038/ng0793-300 }}
* {{cite journal | vauthors = Paulson HL, Das SS, Crino PB, Perez MK, Patel SC, Gotsdiner D, Fischbeck KH, Pittman RN | title = Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain | journal = Annals of Neurology | volume = 41 | issue = 4 | pages = 453–62 | date = Apr 1997 | pmid = 9124802 | doi = 10.1002/ana.410410408 }}
*{{cite journal | author=Ikeda H, Yamaguchi M, Sugai S, ''et al.'' |title=Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. |journal=Nat. Genet. |volume=13 |issue= 2 |pages= 196-202 |year= 1996 |pmid= 8640226 |doi= 10.1038/ng0696-196 }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Paulson HL, Das SS, Crino PB, ''et al.'' |title=Machado-Joseph disease gene product is a cytoplasmic protein widely expressed in brain. |journal=Ann. Neurol. |volume=41 |issue= 4 |pages= 453-62 |year= 1997 |pmid= 9124802 |doi= 10.1002/ana.410410408 }}
* {{cite journal | vauthors = 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 | title = Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract | journal = The Journal of Biological Chemistry | volume = 273 | issue = 15 | pages = 9158–67 | date = Apr 1998 | pmid = 9535906 | doi = 10.1074/jbc.273.15.9158 }}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
* {{cite journal | vauthors = Tait D, Riccio M, Sittler A, Scherzinger E, Santi S, Ognibene A, Maraldi NM, Lehrach H, Wanker EE | title = Ataxin-3 is transported into the nucleus and associates with the nuclear matrix | journal = Human Molecular Genetics | volume = 7 | issue = 6 | pages = 991–7 | date = Jun 1998 | pmid = 9580663 | doi = 10.1093/hmg/7.6.991 }}
*{{cite journal | author=Wellington CL, Ellerby LM, Hackam AS, ''et al.'' |title=Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. |journal=J. Biol. Chem. |volume=273 |issue= 15 |pages= 9158-67 |year= 1998 |pmid= 9535906 |doi= }}
* {{cite journal | vauthors = Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N | title = Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B | journal = Human Molecular Genetics | volume = 9 | issue = 12 | pages = 1795–803 | date = Jul 2000 | pmid = 10915768 | doi = 10.1093/hmg/9.12.1795 }}
*{{cite journal | author=Tait D, Riccio M, Sittler A, ''et al.'' |title=Ataxin-3 is transported into the nucleus and associates with the nuclear matrix. |journal=Hum. Mol. Genet. |volume=7 |issue= 6 |pages= 991-7 |year= 1998 |pmid= 9580663 |doi= }}
* {{cite journal | vauthors = 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 | title = The genomic structure and expression of MJD, the Machado-Joseph disease gene | journal = Journal of Human Genetics | volume = 46 | issue = 7 | pages = 413–22 | year = 2001 | pmid = 11450850 | doi = 10.1007/s100380170060 }}
*{{cite journal | author=Wang G, Sawai N, Kotliarova S, ''et al.'' |title=Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B. |journal=Hum. Mol. Genet. |volume=9 |issue= 12 |pages= 1795-803 |year= 2000 |pmid= 10915768 |doi= }}
* {{cite journal | vauthors = Chai Y, Shao J, Miller VM, Williams A, Paulson HL | title = Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 99 | issue = 14 | pages = 9310–5 | date = Jul 2002 | pmid = 12084819 | pmc = 123137 | doi = 10.1073/pnas.152101299 }}
*{{cite journal | author=Ichikawa Y, Goto J, Hattori M, ''et al.'' |title=The genomic structure and expression of MJD, the Machado-Joseph disease gene. |journal=J. Hum. Genet. |volume=46 |issue= 7 |pages= 413-22 |year= 2001 |pmid= 11450850 |doi= }}
* {{cite journal | vauthors = Yoshida H, Yoshizawa T, Shibasaki F, Shoji S, Kanazawa I | title = Chemical chaperones reduce aggregate formation and cell death caused by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch | journal = Neurobiology of Disease | volume = 10 | issue = 2 | pages = 88–99 | date = Jul 2002 | pmid = 12127147 | doi = 10.1006/nbdi.2002.0502 }}
*{{cite journal | author=Chai Y, Shao J, Miller VM, ''et al.'' |title=Live-cell imaging reveals divergent intracellular dynamics of polyglutamine disease proteins and supports a sequestration model of pathogenesis. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 14 |pages= 9310-5 |year= 2002 |pmid= 12084819 |doi= 10.1073/pnas.152101299 }}
* {{cite journal | vauthors = Li F, Macfarlan T, Pittman RN, Chakravarti D | title = Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities | journal = The Journal of Biological Chemistry | volume = 277 | issue = 47 | pages = 45004–12 | date = Nov 2002 | pmid = 12297501 | doi = 10.1074/jbc.M205259200 }}
*{{cite journal | author=Yoshida H, Yoshizawa T, Shibasaki F, ''et al.'' |title=Chemical chaperones reduce aggregate formation and cell death caused by the truncated Machado-Joseph disease gene product with an expanded polyglutamine stretch. |journal=Neurobiol. Dis. |volume=10 |issue= 2 |pages= 88-99 |year= 2002 |pmid= 12127147 |doi= }}
* {{cite journal | vauthors = Albrecht M, Hoffmann D, Evert BO, Schmitt I, Wüllner U, Lengauer T | title = Structural modeling of ataxin-3 reveals distant homology to adaptins | journal = Proteins | volume = 50 | issue = 2 | pages = 355–70 | date = Feb 2003 | pmid = 12486728 | doi = 10.1002/prot.10280 }}
*{{cite journal | author=Li F, Macfarlan T, Pittman RN, Chakravarti D |title=Ataxin-3 is a histone-binding protein with two independent transcriptional corepressor activities. |journal=J. Biol. Chem. |volume=277 |issue= 47 |pages= 45004-12 |year= 2003 |pmid= 12297501 |doi= 10.1074/jbc.M205259200 }}
* {{cite journal | vauthors = Marchal S, Shehi E, Harricane MC, Fusi P, Heitz F, Tortora P, Lange R | title = Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature | journal = The Journal of Biological Chemistry | volume = 278 | issue = 34 | pages = 31554–63 | date = Aug 2003 | pmid = 12766160 | doi = 10.1074/jbc.M304205200 }}
*{{cite journal | author=Strausberg RL, Feingold EA, Grouse LH, ''et al.'' |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899-903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 }}
*{{cite journal  | author=Albrecht M, Hoffmann D, Evert BO, ''et al.'' |title=Structural modeling of ataxin-3 reveals distant homology to adaptins. |journal=Proteins |volume=50 |issue= 2 |pages= 355-70 |year= 2003 |pmid= 12486728 |doi= 10.1002/prot.10280 }}
*{{cite journal  | author=Marchal S, Shehi E, Harricane MC, ''et al.'' |title=Structural instability and fibrillar aggregation of non-expanded human ataxin-3 revealed under high pressure and temperature. |journal=J. Biol. Chem. |volume=278 |issue= 34 |pages= 31554-63 |year= 2003 |pmid= 12766160 |doi= 10.1074/jbc.M304205200 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
* [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=sca3  GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 3]
* {{UCSC gene info|ATXN3}}
 
{{PDB Gallery|geneid=4287}}
{{Posttranslational modification}}
 
[[Category:Proteins]]

Latest revision as of 01:41, 30 August 2017

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

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:

Model organisms

Model organisms have been used in the study of ATXN3 function. A conditional knockout mouse line called Atxn3tm1a(KOMP)Wtsi was generated at the Wellcome Trust Sanger Institute.[6] Male and female animals underwent a standardized phenotypic screen[7] to determine the effects of deletion.[8][9][10][11] Additional screens performed: - In-depth immunological phenotyping[12] - in-depth bone and cartilage phenotyping[13]

References

  1. ↑ 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.
  2. ↑ 2.0 2.1 "Entrez Gene: ATXN3 ataxin 3".
  3. ↑ 3.0 3.1 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
  7. ↑ 7.0 7.1 "International Mouse Phenotyping Consortium".
  8. ↑ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
  9. ↑ Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  10. ↑ Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
  11. ↑ White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Sanger Institute Mouse Genetics Project, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
  12. ↑ 12.0 12.1 "Infection and Immunity Immunophenotyping (3i) Consortium".
  13. ↑ 13.0 13.1 "OBCD Consortium".

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.
  • 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.
  • 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.
  • 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.
  • 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. 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. 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.
  • 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.
  • 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

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