Reviewed, UniProtKB/Swiss-Prot P54253 (ATX1_HUMAN)

Names and origin

Protein names

Recommended name:
    Ataxin-1
Alternative name(s):
    Spinocerebellar ataxia type 1 protein

Gene names

Name:	ATXN1
Synonyms:	ATX1, SCA1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	815 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Binds RNA in vitro. May be involved in RNA metabolism. The expansion of the polyglutamine tract may alter this function.
Subunit structure	Interacts with CIC By similarity. Interacts with ANP32A, PQBP1, UBIN, ATXN1L and USP7.
Subcellular location	CytoplasmBy similarity. Nucleus. Note= Colocalizes with USP7 in the nucleus.
Tissue specificity	Widely expressed throughout the body.
Domain	The AXH domain is required for interaction with CIC By similarity.
Polymorphism	The poly-Gln region of ATXN1 is highly polymorphic (4 to 39 repeats) in the normal population and is expanded to about 40-83 repeats in spinocerebellar ataxia 1 (SCA1) patients.
Involvement in disease	Defects in ATXN1 are the cause of spinocerebellar ataxia type 1 (SCA1) [MIM:164400]; also known as olivopontocerebellar atrophy I (OPCA I or OPCA1). Spinocerebellar ataxia is a clinically and genetically heterogeneous group of cerebellar disorders. Patients show progressive incoordination of gait and often poor coordination of hands, speech and eye movements, due to cerebellum degeneration with variable involvement of the brainstem and spinal cord. SCA1 belongs to the autosomal dominant cerebellar ataxias type I (ADCA I) which are characterized by cerebellar ataxia in combination with additional clinical features like optic atrophy, ophthalmoplegia, bulbar and extrapyramidal signs, peripheral neuropathy and dementia. SCA1 is caused by expansion of a CAG repeat in the coding region of ATXN1. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.
Miscellaneous	The self-association seems to be necessary to form nuclear aggregates.
Sequence similarities	Belongs to the ATXN1 family. Contains 1 AXH domain.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing Polymorphism Triplet repeat expansion
Disease	Neurodegeneration Spinocerebellar ataxia
Ligand	RNA-binding
PTM	Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	RNA processing Non-traceable author statement. Source: UniProtKB cell death Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription Inferred from direct assay. Source: UniProtKB nuclear export Inferred from direct assay. Source: UniProtKB
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB nuclear inclusion body Inferred from direct assay. Source: UniProtKB nuclear matrix Inferred from direct assay. Source: UniProtKB nucleoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct poly(U) binding Ref.7 Inferred from direct assay. Source: UniProtKB poly(rG) binding Ref.7 Inferred from direct assay. Source: UniProtKB protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein self-association Ref.5 Inferred from direct assay. Source: UniProtKB transcription repressor activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-930964,EBI-930964
ATXN2	Q99700	1	EBI-930964,EBI-697691
BAT2	P48634	1	EBI-930964,EBI-347545
C1orf94	Q6P1W5	1	EBI-930964,EBI-946029
CCNK	O75909	1	EBI-930964,EBI-739806
CFL1	P23528	1	EBI-930964,EBI-352733
COIL	P38432	5	EBI-930975,EBI-945751
CPSF7	Q8N684	1	EBI-930964,EBI-746909
CRK	P46108	1	EBI-930964,EBI-886
DAZAP2	Q15038	1	EBI-930964,EBI-724310
DERP6	Q8TE02	1	EBI-930964,EBI-946189
FOX1	Q9NWB1	1	EBI-930964,EBI-945906
HIVEP1	P15822	1	EBI-930964,EBI-722264
HTATIP	Q92993	1	EBI-930964,EBI-399080
KIAA0174	P53990	1	EBI-930964,EBI-945994
KLHL12	Q53G59	1	EBI-930964,EBI-740929
NUDT21	O43809	1	EBI-930964,EBI-355720
PLEKHA5	Q9HAU0	1	EBI-930964,EBI-945934
RBM9	O43251	1	EBI-930964,EBI-746056
RBPMS	Q93062	1	EBI-930964,EBI-740322
SIX5	Q8N196	1	EBI-930964,EBI-946167
TBC1D5	Q92609	1	EBI-930964,EBI-742381
TRAF2	Q12933	1	EBI-930964,EBI-355744
TRIM32	Q13049	1	EBI-930964,EBI-742790
U2AF2	Q96HC5	1	EBI-930964,EBI-742339
UBQLN4	Q9NRR5	3	EBI-930964,EBI-711226
USP54	Q6P1N6	1	EBI-930964,EBI-946185
YY1AP1	Q9H869	1	EBI-930964,EBI-946122
ZHX1	Q9UKY1	1	EBI-930964,EBI-347767

Alternative products

This entry describes 1 isoform produced by alternative splicing. [Select]

Notes: At least 2 isoforms are produced.

Isoform 1 (identifier: P54253-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 815

815

Ataxin-1

PRO_0000064751

Regions

Domain

562 – 693

132

AXH

Region

494 – 604

111

Self-association

Region

538 – 815

278

Interaction with USP7

Region

540 – 766

227

RNA-binding

Motif

794 – 797

4

Nuclear localization signal By similarity

Compositional bias

197 – 225

29

Poly-Gln

Amino acid modifications

Modified residue

238

1

Phosphoserine

Modified residue

253

1

Phosphoserine

Natural variations

Natural variant

209

1

H → Q: dbSNP rs11969612.

VAR_046616

Natural variant

753

1

P → S: dbSNP rs16885.

VAR_046617

Experimental info

Sequence conflict

211

1

H → HQ in CAA55793. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

815

Helix Strand Turn

Details...

Helix

572 – 574

3

Beta strand

579 – 581

3

Beta strand

587 – 589

3

Helix

590 – 592

3

Helix

595 – 604

10

Beta strand

606 – 620

15

Beta strand

626 – 633

8

Turn

634 – 637

4

Beta strand

638 – 645

8

Beta strand

650 – 652

3

Turn

653 – 655

3

Beta strand

656 – 660

5

Helix

662 – 669

8

Beta strand

681 – 687

7

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 23, 2008. Version 2. Checksum: 657876F8FD19ECB2	FASTA	815	86,923
	10 20 30 40 50 60 MKSNQERSNE CLPPKKREIP ATSRSSEEKA PTLPSDNHRV EGTAWLPGNP GGRGHGGGRH 70 80 90 100 110 120 GPAGTSVELG LQQGIGLHKA LSTGLDYSPP SAPRSVPVAT TLPAAYATPQ PGTPVSPVQY 130 140 150 160 170 180 AHLPHTFQFI GSSQYSGTYA SFIPSQLIPP TANPVTSAVA SAAGATTPSQ RSQLEAYSTL 190 200 210 220 230 240 LANMGSLSQT PGHKAEQQQQ QQQQQQQQHQ HQQQQQQQQQ QQQQQHLSRA PGLITPGSPP 250 260 270 280 290 300 PAQQNQYVHI SSSPQNTGRT ASPPAIPVHL HPHQTMIPHT LTLGPPSQVV MQYADSGSHF 310 320 330 340 350 360 VPREATKKAE SSRLQQAIQA KEVLNGEMEK SRRYGAPSSA DLGLGKAGGK SVPHPYESRH 370 380 390 400 410 420 VVVHPSPSDY SSRDPSGVRA SVMVLPNSNT PAADLEVQQA THREASPSTL NDKSGLHLGK 430 440 450 460 470 480 PGHRSYALSP HTVIQTTHSA SEPLPVGLPA TAFYAGTQPP VIGYLSGQQQ AITYAGSLPQ 490 500 510 520 530 540 HLVIPGTQPL LIPVGSTDME ASGAAPAIVT SSPQFAAVPH TFVTTALPKS ENFNPEALVT 550 560 570 580 590 600 QAAYPAMVQA QIHLPVVQSV ASPAAAPPTL PPYFMKGSII QLANGELKKV EDLKTEDFIQ 610 620 630 640 650 660 SAEISNDLKI DSSTVERIED SHSPGVAVIQ FAVGEHRAQV SVEVLVEYPF FVFGQGWSSC 670 680 690 700 710 720 CPERTSQLFD LPCSKLSVGD VCISLTLKNL KNGSVKKGQP VDPASVLLKH SKADGLAGSR 730 740 750 760 770 780 HRYAEQENGI NQGSAQMLSE NGELKFPEKM GLPAAPFLTK IEPSKPAATR KRRWSAPESR 790 800 810 KLEKSEDEPP LTLPKPSLIP QEVKICIEGR SNVGK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Identification and characterization of the gene causing type 1 spinocerebellar ataxia." Banfi S., Servadio A., Chung M.-Y., Kwiatkowski T.J. Jr., McCall A.E., Duvick L.A., Shen Y., Roth E.J., Orr H.T., Zoghbi H.Y. Nat. Genet. 7:513-519(1994) [PubMed: 7951322] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INVOLVEMENT IN SCA1. Tissue: Brain and Cerebellum.
[2]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"A novel CAG repeat configuration in the SCA1 gene: implications for the molecular diagnostics of spinocerebellar ataxia type 1." Quan F., Janas J., Popovich B.W. Hum. Mol. Genet. 4:2411-2413(1995) [PubMed: 8634720] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 189-230, INVOLVEMENT IN SCA1.
[5]	"Identification of a self-association region within the SCA1 gene product, ataxin-1." Burright E.N., Davidson J.D., Duvick L.A., Koshy B., Zoghbi H.Y., Orr H.T. Hum. Mol. Genet. 6:513-518(1997) [PubMed: 9097953] [Abstract] Cited for: SELF-ASSOCIATION SITE.
[6]	"The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1." Matilla A., Koshy B.T., Cummings C.J., Isobe T., Orr H.T., Zoghbi H.Y. Nature 389:974-978(1997) [PubMed: 9353121] [Abstract] Cited for: INTERACTION WITH ANP32A.
[7]	"The spinocerebellar ataxia type 1 protein, ataxin-1, has RNA-binding activity that is inversely affected by the length of its polyglutamine tract." Yue S., Serra H.G., Zoghbi H.Y., Orr H.T. Hum. Mol. Genet. 10:25-30(2001) [PubMed: 11136710] [Abstract] Cited for: RNA-BINDING DOMAIN.
[8]	"Identification and characterization of an ataxin-1-interacting protein: A1Up, a ubiquitin-like nuclear protein." Davidson J.D., Riley B., Burright E.N., Duvick L.A., Zoghbi H.Y., Orr H.T. Hum. Mol. Genet. 9:2305-2312(2000) [PubMed: 11001934] [Abstract] Cited for: INTERACTION WITH UBIN.
[9]	"Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death." Okazawa H., Rich T., Chang A., Lin X., Waragai M., Kajikawa M., Enokido Y., Komuro A., Kato S., Shibata M., Hatanaka H., Mouradian M.M., Sudol M., Kanazawa I. Neuron 34:701-713(2002) [PubMed: 12062018] [Abstract] Cited for: INTERACTION WITH PQBP1.
[10]	"USP7, a ubiquitin-specific protease, interacts with ataxin-1, the SCA1 gene product." Hong S., Kim S.J., Ka S., Choi I., Kang S. Mol. Cell. Neurosci. 20:298-306(2002) [PubMed: 12093161] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH USP7.
[11]	"Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1." Mizutani A., Wang L., Rajan H., Vig P.J.S., Alaynick W.A., Thaler J.P., Tsai C.-C. EMBO J. 24:3339-3351(2005) [PubMed: 16121196] [Abstract] Cited for: INTERACTION WITH ATXN1L.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-238 AND SER-253, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Ataxin-1 entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

X79204 mRNA. Translation: CAA55793.1.
AL009031 Genomic DNA. Translation: CAA15622.1.
BC117125 mRNA. Translation: AAI17126.1.
S82497 Genomic DNA. Translation: AAD14401.1.

PIR

S46268.

RefSeq

NP_000323.2.
NP_001121636.1.

UniGene

Hs.434961

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1OA8	X-ray	1.70	A/B/C/D	562-693	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P54253.

PTM databases

PhosphoSite

P54253.

Genome annotation databases

Ensembl

ENSG00000124788. Homo sapiens. [Contig view]

GeneID

6310.

KEGG

hsa:6310.

Organism-specific databases

H-InvDB

HIX0032878.

HGNC

HGNC:10548. ATXN1.

HPA

HPA008335.

MIM

164400. phenotype.
601556. gene.

Orphanet

99. Cerebellar ataxia, autosomal dominant.
98755. Spinocerebellar ataxia 1.

PharmGKB

PA34958.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

P54253.

HOVERGEN

P54253.

Gene expression databases

ArrayExpress

P54253.

CleanEx

HS_ATXN1.

GermOnline

ENSG00000124788. Homo sapiens.

Family and domain databases

InterPro

IPR013723. Ataxin-1_HBP1.
IPR003652. Ataxin_AXH.
[Graphical view]

Pfam

PF08517. AXH. 1 hit.
[Graphical view]

SMART

SM00536. AXH. 1 hit.
[Graphical view]

PROSITE

PS51148. AXH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

LinkHub

P54253.

SOURCE

Search...

Entry information

Entry name

ATX1_HUMAN

Accession

Primary (citable) accession number: P54253
Secondary accession number(s): Q17S02, Q9UJG2, Q9Y4J1

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence upda