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Protein

Atrophin-1

Gene

ATN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Transcriptional corepressor. Recruits NR2E1 to repress transcription. Promotes vascular smooth cell (VSMC) migration and orientation (By similarity). Corepressor of MTG8 transcriptional repression. Has some intrinsic repression activity which is independent of the number of poly-Asn (polyQ) repeats.By similarity2 Publications

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB

GO - Biological processi

  • central nervous system development Source: ProtInc
  • negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • neuron apoptotic process Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

SIGNORiP54259.

Names & Taxonomyi

Protein namesi
Recommended name:
Atrophin-1
Alternative name(s):
Dentatorubral-pallidoluysian atrophy protein
Gene namesi
Name:ATN1
Synonyms:D12S755E, DRPLA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:3033. ATN1.

Subcellular locationi

  • Nucleus
  • Cytoplasmperinuclear region
  • Cell junction By similarity

  • Note: Shuttles between nucleus and cytoplasm. Colocalizes with FAT1 in the perinuclear area, at cell-cell junctions and leading edges of cells (By similarity). Colocalizes with MTG8 in discrete nuclear dots. Proteolytic fragment F1 appears to remain in nucleus. Fragment F2 is exported into the cytoplasm. Fragment F2 from mutant sequences with longer poly-Asn (polyQ) tracts are additionally located to the cytoplasmic membrane and to certain organelles.By similarity

GO - Cellular componenti

  • cell junction Source: UniProtKB-SubCell
  • cytoplasm Source: ProtInc
  • nuclear matrix Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Dentatorubral-pallidoluysian atrophy (DRPLA)
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAutosomal dominant neurodegenerative disorder characterized by a loss of neurons in the dentate nucleus, rubrum, glogus pallidus and Luys'body. Clinical features are myoclonus epilepsy, dementia, and cerebellar ataxia. Onset of the disease occurs usually in the second decade of life and death in the fourth.
See also OMIM:125370

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi109 – 1091D → N: Prevents cleavage and suppresses apoptosis. 1 Publication
Mutagenesisi739 – 7391S → A: Abolishes phosphorylation.

Keywords - Diseasei

Epilepsy, Neurodegeneration

Organism-specific databases

MalaCardsiATN1.
MIMi125370. phenotype.
Orphaneti101. Dentatorubral pallidoluysian atrophy.
PharmGKBiPA27487.

Polymorphism and mutation databases

BioMutaiATN1.
DMDMi317373480.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 11901190Atrophin-1PRO_0000064730Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei34 – 341PhosphoserineCombined sources
Modified residuei77 – 771PhosphoserineCombined sources
Modified residuei79 – 791PhosphoserineCombined sources
Modified residuei101 – 1011PhosphoserineCombined sources
Modified residuei103 – 1031PhosphoserineCombined sources
Modified residuei107 – 1071PhosphoserineCombined sources
Modified residuei632 – 6321PhosphoserineCombined sources
Modified residuei641 – 6411N6-acetyllysineCombined sources
Modified residuei653 – 6531PhosphothreonineCombined sources
Modified residuei661 – 6611PhosphoserineCombined sources
Modified residuei669 – 6691PhosphothreonineCombined sources
Modified residuei739 – 7391Phosphoserine; by MAPK81 Publication
Modified residuei746 – 7461PhosphoserineCombined sources
Modified residuei748 – 7481PhosphoserineCombined sources
Modified residuei896 – 8961PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated in vitro by MAPK8/JNK1 on Ser-739. Mutant ATN1 sequences with expanded poly-Asn (polyQ) traits are more slowly phosphorylated.1 Publication
Proteolytically cleaved, probably in the nucleus, to produce two C-terminal fragments of 140 kDa (F1) and 125 kDa (F2) each containing poly-Asn (polyQ) tracts. F2 is produced by cleavage by caspases and is exported into the cytoplasm. In vitro, cleavage increases with an increase in the number of polyQ tracts. C-terminal proteolytic products appear to be the cause of cell toxicity. In vitro cleavage at Asp-109.4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei109 – 1102Cleavage

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP54259.
MaxQBiP54259.
PaxDbiP54259.
PeptideAtlasiP54259.
PRIDEiP54259.

PTM databases

iPTMnetiP54259.
PhosphoSiteiP54259.

Expressioni

Tissue specificityi

Widely expressed in various tissues including heart, lung, kidney, ovary, testis, prostate, placenta, skeletal Low levels in the liver, thymus and leukocytes. In the adult brain, broadly expressed in amygdala, caudate nucleus, corpus callosum, hippocampus, hypothalamus, substantia nigra, subthalamic nucleus, and thalamus. High levels in fetal tissues, especially brain.3 Publications

Gene expression databases

BgeeiENSG00000111676.
CleanExiHS_ATN1.
GenevisibleiP54259. HS.

Organism-specific databases

HPAiHPA031619.

Interactioni

Subunit structurei

Interacts with NR2E1; the interaction represses the transcriptional activity of NR2E1. Interacts (via its N-terminus) with FAT1 (via a C-terminal domain) (By similarity). Interacts with BAIAP2, WWP1, WWP2, WWP3 and RERE. Interacts (via its N-terminus) with MTG8; the interaction enhances transcriptional repression of MTG8. Interacts with PQBP1.By similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EFEMP1Q128053EBI-945980,EBI-536772
EFEMP2O959673EBI-945980,EBI-743414
PLEKHA5Q9HAU02EBI-945980,EBI-945934
PSME3P612893EBI-945980,EBI-355546
RBFOX1Q9NWB12EBI-945980,EBI-945906
REREQ9P2R63EBI-945980,EBI-948076
TRIP6Q156542EBI-945980,EBI-742327

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB

Protein-protein interaction databases

BioGridi108156. 98 interactions.
DIPiDIP-29423N.
IntActiP54259. 88 interactions.
MINTiMINT-92928.
STRINGi9606.ENSP00000349076.

Structurei

3D structure databases

ProteinModelPortaliP54259.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni517 – 56751Involved in binding BAIAP2Add
BLAST
Regioni879 – 89416Required for interaction with FAT1Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi16 – 3217Nuclear localization signal1 PublicationAdd
BLAST
Motifi1033 – 10419Nuclear export signal

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi73 – 8210Glu/Ser-rich
Compositional biasi302 – 3054Poly-Pro
Compositional biasi376 – 3827Poly-Ser
Compositional biasi386 – 39712Poly-SerAdd
BLAST
Compositional biasi442 – 4476Poly-Pro
Compositional biasi479 – 4835Poly-His
Compositional biasi484 – 50219Poly-GlnAdd
BLAST
Compositional biasi509 – 5124Poly-Pro
Compositional biasi569 – 57911Poly-SerAdd
BLAST
Compositional biasi709 – 7124Poly-Pro
Compositional biasi807 – 82014Ala/Arg-richAdd
BLAST
Compositional biasi821 – 83212Arg/Glu-rich (mixed charge)Add
BLAST
Compositional biasi930 – 93910Arg/Glu-rich (mixed charge)

Phylogenomic databases

eggNOGiKOG2133. Eukaryota.
ENOG410ZIND. LUCA.
GeneTreeiENSGT00580000081398.
HOVERGENiHBG075369.
InParanoidiP54259.
KOiK05626.
OMAiGPEKGPT.
OrthoDBiEOG091G0O1H.
PhylomeDBiP54259.
TreeFamiTF328554.

Family and domain databases

InterProiIPR017993. Atrophin-1.
IPR002951. Atrophin-like.
[Graphical view]
PfamiPF03154. Atrophin-1. 2 hits.
[Graphical view]
PRINTSiPR01222. ATROPHIN.

Sequencei

Sequence statusi: Complete.

P54259-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTRQNKDSM SMRSGRKKEA PGPREELRSR GRASPGGVST SSSDGKAEKS
60 70 80 90 100
RQTAKKARVE EASTPKVNKQ GRSEEISESE SEETNAPKKT KTEQELPRPQ
110 120 130 140 150
SPSDLDSLDG RSLNDDGSSD PRDIDQDNRS TSPSIYSPGS VENDSDSSSG
160 170 180 190 200
LSQGPARPYH PPPLFPPSPQ PPDSTPRQPE ASFEPHPSVT PTGYHAPMEP
210 220 230 240 250
PTSRMFQAPP GAPPPHPQLY PGGTGGVLSG PPMGPKGGGA ASSVGGPNGG
260 270 280 290 300
KQHPPPTTPI SVSSSGASGA PPTKPPTTPV GGGNLPSAPP PANFPHVTPN
310 320 330 340 350
LPPPPALRPL NNASASPPGL GAQPLPGHLP SPHAMGQGMG GLPPGPEKGP
360 370 380 390 400
TLAPSPHSLP PASSSAPAPP MRFPYSSSSS SSAAASSSSS SSSSSASPFP
410 420 430 440 450
ASQALPSYPH SFPPPTSLSV SNQPPKYTQP SLPSQAVWSQ GPPPPPPYGR
460 470 480 490 500
LLANSNAHPG PFPPSTGAQS TAHPPVSTHH HHHQQQQQQQ QQQQQQQQQQ
510 520 530 540 550
QQHHGNSGPP PPGAFPHPLE GGSSHHAHPY AMSPSLGSLR PYPPGPAHLP
560 570 580 590 600
PPHSQVSYSQ AGPNGPPVSS SSNSSSSTSQ GSYPCSHPSP SQGPQGAPYP
610 620 630 640 650
FPPVPTVTTS SATLSTVIAT VASSPAGYKT ASPPGPPPYG KRAPSPGAYK
660 670 680 690 700
TATPPGYKPG SPPSFRTGTP PGYRGTSPPA GPGTFKPGSP TVGPGPLPPA
710 720 730 740 750
GPSGLPSLPP PPAAPASGPP LSATQIKQEP AEEYETPESP VPPARSPSPP
760 770 780 790 800
PKVVDVPSHA SQSARFNKHL DRGFNSCARS DLYFVPLEGS KLAKKRADLV
810 820 830 840 850
EKVRREAEQR AREEKERERE REREKERERE KERELERSVK LAQEGRAPVE
860 870 880 890 900
CPSLGPVPHR PPFEPGSAVA TVPPYLGPDT PALRTLSEYA RPHVMSPGNR
910 920 930 940 950
NHPFYVPLGA VDPGLLGYNV PALYSSDPAA REREREARER DLRDRLKPGF
960 970 980 990 1000
EVKPSELEPL HGVPGPGLDP FPRHGGLALQ PGPPGLHPFP FHPSLGPLER
1010 1020 1030 1040 1050
ERLALAAGPA LRPDMSYAER LAAERQHAER VAALGNDPLA RLQMLNVTPH
1060 1070 1080 1090 1100
HHQHSHIHSH LHLHQQDAIH AASASVHPLI DPLASGSHLT RIPYPAGTLP
1110 1120 1130 1140 1150
NPLLPHPLHE NEVLRHQLFA APYRDLPASL SAPMSAAHQL QAMHAQSAEL
1160 1170 1180 1190
QRLALEQQQW LHAHHPLHSV PLPAQEDYYS HLKKESDKPL
Length:1,190
Mass (Da):125,414
Last modified:January 11, 2011 - v3
Checksum:iB47603486C672637
GO

Sequence cautioni

The sequence BAA07534 differs from that shown. Reason: Frameshift at positions 961, 970, 977, 980, 983 and 1005. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti94 – 941Missing in AAB50276 (PubMed:8965642).Curated
Sequence conflicti333 – 3331H → Y in BAA06626 (PubMed:7842016).Curated
Sequence conflicti1033 – 10331A → G in BAA06626 (PubMed:7842016).Curated

Polymorphismi

The poly-Gln region of ATN1 is highly polymorphic (7 to 23 repeats) in the normal population and is expanded to about 49-75 repeats in DRPLA and HRS patients. Longer expansions result in earlier onset and more severe clinical manifestations of the disease.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti339 – 3391M → I.1 Publication
Corresponds to variant rs1058045 [ dbSNP | Ensembl ].
VAR_030937
Natural varianti484 – 4885Missing .3 Publications
VAR_064038

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31840 mRNA. Translation: BAA06626.1.
D38529 mRNA. Translation: BAA07534.1. Frameshift.
U23851 mRNA. Translation: AAB50276.1.
U47924 Genomic DNA. Translation: AAB51321.1.
D63808 Genomic DNA. Translation: BAA23631.1.
CCDSiCCDS31734.1.
PIRiG01763.
S50832.
RefSeqiNP_001007027.1. NM_001007026.1.
NP_001931.2. NM_001940.3.
UniGeneiHs.143766.

Genome annotation databases

EnsembliENST00000356654; ENSP00000349076; ENSG00000111676.
ENST00000396684; ENSP00000379915; ENSG00000111676.
GeneIDi1822.
KEGGihsa:1822.
UCSCiuc001qrw.2. human.

Keywords - Coding sequence diversityi

Polymorphism, Triplet repeat expansion

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D31840 mRNA. Translation: BAA06626.1.
D38529 mRNA. Translation: BAA07534.1. Frameshift.
U23851 mRNA. Translation: AAB50276.1.
U47924 Genomic DNA. Translation: AAB51321.1.
D63808 Genomic DNA. Translation: BAA23631.1.
CCDSiCCDS31734.1.
PIRiG01763.
S50832.
RefSeqiNP_001007027.1. NM_001007026.1.
NP_001931.2. NM_001940.3.
UniGeneiHs.143766.

3D structure databases

ProteinModelPortaliP54259.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108156. 98 interactions.
DIPiDIP-29423N.
IntActiP54259. 88 interactions.
MINTiMINT-92928.
STRINGi9606.ENSP00000349076.

PTM databases

iPTMnetiP54259.
PhosphoSiteiP54259.

Polymorphism and mutation databases

BioMutaiATN1.
DMDMi317373480.

Proteomic databases

EPDiP54259.
MaxQBiP54259.
PaxDbiP54259.
PeptideAtlasiP54259.
PRIDEiP54259.

Protocols and materials databases

DNASUi1822.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000356654; ENSP00000349076; ENSG00000111676.
ENST00000396684; ENSP00000379915; ENSG00000111676.
GeneIDi1822.
KEGGihsa:1822.
UCSCiuc001qrw.2. human.

Organism-specific databases

CTDi1822.
GeneCardsiATN1.
GeneReviewsiATN1.
H-InvDBHIX0079489.
HGNCiHGNC:3033. ATN1.
HPAiHPA031619.
MalaCardsiATN1.
MIMi125370. phenotype.
607462. gene.
neXtProtiNX_P54259.
Orphaneti101. Dentatorubral pallidoluysian atrophy.
PharmGKBiPA27487.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2133. Eukaryota.
ENOG410ZIND. LUCA.
GeneTreeiENSGT00580000081398.
HOVERGENiHBG075369.
InParanoidiP54259.
KOiK05626.
OMAiGPEKGPT.
OrthoDBiEOG091G0O1H.
PhylomeDBiP54259.
TreeFamiTF328554.

Enzyme and pathway databases

SIGNORiP54259.

Miscellaneous databases

ChiTaRSiATN1. human.
GeneWikiiATN1.
GenomeRNAii1822.
PROiP54259.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000111676.
CleanExiHS_ATN1.
GenevisibleiP54259. HS.

Family and domain databases

InterProiIPR017993. Atrophin-1.
IPR002951. Atrophin-like.
[Graphical view]
PfamiPF03154. Atrophin-1. 2 hits.
[Graphical view]
PRINTSiPR01222. ATROPHIN.
ProtoNetiSearch...

Entry informationi

Entry nameiATN1_HUMAN
AccessioniPrimary (citable) accession number: P54259
Secondary accession number(s): Q99495, Q99621, Q9UEK7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: September 7, 2016
This is version 154 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.