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UniProtKB - P54259 (ATN1_HUMAN)

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Protein

Atrophin-1

Gene

ATN1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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-Gln (polyQ) repeats.By similarity2 Publications

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • central nervous system development Source: ProtInc
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • neuron apoptotic process Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

Keywordsi

Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-8943724 Regulation of PTEN gene transcription
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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000111676.14
HGNCiHGNC:3033 ATN1
MIMi607462 gene
neXtProtiNX_P54259

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Mutagenesisi109D → N: Prevents cleavage and suppresses apoptosis. 1 Publication1
Mutagenesisi739S → A: Abolishes phosphorylation. 1

Keywords - Diseasei

Epilepsy, Neurodegeneration

Organism-specific databases

DisGeNETi1822
GeneReviewsiATN1
MalaCardsiATN1
MIMi125370 phenotype
OpenTargetsiENSG00000111676
Orphaneti101 Dentatorubral pallidoluysian atrophy
PharmGKBiPA27487

Polymorphism and mutation databases

BioMutaiATN1
DMDMi317373480

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000647301 – 1190Atrophin-1Add BLAST1190

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34PhosphoserineCombined sources1
Modified residuei77PhosphoserineCombined sources1
Modified residuei79PhosphoserineCombined sources1
Modified residuei101PhosphoserineCombined sources1
Modified residuei103PhosphoserineCombined sources1
Modified residuei107PhosphoserineCombined sources1
Modified residuei632PhosphoserineCombined sources1
Modified residuei641N6-acetyllysineCombined sources1
Modified residuei653PhosphothreonineCombined sources1
Modified residuei661PhosphoserineCombined sources1
Modified residuei669PhosphothreonineCombined sources1
Modified residuei739Phosphoserine; by MAPK81 Publication1
Modified residuei746PhosphoserineCombined sources1
Modified residuei748PhosphoserineCombined sources1
Modified residuei896PhosphoserineCombined sources1
Modified residuei1115Asymmetric dimethylarginineBy similarity1
Cross-linki1183Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Post-translational modificationi

Phosphorylated in vitro by MAPK8/JNK1 on Ser-739. Mutant ATN1 sequences with expanded poly-Gln (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-Gln (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)DescriptionActionsGraphical viewLength
Sitei109 – 110Cleavage; by CASP-32 Publications2

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP54259
MaxQBiP54259
PaxDbiP54259
PeptideAtlasiP54259
PRIDEiP54259
ProteomicsDBi56663

PTM databases

iPTMnetiP54259
PhosphoSitePlusiP54259

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

Show more details

GO - Molecular functioni

  • protein domain specific binding Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi108156, 98 interactors
DIPiDIP-29423N
IntActiP54259, 91 interactors
MINTiP54259
STRINGi9606.ENSP00000349076

Structurei

3D structure databases

ProteinModelPortaliP54259
SMRiP54259
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni517 – 567Involved in binding BAIAP2Add BLAST51
Regioni879 – 894Required for interaction with FAT11 PublicationAdd BLAST16

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi16 – 32Nuclear localization signal1 PublicationAdd BLAST17
Motifi1033 – 1041Nuclear export signal9

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi73 – 82Glu/Ser-rich10
Compositional biasi302 – 305Poly-Pro4
Compositional biasi376 – 382Poly-Ser7
Compositional biasi386 – 397Poly-SerAdd BLAST12
Compositional biasi442 – 447Poly-Pro6
Compositional biasi479 – 483Poly-His5
Compositional biasi484 – 502Poly-GlnAdd BLAST19
Compositional biasi509 – 512Poly-Pro4
Compositional biasi569 – 579Poly-SerAdd BLAST11
Compositional biasi709 – 712Poly-Pro4
Compositional biasi807 – 820Ala/Arg-richAdd BLAST14
Compositional biasi821 – 832Arg/Glu-rich (mixed charge)Add BLAST12
Compositional biasi930 – 939Arg/Glu-rich (mixed charge)10

Phylogenomic databases

eggNOGiKOG2133 Eukaryota
ENOG410ZIND LUCA
GeneTreeiENSGT00580000081398
HOVERGENiHBG075369
InParanoidiP54259
KOiK05626
OMAiQPPKYTQ
OrthoDBiEOG091G0O1H
PhylomeDBiP54259
TreeFamiTF328554

Family and domain databases

InterProiView protein in InterPro
IPR017993 Atrophin-1
IPR002951 Atrophin-like
PfamiView protein in Pfam
PF03154 Atrophin-1, 2 hits
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)DescriptionActionsGraphical viewLength
Sequence conflicti94Missing in AAB50276 (PubMed:8965642).Curated1
Sequence conflicti333H → Y in BAA06626 (PubMed:7842016).Curated1
Sequence conflicti1033A → G in BAA06626 (PubMed:7842016).Curated1

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_030937339M → I1 PublicationCorresponds to variant dbSNP:rs1058045Ensembl.1
Natural variantiVAR_064038484 – 488Missing 3 Publications5

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

Similar proteinsi

Entry informationi

Entry nameiATN1_HUMAN
AccessioniPrimary (citable) accession number: P54259
Secondary accession number(s): Q99495, Q99621, Q9UEK7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 11, 2011
Last modified: July 18, 2018
This is version 172 of the entry and version 3 of the sequence. See 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

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