UniProtKB - P54259 (ATN1_HUMAN)
Protein
Atrophin-1
Gene
ATN1
Organism
Homo sapiens (Human)
Status
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
- RNA polymerase II transcription factor binding Source: GO_Central
- transcription corepressor activity Source: UniProtKB
GO - Biological processi
- central nervous system development Source: ProtInc
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- neuron apoptotic process Source: UniProtKB
Keywordsi
Biological process | Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P54259 |
Reactomei | R-HSA-8943724, Regulation of PTEN gene transcription |
SIGNORi | P54259 |
Names & Taxonomyi
Protein namesi | Recommended name: Atrophin-1Alternative name(s): Dentatorubral-pallidoluysian atrophy protein |
Gene namesi | Name:ATN1 Synonyms:D12S755E, DRPLA |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:3033, ATN1 |
MIMi | 607462, gene |
neXtProti | NX_P54259 |
VEuPathDBi | HostDB:ENSG00000111676.14 |
Subcellular locationi
Nucleus
Other locations
- perinuclear 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-Gln (polyQ) tracts are additionally located to the cytoplasmic membrane and to certain organelles.By similarity
Nucleus
- nuclear matrix Source: UniProtKB
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- cell junction Source: UniProtKB-SubCell
- cytoplasm Source: ProtInc
- perinuclear region of cytoplasm Source: UniProtKB-SubCell
Keywords - Cellular componenti
Cell junction, Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
Dentatorubral-pallidoluysian atrophy (DRPLA)2 Publications
The disease is caused by variants 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.
Related information in OMIMCongenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant neurodevelopmental syndrome characterized by severe global developmental delay, impaired intellectual development, poor or absent language, significant motor disability with inability to walk, dysmorphic facial features, skeletal anomalies, and variable congenital malformations. Most patients also have seizures and structural brain abnormalities.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_083058 | 1054 | H → N in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083059 | 1058 | H → Y in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083060 | 1059 – 1060 | SH → DL in CHEDDA; unknown pathological significance. 1 Publication | 2 | |
Natural variantiVAR_083061 | 1059 – 1060 | SH → NL in CHEDDA; unknown pathological significance. 1 Publication | 2 | |
Natural variantiVAR_083062 | 1060 | H → Y in CHEDDA; the mutation resulted in a perturbation of the structural and functional integrity of the HX repeat; altered zinc-binding properties of the HX repeat. 1 Publication | 1 | |
Natural variantiVAR_083063 | 1062 | H → D in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083064 | 1062 | H → R in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083065 | 1063 | L → R in CHEDDA. 1 Publication | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 109 | D → N: Prevents cleavage and suppresses apoptosis. 1 Publication | 1 | |
Mutagenesisi | 739 | S → A: Abolishes phosphorylation. | 1 |
Keywords - Diseasei
Disease variant, Epilepsy, Mental retardation, NeurodegenerationOrganism-specific databases
DisGeNETi | 1822 |
GeneReviewsi | ATN1 |
MalaCardsi | ATN1 |
MIMi | 125370, phenotype 618494, phenotype |
OpenTargetsi | ENSG00000111676 |
Orphaneti | 101, Dentatorubral pallidoluysian atrophy |
PharmGKBi | PA27487 |
Miscellaneous databases
Pharosi | P54259, Tbio |
Genetic variation databases
BioMutai | ATN1 |
DMDMi | 317373480 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000064730 | 1 – 1190 | Atrophin-1Add BLAST | 1190 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 34 | PhosphoserineCombined sources | 1 | |
Modified residuei | 77 | PhosphoserineCombined sources | 1 | |
Modified residuei | 79 | PhosphoserineCombined sources | 1 | |
Modified residuei | 101 | PhosphoserineCombined sources | 1 | |
Modified residuei | 103 | PhosphoserineCombined sources | 1 | |
Modified residuei | 107 | PhosphoserineCombined sources | 1 | |
Modified residuei | 632 | PhosphoserineCombined sources | 1 | |
Modified residuei | 641 | N6-acetyllysineCombined sources | 1 | |
Modified residuei | 653 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 661 | PhosphoserineCombined sources | 1 | |
Modified residuei | 669 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 739 | Phosphoserine; by MAPK81 Publication | 1 | |
Modified residuei | 746 | PhosphoserineCombined sources | 1 | |
Modified residuei | 748 | PhosphoserineCombined sources | 1 | |
Modified residuei | 896 | PhosphoserineCombined sources | 1 | |
Modified residuei | 1115 | Asymmetric dimethylarginineBy similarity | 1 | |
Cross-linki | 1183 | Glycyl 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sitei | 109 – 110 | Cleavage; by CASP-32 Publications | 2 |
Keywords - PTMi
Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | P54259 |
jPOSTi | P54259 |
MassIVEi | P54259 |
MaxQBi | P54259 |
PaxDbi | P54259 |
PeptideAtlasi | P54259 |
PRIDEi | P54259 |
ProteomicsDBi | 56663 |
PTM databases
iPTMneti | P54259 |
PhosphoSitePlusi | P54259 |
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
Bgeei | ENSG00000111676, Expressed in left lobe of thyroid gland and 190 other tissues |
Genevisiblei | P54259, HS |
Organism-specific databases
HPAi | ENSG00000111676, Low tissue specificity |
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 PublicationsBinary interactionsi
Hide detailsP54259
GO - Molecular functioni
- protein domain specific binding Source: UniProtKB
- RNA polymerase II transcription factor binding Source: GO_Central
Protein-protein interaction databases
BioGRIDi | 108156, 129 interactors |
DIPi | DIP-29423N |
IntActi | P54259, 93 interactors |
MINTi | P54259 |
STRINGi | 9606.ENSP00000349076 |
Miscellaneous databases
RNActi | P54259, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 517 – 567 | Involved in binding BAIAP2Add BLAST | 51 | |
Regioni | 879 – 894 | Required for interaction with FAT11 PublicationAdd BLAST | 16 | |
Regioni | 1049 – 1065 | HX repeat1 PublicationAdd BLAST | 17 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 16 – 32 | Nuclear localization signal1 PublicationAdd BLAST | 17 | |
Motifi | 1033 – 1041 | Nuclear export signal | 9 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 73 – 82 | Glu/Ser-rich | 10 | |
Compositional biasi | 302 – 305 | Poly-Pro | 4 | |
Compositional biasi | 376 – 382 | Poly-Ser | 7 | |
Compositional biasi | 386 – 397 | Poly-SerAdd BLAST | 12 | |
Compositional biasi | 442 – 447 | Poly-Pro | 6 | |
Compositional biasi | 479 – 483 | Poly-His | 5 | |
Compositional biasi | 484 – 502 | Poly-GlnAdd BLAST | 19 | |
Compositional biasi | 509 – 512 | Poly-Pro | 4 | |
Compositional biasi | 569 – 579 | Poly-SerAdd BLAST | 11 | |
Compositional biasi | 709 – 712 | Poly-Pro | 4 | |
Compositional biasi | 807 – 820 | Ala/Arg-richAdd BLAST | 14 | |
Compositional biasi | 821 – 832 | Arg/Glu-rich (mixed charge)Add BLAST | 12 | |
Compositional biasi | 930 – 939 | Arg/Glu-rich (mixed charge) | 10 |
Domaini
The HX repeat motif is a specific pH-dependent interaction motif for ions and/or proteins or other biomolecules. This motif could be involved in the control of embryonic development.1 Publication
Phylogenomic databases
eggNOGi | KOG2133, Eukaryota |
GeneTreei | ENSGT00940000153615 |
HOGENOMi | CLU_005292_0_0_1 |
InParanoidi | P54259 |
OMAi | HAYPGYA |
OrthoDBi | 215918at2759 |
PhylomeDBi | P54259 |
TreeFami | TF328554 |
Family and domain databases
InterProi | View protein in InterPro IPR017993, Atrophin-1 IPR002951, Atrophin-like |
Pfami | View protein in Pfam PF03154, Atrophin-1, 2 hits |
PRINTSi | PR01222, ATROPHIN |
i Sequence
Sequence statusi: Complete.
P54259-1 [UniParc]FASTAAdd to basket
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
Sequence cautioni
The sequence BAA07534 differs from that shown. Reason: Frameshift.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 94 | Missing in AAB50276 (PubMed:8965642).Curated | 1 | |
Sequence conflicti | 333 | H → Y in BAA06626 (PubMed:7842016).Curated | 1 | |
Sequence conflicti | 1033 | A → G in BAA06626 (PubMed:7842016).Curated | 1 |
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.1 Publication
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_030937 | 339 | M → I1 PublicationCorresponds to variant dbSNP:rs1058045Ensembl. | 1 | |
Natural variantiVAR_064038 | 484 – 488 | Missing 3 Publications | 5 | |
Natural variantiVAR_083058 | 1054 | H → N in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083059 | 1058 | H → Y in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083060 | 1059 – 1060 | SH → DL in CHEDDA; unknown pathological significance. 1 Publication | 2 | |
Natural variantiVAR_083061 | 1059 – 1060 | SH → NL in CHEDDA; unknown pathological significance. 1 Publication | 2 | |
Natural variantiVAR_083062 | 1060 | H → Y in CHEDDA; the mutation resulted in a perturbation of the structural and functional integrity of the HX repeat; altered zinc-binding properties of the HX repeat. 1 Publication | 1 | |
Natural variantiVAR_083063 | 1062 | H → D in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083064 | 1062 | H → R in CHEDDA. 1 Publication | 1 | |
Natural variantiVAR_083065 | 1063 | L → R in CHEDDA. 1 Publication | 1 |
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 |
CCDSi | CCDS31734.1 |
PIRi | G01763 S50832 |
RefSeqi | NP_001007027.1, NM_001007026.1 NP_001931.2, NM_001940.3 |
Genome annotation databases
Ensembli | ENST00000356654; ENSP00000349076; ENSG00000111676 ENST00000396684; ENSP00000379915; ENSG00000111676 |
GeneIDi | 1822 |
KEGGi | hsa:1822 |
UCSCi | uc001qrw.2, human |
Keywords - Coding sequence diversityi
Triplet repeat expansionSimilar proteinsi
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 |
CCDSi | CCDS31734.1 |
PIRi | G01763 S50832 |
RefSeqi | NP_001007027.1, NM_001007026.1 NP_001931.2, NM_001940.3 |
3D structure databases
SMRi | P54259 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 108156, 129 interactors |
DIPi | DIP-29423N |
IntActi | P54259, 93 interactors |
MINTi | P54259 |
STRINGi | 9606.ENSP00000349076 |
PTM databases
iPTMneti | P54259 |
PhosphoSitePlusi | P54259 |
Genetic variation databases
BioMutai | ATN1 |
DMDMi | 317373480 |
Proteomic databases
EPDi | P54259 |
jPOSTi | P54259 |
MassIVEi | P54259 |
MaxQBi | P54259 |
PaxDbi | P54259 |
PeptideAtlasi | P54259 |
PRIDEi | P54259 |
ProteomicsDBi | 56663 |
Protocols and materials databases
Antibodypediai | 22787, 139 antibodies |
DNASUi | 1822 |
Genome annotation databases
Ensembli | ENST00000356654; ENSP00000349076; ENSG00000111676 ENST00000396684; ENSP00000379915; ENSG00000111676 |
GeneIDi | 1822 |
KEGGi | hsa:1822 |
UCSCi | uc001qrw.2, human |
Organism-specific databases
CTDi | 1822 |
DisGeNETi | 1822 |
GeneCardsi | ATN1 |
GeneReviewsi | ATN1 |
HGNCi | HGNC:3033, ATN1 |
HPAi | ENSG00000111676, Low tissue specificity |
MalaCardsi | ATN1 |
MIMi | 125370, phenotype 607462, gene 618494, phenotype |
neXtProti | NX_P54259 |
OpenTargetsi | ENSG00000111676 |
Orphaneti | 101, Dentatorubral pallidoluysian atrophy |
PharmGKBi | PA27487 |
VEuPathDBi | HostDB:ENSG00000111676.14 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2133, Eukaryota |
GeneTreei | ENSGT00940000153615 |
HOGENOMi | CLU_005292_0_0_1 |
InParanoidi | P54259 |
OMAi | HAYPGYA |
OrthoDBi | 215918at2759 |
PhylomeDBi | P54259 |
TreeFami | TF328554 |
Enzyme and pathway databases
PathwayCommonsi | P54259 |
Reactomei | R-HSA-8943724, Regulation of PTEN gene transcription |
SIGNORi | P54259 |
Miscellaneous databases
BioGRID-ORCSi | 1822, 8 hits in 877 CRISPR screens |
ChiTaRSi | ATN1, human |
GeneWikii | ATN1 |
GenomeRNAii | 1822 |
Pharosi | P54259, Tbio |
PROi | PR:P54259 |
RNActi | P54259, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000111676, Expressed in left lobe of thyroid gland and 190 other tissues |
Genevisiblei | P54259, HS |
Family and domain databases
InterProi | View protein in InterPro IPR017993, Atrophin-1 IPR002951, Atrophin-like |
Pfami | View protein in Pfam PF03154, Atrophin-1, 2 hits |
PRINTSi | PR01222, ATROPHIN |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ATN1_HUMAN | |
Accessioni | P54259Primary (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: | February 10, 2021 | |
This is version 189 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human entries with genetic variants
List of human entries with genetic variants