ATN1_HUMAN
ID ATN1_HUMAN Reviewed; 1190 AA.
AC P54259; Q99495; Q99621; Q9UEK7;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Atrophin-1;
DE AltName: Full=Dentatorubral-pallidoluysian atrophy protein;
GN Name=ATN1; Synonyms=D12S755E, DRPLA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT 484-GLN--GLN-488
RP DEL, AND INVOLVEMENT IN DRPLA.
RC TISSUE=Brain;
RX PubMed=7842016; DOI=10.1038/ng1094-177;
RA Nagafuchi S., Yanagisawa H., Ohsaki E., Shirayama T., Tadokoro K.,
RA Inoue T., Yamada M.;
RT "Structure and expression of the gene responsible for the triplet repeat
RT disorder, dentatorubral and pallidoluysian atrophy (DRPLA).";
RL Nat. Genet. 8:177-182(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANT
RP 484-GLN--GLN-488 DEL.
RC TISSUE=Brain;
RX PubMed=7485154;
RA Onodera O., Oyake M., Takano H., Ikeuchi T., Igarashi S., Tsuji S.;
RT "Molecular cloning of a full-length cDNA for dentatorubral-pallidoluysian
RT atrophy and regional expressions of the expanded alleles in the CNS.";
RL Am. J. Hum. Genet. 57:1050-1060(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND VARIANTS ILE-339 AND
RP 484-GLN--GLN-488 DEL.
RX PubMed=8965642; DOI=10.1016/0169-328x(95)00241-j;
RA Margolis R.L., Li S.-H., Young W.S., Wagster M.V., Stine O.C., Kidwai A.S.,
RA Ashworth R.G., Ross C.A.;
RT "DRPLA gene (atrophin-1) sequence and mRNA expression in human brain.";
RL Brain Res. Mol. Brain Res. 36:219-226(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND POLYMORPHISM OF POLY-GLN REGION.
RC TISSUE=Brain;
RX PubMed=9074930; DOI=10.1101/gr.7.3.268;
RA Ansari-Lari M.A., Shen Y., Muzny D.M., Lee W., Gibbs R.A.;
RT "Large-scale sequencing in human chromosome 12p13: experimental and
RT computational gene structure determination.";
RL Genome Res. 7:268-280(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-76.
RX PubMed=8852663; DOI=10.1093/hmg/5.3.373;
RA Yanagisawa H., Fujii K., Nagafuchi S., Nakahori Y., Nakagome Y., Akane A.,
RA Nakamura M., Sano A., Komure O., Kondo I., Jin D.K., Soerensen S.A.,
RA Potter N.T., Young S.R., Nakamura K., Nukina N., Nagao Y., Tadokoro K.,
RA Okuyama T., Miyashita T., Inoue T., Kanazawa I., Yamada M.;
RT "A unique origin and multistep process for the generation of expanded DRPLA
RT triplet repeats.";
RL Hum. Mol. Genet. 5:373-379(1996).
RN [6]
RP INVOLVEMENT IN DRPLA.
RX PubMed=8136840; DOI=10.1038/ng0194-9;
RA Koide R., Ikeuchi T., Onodera O., Tanaka H., Igarashi S., Endo K.,
RA Takahashi H., Kondo R., Ishikawa A., Hayashi T.;
RT "Unstable expansion of CAG repeat in hereditary dentatorubral-
RT pallidoluysian atrophy (DRPLA).";
RL Nat. Genet. 6:9-13(1994).
RN [7]
RP INVOLVEMENT IN HRS.
RX PubMed=7951323; DOI=10.1038/ng0894-521;
RA Burke J.R., Wingfield M.S., Lewis K.E., Roses A.D., Lee J.E., Hulette C.,
RA Pericak-Vance M.A., Vance J.M.;
RT "The Haw River syndrome: dentatorubropallidoluysian atrophy (DRPLA) in an
RT African-American family.";
RL Nat. Genet. 7:521-524(1994).
RN [8]
RP PROTEOLYTIC CLEAVAGE BY CASP-3 AT ASP-109.
RX PubMed=9361003; DOI=10.1074/jbc.272.46.29238;
RA Miyashita T., Okamura-Oho Y., Mito Y., Nagafuchi S., Yamada M.;
RT "Dentatorubral pallidoluysian atrophy (DRPLA) protein is cleaved by
RT caspase-3 during apoptosis.";
RL J. Biol. Chem. 272:29238-29242(1997).
RN [9]
RP INTERACTION WITH WWP1; WWP2 AND WWP3.
RX PubMed=9647693; DOI=10.1006/mcne.1998.0677;
RA Wood J.D., Yuan J., Margolis R.L., Colomer V., Duan K., Kushi J.,
RA Kaminsky Z., Kleiderlein J.J. Jr., Sharp A.H., Ross C.A.;
RT "Atrophin-1, the DRPLA gene product, interacts with two families of WW
RT domain-containing proteins.";
RL Mol. Cell. Neurosci. 11:149-160(1998).
RN [10]
RP INTERACTION WITH BAIAP2, AND SUBCELLULAR LOCATION.
RX PubMed=10332026; DOI=10.1093/hmg/8.6.947;
RA Okamura-Oho Y., Miyashita T., Ohmi K., Yamada M.;
RT "Dentatorubral-pallidoluysian atrophy protein interacts through a proline-
RT rich region near polyglutamine with the SH3 domain of an insulin receptor
RT tyrosine kinase substrate.";
RL Hum. Mol. Genet. 8:947-957(1999).
RN [11]
RP PROTEOLYTIC CLEAVAGE AT ASP-109, FUNCTION, SUBCELLULAR LOCATION, AND
RP MUTAGENESIS OF ASP-109.
RX PubMed=10085113; DOI=10.1074/jbc.274.13.8730;
RA Ellerby L.M., Andrusiak R.L., Wellington C.L., Hackam A.S., Propp S.S.,
RA Wood J.D., Sharp A.H., Margolis R.L., Ross C.A., Salvesen G.S.,
RA Hayden M.R., Bredesen D.E.;
RT "Cleavage of atrophin-1 at caspase site aspartic acid 109 modulates
RT cytotoxicity.";
RL J. Biol. Chem. 274:8730-8736(1999).
RN [12]
RP INTERACTION WITH RERE.
RX PubMed=10814707; DOI=10.1093/hmg/9.9.1433;
RA Yanagisawa H., Bundo M., Miyashita T., Okamura-Oho Y., Tadokoro K.,
RA Tokunaga K., Yamada M.;
RT "Protein binding of a DRPLA family through arginine-glutamic acid dipeptide
RT repeats is enhanced by extended polyglutamine.";
RL Hum. Mol. Genet. 9:1433-1442(2000).
RN [13]
RP INTERACTION WITH MTG8, SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=10973986; DOI=10.1083/jcb.150.5.939;
RA Wood J.D., Nucifora F.C. Jr., Duan K., Zhang C., Wang J., Kim Y.,
RA Schilling G., Sacchi N., Liu J.M., Ross C.A.;
RT "Atrophin-1, the dentato-rubral and pallido-luysian atrophy gene product,
RT interacts with ETO/MTG8 in the nuclear matrix and represses
RT transcription.";
RL J. Cell Biol. 150:939-948(2000).
RN [14]
RP PHOSPHORYLATION AT SER-739.
RX PubMed=12812981; DOI=10.1093/hmg/ddg168;
RA Okamura-Oho Y., Miyashita T., Nagao K., Shima S., Ogata Y., Katada T.,
RA Nishina H., Yamada M.;
RT "Dentatorubral-pallidoluysian atrophy protein is phosphorylated by c-Jun
RT NH2-terminal kinase.";
RL Hum. Mol. Genet. 12:1535-1542(2003).
RN [15]
RP PROTEOLYTIC PROCESSING, NUCLEAR LOCALIZATION SIGNAL, NUCLEAR EXPORT SIGNAL,
RP AND SUBCELLULAR LOCATION.
RX PubMed=12464607; DOI=10.1074/jbc.m211224200;
RA Nucifora F.C. Jr., Ellerby L.M., Wellington C.L., Wood J.D., Herring W.J.,
RA Sawa A., Hayden M.R., Dawson V.L., Dawson T.M., Ross C.A.;
RT "Nuclear localization of a non-caspase truncation product of atrophin-1,
RT with an expanded polyglutamine repeat, increases cellular toxicity.";
RL J. Biol. Chem. 278:13047-13055(2003).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-79; SER-101; SER-103;
RP SER-107; THR-653; SER-661; SER-746 AND SER-748, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP INTERACTION WITH FAT1.
RX PubMed=19131340; DOI=10.1074/jbc.m809333200;
RA Hou R., Sibinga N.E.;
RT "Atrophin proteins interact with the Fat1 cadherin and regulate migration
RT and orientation in vascular smooth muscle cells.";
RL J. Biol. Chem. 284:6955-6965(2009).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-641, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
RP PROTEOLYTIC PROCESSING, AND SUBCELLULAR LOCATION.
RX PubMed=20977674; DOI=10.1111/j.1742-4658.2010.07893.x;
RA Suzuki Y., Nakayama K., Hashimoto N., Yazawa I.;
RT "Proteolytic processing regulates pathological accumulation in
RT dentatorubral-pallidoluysian atrophy.";
RL FEBS J. 277:4873-4887(2010).
RN [21]
RP INTERACTION WITH PQBP1.
RX PubMed=20410308; DOI=10.1074/jbc.m109.084525;
RA Tapia V.E., Nicolaescu E., McDonald C.B., Musi V., Oka T., Inayoshi Y.,
RA Satteson A.C., Mazack V., Humbert J., Gaffney C.J., Beullens M.,
RA Schwartz C.E., Landgraf C., Volkmer R., Pastore A., Farooq A., Bollen M.,
RA Sudol M.;
RT "Y65C missense mutation in the WW domain of the Golabi-Ito-Hall syndrome
RT protein PQBP1 affects its binding activity and deregulates pre-mRNA
RT splicing.";
RL J. Biol. Chem. 285:19391-19401(2010).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-34, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-661, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-632; SER-661; THR-669
RP AND SER-896, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-101, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [26]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-1183, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [27]
RP INVOLVEMENT IN CHEDDA, VARIANTS CHEDDA ASN-1054; TYR-1058;
RP 1059-SER-HIS-1060 DELINS ASN-LEU; 1059-SER-HIS-1060 DELINS ASP-LEU;
RP TYR-1060; ARG-1062; ASP-1062 AND ARG-1063, CHARACTERIZATION OF VARIANT
RP CHEDDA TYR-1060, AND REGION.
RX PubMed=30827498; DOI=10.1016/j.ajhg.2019.01.013;
RA Palmer E.E., Hong S., Al Zahrani F., Hashem M.O., Aleisa F.A.,
RA Ahmed H.M.J., Kandula T., Macintosh R., Minoche A.E., Puttick C.,
RA Gayevskiy V., Drew A.P., Cowley M.J., Dinger M., Rosenfeld J.A., Xiao R.,
RA Cho M.T., Yakubu S.F., Henderson L.B., Guillen Sacoto M.J., Begtrup A.,
RA Hamad M., Shinawi M., Andrews M.V., Jones M.C., Lindstrom K., Bristol R.E.,
RA Kayani S., Snyder M., Villanueva M.M., Schteinschnaider A., Faivre L.,
RA Thauvin C., Vitobello A., Roscioli T., Kirk E.P., Bye A., Merzaban J.,
RA Jaremko L., Jaremko M., Sachdev R.K., Alkuraya F.S., Arold S.T.;
RT "De novo variants disrupting the HX repeat motif of ATN1 cause a
RT recognizable non-progressive neurocognitive syndrome.";
RL Am. J. Hum. Genet. 104:542-552(2019).
CC -!- FUNCTION: Transcriptional corepressor. Recruits NR2E1 to repress
CC transcription. Promotes vascular smooth cell (VSMC) migration and
CC orientation (By similarity). Corepressor of MTG8 transcriptional
CC repression. Has some intrinsic repression activity which is independent
CC of the number of poly-Gln (polyQ) repeats.
CC {ECO:0000250|UniProtKB:O35126, ECO:0000269|PubMed:10085113,
CC ECO:0000269|PubMed:10973986}.
CC -!- SUBUNIT: Interacts with NR2E1; the interaction represses the
CC transcriptional activity of NR2E1. Interacts (via its N-terminus) with
CC FAT1 (via a C-terminal domain) (By similarity). Interacts with BAIAP2,
CC WWP1, WWP2, WWP3 and RERE. Interacts (via its N-terminus) with MTG8;
CC the interaction enhances transcriptional repression of MTG8. Interacts
CC with PQBP1. {ECO:0000250|UniProtKB:O35126, ECO:0000269|PubMed:10332026,
CC ECO:0000269|PubMed:10814707, ECO:0000269|PubMed:10973986,
CC ECO:0000269|PubMed:19131340, ECO:0000269|PubMed:20410308,
CC ECO:0000269|PubMed:9647693}.
CC -!- INTERACTION:
CC P54259; Q12805: EFEMP1; NbExp=3; IntAct=EBI-945980, EBI-536772;
CC P54259; O95967: EFEMP2; NbExp=3; IntAct=EBI-945980, EBI-743414;
CC P54259; P46934: NEDD4; NbExp=2; IntAct=EBI-945980, EBI-726944;
CC P54259; Q9HAU0: PLEKHA5; NbExp=2; IntAct=EBI-945980, EBI-945934;
CC P54259; P61289: PSME3; NbExp=3; IntAct=EBI-945980, EBI-355546;
CC P54259; Q9NWB1: RBFOX1; NbExp=2; IntAct=EBI-945980, EBI-945906;
CC P54259; Q9P2R6: RERE; NbExp=3; IntAct=EBI-945980, EBI-948076;
CC P54259; Q15654: TRIP6; NbExp=2; IntAct=EBI-945980, EBI-742327;
CC P54259; P61964: WDR5; NbExp=4; IntAct=EBI-945980, EBI-540834;
CC P54259; P46937: YAP1; NbExp=2; IntAct=EBI-945980, EBI-1044059;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, perinuclear region. Cell
CC junction {ECO:0000250|UniProtKB:P54258}. Note=Shuttles between nucleus
CC and cytoplasm. Colocalizes with FAT1 in the perinuclear area, at cell-
CC cell junctions and leading edges of cells (By similarity). Colocalizes
CC with MTG8 in discrete nuclear dots. Proteolytic fragment F1 appears to
CC remain in nucleus. Fragment F2 is exported into the cytoplasm. Fragment
CC F2 from mutant sequences with longer poly-Gln (polyQ) tracts are
CC additionally located to the cytoplasmic membrane and to certain
CC organelles. {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Widely expressed in various tissues including
CC heart, lung, kidney, ovary, testis, prostate, placenta, skeletal Low
CC levels in the liver, thymus and leukocytes. In the adult brain, broadly
CC expressed in amygdala, caudate nucleus, corpus callosum, hippocampus,
CC hypothalamus, substantia nigra, subthalamic nucleus, and thalamus. High
CC levels in fetal tissues, especially brain. {ECO:0000269|PubMed:7485154,
CC ECO:0000269|PubMed:7842016, ECO:0000269|PubMed:8965642}.
CC -!- DOMAIN: The HX repeat motif is a specific pH-dependent interaction
CC motif for ions and/or proteins or other biomolecules. This motif could
CC be involved in the control of embryonic development.
CC {ECO:0000269|PubMed:30827498}.
CC -!- PTM: Phosphorylated in vitro by MAPK8/JNK1 on Ser-739. Mutant ATN1
CC sequences with expanded poly-Gln (polyQ) traits are more slowly
CC phosphorylated. {ECO:0000269|PubMed:12812981}.
CC -!- PTM: Proteolytically cleaved, probably in the nucleus, to produce two
CC C-terminal fragments of 140 kDa (F1) and 125 kDa (F2) each containing
CC poly-Gln (polyQ) tracts. F2 is produced by cleavage by caspases and is
CC exported into the cytoplasm. In vitro, cleavage increases with an
CC increase in the number of polyQ tracts. C-terminal proteolytic products
CC appear to be the cause of cell toxicity. In vitro cleavage at Asp-109.
CC {ECO:0000269|PubMed:10085113, ECO:0000269|PubMed:12464607,
CC ECO:0000269|PubMed:20977674, ECO:0000269|PubMed:9361003}.
CC -!- POLYMORPHISM: The poly-Gln region of ATN1 is highly polymorphic (7 to
CC 23 repeats) in the normal population and is expanded to about 49-75
CC repeats in DRPLA and HRS patients. Longer expansions result in earlier
CC onset and more severe clinical manifestations of the disease.
CC {ECO:0000269|PubMed:7951323}.
CC -!- DISEASE: Dentatorubral-pallidoluysian atrophy (DRPLA) [MIM:125370]:
CC Autosomal dominant neurodegenerative disorder characterized by a loss
CC of neurons in the dentate nucleus, rubrum, glogus pallidus and
CC Luys'body. Clinical features are myoclonus epilepsy, dementia, and
CC cerebellar ataxia. Onset of the disease occurs usually in the second
CC decade of life and death in the fourth. {ECO:0000269|PubMed:7842016,
CC ECO:0000269|PubMed:8136840}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Congenital hypotonia, epilepsy, developmental delay, and
CC digital anomalies (CHEDDA) [MIM:618494]: An autosomal dominant
CC neurodevelopmental syndrome characterized by severe global
CC developmental delay, impaired intellectual development, poor or absent
CC language, significant motor disability with inability to walk,
CC dysmorphic facial features, skeletal anomalies, and variable congenital
CC malformations. Most patients also have seizures and structural brain
CC abnormalities. {ECO:0000269|PubMed:30827498}. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA07534.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; D31840; BAA06626.1; -; mRNA.
DR EMBL; D38529; BAA07534.1; ALT_FRAME; mRNA.
DR EMBL; U23851; AAB50276.1; -; mRNA.
DR EMBL; U47924; AAB51321.1; -; Genomic_DNA.
DR EMBL; D63808; BAA23631.1; -; Genomic_DNA.
DR CCDS; CCDS31734.1; -.
DR PIR; G01763; G01763.
DR PIR; S50832; S50832.
DR RefSeq; NP_001007027.1; NM_001007026.1.
DR RefSeq; NP_001931.2; NM_001940.3.
DR AlphaFoldDB; P54259; -.
DR SMR; P54259; -.
DR BioGRID; 108156; 169.
DR DIP; DIP-29423N; -.
DR IntAct; P54259; 105.
DR MINT; P54259; -.
DR STRING; 9606.ENSP00000349076; -.
DR GlyGen; P54259; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P54259; -.
DR PhosphoSitePlus; P54259; -.
DR BioMuta; ATN1; -.
DR DMDM; 317373480; -.
DR EPD; P54259; -.
DR jPOST; P54259; -.
DR MassIVE; P54259; -.
DR MaxQB; P54259; -.
DR PaxDb; P54259; -.
DR PeptideAtlas; P54259; -.
DR PRIDE; P54259; -.
DR ProteomicsDB; 56663; -.
DR Antibodypedia; 22787; 151 antibodies from 28 providers.
DR DNASU; 1822; -.
DR Ensembl; ENST00000356654.8; ENSP00000349076.3; ENSG00000111676.15.
DR Ensembl; ENST00000396684.3; ENSP00000379915.2; ENSG00000111676.15.
DR GeneID; 1822; -.
DR KEGG; hsa:1822; -.
DR MANE-Select; ENST00000396684.3; ENSP00000379915.2; NM_001940.4; NP_001931.2.
DR UCSC; uc001qrw.2; human.
DR CTD; 1822; -.
DR DisGeNET; 1822; -.
DR GeneCards; ATN1; -.
DR GeneReviews; ATN1; -.
DR HGNC; HGNC:3033; ATN1.
DR HPA; ENSG00000111676; Low tissue specificity.
DR MalaCards; ATN1; -.
DR MIM; 125370; phenotype.
DR MIM; 607462; gene.
DR MIM; 618494; phenotype.
DR neXtProt; NX_P54259; -.
DR OpenTargets; ENSG00000111676; -.
DR Orphanet; 101; Dentatorubral pallidoluysian atrophy.
DR PharmGKB; PA27487; -.
DR VEuPathDB; HostDB:ENSG00000111676; -.
DR eggNOG; KOG2133; Eukaryota.
DR GeneTree; ENSGT00940000153615; -.
DR HOGENOM; CLU_005292_0_0_1; -.
DR InParanoid; P54259; -.
DR OMA; SNRAKEN; -.
DR OrthoDB; 215918at2759; -.
DR PhylomeDB; P54259; -.
DR TreeFam; TF328554; -.
DR PathwayCommons; P54259; -.
DR Reactome; R-HSA-8943724; Regulation of PTEN gene transcription.
DR SignaLink; P54259; -.
DR SIGNOR; P54259; -.
DR BioGRID-ORCS; 1822; 18 hits in 1078 CRISPR screens.
DR ChiTaRS; ATN1; human.
DR GeneWiki; ATN1; -.
DR GenomeRNAi; 1822; -.
DR Pharos; P54259; Tbio.
DR PRO; PR:P54259; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P54259; protein.
DR Bgee; ENSG00000111676; Expressed in right hemisphere of cerebellum and 148 other tissues.
DR Genevisible; P54259; HS.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; TAS:ProtInc.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0019904; F:protein domain specific binding; IPI:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IEA:Ensembl.
DR GO; GO:0003713; F:transcription coactivator activity; IEA:Ensembl.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0016477; P:cell migration; IEA:Ensembl.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0008340; P:determination of adult lifespan; IEA:Ensembl.
DR GO; GO:0030011; P:maintenance of cell polarity; IEA:Ensembl.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IDA:UniProtKB.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:0032094; P:response to food; IEA:Ensembl.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR GO; GO:0009404; P:toxin metabolic process; IEA:Ensembl.
DR InterPro; IPR017993; Atrophin-1.
DR InterPro; IPR002951; Atrophin-like.
DR Pfam; PF03154; Atrophin-1; 2.
DR PRINTS; PR01222; ATROPHIN.
PE 1: Evidence at protein level;
KW Acetylation; Cell junction; Cytoplasm; Disease variant; Epilepsy;
KW Intellectual disability; Isopeptide bond; Methylation; Neurodegeneration;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Triplet repeat expansion; Ubl conjugation.
FT CHAIN 1..1190
FT /note="Atrophin-1"
FT /id="PRO_0000064730"
FT REGION 1..608
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 517..567
FT /note="Involved in binding BAIAP2"
FT REGION 622..767
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 785..862
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 879..894
FT /note="Required for interaction with FAT1"
FT /evidence="ECO:0000269|PubMed:19131340"
FT REGION 1049..1065
FT /note="HX repeat"
FT /evidence="ECO:0000269|PubMed:30827498"
FT MOTIF 16..32
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:12464607"
FT MOTIF 1033..1041
FT /note="Nuclear export signal"
FT COMPBIAS 1..31
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 48..95
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 109..127
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..178
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 203..220
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 255..271
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 272..311
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..368
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 370..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 414..436
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 459..507
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 553..590
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 591..605
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 683..718
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 736..754
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 791..843
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 109..110
FT /note="Cleavage; by CASP-3"
FT /evidence="ECO:0000269|PubMed:10085113,
FT ECO:0000269|PubMed:9361003"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 632
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 641
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 653
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 661
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 669
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 739
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000269|PubMed:12812981"
FT MOD_RES 746
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 748
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 896
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 1115
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0000250|UniProtKB:O35126"
FT CROSSLNK 1183
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 339
FT /note="M -> I (in dbSNP:rs1058045)"
FT /evidence="ECO:0000269|PubMed:8965642"
FT /id="VAR_030937"
FT VARIANT 484..488
FT /note="Missing"
FT /evidence="ECO:0000269|PubMed:7485154,
FT ECO:0000269|PubMed:7842016, ECO:0000269|PubMed:8965642"
FT /id="VAR_064038"
FT VARIANT 1054
FT /note="H -> N (in CHEDDA)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083058"
FT VARIANT 1058
FT /note="H -> Y (in CHEDDA)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083059"
FT VARIANT 1059..1060
FT /note="SH -> DL (in CHEDDA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083060"
FT VARIANT 1059..1060
FT /note="SH -> NL (in CHEDDA; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083061"
FT VARIANT 1060
FT /note="H -> Y (in CHEDDA; the mutation resulted in a
FT perturbation of the structural and functional integrity of
FT the HX repeat; altered zinc-binding properties of the HX
FT repeat)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083062"
FT VARIANT 1062
FT /note="H -> D (in CHEDDA)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083063"
FT VARIANT 1062
FT /note="H -> R (in CHEDDA)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083064"
FT VARIANT 1063
FT /note="L -> R (in CHEDDA)"
FT /evidence="ECO:0000269|PubMed:30827498"
FT /id="VAR_083065"
FT MUTAGEN 109
FT /note="D->N: Prevents cleavage and suppresses apoptosis."
FT /evidence="ECO:0000269|PubMed:10085113"
FT MUTAGEN 739
FT /note="S->A: Abolishes phosphorylation."
FT CONFLICT 94
FT /note="Missing (in Ref. 3; AAB50276)"
FT /evidence="ECO:0000305"
FT CONFLICT 333
FT /note="H -> Y (in Ref. 1; BAA06626)"
FT /evidence="ECO:0000305"
FT CONFLICT 1033
FT /note="A -> G (in Ref. 1; BAA06626)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1190 AA; 125414 MW; B47603486C672637 CRC64;
MKTRQNKDSM SMRSGRKKEA PGPREELRSR GRASPGGVST SSSDGKAEKS RQTAKKARVE
EASTPKVNKQ GRSEEISESE SEETNAPKKT KTEQELPRPQ SPSDLDSLDG RSLNDDGSSD
PRDIDQDNRS TSPSIYSPGS VENDSDSSSG LSQGPARPYH PPPLFPPSPQ PPDSTPRQPE
ASFEPHPSVT PTGYHAPMEP PTSRMFQAPP GAPPPHPQLY PGGTGGVLSG PPMGPKGGGA
ASSVGGPNGG KQHPPPTTPI SVSSSGASGA PPTKPPTTPV GGGNLPSAPP PANFPHVTPN
LPPPPALRPL NNASASPPGL GAQPLPGHLP SPHAMGQGMG GLPPGPEKGP TLAPSPHSLP
PASSSAPAPP MRFPYSSSSS SSAAASSSSS SSSSSASPFP ASQALPSYPH SFPPPTSLSV
SNQPPKYTQP SLPSQAVWSQ GPPPPPPYGR LLANSNAHPG PFPPSTGAQS TAHPPVSTHH
HHHQQQQQQQ QQQQQQQQQQ QQHHGNSGPP PPGAFPHPLE GGSSHHAHPY AMSPSLGSLR
PYPPGPAHLP PPHSQVSYSQ AGPNGPPVSS SSNSSSSTSQ GSYPCSHPSP SQGPQGAPYP
FPPVPTVTTS SATLSTVIAT VASSPAGYKT ASPPGPPPYG KRAPSPGAYK TATPPGYKPG
SPPSFRTGTP PGYRGTSPPA GPGTFKPGSP TVGPGPLPPA GPSGLPSLPP PPAAPASGPP
LSATQIKQEP AEEYETPESP VPPARSPSPP PKVVDVPSHA SQSARFNKHL DRGFNSCARS
DLYFVPLEGS KLAKKRADLV EKVRREAEQR AREEKERERE REREKERERE KERELERSVK
LAQEGRAPVE CPSLGPVPHR PPFEPGSAVA TVPPYLGPDT PALRTLSEYA RPHVMSPGNR
NHPFYVPLGA VDPGLLGYNV PALYSSDPAA REREREARER DLRDRLKPGF EVKPSELEPL
HGVPGPGLDP FPRHGGLALQ PGPPGLHPFP FHPSLGPLER ERLALAAGPA LRPDMSYAER
LAAERQHAER VAALGNDPLA RLQMLNVTPH HHQHSHIHSH LHLHQQDAIH AASASVHPLI
DPLASGSHLT RIPYPAGTLP NPLLPHPLHE NEVLRHQLFA APYRDLPASL SAPMSAAHQL
QAMHAQSAEL QRLALEQQQW LHAHHPLHSV PLPAQEDYYS HLKKESDKPL
