ATN1_MOUSE
ID ATN1_MOUSE Reviewed; 1175 AA.
AC O35126; P70200; Q80YQ0;
DT 16-DEC-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Atrophin-1;
DE AltName: Full=Dentatorubral-pallidoluysian atrophy protein homolog;
GN Name=Atn1; Synonyms=Drpla;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP POLYMORPHISM OF POLY-GLN REGION.
RX PubMed=9070948; DOI=10.1006/geno.1996.4522;
RA Oyake M., Onodera O., Shiroishi T., Takano H., Takahashi Y., Komonami R.,
RA Moriwaki K., Ikeuchi T., Igarashi S., Tanaka H., Tsuji S.;
RT "Molecular cloning of murine homologue dentatorubral-pallidoluysian atrophy
RT (DRPLA) cDNA: strong conservation of a polymorphic CAG repeat in the murine
RT gene.";
RL Genomics 40:205-207(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9445485;
RA Ansari-Lari M.A., Oeltjen J.C., Schwartz S., Zhang Z., Muzny D.M., Lu J.,
RA Gorrell J.H., Chinault A.C., Belmont J.W., Miller W., Gibbs R.A.;
RT "Comparative sequence analysis of a gene-rich cluster at human chromosome
RT 12p13 and its syntenic region in mouse chromosome 6.";
RL Genome Res. 8:29-40(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP INTERACTION WITH NR2E1, AND FUNCTION.
RX PubMed=16702404; DOI=10.1101/gad.1413606;
RA Zhang C.L., Zou Y., Yu R.T., Gage F.H., Evans R.M.;
RT "Nuclear receptor TLX prevents retinal dystrophy and recruits the
RT corepressor atrophin1.";
RL Genes Dev. 20:1308-1320(2006).
RN [6]
RP CHARACTERISTICS OF THE MOUSE MODEL OF DRPLA.
RX PubMed=19039037; DOI=10.1093/hmg/ddn403;
RA Sato T., Miura M., Yamada M., Yoshida T., Wood J.D., Yazawa I., Masuda M.,
RA Suzuki T., Shin R.M., Yau H.J., Liu F.C., Shimohata T., Onodera O.,
RA Ross C.A., Katsuki M., Takahashi H., Kano M., Aosaki T., Tsuji S.;
RT "Severe neurological phenotypes of Q129 DRPLA transgenic mice
RT serendipitously created by en masse expansion of CAG repeats in Q76 DRPLA
RT mice.";
RL Hum. Mol. Genet. 18:723-736(2009).
RN [7]
RP INTERACTION WITH FAT1, INDUCTION, AND FUNCTION.
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 [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-77; SER-79; SER-101 AND
RP SER-107, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-1100, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryo;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
CC -!- FUNCTION: Transcriptional corepressor. Corepressor of MTG8
CC transcriptional repression. Has some intrinsic repression activity
CC which is independent of the number of the poly-Q repeats (By
CC similarity). Recruits NR2E1 to repress transcription. Promotes vascular
CC smooth cell (VSMC) migration and orientation.
CC {ECO:0000250|UniProtKB:P54259, ECO:0000269|PubMed:16702404,
CC ECO:0000269|PubMed:19131340}.
CC -!- SUBUNIT: Interacts with BAIAP2, WWP1, WWP2, WWP3 and RERE. Interacts
CC (via its N-terminus) with MTG8; the interaction enhances
CC transcriptional repression of MTG8. Interacts with PQBP1 (By
CC similarity). Interacts with NR2E1; the interaction represses the
CC transcriptional activity of NR2E1. Interacts with FAT1 (via a C-
CC terminal domain). {ECO:0000250|UniProtKB:P54259,
CC ECO:0000269|PubMed:16702404, ECO:0000269|PubMed:19131340}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000250|UniProtKB:P54258}. Cell junction
CC {ECO:0000250|UniProtKB:P54258}. Nucleus {ECO:0000250|UniProtKB:P54258}.
CC Note=Shuttles between nucleus and cytoplasm. Colocalizes with FAT1 in
CC the perinuclear area, at cell-cell junctions and leading edges of
CC cells. Colocalizes with MTG8 in discrete nuclear dots (By similarity).
CC {ECO:0000250|UniProtKB:P54258}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Most abundant in the brain.
CC {ECO:0000269|PubMed:9070948}.
CC -!- DEVELOPMENTAL STAGE: Expressed as early as 5 days and thereafter shows
CC little variation throughout 17 days. {ECO:0000269|PubMed:9070948}.
CC -!- INDUCTION: In vascular smooth muscle, induced by angiotensin II, FGF;
CC PGF and IL1B. {ECO:0000269|PubMed:19131340}.
CC -!- PTM: Phosphorylated in vitro by MAPK8/JNK1 on Ser-724. {ECO:0000250}.
CC -!- POLYMORPHISM: The poly-Gln region of Atn1 is polymorphic (3 to 8
CC repeats).
CC -!- MISCELLANEOUS: The mouse model of DRPLA with 129 CAG repeats (Q129)
CC exhibited severe neurological defects similar to those of juvenile-
CC onset DRPLA patients including age-dependent and region-specific
CC presynaptic dysfunction in the globus pallidus and cerebellum.
CC Progressive shrinkage of distal dendrites of Purkinje cells and
CC decreased currents through alpha-amino-3-hydroxy-5-methyl-4-
CC isoxazolepropionic acid and gamma-aminobutyrate type A receptors in CA1
CC neurons was observed. There is progressive brain atrophy.
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DR EMBL; D87744; BAA13450.1; -; mRNA.
DR EMBL; AC002397; AAC36003.1; -; Genomic_DNA.
DR EMBL; CH466523; EDK99754.1; -; Genomic_DNA.
DR EMBL; CH466523; EDK99755.1; -; Genomic_DNA.
DR EMBL; BC050920; AAH50920.2; -; mRNA.
DR EMBL; BC053051; AAH53051.1; -; mRNA.
DR CCDS; CCDS20526.1; -.
DR RefSeq; NP_031907.2; NM_007881.4.
DR AlphaFoldDB; O35126; -.
DR SMR; O35126; -.
DR BioGRID; 199314; 4.
DR STRING; 10090.ENSMUSP00000085695; -.
DR iPTMnet; O35126; -.
DR PhosphoSitePlus; O35126; -.
DR EPD; O35126; -.
DR jPOST; O35126; -.
DR MaxQB; O35126; -.
DR PaxDb; O35126; -.
DR PeptideAtlas; O35126; -.
DR PRIDE; O35126; -.
DR ProteomicsDB; 277192; -.
DR DNASU; 13498; -.
DR Ensembl; ENSMUST00000088357; ENSMUSP00000085695; ENSMUSG00000004263.
DR Ensembl; ENSMUST00000129411; ENSMUSP00000115407; ENSMUSG00000107478.
DR GeneID; 13498; -.
DR KEGG; mmu:13498; -.
DR UCSC; uc009drq.1; mouse.
DR CTD; 1822; -.
DR MGI; MGI:104725; Atn1.
DR VEuPathDB; HostDB:ENSMUSG00000004263; -.
DR VEuPathDB; HostDB:ENSMUSG00000107478; -.
DR eggNOG; KOG2133; Eukaryota.
DR GeneTree; ENSGT00940000153615; -.
DR HOGENOM; CLU_005292_0_0_1; -.
DR InParanoid; O35126; -.
DR OMA; SNRAKEN; -.
DR OrthoDB; 215918at2759; -.
DR PhylomeDB; O35126; -.
DR TreeFam; TF328554; -.
DR BioGRID-ORCS; 13498; 3 hits in 74 CRISPR screens.
DR ChiTaRS; Atn1; mouse.
DR PRO; PR:O35126; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; O35126; protein.
DR Bgee; ENSMUSG00000004263; Expressed in embryonic brain and 187 other tissues.
DR ExpressionAtlas; O35126; baseline and differential.
DR Genevisible; O35126; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0031252; C:cell leading edge; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0016363; C:nuclear matrix; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0008432; F:JUN kinase binding; ISO:MGI.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0090729; F:toxin activity; IDA:MGI.
DR GO; GO:0003713; F:transcription coactivator activity; IDA:MGI.
DR GO; GO:0003714; F:transcription corepressor activity; IGI:MGI.
DR GO; GO:0016477; P:cell migration; IDA:UniProtKB.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:MGI.
DR GO; GO:0030011; P:maintenance of cell polarity; IDA:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; ISO:MGI.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:0045664; P:regulation of neuron differentiation; ISO:MGI.
DR GO; GO:0032094; P:response to food; IMP:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR GO; GO:0009404; P:toxin metabolic process; IDA:MGI.
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; Isopeptide bond; Methylation;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Triplet repeat expansion; Ubl conjugation.
FT CHAIN 1..1175
FT /note="Atrophin-1"
FT /id="PRO_0000356253"
FT REGION 1..595
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 503..553
FT /note="Involved in binding BAIAP2"
FT /evidence="ECO:0000250"
FT REGION 608..752
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 770..847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 864..879
FT /note="Required for interaction with FAT1"
FT /evidence="ECO:0000250"
FT REGION 913..932
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 16..32
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250"
FT MOTIF 1018..1026
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250"
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..218
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 274..313
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 349..370
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 372..404
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..435
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 457..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..582
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 668..703
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 720..739
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 776..828
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 109..110
FT /note="Cleavage"
FT /evidence="ECO:0000255"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 101
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 107
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 617
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 626
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 638
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 646
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 654
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 724
FT /note="Phosphoserine; by MAPK8"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 731
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 733
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 881
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT MOD_RES 1100
FT /note="Asymmetric dimethylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT CROSSLNK 1168
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P54259"
FT CONFLICT 452
FT /note="A -> G (in Ref. 1; BAA13450)"
FT /evidence="ECO:0000305"
FT CONFLICT 495
FT /note="P -> A (in Ref. 1; BAA13450)"
FT /evidence="ECO:0000305"
FT CONFLICT 532
FT /note="P -> A (in Ref. 1; BAA13450)"
FT /evidence="ECO:0000305"
FT CONFLICT 691
FT /note="S -> L (in Ref. 1; BAA13450)"
FT /evidence="ECO:0000305"
FT CONFLICT 734
FT /note="P -> A (in Ref. 1; BAA13450)"
FT /evidence="ECO:0000305"
FT CONFLICT 766
FT /note="D -> T (in Ref. 1; BAA13450)"
FT /evidence="ECO:0000305"
FT CONFLICT 926
FT /note="D -> N (in Ref. 1; BAA13450)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1175 AA; 123724 MW; 8BEFFAB75DDC0F36 CRC64;
MKTRQNKDSM SMRSGRKKEA PGPREELRSR GRASPGGVST SSSDGKAEKS RQTAKKARIE
EPSAPKASKQ GRSEEISESE SEETSAPKKT KTEQELPRPQ SPSDLDSLDG RSINDDGSSD
PRDIDQDNRS TSPSIYSPGS VENDSDSSSG LSQGPARPYH PPPLFPPSPP PPDSTPRQPE
SGFEPHPSVP PTGYHAPMEP PTSRLFQGPP PGAPPTHPQL YPGNASGGVL SGPPMGPKGG
AAASSVGAPS GGKQHPPPTT PIPISSSGAS GAPPAKPPSA PVGGGSLPSA PPPASFPHVT
PNLPPPPALR PLNNASASPP GMGAQPIPGH LPSPHAMGQG MSGLPPGPEK GPTLAPSPHP
LPPASSSAPG PPMRYPYSSS SSSAAASSSS SSSSASQYPA SQALPSYPHS FPPPTSMSVS
NQPPKYTQPS LPSQAVWSQG PPPPPPYGRL LANNNTHPGP FPPTGGQSTA HPAAPTHHHH
QQQPQQQHHH GNSGPPPPGA YPHPLESSNS HHAHPYNMSP SLGSLRPYPP GPAHLPPPHG
QVSYNQAGPN GPPVSSSNSS GSSSQASYSC SHPSSSQGPQ GASYPFPPVP PVTTSSATLS
TVIATVASSP AGYKTASPPG PPQYSKRAPS PGSYKTATPP GYKPGSPPSF RTGTPPGYRG
TSPPAGPGTF KPGSPTVGPG PLPPAGPSSL SSLPPPPAAP TTGPPLTATQ IKQEPAEEYE
PPESPVPPAR SPSPPPKVVD VPSHASQSAR FNKHLDRGFN SCARSDLYFV PLEGSKLAKK
RADLVEKVRR EAEQRAREEK EREREREREK EREREKEREL ERSVKLAQEG RAPVECPSLG
PVPHRPPFEP GSAVATVPPY LGPDTPALRT LSEYARPHVM SPGNRNHPFY VPLGAVDPGL
LGYNVPALYS SDPAARERER EARERDLRDR LKPGFEVKPS ELEPLHGVPG PGLDPFPRHG
GLALQPGPPG LHPFPFHPSL GPLERERLAL AAGPALRPDM SYAERLAAER QHAERVAALG
NDPLARLQML NVTPHHHQHS HIHSHLHLHQ QDAIHAASAS VHPLIDPLAS GSHLTRIPYP
AGTLPNPLLP HPLHENEVLR HQLFAAPYRD LPASLSAPMS AAHQLQAMHA QSAELQRLAL
EQQQWLHAHH PLHSVPLPAQ EDYYSHLKKE SDKPL
