P54259

FUNCTION: 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. SUBUNIT: Interacts with NR2E1; the interaction represses the transcriptional activity of NR2E1. Interacts (via its N-terminus) with FAT1 (via a C-terminus 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. SUBCELLULAR LOCATION: Nucleus. Cytoplasm, perinuclear region. Cell junction (By similarity). Nucleus. 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. TISSUE SPECIFICITY: 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. PTM: Phosphorylated in vitro by MAPK8/JNK1 on Ser-739. Mutant ATN1 sequences with expanded poly-Asn (polyQ) traits are more slowly phosphorylated. PTM: 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. POLYMORPHISM: 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. DISEASE: Defects in ATN1 are the cause of dentatorubral- pallidoluysian atrophy (DRPLA) [MIM:125370]. DRPLA is an autosomal 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. SEQUENCE CAUTION: Sequence=BAA07534.1; Type=Frameshift; Positions=961, 970, 977, 980, 983, 1005; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ATN1"; GENE SYNONYMS:ATN1 D12S755E DRPLA. COPYRIGHT: Protein annotation is derived from the UniProt Consortium (http://www.uniprot.org/). Distributed under the Creative Commons Attribution-NoDerivs License., SEQUENCE 1190 AA; 125414 MW; B47603486C672637 CRC64;

ATN1_HUMAN

urn:biopax:ModificationFeature:ATN1_HUMAN_1, urn:biopax:ModificationFeature:ATN1_HUMAN_10, urn:biopax:ModificationFeature:ATN1_HUMAN_11, urn:biopax:ModificationFeature:ATN1_HUMAN_12, urn:biopax:ModificationFeature:ATN1_HUMAN_13, urn:biopax:ModificationFeature:ATN1_HUMAN_14, urn:biopax:ModificationFeature:ATN1_HUMAN_15, urn:biopax:ModificationFeature:ATN1_HUMAN_16, urn:biopax:ModificationFeature:ATN1_HUMAN_17, urn:biopax:ModificationFeature:ATN1_HUMAN_18, urn:biopax:ModificationFeature:ATN1_HUMAN_19, urn:biopax:ModificationFeature:ATN1_HUMAN_2, urn:biopax:ModificationFeature:ATN1_HUMAN_3, urn:biopax:ModificationFeature:ATN1_HUMAN_4, urn:biopax:ModificationFeature:ATN1_HUMAN_5, urn:biopax:ModificationFeature:ATN1_HUMAN_6, urn:biopax:ModificationFeature:ATN1_HUMAN_7, urn:biopax:ModificationFeature:ATN1_HUMAN_8, urn:biopax:ModificationFeature:ATN1_HUMAN_9

MKTRQNKDSMSMRSGRKKEAPGPREELRSRGRASPGGVSTSSSDGKAEKSRQTAKKARVEEASTPKVNKQGRSEEISESESEETNAPKKTKTEQELPRPQSPSDLDSLDGRSLNDDGSSDPRDIDQDNRSTSPSIYSPGSVENDSDSSSGLSQGPARPYHPPPLFPPSPQPPDSTPRQPEASFEPHPSVTPTGYHAPMEPPTSRMFQAPPGAPPPHPQLYPGGTGGVLSGPPMGPKGGGAASSVGGPNGGKQHPPPTTPISVSSSGASGAPPTKPPTTPVGGGNLPSAPPPANFPHVTPNLPPPPALRPLNNASASPPGLGAQPLPGHLPSPHAMGQGMGGLPPGPEKGPTLAPSPHSLPPASSSAPAPPMRFPYSSSSSSSAAASSSSSSSSSSASPFPASQALPSYPHSFPPPTSLSVSNQPPKYTQPSLPSQAVWSQGPPPPPPYGRLLANSNAHPGPFPPSTGAQSTAHPPVSTHHHHHQQQQQQQQQQQQQQQQQQQHHGNSGPPPPGAFPHPLEGGSSHHAHPYAMSPSLGSLRPYPPGPAHLPPPHSQVSYSQAGPNGPPVSSSSNSSSSTSQGSYPCSHPSPSQGPQGAPYPFPPVPTVTTSSATLSTVIATVASSPAGYKTASPPGPPPYGKRAPSPGAYKTATPPGYKPGSPPSFRTGTPPGYRGTSPPAGPGTFKPGSPTVGPGPLPPAGPSGLPSLPPPPAAPASGPPLSATQIKQEPAEEYETPESPVPPARSPSPPPKVVDVPSHASQSARFNKHLDRGFNSCARSDLYFVPLEGSKLAKKRADLVEKVRREAEQRAREEKEREREREREKEREREKERELERSVKLAQEGRAPVECPSLGPVPHRPPFEPGSAVATVPPYLGPDTPALRTLSEYARPHVMSPGNRNHPFYVPLGAVDPGLLGYNVPALYSSDPAAREREREARERDLRDRLKPGFEVKPSELEPLHGVPGPGLDPFPRHGGLALQPGPPGLHPFPFHPSLGPLERERLALAAGPALRPDMSYAERLAAERQHAERVAALGNDPLARLQMLNVTPHHHQHSHIHSHLHLHQQDAIHAASASVHPLIDPLASGSHLTRIPYPAGTLPNPLLPHPLHENEVLRHQLFAAPYRDLPASLSAPMSAAHQLQAMHAQSAELQRLALEQQQWLHAHHPLHSVPLPAQEDYYSHLKKESDKPL