Human Gene ATN1 (uc001qrx.1) Description and Page Index
Description: Homo sapiens atrophin 1 (ATN1), transcript variant 2, mRNA. RefSeq Summary (NM_001940): Dentatorubral pallidoluysian atrophy (DRPLA) is a rare neurodegenerative disorder characterized by cerebellar ataxia, myoclonic epilepsy, choreoathetosis, and dementia. The disorder is related to the expansion from 7-35 copies to 49-93 copies of a trinucleotide repeat (CAG/CAA) within this gene. The encoded protein includes a serine repeat and a region of alternating acidic and basic amino acids, as well as the variable glutamine repeat. Alternative splicing results in two transcripts variants that encode the same protein. [provided by RefSeq, Jul 2016]. Transcript (Including UTRs) Position: hg19 chr12:7,037,480-7,053,815 Size: 16,336 Total Exon Count: 10 Strand: + Coding Region Position: hg19 chr12:7,043,165-7,050,943 Size: 7,779 Coding Exon Count: 9
ID:ATN1_HUMAN DESCRIPTION: RecName: Full=Atrophin-1; AltName: Full=Dentatorubral-pallidoluysian atrophy protein; 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. INTERACTION: Q12805:EFEMP1; NbExp=3; IntAct=EBI-945980, EBI-536772; O95967:EFEMP2; NbExp=3; IntAct=EBI-945980, EBI-743414; Q9HAU0:PLEKHA5; NbExp=2; IntAct=EBI-945980, EBI-945934; P61289:PSME3; NbExp=3; IntAct=EBI-945980, EBI-355546; Q9NWB1:RBFOX1; NbExp=2; IntAct=EBI-945980, EBI-945906; Q9P2R6:RERE; NbExp=3; IntAct=EBI-945980, EBI-948076; Q15654:TRIP6; NbExp=2; IntAct=EBI-945980, EBI-742327; SUBCELLULAR LOCATION: Nucleus. Cytoplasm, 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-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";
Genetic Association Studies of Complex Diseases and Disorders
myotonic dystrophy type 1 Savic, D. et al. 2001, Is the 31 CAG repeat allele of the spinocerebellar ataxia 1 (SCA1) gene locus non-specifically associated with trinucleotide expansion diseases?, Psychiatric genetics. 2001 Dec;11(4):201-5.
Allele frequency distributions for all tested loci were similar in these three groups with the exception of the SCA1 locus. In DM1 patients, the SCA1 allele with 31 CAG repeats account for 40.4% of all chromosomes tested, which is significantly higher than in two other groups (11.3% in healthy controls and 6.6% in the group of non-triplet diseased patients; P < 0.001, Fisher's exact test). This is consistent with our previous findings in HD patients. The absence of this association in non-triplet diseases as well as in healthy controls could indicate a possible role of this SCA1 allele with 31 repeats in triplet diseases. Here we discuss a possible role of the SCA1 region in pathological trinucleotide repeat expansions.
schizophrenia Morris-Rosendahl DJ et al. 1997, Analysis of the CAG repeats in the SCA1 and B37 genes in schizophrenic and bipolar I disorder patients: tentative association between B37 and schizophrenia., American journal of medical genetics. 1997 May;74(3):324-30.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P54259
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000122 negative regulation of transcription from RNA polymerase II promoter GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0007417 central nervous system development GO:0051402 neuron apoptotic process