caution:The N-terminus of isoform 4 has been derived from EST and genomic sequences.,disease:Defects in ADAR are a cause of dyschromatosis symmetrical hereditaria (DSH) [MIM:127400]; also known as reticulate acropigmentation of Dohi. DSH is a pigmentary genodermatosis of autosomal dominant inheritance characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the dorsal parts of the hands and feet.,function:Converts multiple adenosines to inosines and creates I/U mismatched base pairs in double-helical RNA substrates without apparent sequence specificity. Has been found to modify more frequently adenosines in AU-rich regions, probably due to the relative ease of melting A/U base pairs as compared to G/C pairs. Functions to modify viral RNA genomes and may be responsible for hypermutation of certain negative-stranded viruses. Edits the messenger RNAs for glutamate receptor (GLUR) subunits by site-selective adenosine deamination. Produces low-level editing at the GLUR-B Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Binds to short interfering RNAs (siRNA) without editing them and suppresses siRNA-mediated RNA interference. Binds to ILF3/NF90 and up-regulates ILF3-mediated gene expression.,induction:Isoform 1 is induced by interferon alpha. Isoform 5 is constitutively expressed.,PTM:Sumoylation reduces RNA-editing activity.,similarity:Contains 1 A to I editase domain.,similarity:Contains 2 DRADA repeats.,similarity:Contains 3 DRBM (double-stranded RNA-binding) domains.,subcellular location:Isoform 1 is found predominantly in cytoplasm but appears to shuttle between the cytoplasm and nucleus. Isoform 5 is found exclusively in the nucleolus.,subunit:Homodimer. Isoform 1 interacts with ILF2/NF45 and ILF3/NF90.,tissue specificity:Ubiquitously expressed, highest levels were found in brain and lung.,
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Function:
RNA processing, mRNA processing, RNA modification, negative regulation of macromolecule metabolic process,negative regulation of gene expression, mRNA metabolic process, gene silencing, base conversion or substitution editing, gene silencing by RNA,
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Cellular Localization:
[Isoform 1]: Cytoplasm . Nucleus . Shuttles between the cytoplasm and nucleus (PubMed:7565688, PubMed:24753571). Nuclear import is mediated by TNPO1 (PubMed:24753571). .; [Isoform 5]: Cytoplasm . Nucleus . Nucleus, nucleolus . Predominantly nuclear but can shuttle between nucleus and cytoplasm. TNPO1 can mediate its nuclear import whereas XPO5 can mediate its nuclear export. .
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Tissue Expression:
Ubiquitously expressed, highest levels were found in brain and lung (PubMed:7972084). Isoform 5 is expressed at higher levels in astrocytomas as compared to normal brain tissue and expression increases strikingly with the severity of the tumor, being higher in the most aggressive tumors.