InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: ADAR

Summary

InnateDB Protein

IDBP-102970.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

ADAR

Protein Name

adenosine deaminase, RNA-specific

Synonyms

ADAR1; AGS6; DRADA; DSH; DSRAD; G1P1; IFI-4; IFI4; K88DSRBP; P136;

Species

Homo sapiens

Ensembl Protein

ENSP00000357459

InnateDB Gene

IDBG-102968 (ADAR)

Protein Structure

UniProt Annotation

Function

Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer- associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing- independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication. {ECO:0000269PubMed:15556947, ECO:0000269PubMed:15858013, ECO:0000269PubMed:16475990, ECO:0000269PubMed:17079286, ECO:0000269PubMed:19605474, ECO:0000269PubMed:19651874, ECO:0000269PubMed:19710021, ECO:0000269PubMed:19908260, ECO:0000269PubMed:21289159, ECO:0000269PubMed:22278222}.

Subcellular Localization

Isoform 1: Cytoplasm. Nucleus. Note=Shuttles between the cytoplasm and nucleus.Isoform 5: Cytoplasm. Nucleus. Nucleus, nucleolus. Note=Predominantly nuclear but can shuttle between nucleus and cytoplasm. TNPO1 can mediate its nuclear import whereas XPO1 can mediate its nuclear export.

Disease Associations

Dyschromatosis symmetrica hereditaria (DSH) [MIM:127400]: An autosomal dominant pigmentary genodermatosis characterized by a mixture of hyperpigmented and hypopigmented macules distributed on the face and the dorsal parts of the hands and feet, that appear in infancy or early childhood. {ECO:0000269PubMed:12916015, ECO:0000269PubMed:15146470, ECO:0000269PubMed:15659327}. Note=The disease is caused by mutations affecting the gene represented in this entry.Aicardi-Goutieres syndrome 6 (AGS6) [MIM:615010]: A form of Aicardi-Goutieres syndrome, a genetically heterogeneous disease characterized by cerebral atrophy, leukoencephalopathy, intracranial calcifications, chronic cerebrospinal fluid (CSF) lymphocytosis, increased CSF alpha-interferon, and negative serologic investigations for common prenatal infection. Clinical features as thrombocytopenia, hepatosplenomegaly and elevated hepatic transaminases along with intermittent fever may erroneously suggest an infective process. Severe neurological dysfunctions manifest in infancy as progressive microcephaly, spasticity, dystonic posturing and profound psychomotor retardation. Death often occurs in early childhood. {ECO:0000269PubMed:23001123}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitously expressed, highest levels were found in brain and lung. 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. {ECO:0000269PubMed:18178553}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 41 experimentally validated interaction(s) in this database.
They are also associated with 3 interaction(s) predicted by orthology.

Experimentally validated
Total	41 [view]
Protein-Protein	37 [view]
Protein-DNA	4 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	3 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003677	DNA binding
GO:0003723	RNA binding
GO:0003726	double-stranded RNA adenosine deaminase activity
GO:0004000	adenosine deaminase activity
GO:0005515	protein binding
GO:0044822	poly(A) RNA binding
GO:0046872	metal ion binding

Biological Process

GO:0001701	in utero embryonic development
GO:0006382	adenosine to inosine editing
GO:0006396	RNA processing
GO:0006397	mRNA processing
GO:0006606	protein import into nucleus
GO:0006611	protein export from nucleus
GO:0009615	response to virus
GO:0010467	gene expression
GO:0016553	base conversion or substitution editing
GO:0016556	mRNA modification
GO:0019221	cytokine-mediated signaling pathway
GO:0031047	gene silencing by RNA
GO:0035455	response to interferon-alpha
GO:0043066	negative regulation of apoptotic process
GO:0044387	negative regulation of protein kinase activity by regulation of protein phosphorylation
GO:0045070	positive regulation of viral genome replication
GO:0045071	negative regulation of viral genome replication
GO:0045087	innate immune response (InnateDB)
GO:0051607	defense response to virus
GO:0060337	type I interferon signaling pathway