CPLM-008975

Genbank Nucleotide ID

Double-stranded RNA-specific adenosine deaminase

Protein Synonyms/Alias

DRADA; 136 kDa double-stranded RNA-binding protein; p136; Interferon-inducible protein 4; IFI-4; K88DSRBP

ADAR1; DSRAD; G1P1; IFI4

Homo sapiens (Human)

Position	Peptide	Type	References
91	LKQIEFLKGQLPEAP	ubiquitination	[1]
712	APSKKVAKQMAAEEA	ubiquitination	[1]
841	VLIGENEKAERMGFT	ubiquitination	[1]
1158	RVSIYDSKRQSGKTK	ubiquitination	[1]

[1] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]

Functional Description

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.

REPEAT 133 202 DRADA 1.
REPEAT 293 360 DRADA 2.
DOMAIN 503 571 DRBM 1.
DOMAIN 614 682 DRBM 2.
DOMAIN 726 794 DRBM 3.
DOMAIN 886 1221 A to I editase.
DNA_BIND 169 195
ACT_SITE 912 912 Proton donor (By similarity).
METAL 910 910 Zinc (By similarity).
METAL 966 966 Zinc (By similarity).
METAL 1036 1036 Zinc (By similarity).
MOD_RES 601 601 Phosphothreonine.
MOD_RES 614 614 Phosphoserine.
MOD_RES 808 808 Phosphothreonine.
MOD_RES 823 823 Phosphoserine.
MOD_RES 825 825 Phosphoserine.
CROSSLNK 418 418 Glycyl lysine isopeptide (Lys-Gly)

3D-structure; Aicardi-Goutieres syndrome; Alternative promoter usage; Alternative splicing; Antiviral defense; Complete proteome; Cytoplasm; Direct protein sequencing; Disease mutation; DNA-binding; Hydrolase; Immunity; Innate immunity; Isopeptide bond; Metal-binding; mRNA processing; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; RNA-binding; RNA-mediated gene silencing; Ubl conjugation; Zinc.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0005737; C:cytoplasm; IDA:UniProtKB.
GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell.
GO:0005654; C:nucleoplasm; TAS:Reactome.
GO:0005634; C:nucleus; IDA:UniProtKB.
GO:0044530; C:supraspliceosomal complex; IDA:UniProtKB.
GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
GO:0003726; F:double-stranded RNA adenosine deaminase activity; NAS:UniProtKB.
GO:0003725; F:double-stranded RNA binding; IEA:InterPro.
GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO:0006382; P:adenosine to inosine editing; IDA:UniProtKB.
GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
GO:0010467; P:gene expression; TAS:Reactome.
GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
GO:0016556; P:mRNA modification; TAS:Reactome.
GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
GO:0043066; P:negative regulation of apoptotic process; IEA:Compara.
GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; IDA:UniProtKB.
GO:0045070; P:positive regulation of viral genome replication; IDA:UniProtKB.
GO:0006611; P:protein export from nucleus; IDA:UniProtKB.
GO:0006606; P:protein import into nucleus; IDA:UniProtKB.
GO:0035455; P:response to interferon-alpha; IDA:UniProtKB.
GO:0009615; P:response to virus; IMP:UniProtKB.
GO:0060337; P:type I interferon-mediated signaling pathway; TAS:Reactome.

IPR002466; A_deamin.
IPR001159; Ds-RNA-bd.
IPR014720; dsRNA-bd-like_dom.
IPR000607; dsRNA_A_deaminase.
IPR011991; WHTH_DNA-bd_dom.

PF02137; A_deamin
PF00035; dsrm
PF02295; z-alpha

SM00552; ADEAMc
SM00358; DSRM
SM00550; Zalpha

PS50141; A_DEAMIN_EDITASE
PS50139; DRADA_REPEAT
PS50137; DS_RBD