DegronMD - P55265(ADAR)

FUNCTION: Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:7972084, PubMed:7565688, PubMed:12618436). 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 since the translational machinery read the inosine as a guanosine; 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:0000269|PubMed:12618436, ECO:0000269|PubMed:15556947, ECO:0000269|PubMed:15858013, ECO:0000269|PubMed:16120648, ECO:0000269|PubMed:16475990, ECO:0000269|PubMed:17079286, ECO:0000269|PubMed:19605474, ECO:0000269|PubMed:19651874, ECO:0000269|PubMed:19710021, ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159, ECO:0000269|PubMed:22278222, ECO:0000269|PubMed:7565688, ECO:0000269|PubMed:7972084}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.Q600H	TCGA-50-5933	LUAD	TCGA	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.2778
p.Q600R	TCGA-AX-A2HD	UCEC	TCGA	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.2778
p.V616I	TCGA-CG-5727	STAD	TCGA	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.0833
p.V616I	TCGA-FI-A2D5	UCEC	TCGA	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.0833
p.N173S	TCGA-CN-4734	HNSC	TCGA	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.2778
p.G612V	TCGA-D3-A3CE	SKCM	TCGA	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.1944
p.S178F	TCGA-EE-A181	SKCM	TCGA	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.1389
p.S178F	TCGA-EE-A29V	SKCM	TCGA	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.1389
p.K613N	TCGA-SY-A9G5	BLCA	TCGA	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation blocking ubiquitination signal	0.6111
p.R159S	DO44035	BLCA	ICGC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.1667
p.P162S	DO10373	COAD	ICGC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.25
p.L176Q	DO20809	KIRP	ICGC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.1944
p.L169P	DO20870	KIRP	ICGC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation altering degron motif	0.7582
p.A608D	DO229019	LICA	ICGC	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation blocking phosphorylation signal	0.75
p.R157H	DO38563	STAD	ICGC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.1111
p.A608V	DO42280	UCEC	ICGC	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation blocking phosphorylation signal	0.75
p.E594D	SIDM00920	Breast Carcinoma	GDSC	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.1111
p.E594D	ACH-000783	Breast Cancer	CCLE	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.1111
p.E594D	CAMA-1	breast	COSMIC	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation rewiring degron network	0.1111
p.S603F	HCT-15	large intestine	COSMIC	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation altering degron motif	0.7982
p.R179L	RMG-I	ovary	COSMIC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.1111
p.S603C	SW684	soft tissue	COSMIC	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation altering degron motif	0.7541
p.A173T	LOXIMVI	skin	COSMIC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.2778
p.D602N	HCC-366	lung	COSMIC	PTPSAT	DEG_SCF_FBW7_1	602:607	Mutation altering degron motif	0.6932
p.T161A	TE-4	oesophagus	COSMIC	LGTPKKE	DEG_SCF_FBW7_2	165:171	Mutation rewiring degron network	0.2222

Kaplan plot for ADAR in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

ADAR

UniProt ID: P55265

Entrez ID: 103

Protein name: Double-stranded RNA-specific adenosine deaminase (DRADA) (EC 3.5.4.37) (136 kDa double-stranded RNA-binding protein) (p136) (Interferon-inducible protein 4) (IFI-4) (K88DSRBP)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for ADAR in