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Information on EC 3.5.4.37 - double-stranded RNA adenine deaminase and Organism(s) Homo sapiens and UniProt Accession P55265
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3.5.4.37 double-stranded RNA adenine deaminaseIUBMB Comments
This eukaryotic enzyme is involved in RNA editing. It destabilizes double-stranded RNA through conversion of adenosine to inosine. Inositol hexakisphosphate is required for activity .
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Word Map
- 3.5.4.37
- inosine
-
a-to-i
- deaminases
-
deamination
-
adenosine-to-inosine
-
hereditaria
-
rna-editing
- pre-mrnas
-
dyschromatosis
-
symmetrica
- z-dna
- duplex
- ampa
-
left-handed
-
unedited
-
glur-b
-
recoding
-
site-selective
-
macules
-
interferon-inducible
- mda5
-
hypopigmented
-
ifn-inducible
-
dsrbds
-
interferon-stimulated
-
ca2+-permeable
-
5-ht2cr
- dicer
- samhd1
-
genodermatosis
- rig-i
-
hypermutation
-
ifn-stimulated
-
pigmentary
-
interferonopathy
-
autoinflammatory
- medicine
-
inosine-containing
-
dsrna-binding
- drug development
-
protein-rna
-
antigenome
The taxonomic range for the selected organisms is: Homo sapiens
The enzyme appears in selected viruses and cellular organisms
The enzyme appears in selected viruses and cellular organisms
Reaction Schemes
adenine in double-stranded RNA
+
=
hypoxanthine in double-stranded RNA
+
Synonyms
adar1, adar2, dsrad, dadar, adenosine deaminase acting on rna 1, double-stranded rna adenosine deaminase, double-stranded rna-specific adenosine deaminase, ciadar1, dsrna adenosine deaminase, adar2 deaminase, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
ADAR1
-
ADAR2
hADAR2
ADAR2
-
ADAR2 lacks a part of the N-terminus region of ADAR1, upstream of its RNA binding domain, where ADAR1 contains two repeats of a Z-DNA binding motif
SYSTEMATIC NAME
IUBMB Comments
double-stranded RNA(adenine) aminohydrolase
This eukaryotic enzyme is involved in RNA editing. It destabilizes double-stranded RNA through conversion of adenosine to inosine. Inositol hexakisphosphate is required for activity [4].
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
8-azaadenine in double-stranded RNA + H2O
8-azahypoxanthine in double-stranded RNA + NH3
-
8-aza substitution at adenosine in various RNA substrates accelerates the rate of deamination at these sites by ADAR2 (2.8-17-fold). The magnitude of this effect depends on the RNA structural context of the reacting nucleotide
-
-
?
N6-methyladenine in double-stranded RNA + H2O
N6-methylhypoxanthine in double-stranded RNA + NH3
-
slow substrate for ADAR2, 2% of the rate compared to that of adenosine
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with the NF90 family proteins
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
ADAR1 is an editing enzyme that deaminates adenosine to inosine in long double stranded RNA duplexes and specific pre-mRNA transcripts
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
ADAR1 has a preference for binding simple duplex RNA as compared to highly structured RNA substrates
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
-
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
-
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
A-to-I editing is a form of nucleotide substitution editing, because I is decoded as guanosine instead of A by ribosomes during translation and by polymerases during RNA-dependent RNA replication. Additionally, A-to-I editing can alter RNA structure stability as I:U mismatches are less stable than A:U base pairs. Both viral and cellular RNAs are edited by ADARs. A-to-I editing is of broad physiologic significance. Among the outcomes of A-to-I editing are biochemical changes that affect how viruses interact with their hosts, changes that can lead to either enhanced or reduced virus growth and persistence depending upon the specific virus
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
ADAR2 is an editing enzymes that deaminates adenosine to inosine in long double stranded RNA duplexes and specific pre-mRNA transcripts
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
although codon editing is important, it represents only a small fraction of the editing events in the transcriptome. Editing sites in non-coding regions of RNA are more prevalent. Introns and untranslated regions of mRNA are the primary non-coding targets, but editing also occurs in small RNAs, such as miRNAs. The enzyme functions in the regulation of a variety of post-transcriptional processes. Inosine has different base-pairing properties from adenosine, and thus, editing alters RNA structure, coding potential and splicing patterns. Function primarily in proteome diversification, especially in the nervous system. Inosine is recognized as guanosine by the translation and splicing machineries, and thus, ADARs can alter the protein-coding information of an mRNA. In addition, because inosine prefers to pair with cytidine, ADARs destabilize dsRNA by changing AU base-pairs to IU mismatches, or increase its stability by changing AC mismatches to IC base-pairs
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
editing of RNA changes the read-out of information from DNA by altering the nucleotide sequence of a transcript. One type of RNA editing found in all metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the deamination of adenosine to give inosine, which is translated as guanosine
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
the enzyme catalyzes the hydrolytic deamination of adenosine to inosine in completely or partially double-stranded RNA
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
ADAR1 contains a domain (Zalpha) that binds specifically to the left-handed Z-DNA conformation with high affinity. As formation of Z-DNA in vivo occurs 5' to, or behind, a moving RNA polymerase during transcription, recognition of Z-DNA by DRADA1 provides a plausible mechanism by which DRADA1 can be targeted to a nascent RNA so that editing occurs before splicing
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
ADAR1-S edits HDV RNA during replication
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
identification of ADAR substrates. RNA hairpins in noncoding regions of human brain mRNA are edited
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
like ADAR1, ADAR2 has a 5' neighbor preference (A = U > C = G), but, unlike ADAR1, also has a 3' neighbor preference (U = G > C = A). ADAR2 prefers certain trinucleotide sequences (UAU, AAG, UAG, AAU). ADAR1 and ADAR2 have overlapping specificities. Xenopus and human ADAR1 have a highly similar, or identical, deamination specificity
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
RNA editing catalyzed by ADAR1 and ADAR2 involves the site-specific conversion of adenosine to inosine within imperfectly duplexed RNA. ADAR1- and ADAR2-mediated editing occurs within transcripts of glutamate receptors in the brain and in hepatitis delta virus RNA in the liver. The Q/R site within the GluR-B premessage is edited more efficiently by ADAR2 than it is by ADAR1. The converse is true for the 160 site within this same transcript. The base-pairing status of the targeted adenosine can affect the efficiency of editing by both ADAR1 and ADAR2. When the the substrate contains an A:C mismatch at the editing site, editing by both ADARs is enhanced compared to when A:A or A:G mismatches or A:U base pairs occurr at the same site. The deaminase domains plays a dominant role in defining the substrate specificity of the resulting enzyme
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
the specificity of the ADAR1 and ADAR2 deaminases ranges from highly site-selective to non-selective, dependent on the duplex structure of the substrate RNA
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
the nucleoside analog 8-azanebularine is introduced into this RNA (and derived constructs) to mechanistically trap the protein-RNA complex without catalytic turnover for EMSA and ribonuclease footprinting analyses. The human ADAR2 deaminase domain requires duplex RNA and is sensitive to 2-deoxy substitution at nucleotides opposite the editing site, the local sequence and 8-azanebularine nucleotide positioning on the duplex. The human ADAR2 deaminase domain protects about 23 nt on the edited strand around the editing site in an asymmetric fashion (about 18 nt on the 5' side and about 5 nt on the 3x02 side)
-
-
?
additional information
?
-
overexpression of p150 ADAR1 has no significant effect on the yield of vesicular stomatitis virus. reduction of p110 and p150 ADAR1 proteins to less than 10% to 15% of parental levels (ADAR1-deficient) has no significant effect on growth of Vesicular Stomatitis Virus in the absence of interferon treatment. The level of phosphorylated protein kinase PKR is increased in ADAR1-deficient cells compared to ADAR1-sufficient cells following IFN treatment, regardless of viral infection. ADAR1 suppresses activation of protein kinase PKR and inhibition of growth of Vesicular Stomatitis Virus in response to interferon treatment
-
-
?
additional information
?
-
human APOBEC1 possesses no antiviral activity
-
-
?
additional information
?
-
-
no product is observed with N6-ethyladenosine or 2,6-diaminopurine ribonucleoside in double-stranded RNA
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
additional information
?
-
overexpression of p150 ADAR1 has no significant effect on the yield of vesicular stomatitis virus. reduction of p110 and p150 ADAR1 proteins to less than 10% to 15% of parental levels (ADAR1-deficient) has no significant effect on growth of Vesicular Stomatitis Virus in the absence of interferon treatment. The level of phosphorylated protein kinase PKR is increased in ADAR1-deficient cells compared to ADAR1-sufficient cells following IFN treatment, regardless of viral infection. ADAR1 suppresses activation of protein kinase PKR and inhibition of growth of Vesicular Stomatitis Virus in response to interferon treatment
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with the NF90 family proteins
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
ADAR1 is an editing enzyme that deaminates adenosine to inosine in long double stranded RNA duplexes and specific pre-mRNA transcripts
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
-
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
A-to-I editing is a form of nucleotide substitution editing, because I is decoded as guanosine instead of A by ribosomes during translation and by polymerases during RNA-dependent RNA replication. Additionally, A-to-I editing can alter RNA structure stability as I:U mismatches are less stable than A:U base pairs. Both viral and cellular RNAs are edited by ADARs. A-to-I editing is of broad physiologic significance. Among the outcomes of A-to-I editing are biochemical changes that affect how viruses interact with their hosts, changes that can lead to either enhanced or reduced virus growth and persistence depending upon the specific virus
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
ADAR2 is an editing enzymes that deaminates adenosine to inosine in long double stranded RNA duplexes and specific pre-mRNA transcripts
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
although codon editing is important, it represents only a small fraction of the editing events in the transcriptome. Editing sites in non-coding regions of RNA are more prevalent. Introns and untranslated regions of mRNA are the primary non-coding targets, but editing also occurs in small RNAs, such as miRNAs. The enzyme functions in the regulation of a variety of post-transcriptional processes. Inosine has different base-pairing properties from adenosine, and thus, editing alters RNA structure, coding potential and splicing patterns. Function primarily in proteome diversification, especially in the nervous system. Inosine is recognized as guanosine by the translation and splicing machineries, and thus, ADARs can alter the protein-coding information of an mRNA. In addition, because inosine prefers to pair with cytidine, ADARs destabilize dsRNA by changing AU base-pairs to IU mismatches, or increase its stability by changing AC mismatches to IC base-pairs
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
-
editing of RNA changes the read-out of information from DNA by altering the nucleotide sequence of a transcript. One type of RNA editing found in all metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the deamination of adenosine to give inosine, which is translated as guanosine
-
-
?
adenine in double-stranded RNA + H2O
hypoxanthine in double-stranded RNA + NH3
the enzyme catalyzes the hydrolytic deamination of adenosine to inosine in completely or partially double-stranded RNA
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Inositol hexakisphosphate
is buried within the enzyme core, contributing to the protein fold. Inositol hexakisphosphate is required for activity. Amino acids that coordinate inositol hexakisphosphate in the crystal structure are conserved in some adenosine deaminases that act on tRNA
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
30
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
-
SwissProt
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
full-length and N-terminally truncated forms of ADAR1 are simultaneously expressed in HeLa cells owing to the usage of alternative starting methionines
-
ubiquitously expressed in most tissues but is most abundant in the brain
-
ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
full-length and N-terminally truncated forms of ADAR1 are simultaneously expressed in HeLa cells. Because the N-terminus of ADAR1 contains a nuclear export signal, the full-length protein (150000 Da) localizes predominantly in the cytoplasm, whereas the N-terminally truncated forms (110000 Da) are exclusively nuclear and accumulate in the nucleolus. In living cells, editing might be regulated by the intracellular compartmentalization of editing enzymes. ADAR1 shuttles between the nucleolus, the nucleoplasm and the cytoplasm
full-length and N-terminally truncated forms of ADAR1 are simultaneously expressed in HeLa cells. Because the N-terminus of ADAR1 contains a nuclear export signal, the full-length protein (150000 Da) localizes predominantly in the cytoplasm, whereas the N-terminally truncated forms (110000 Da) are exclusively nuclear and accumulate in the nucleolus. In living cells, editing might be regulated by the intracellular compartmentalization of editing enzymes. ADAR1 shuttles between the nucleolus, the nucleoplasm and the cytoplasm
-
the ADAR1 p150 protein is found in both the cytoplasm and the nucleus, whereas the p110 protein localizes predominantly if not exclusively to the nucleus
ADAR2 localizes exclusively to the nucleus and accumulates in the nucleolus. In living cells, editing might be regulated by the intracellular compartmentalization of editing enzymes. ADAR2 shuttles between the nucleolus and the nucleoplasm
-
the ADAR1 p150 protein is found in both the cytoplasm and the nucleus, whereas the p110 protein localizes predominantly if not exclusively to the nucleus
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
malfunction
metabolism
physiological function
ADAR1 has the potential both to change information content through editing of mRNA and to regulate gene expression through interacting with the NF90 family proteins
malfunction
metabolism
ADAR2 is the main enzyme responsible for A-to-I editing in humans
physiological function
malfunction
dysregulation of A-to-I editing by ADAR1 can have profound consequences, ranging from effects on cell growth and development to autoimmune disorders
malfunction
knockdown of ADARa in lung adenocarcinoma cells with amplified ADAR leads to decreased migration and invasion
metabolism
ADAR1 is an essential enzyme for normal development. The interferon-inducible ADAR1p150 is involved in immune responses to both exogenous and endogenous triggers, whereas the functions of the constitutively expressed ADAR1p110 are variable. ADAR1 is involved in the recognition of self versus non-self dsRNA. This provides potential explanations for its links to hematopoiesis, type I interferonopathies, and viral infections. Editing in both coding and noncoding sequences results in diseases ranging from cancers to neurological abnormalities. Furthermore, editing of noncoding sequences, like microRNAs, can regulate protein expression, while editing of Alu sequences can affect translational efficiency and editing of proximal sequences. Identifications of long noncoding RNA and retrotransposons as editing targets expand the effects of A-to-I editing. Besides editing, ADAR1 also interacts with other dsRNA-binding proteins in editing-independent manners
metabolism
role of ADAR1 as a suppressor of dsRNA-triggered innate immune responses
metabolism
the enzyme (ADAR1) regulates the phosphorylation of activation of protein kinase (PKR) and eukaryotic translation initiation factor 2 alpha (eIF2) in both an IFN-dependent and IFN-independent manner, and its inhibitory effect on the IFN production partially contributes to its proviral effect. The enzyme promotes the Zika virus replication by inhibiting the activation of protein kinase PKR
metabolism
the enzyme is an essential gene for the survival of a subset of cancer cell lines. ADAR1-dependent cell lines display increased expression of interferon-stimulated genes. Activation of type I interferon signaling in the context of ADAR1 deficiency can induce cell lethality in non-ADAR1-dependent cell lines
malfunction
-
knock-down of ADAR1 increases HIV-1 replication in primary macrophages
malfunction
A-to-I underediting at the glutamine (Q)/arginine (R) site of the glutamate receptor subunit B (GluR-B) is associated with the pathogenesis and invasiveness of glioma and is confirmed in the glioma cell lines U87, U251 and A172 compared with that in normal human astrocytes. The expression of ADAR2 mRNA was not significantly altered in the glioma cell lines. Aberrant alternative splicing pattern of ADAR2 downregulates A-to-I editing in glioma
physiological function
-
ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis
physiological function
-
editing of RNA changes the read-out of information from DNA by altering the nucleotide sequence of a transcript. One type of RNA editing found in all metazoans uses double-stranded RNA (dsRNA) as a substrate and results in the deamination of adenosine to give inosine, which is translated as guanosine
physiological function
-
the enzyme is involved in RNA editing in order to generate many different mRNAs from the same gene, increasing the transcriptome and then the proteome. The most frequent RNA editing mechanism in mammals involves the conversion of specific adenosines into inosines by the ADAR family of enzymes. This editing event can change both the sequence and the secondary structure of RNA molecules, with important consequences on both the final proteins and regulatory RNAs. Alteration in RNA editing has been connected to numerous human pathologies and is important in tumor progression. RNA editing on non-coding RNA can affect the secondary (and consequently the tertiary) structure of the RNAs and then modulate and/or prevent RNA-protein and RNA-RNA interactions. RNA editing on non-coding portions of the transcripts could influence splicing, localization, stability and translation efficiency of the transcripts
physiological function
-
ADAR1 restricts HIV-1 replication post-transcriptionally in macrophages harboring HIV-1 provirus
physiological function
the enzyme (ADAR2) is a radar enzyme that maintains a degree of editing in the miRNA population and balances miRNA expression, maintaining them at physiological, that is, safe, levels. Whenever ADAR2 is impaired (that is, in glioblastoma), miRNA homeostasis is altered and this may contribute to cancer progression. The major effect of ADAR2 is to reduce the expression of a large number of miRNAs, most of which act as onco-miRNAs. ADAR2 can edit miR-222/221 and miR-21 precursors and decrease the expression of the corresponding mature onco-miRNAs in vivo and in vitro, with important effects on cell proliferation and migration
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). DSRAD_HUMAN
1226
0
136066
Swiss-Prot
other Location (Reliability: 4)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
150000
2 * 150000, ADAR1 forms a stable enzymatically active homodimer complex, SDS-PAGE
90000
2 * 90000, ADAR2 forms a stable enzymatically active homodimer complex, SDS-PAGE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
dimer
2 * 150000, ADAR1 forms a stable enzymatically active homodimer complex, SDS-PAGE
dimer
dimer
2 * 90000, ADAR2 forms a stable enzymatically active homodimer complex, SDS-PAGE
dimer
-
ADAR1 and ADAR2 form respective homodimers, and this association is essential for their enzymatic activities. ADAR dimerization independent of their binding to dsRNA
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the proteolytically defined Z-DNA binding domain Za of adenosine deaminase type 1 is crystallized in complex with the DNA oligomer d(TCGCGCG). The crystals are obtained from a solution containing ammonium sulfate as precipitating agent and belong to the tetragonal space group P4212
-
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
-
exchange of deaminase domains between ADAR1 and ADAR2 shows that this domain plays a dominant role in defining the substrate specificity of the resulting enzyme
additional information
exchange of deaminase domains between ADAR1 and ADAR2 shows that this domain plays a dominant role in defining the substrate specificity of the resulting enzyme
additional information
-
mutations for ADAR1 and ADAR2 within the double-stranded RNA binding domains, that result in the total loss of all binding for long and short dsRNA. These dsRNA binding-deficient ADARs nevertheless dimerize identically to their wild type counterparts, revealing that ADAR dimerization is not mediated by dsRNA. Two monomers with functional double-stranded RNA binding domains are required by a dimer for dsRNA binding and A to I editing activities
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
expression in Sf9 cells
large-scale overexpression in Saccharomyces cerevisiae with an N-terminal histidine tag that is cleaved by the tobacco etch virus protease
-
overexpression in Escherichia coli and Pichia pastoris, advantages of using Pichia pastoris for overexpression, large scale expression
-
the Z-DNA binding domain is expressed as a C-terminal glutathione S-transferase fusion in Escherichia coli using a pGEX-5X1 cloning vector
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
isoform ADAR1L is induced by interferon gamma or HIV-1 infection in primary macrophages but not in primary CD4 T cells
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
drug development
medicine
medicine
ADAR2 is a promising target for an anti-tumoral strategy, since ADAR2 alone can simultaneously modulate more than one miRNA and cellular pathway altered in cancer cells
drug development
ADAR1 is a potential therapeutic target in a subset of cancers
drug development
the enzyme (ADAR1) promotes the Zika virus replication by inhibiting the activation of protein kinase PKR. The enzyme can be a potential target of antiviral drugs
medicine
enzyme (ADAR1) expression is an independent predictor of tumor recurrence. Small molecule inhibition of focal adhesion kinase activity may be a potential therapeutic strategy for the treatment of lung adenocarcinoma with high ADAR1 expression
medicine
the levels of RNA editing by ADAR1 can serve as new tools for diagnosis in cancer stem cell-related illnesses. In situations where ADAR1 overexpression contributes to disease progression, as in several cancers, or where ADAR1 interacts with other proteins in editing-independent manners, inhibition of ADAR1 could potentially be another strategy in treatment
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Schwartz, T.; Shafer, K.; Lowenhaupt, K.; Hanlon, E.; Herbert, A.; Rich, A.
Crystallization and preliminary studies of the DNA-binding domain Za from ADAR1 complexed to left-handed DNA
Acta Crystallogr. Sect. D
55
1362-1364
1999
Homo sapiens
Lehmann, K.A.; Bass, B.L.
Double-stranded RNA adenosine deaminases ADAR1 and ADAR2 have overlapping specificities
Biochemistry
39
12875-12884
2000
Homo sapiens
Veliz, E.A.; Easterwood, L.M.; Beal, P.A.
Substrate analogues for an RNA-editing adenosine deaminase: mechanistic investigation and inhibitor design
J. Am. Chem. Soc.
125
10867-10876
2003
Homo sapiens
Cho, D.S.; Yang, W.; Lee, J.T.; Shiekhattar, R.; Murray, J.M.; Nishikura, K.
Requirement of dimerization for RNA editing activity of adenosine deaminases acting on RNA
J. Biol. Chem.
278
17093-17102
2003
Homo sapiens, Homo sapiens (P55265), Mus musculus (Q99MU3), Mus musculus
Valente, L.; Nishikura, K.
RNA binding-independent dimerization of adenosine deaminases acting on RNA and dominant negative effects of nonfunctional subunits on dimer functions
J. Biol. Chem.
282
16054-16061
2007
Homo sapiens
Desterro, J.M.; Keegan, L.P.; Lafarga, M.; Berciano, M.T.; O'Connell, M.; Carmo-Fonseca, M.
Dynamic association of RNA-editing enzymes with the nucleolus
J. Cell Sci.
116
1805-1818
2003
Homo sapiens, Homo sapiens (P55265)
Macbeth, M.R.; Bass, B.L.
Large-scale overexpression and purification of ADARs from Saccharomyces cerevisiae for biophysical and biochemical studies
Methods Enzymol.
424
319-331
2007
Homo sapiens
O'Connell, M.A.; Gerber, A.; Keegan, L.P.
Purification of native and recombinant double-stranded RNA-specific adenosine deaminases
Methods
15
51-62
1998
Bos taurus, Homo sapiens
Nie, Y.; Ding, L.; Kao, P.N.; Braun, R.; Yang, J.H.
ADAR1 interacts with NF90 through double-stranded RNA and regulates NF90-mediated gene expression independently of RNA editing
Mol. Cell. Biol.
25
6956-6963
2005
Homo sapiens (P55265)
Ikeda, T.; Ohsugi, T.; Kimura, T.; Matsushita, S.; Maeda, Y.; Harada, S.; Koito, A.
The antiretroviral potency of APOBEC1 deaminase from small animal species
Nucleic Acids Res.
36
6859-6871
2008
Homo sapiens (P41238)
Galeano, F.; Rossetti, C.; Tomaselli, S.; Cifaldi, L.; Lezzerini, M.; Pezzullo, M.; Boldrini, R.; Massimi, L.; Di Rocco, C.M.; Locatelli, F.; Gallo, A.
ADAR2-editing activity inhibits glioblastoma growth through the modulation of the CDC14B/Skp2/p21/p27 axis
Oncogene
32
998-1009
2013
Homo sapiens
Herbert, A.; Alfken, J.; Kim, Y.G.; Mian, I.S.; Nishikura, K.; Rich, A.
A Z-DNA binding domain present in the human editing enzyme, double-stranded RNA adenosine deaminase
Proc. Natl. Acad. Sci. USA
94
8421-8426
1997
Homo sapiens
Wong, S.K.; Lazinski, D.W.
Replicating hepatitis delta virus RNA is edited in the nucleus by the small form of ADAR1
Proc. Natl. Acad. Sci. USA
99
15118-15123
2002
Homo sapiens
Morse, D.P.; Aruscavage, P.J.; Bass, B.L.
RNA hairpins in noncoding regions of human brain and Caenorhabditis elegans mRNA are edited by adenosine deaminases that act on RNA
Proc. Natl. Acad. Sci. USA
99
7906-7911
2002
Caenorhabditis elegans, Homo sapiens
Gallo, A.; Galardi, S.
A-to-I RNA editing and cancer: from pathology to basic science
RNA Biol.
5
135-139
2008
Homo sapiens
Wong, S.K.; Sato, S.; Lazinski, D.W.
Substrate recognition by ADAR1 and ADAR2
RNA
7
846-858
2001
Homo sapiens, Homo sapiens (P78563)
Macbeth, M.R.; Schubert, H.L.; Vandemark, A.P.; Lingam, A.T.; Hill, C.P.; Bass B.L.
Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA editing
Science
309
1534-1539
2005
Homo sapiens (P78563), Homo sapiens
Hundley, H.A.; Bass, B.L.
ADAR editing in double-stranded UTRs and other noncoding RNA sequences
Trends Biochem. Sci.
35
377-383
2010
Caenorhabditis elegans, Drosophila melanogaster, Homo sapiens
Li, Z.; Wolff, K.C.; Samuel, C.E.
RNA adenosine deaminase ADAR1 deficiency leads to increased activation of protein kinase PKR and reduced vesicular stomatitis virus growth following interferon treatment
Virology
396
316-322
2009
Homo sapiens (P55265)
Samuel, C.E.
Adenosine deaminases acting on RNA (ADARs) are both antiviral and proviral
Virology
411
180-193
2011
Homo sapiens
Weiden, M.D.; Hoshino, S.; Levy, D.N.; Li, Y.; Kumar, R.; Burke, S.A.; Dawson, R.; Hioe, C.E.; Borkowsky, W.; Rom, W.N.; Hoshino, Y.
Adenosine deaminase acting on RNA-1 (ADAR1) inhibits HIV-1 replication in human alveolar macrophages
PLoS ONE
9
e108476
2014
Homo sapiens
Song, C.; Sakurai, M.; Shiromoto, Y.; Nishikura, K.
Functions of the RNA editing enzyme ADAR1 and their relevance to human diseases
Genes (Basel)
7
E129
2016
Homo sapiens (P55265), Homo sapiens
Tomaselli, S.; Galeano, F.; Alon, S.; Raho, S.; Galardi, S.; Polito, V.A.; Presutti, C.; Vincenti, S.; Eisenberg, E.; Locatelli, F.; Gallo, A.
Modulation of microRNA editing, expression and processing by ADAR2 deaminase in glioblastoma
Genome Biol.
16
5
2015
Homo sapiens (P78563), Homo sapiens
Samuel, C.E.
Adenosine deaminase acting on RNA (ADAR1), a suppressor of double-stranded RNA-triggered innate immune responses
J. Biol. Chem.
294
1710-1720
2019
Homo sapiens (P55265)
Zhou, S.; Yang, C.; Zhao, F.; Huang, Y.; Lin, Y.; Huang, C.; Ma, X.; Du, J.; Wang, Y.; Long, G.; He, J.; Liu, C.; Zhang, P.
Double-stranded RNA deaminase ADAR1 promotes the Zika virus replication by inhibiting the activation of protein kinase PKR
J. Biol. Chem.
294
18168-18180
2019
Homo sapiens (P55265), Homo sapiens
Gannon, H.S.; Zou, T.; Kiessling, M.K.; Gao, G.F.; Cai, D.; Choi, P.S.; Ivan, A.P.; Buchumenski, I.; Berger, A.C.; Goldstein, J.T.; Cherniack, A.D.; Vazquez, F.; Tsherniak, A.; Levanon, E.Y.; Hahn, W.C.; Meyerson, M.
Identification of ADAR1 adenosine deaminase dependency in a subset of cancer cells
Nat. Commun.
9
5450
2018
Homo sapiens (P55265)
Phelps, K.J.; Tran, K.; Eifler, T.; Erickson, A.I.; Fisher, A.J.; Beal, P.A.
Recognition of duplex RNA by the deaminase domain of the RNA editing enzyme ADAR2
Nucleic Acids Res.
43
1123-1132
2015
Homo sapiens (P78563), Homo sapiens
Wang, X.; Vukovic, L.; Koh, H.R.; Schulten, K.; Myong, S.
Dynamic profiling of double-stranded RNA binding proteins
Nucleic Acids Res.
43
7566-7576
2015
Homo sapiens (P55265), Homo sapiens
Li, Z.; Tian, Y.; Tian, N.; Zhao, X.; Du, C.; Han, L.; Zhang, H.
Aberrant alternative splicing pattern of ADAR2 downregulates adenosine-to-inosine editing in glioma
Oncol. Rep.
33
2845-2852
2015
Homo sapiens (P78563), Homo sapiens
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