ADAR

Protein identityUniProt · HPA

UniProt accession

P55265

Gene

ADAR

Ensembl

ENSG00000160710

Chromosome

1

Canonical length

1226 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Nucleoli

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes the enzyme responsible for RNA editing by site-specific deamination of adenosines. This enzyme destabilizes double-stranded RNA through conversion of adenosine to inosine. Mutations in this gene have been associated with dyschromatosis symmetrica hereditaria. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2010]

Canonical amino-acid sequenceUniProt

1226 residues, UniProt reviewed canonical sequence.

>P55265|ADAR
     1  MNPRQGYSLS GYYTHPFQGY EHRQLRYQQP GPGSSPSSFL LKQIEFLKGQ LPEAPVIGKQ
    61  TPSLPPSLPG LRPRFPVLLA SSTRGRQVDI RGVPRGVHLR SQGLQRGFQH PSPRGRSLPQ
   121  RGVDCLSSHF QELSIYQDQE QRILKFLEEL GEGKATTAHD LSGKLGTPKK EINRVLYSLA
   181  KKGKLQKEAG TPPLWKIAVS TQAWNQHSGV VRPDGHSQGA PNSDPSLEPE DRNSTSVSED
   241  LLEPFIAVSA QAWNQHSGVV RPDSHSQGSP NSDPGLEPED SNSTSALEDP LEFLDMAEIK
   301  EKICDYLFNV SDSSALNLAK NIGLTKARDI NAVLIDMERQ GDVYRQGTTP PIWHLTDKKR
   361  ERMQIKRNTN SVPETAPAAI PETKRNAEFL TCNIPTSNAS NNMVTTEKVE NGQEPVIKLE
   421  NRQEARPEPA RLKPPVHYNG PSKAGYVDFE NGQWATDDIP DDLNSIRAAP GEFRAIMEMP
   481  SFYSHGLPRC SPYKKLTECQ LKNPISGLLE YAQFASQTCE FNMIEQSGPP HEPRFKFQVV
   541  INGREFPPAE AGSKKVAKQD AAMKAMTILL EEAKAKDSGK SEESSHYSTE KESEKTAESQ
   601  TPTPSATSFF SGKSPVTTLL ECMHKLGNSC EFRLLSKEGP AHEPKFQYCV AVGAQTFPSV
   661  SAPSKKVAKQ MAAEEAMKAL HGEATNSMAS DNQPEGMISE SLDNLESMMP NKVRKIGELV
   721  RYLNTNPVGG LLEYARSHGF AAEFKLVDQS GPPHEPKFVY QAKVGGRWFP AVCAHSKKQG
   781  KQEAADAALR VLIGENEKAE RMGFTEVTPV TGASLRRTML LLSRSPEAQP KTLPLTGSTF
   841  HDQIAMLSHR CFNTLTNSFQ PSLLGRKILA AIIMKKDSED MGVVVSLGTG NRCVKGDSLS
   901  LKGETVNDCH AEIISRRGFI RFLYSELMKY NSQTAKDSIF EPAKGGEKLQ IKKTVSFHLY
   961  ISTAPCGDGA LFDKSCSDRA MESTESRHYP VFENPKQGKL RTKVENGEGT IPVESSDIVP
  1021  TWDGIRLGER LRTMSCSDKI LRWNVLGLQG ALLTHFLQPI YLKSVTLGYL FSQGHLTRAI
  1081  CCRVTRDGSA FEDGLRHPFI VNHPKVGRVS IYDSKRQSGK TKETSVNWCL ADGYDLEILD
  1141  GTRGTVDGPR NELSRVSKKN IFLLFKKLCS FRYRRDLLRL SYGEAKKAAR DYETAKNYFK
  1201  KGLKDMGYGN WISKPQEEKN FYLCPV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ADAR can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

80 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ADAR.

Disease | AllUniProt

Conditions ADAR is implicated in, by any mechanism.

• Dyschromatosis symmetrica hereditaria (DSH) MIM:127400
• Aicardi-Goutieres syndrome 6 (AGS6) MIM:615010

Disease | GeneticClinVar

111 pathogenic / likely-pathogenic of 1,729 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Aicardi-Goutieres syndrome 6
• Symmetrical dyschromatosis of extremities
• Inborn genetic diseases
• ADAR-related disorder
• Leukodystrophy, Adult-Onset

ReferencesPubMed · IEDB

Publications for ADAR from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.42

gnomAD pLI

0.03

gnomAD missense Z

2.27

DepMap mean gene effect

-0.57

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 12% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adenosine to inosine editing
• base conversion or substitution editing
• cellular response to virus
• defense response to virus
• definitive hemopoiesis
• erythrocyte differentiation
• hematopoietic progenitor cell differentiation
• hematopoietic stem cell homeostasis
• hepatocyte apoptotic process
• innate immune response
• mRNA modification
• mRNA processing
• negative regulation of hepatocyte apoptotic process
• negative regulation of protein kinase activity by regulation of protein phosphorylation
• negative regulation of type I interferon-mediated signaling pathway
• osteoblast differentiation
• positive regulation of viral genome replication
• pre-miRNA processing
• protein export from nucleus
• protein import into nucleus
• response to interferon-alpha
• response to virus
• RISC complex assembly
• RNA processing
• negative regulation of post-transcriptional gene silencing by regulatory ncRNA
• somatic diversification of immune receptors via somatic mutation

Molecular functions

• DNA binding
• double-stranded RNA adenosine deaminase activity
• double-stranded RNA binding
• metal ion binding
• RNA binding
• tRNA-specific adenosine deaminase activity

Cellular components

• cytoplasm
• cytosol
• membrane
• mitochondrion
• nucleolus
• nucleoplasm
• nucleus
• supraspliceosomal complex

Protein domainsUniProt · Pfam · InterPro

• Adenosine deaminase/editase
• Double-stranded RNA-binding domain
• Winged helix-like DNA-binding domain superfamily
• Winged helix DNA-binding domain superfamily
• Z-binding domain
• Double-stranded RNA binding motif
• Adenosine-deaminase (editase) domain
• Adenosine deaminase z-alpha domain
• ADAR1, first double-stranded RNA binding domain
• ADAR1, third double-stranded RNA binding domain

KeywordsUniProt

• Aicardi-Goutieres syndrome
• Alternative promoter usage
• Antiviral defense
• Cytoplasm
• DNA-binding
• Hydrolase
• Immunity
• Innate immunity
• Isopeptide bond
• Metal-binding
• Methylation
• mRNA processing
• Nucleus
• Phosphoprotein
• Repeat
• RNA-binding
• RNA-mediated gene silencing
• Ubl conjugation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of ADAR in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• XPO5
• CPSF6
• DHX9
• EIF2AK2
• HNRNPL
• ILF3
• RBM39
• SNRPB
• UPF1