RED1_HUMAN
ID RED1_HUMAN Reviewed; 741 AA.
AC P78563; A6NFK8; A6NJ84; C3TTQ1; C3TTQ2; C9JUP4; G5E9B4; O00395; O00465;
AC O00691; O00692; P78555; Q4AE77; Q4AE79; Q6P0M9; Q8NFA1; Q8NFD1;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Double-stranded RNA-specific editase 1 {ECO:0000305};
DE EC=3.5.4.37 {ECO:0000269|PubMed:16141067, ECO:0000269|PubMed:9149227};
DE AltName: Full=RNA-editing deaminase 1;
DE AltName: Full=RNA-editing enzyme 1;
DE AltName: Full=dsRNA adenosine deaminase;
GN Name=ADARB1 {ECO:0000312|HGNC:HGNC:226};
GN Synonyms=ADAR2 {ECO:0000303|PubMed:32220291}, DRADA2, RED1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY, AND
RP CATALYTIC ACTIVITY.
RC TISSUE=Brain;
RX PubMed=9149227;
RA Gerber A., O'Connell M.A., Keller W.;
RT "Two forms of human double-stranded RNA-specific editase 1 (hRED1)
RT generated by the insertion of an Alu cassette.";
RL RNA 3:453-463(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Fetal brain;
RX PubMed=9143496; DOI=10.1006/geno.1997.4655;
RA Mittaz L., Scott H.S., Rossier C., Seeburg P.H., Higuchi M.,
RA Antonarakis S.E.;
RT "Cloning of a human RNA editing deaminase (ADARB1) of glutamate receptors
RT that maps to chromosome 21q22.3.";
RL Genomics 41:210-217(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RX PubMed=9111310; DOI=10.1128/mcb.17.5.2413;
RA Lai F., Chen C.-X., Carter K.C., Nishikura K.;
RT "Editing of glutamate receptor B subunit ion channel RNAs by four
RT alternatively spliced DRADA2 double-stranded RNA adenosine deaminases.";
RL Mol. Cell. Biol. 17:2413-2424(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9330641; DOI=10.1007/bf02679972;
RA Villard L., Tassone F., Haymowicz M., Welborn R., Gardiner K.;
RT "Map location, genomic organization and expression patterns of the human
RT RED1 RNA editase.";
RL Somat. Cell Mol. Genet. 23:135-145(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 4).
RX PubMed=12459255; DOI=10.1016/s0378-1119(02)01016-8;
RA Slavov D., Gardiner K.;
RT "Phylogenetic comparison of the pre-mRNA adenosine deaminase ADAR2 genes
RT and transcripts: conservation and diversity in editing site sequence and
RT alternative splicing patterns.";
RL Gene 299:83-94(2002).
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 6).
RX PubMed=16297572; DOI=10.1016/j.gene.2005.07.028;
RA Kawahara Y., Ito K., Ito M., Tsuji S., Kwak S.;
RT "Novel splice variants of human ADAR2 mRNA: skipping of the exon encoding
RT the dsRNA-binding domains, and multiple C-terminal splice sites.";
RL Gene 363:193-201(2005).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10830953; DOI=10.1038/35012518;
RA Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S.,
RA Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M.,
RA Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A., Menzel U.,
RA Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A.,
RA Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J.,
RA Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K.,
RA Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G.,
RA Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J.,
RA Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S.,
RA Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K.,
RA Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.;
RT "The DNA sequence of human chromosome 21.";
RL Nature 405:311-319(2000).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ALA-224.
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-75 (ISOFORM 5), ALTERNATIVE PROMOTER USAGE,
RP AND TISSUE SPECIFICITY.
RX PubMed=19156214; DOI=10.1371/journal.pone.0004225;
RA Maas S., Gommans W.M.;
RT "Novel exon of mammalian ADAR2 extends open reading frame.";
RL PLoS ONE 4:E4225-E4225(2009).
RN [11]
RP SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
RX PubMed=14759258; DOI=10.1186/gb-2004-5-2-r8;
RA Hillman R.T., Green R.E., Brenner S.E.;
RT "An unappreciated role for RNA surveillance.";
RL Genome Biol. 5:R8.1-R8.16(2004).
RN [12]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18178553; DOI=10.1074/jbc.m708316200;
RA Cenci C., Barzotti R., Galeano F., Corbelli S., Rota R., Massimi L.,
RA Di Rocco C., O'Connell M.A., Gallo A.;
RT "Down-regulation of RNA editing in pediatric astrocytomas: ADAR2 editing
RT activity inhibits cell migration and proliferation.";
RL J. Biol. Chem. 283:7251-7260(2008).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP REVIEW.
RX PubMed=20192758; DOI=10.1146/annurev-biochem-060208-105251;
RA Nishikura K.;
RT "Functions and regulation of RNA editing by ADAR deaminases.";
RL Annu. Rev. Biochem. 79:321-349(2010).
RN [16]
RP FUNCTION.
RX PubMed=19908260; DOI=10.1002/ijc.25022;
RA Galeano F., Leroy A., Rossetti C., Gromova I., Gautier P., Keegan L.P.,
RA Massimi L., Di Rocco C., O'Connell M.A., Gallo A.;
RT "Human BLCAP transcript: new editing events in normal and cancerous
RT tissues.";
RL Int. J. Cancer 127:127-137(2010).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-26, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP REVIEW.
RX PubMed=22022963; DOI=10.1134/s0006297911080050;
RA Wang Q.;
RT "RNA editing catalyzed by ADAR1 and its function in mammalian cells.";
RL Biochemistry (Mosc.) 76:900-911(2011).
RN [19]
RP FUNCTION.
RX PubMed=21289159; DOI=10.1099/vir.0.028043-0;
RA Doria M., Tomaselli S., Neri F., Ciafre S.A., Farace M.G., Michienzi A.,
RA Gallo A.;
RT "ADAR2 editing enzyme is a novel human immunodeficiency virus-1 proviral
RT factor.";
RL J. Gen. Virol. 92:1228-1232(2011).
RN [20]
RP REVIEW.
RX PubMed=21182352; DOI=10.1089/jir.2010.0097;
RA George C.X., Gan Z., Liu Y., Samuel C.E.;
RT "Adenosine deaminases acting on RNA, RNA editing, and interferon action.";
RL J. Interferon Cytokine Res. 31:99-117(2011).
RN [21]
RP REVIEW.
RX PubMed=21211811; DOI=10.1016/j.virol.2010.12.004;
RA Samuel C.E.;
RT "Adenosine deaminases acting on RNA (ADARs) are both antiviral and
RT proviral.";
RL Virology 411:180-193(2011).
RN [22]
RP REVIEW.
RX PubMed=22988838; DOI=10.3109/10409238.2012.714350;
RA Mallela A., Nishikura K.;
RT "A-to-I editing of protein coding and noncoding RNAs.";
RL Crit. Rev. Biochem. Mol. Biol. 47:493-501(2012).
RN [23]
RP REVIEW.
RX PubMed=21769729; DOI=10.1007/82_2011_144;
RA Goodman R.A., Macbeth M.R., Beal P.A.;
RT "ADAR proteins: structure and catalytic mechanism.";
RL Curr. Top. Microbiol. Immunol. 353:1-33(2012).
RN [24]
RP REVIEW.
RX PubMed=22113393; DOI=10.1007/s12035-011-8220-2;
RA Orlandi C., Barbon A., Barlati S.;
RT "Activity regulation of adenosine deaminases acting on RNA (ADARs).";
RL Mol. Neurobiol. 45:61-75(2012).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-149, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 299-741 IN COMPLEX WITH IP6, AND
RP CATALYTIC ACTIVITY.
RX PubMed=16141067; DOI=10.1126/science.1113150;
RA Macbeth M.R., Schubert H.L., Vandemark A.P., Lingam A.T., Hill C.P.,
RA Bass B.L.;
RT "Inositol hexakisphosphate is bound in the ADAR2 core and required for RNA
RT editing.";
RL Science 309:1534-1539(2005).
RN [27]
RP INVOLVEMENT IN NEDHYMS, FUNCTION, CATALYTIC ACTIVITY, VARIANTS NEDHYMS
RP GLU-127; ASN-367; ALA-498; GLN-603 AND VAL-722, CHARACTERIZATION OF
RP VARIANTS NEDHYMS GLU-127; ASN-367; ALA-498; GLN-603 AND VAL-722, AND
RP SUBCELLULAR LOCATION.
RX PubMed=32220291; DOI=10.1016/j.ajhg.2020.02.015;
RA Tan T.Y., Sedmik J., Fitzgerald M.P., Halevy R.S., Keegan L.P., Helbig I.,
RA Basel-Salmon L., Cohen L., Straussberg R., Chung W.K., Helal M.,
RA Maroofian R., Houlden H., Juusola J., Sadedin S., Pais L., Howell K.B.,
RA White S.M., Christodoulou J., O'Connell M.A.;
RT "Bi-allelic ADARB1 Variants Associated with Microcephaly, Intellectual
RT Disability, and Seizures.";
RL Am. J. Hum. Genet. 106:467-483(2020).
CC -!- FUNCTION: Catalyzes the hydrolytic deamination of adenosine to inosine
CC in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing. This
CC may affect gene expression and function in a number of ways that
CC include mRNA translation by changing codons and hence the amino acid
CC sequence of proteins; pre-mRNA splicing by altering splice site
CC recognition sequences; RNA stability by changing sequences involved in
CC nuclease recognition; genetic stability in the case of RNA virus
CC genomes by changing sequences during viral RNA replication; and RNA
CC structure-dependent activities such as microRNA production or targeting
CC or protein-RNA interactions. Can edit both viral and cellular RNAs and
CC can edit RNAs at multiple sites (hyper-editing) or at specific sites
CC (site-specific editing). Its cellular RNA substrates include: bladder
CC cancer-associated protein (BLCAP), neurotransmitter receptors for
CC glutamate (GRIA2 and GRIK2) and serotonin (HTR2C), GABA receptor
CC (GABRA3) and potassium voltage-gated channel (KCNA1). Site-specific RNA
CC editing of transcripts encoding these proteins results in amino acid
CC substitutions which consequently alter their functional activities.
CC Edits GRIA2 at both the Q/R and R/G sites efficiently but converts the
CC adenosine in hotspot1 much less efficiently. Can exert a proviral
CC effect towards human immunodeficiency virus type 1 (HIV-1) and enhances
CC its replication via both an editing-dependent and editing-independent
CC mechanism. The former involves editing of adenosines in the 5'UTR while
CC the latter occurs via suppression of EIF2AK2/PKR activation and
CC function. Can inhibit cell proliferation and migration and can
CC stimulate exocytosis. {ECO:0000269|PubMed:18178553,
CC ECO:0000269|PubMed:19908260, ECO:0000269|PubMed:21289159}.
CC -!- FUNCTION: [Isoform 1]: Has a lower catalytic activity than isoform 2.
CC {ECO:0000269|PubMed:9149227}.
CC -!- FUNCTION: [Isoform 2]: Has a higher catalytic activity than isoform 1.
CC {ECO:0000269|PubMed:9149227}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine in double-stranded RNA + H(+) + H2O = inosine in
CC double-stranded RNA + NH4(+); Xref=Rhea:RHEA:10120, Rhea:RHEA-
CC COMP:13885, Rhea:RHEA-COMP:13886, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:28938, ChEBI:CHEBI:74411,
CC ChEBI:CHEBI:82852; EC=3.5.4.37;
CC Evidence={ECO:0000269|PubMed:16141067, ECO:0000269|PubMed:32220291,
CC ECO:0000269|PubMed:9149227};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10121;
CC Evidence={ECO:0000269|PubMed:32220291};
CC -!- COFACTOR:
CC Name=1D-myo-inositol hexakisphosphate; Xref=ChEBI:CHEBI:58130;
CC Note=Binds 1 myo-inositol hexakisphosphate (IP6) per subunit.;
CC -!- SUBUNIT: Homodimer. Homodimerization is essential for its catalytic
CC activity. Can form heterodimers with isoform 5 of ADAR/ADAR1.
CC {ECO:0000269|PubMed:16141067, ECO:0000269|PubMed:18178553}.
CC -!- INTERACTION:
CC P78563; P68400: CSNK2A1; NbExp=3; IntAct=EBI-2967304, EBI-347804;
CC P78563; P05412: JUN; NbExp=3; IntAct=EBI-2967304, EBI-852823;
CC P78563; Q13526: PIN1; NbExp=12; IntAct=EBI-2967304, EBI-714158;
CC P78563; O00308: WWP2; NbExp=5; IntAct=EBI-2967304, EBI-743923;
CC P78563; P0DTC9: N; Xeno; NbExp=4; IntAct=EBI-2967304, EBI-25475856;
CC P78563-4; P78563-4: ADARB1; NbExp=3; IntAct=EBI-12002366, EBI-12002366;
CC P78563-4; Q08426: EHHADH; NbExp=3; IntAct=EBI-12002366, EBI-2339219;
CC P78563-4; P19525: EIF2AK2; NbExp=3; IntAct=EBI-12002366, EBI-640775;
CC P78563-4; O15226: NKRF; NbExp=3; IntAct=EBI-12002366, EBI-766011;
CC P78563-4; Q8TCS8: PNPT1; NbExp=3; IntAct=EBI-12002366, EBI-1052020;
CC P78563-4; O75569: PRKRA; NbExp=3; IntAct=EBI-12002366, EBI-713955;
CC P78563-4; O95793: STAU1; NbExp=3; IntAct=EBI-12002366, EBI-358174;
CC P78563-4; Q6ZVD7: STOX1; NbExp=3; IntAct=EBI-12002366, EBI-3923644;
CC P78563-4; Q96SI9: STRBP; NbExp=3; IntAct=EBI-12002366, EBI-740355;
CC P78563-4; Q15633: TARBP2; NbExp=3; IntAct=EBI-12002366, EBI-978581;
CC P78563-4; Q8N8B7-2: TCEANC; NbExp=3; IntAct=EBI-12002366, EBI-11955057;
CC P78563-4; Q7KZS0: UBE2I; NbExp=3; IntAct=EBI-12002366, EBI-10180829;
CC P78563-4; Q9H898-2: ZMAT4; NbExp=3; IntAct=EBI-12002366, EBI-11529334;
CC P78563-4; Q9UL40: ZNF346; NbExp=3; IntAct=EBI-12002366, EBI-2462313;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:32220291}. Nucleus,
CC nucleolus {ECO:0000269|PubMed:32220291}. Note=Shuttles between nucleoli
CC and the nucleoplasm. {ECO:0000305|PubMed:32220291}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus
CC {ECO:0000269|PubMed:32220291}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:32220291}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Nucleus
CC {ECO:0000269|PubMed:32220291}. Nucleus, nucleolus
CC {ECO:0000269|PubMed:32220291}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative promoter usage, Alternative splicing; Named isoforms=6;
CC Comment=Additional isoforms seem to exist.;
CC Name=1; Synonyms=ADAR2b {ECO:0000303|PubMed:32220291}, ADAR2L
CC {ECO:0000303|PubMed:32220291}, DRADA2B, RED1-L;
CC IsoId=P78563-1; Sequence=Displayed;
CC Name=2; Synonyms=ADAR2a {ECO:0000303|PubMed:32220291}, ADAR2S
CC {ECO:0000303|PubMed:32220291}, DRADA2A, RED1-S;
CC IsoId=P78563-2; Sequence=VSP_000865;
CC Name=3; Synonyms=DRADA2C;
CC IsoId=P78563-3; Sequence=VSP_000866;
CC Name=4;
CC IsoId=P78563-4; Sequence=VSP_019597, VSP_000865;
CC Name=5; Synonyms=ADAR2R;
CC IsoId=P78563-5; Sequence=VSP_041421;
CC Name=6; Synonyms=ADAR2d;
CC IsoId=P78563-6; Sequence=VSP_000865, VSP_000866;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain and heart and at lower
CC levels in placenta. Fair expression in lung, liver and kidney. Detected
CC in brain, heart, kidney, lung and liver (at protein level).
CC {ECO:0000269|PubMed:18178553, ECO:0000269|PubMed:9149227}.
CC -!- TISSUE SPECIFICITY: [Isoform 5]: Highly expressed in hippocampus and
CC colon. Expressed in pediatric astrocytomas and the protein has a
CC decreased RNA-editing activity. The decrease in RNA editing correlates
CC with the grade of malignancy of the tumors, with the high grade tumors
CC showing lower editing is seen. {ECO:0000269|PubMed:19156214}.
CC -!- DISEASE: Neurodevelopmental disorder with hypotonia, microcephaly, and
CC seizures (NEDHYMS) [MIM:618862]: An autosomal recessive
CC neurodevelopmental disorder characterized by global developmental delay
CC with axial hypotonia, inability to sit or walk, impaired intellectual
CC development with absent language, and early-onset intractable seizures
CC in most patients. Additional features include poor overall growth,
CC microcephaly, dysmorphic features, poor eye contact due to cortical
CC blindness, and nonspecific brain abnormalities.
CC {ECO:0000269|PubMed:32220291}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 1]: Alu insert from position 465 to 505. May be
CC produced at very low levels due to a premature stop codon in the mRNA,
CC leading to nonsense-mediated mRNA decay.
CC -!- MISCELLANEOUS: [Isoform 5]: Likely expressed from an alternative
CC promoter. Contains a region highly similar to the so-called ssRNA-
CC binding R-domain of ADARB2. {ECO:0000269|PubMed:19156214}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACN49027.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U82120; AAB61686.1; -; mRNA.
DR EMBL; U82121; AAB61687.1; -; mRNA.
DR EMBL; X99227; CAA67611.1; -; mRNA.
DR EMBL; X99383; CAA67762.1; -; mRNA.
DR EMBL; U76420; AAC51240.1; -; mRNA.
DR EMBL; U76421; AAC51241.1; -; mRNA.
DR EMBL; U76422; AAC51242.1; -; mRNA.
DR EMBL; AF001042; AAB58300.1; -; mRNA.
DR EMBL; AF525422; AAM83100.1; -; mRNA.
DR EMBL; AF533142; AAM97654.1; -; mRNA.
DR EMBL; AY135659; AAN10291.1; -; mRNA.
DR EMBL; AB194370; BAE16326.1; -; mRNA.
DR EMBL; AB194371; BAE16327.1; -; mRNA.
DR EMBL; AB194372; BAE16328.1; -; mRNA.
DR EMBL; AB194373; BAE16329.1; -; mRNA.
DR EMBL; AL163301; CAB90493.1; -; Genomic_DNA.
DR EMBL; AL133499; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AP001579; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX322560; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471079; EAX09357.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09359.1; -; Genomic_DNA.
DR EMBL; CH471079; EAX09360.1; -; Genomic_DNA.
DR EMBL; BC065545; AAH65545.1; -; mRNA.
DR EMBL; FJ169506; ACN49027.1; ALT_INIT; mRNA.
DR CCDS; CCDS33589.1; -. [P78563-1]
DR CCDS; CCDS33590.1; -. [P78563-2]
DR CCDS; CCDS42970.1; -. [P78563-3]
DR RefSeq; NP_001103.1; NM_001112.3. [P78563-2]
DR RefSeq; NP_001153702.1; NM_001160230.1. [P78563-6]
DR RefSeq; NP_001333616.1; NM_001346687.1.
DR RefSeq; NP_001333617.1; NM_001346688.1. [P78563-6]
DR RefSeq; NP_056648.1; NM_015833.3. [P78563-1]
DR RefSeq; NP_056649.1; NM_015834.3. [P78563-3]
DR RefSeq; XP_016883736.1; XM_017028247.1. [P78563-1]
DR RefSeq; XP_016883737.1; XM_017028248.1. [P78563-1]
DR RefSeq; XP_016883738.1; XM_017028249.1. [P78563-1]
DR RefSeq; XP_016883739.1; XM_017028250.1. [P78563-1]
DR RefSeq; XP_016883740.1; XM_017028251.1. [P78563-1]
DR RefSeq; XP_016883743.1; XM_017028254.1. [P78563-3]
DR RefSeq; XP_016883744.1; XM_017028255.1. [P78563-2]
DR PDB; 1ZY7; X-ray; 1.70 A; A/B=299-741.
DR PDB; 5ED1; X-ray; 2.77 A; A/D=299-741.
DR PDB; 5ED2; X-ray; 2.95 A; A/D=299-741.
DR PDB; 5HP2; X-ray; 2.98 A; A/D=299-741.
DR PDB; 5HP3; X-ray; 3.09 A; A/D=299-741.
DR PDB; 6D06; X-ray; 2.55 A; A/D=299-741.
DR PDB; 6VFF; X-ray; 2.80 A; A/B=215-741.
DR PDB; 7KFN; X-ray; 2.50 A; A/D=299-741.
DR PDBsum; 1ZY7; -.
DR PDBsum; 5ED1; -.
DR PDBsum; 5ED2; -.
DR PDBsum; 5HP2; -.
DR PDBsum; 5HP3; -.
DR PDBsum; 6D06; -.
DR PDBsum; 6VFF; -.
DR PDBsum; 7KFN; -.
DR AlphaFoldDB; P78563; -.
DR SMR; P78563; -.
DR BioGRID; 106618; 280.
DR IntAct; P78563; 25.
DR MINT; P78563; -.
DR STRING; 9606.ENSP00000353920; -.
DR iPTMnet; P78563; -.
DR PhosphoSitePlus; P78563; -.
DR BioMuta; ADARB1; -.
DR DMDM; 2829669; -.
DR EPD; P78563; -.
DR jPOST; P78563; -.
DR MassIVE; P78563; -.
DR MaxQB; P78563; -.
DR PaxDb; P78563; -.
DR PeptideAtlas; P78563; -.
DR PRIDE; P78563; -.
DR ProteomicsDB; 11761; -.
DR ProteomicsDB; 33889; -.
DR ProteomicsDB; 57656; -. [P78563-1]
DR ProteomicsDB; 57657; -. [P78563-2]
DR ProteomicsDB; 57658; -. [P78563-3]
DR ProteomicsDB; 57659; -. [P78563-4]
DR Antibodypedia; 10404; 140 antibodies from 27 providers.
DR DNASU; 104; -.
DR Ensembl; ENST00000348831.9; ENSP00000015877.6; ENSG00000197381.17. [P78563-2]
DR Ensembl; ENST00000360697.4; ENSP00000353920.3; ENSG00000197381.17. [P78563-1]
DR Ensembl; ENST00000389863.8; ENSP00000374513.4; ENSG00000197381.17. [P78563-3]
DR Ensembl; ENST00000437626.5; ENSP00000414600.2; ENSG00000197381.17. [P78563-1]
DR Ensembl; ENST00000492414.5; ENSP00000436367.1; ENSG00000197381.17. [P78563-2]
DR Ensembl; ENST00000496664.5; ENSP00000435381.1; ENSG00000197381.17. [P78563-1]
DR Ensembl; ENST00000629643.2; ENSP00000486475.1; ENSG00000197381.17. [P78563-4]
DR GeneID; 104; -.
DR KEGG; hsa:104; -.
DR MANE-Select; ENST00000348831.9; ENSP00000015877.6; NM_001112.4; NP_001103.1. [P78563-2]
DR UCSC; uc002zgr.3; human. [P78563-1]
DR CTD; 104; -.
DR DisGeNET; 104; -.
DR GeneCards; ADARB1; -.
DR HGNC; HGNC:226; ADARB1.
DR HPA; ENSG00000197381; Tissue enhanced (urinary).
DR MalaCards; ADARB1; -.
DR MIM; 601218; gene.
DR MIM; 618862; phenotype.
DR neXtProt; NX_P78563; -.
DR OpenTargets; ENSG00000197381; -.
DR PharmGKB; PA24556; -.
DR VEuPathDB; HostDB:ENSG00000197381; -.
DR eggNOG; KOG2777; Eukaryota.
DR GeneTree; ENSGT00940000155992; -.
DR HOGENOM; CLU_005382_3_1_1; -.
DR InParanoid; P78563; -.
DR OMA; ACLFKAF; -.
DR PhylomeDB; P78563; -.
DR TreeFam; TF315806; -.
DR BRENDA; 3.5.4.37; 2681.
DR PathwayCommons; P78563; -.
DR Reactome; R-HSA-75102; C6 deamination of adenosine.
DR Reactome; R-HSA-77042; Formation of editosomes by ADAR proteins.
DR SignaLink; P78563; -.
DR SIGNOR; P78563; -.
DR BioGRID-ORCS; 104; 8 hits in 1078 CRISPR screens.
DR ChiTaRS; ADARB1; human.
DR EvolutionaryTrace; P78563; -.
DR GeneWiki; ADARB1; -.
DR GenomeRNAi; 104; -.
DR Pharos; P78563; Tbio.
DR PRO; PR:P78563; -.
DR Proteomes; UP000005640; Chromosome 21.
DR RNAct; P78563; protein.
DR Bgee; ENSG00000197381; Expressed in blood vessel layer and 204 other tissues.
DR ExpressionAtlas; P78563; baseline and differential.
DR Genevisible; P78563; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:HGNC-UCL.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0003726; F:double-stranded RNA adenosine deaminase activity; IDA:HGNC-UCL.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:HGNC-UCL.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003729; F:mRNA binding; TAS:BHF-UCL.
DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR GO; GO:0008251; F:tRNA-specific adenosine deaminase activity; IBA:GO_Central.
DR GO; GO:0006382; P:adenosine to inosine editing; IDA:UniProtKB.
DR GO; GO:0016553; P:base conversion or substitution editing; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0021610; P:facial nerve morphogenesis; IEA:Ensembl.
DR GO; GO:0021618; P:hypoglossal nerve morphogenesis; IEA:Ensembl.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:0060384; P:innervation; IEA:Ensembl.
DR GO; GO:0061744; P:motor behavior; IEA:Ensembl.
DR GO; GO:0097049; P:motor neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0060415; P:muscle tissue morphogenesis; IEA:Ensembl.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0044387; P:negative regulation of protein kinase activity by regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0050884; P:neuromuscular process controlling posture; IEA:Ensembl.
DR GO; GO:0007274; P:neuromuscular synaptic transmission; IEA:Ensembl.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0051726; P:regulation of cell cycle; IDA:UniProtKB.
DR GO; GO:0006396; P:RNA processing; IDA:HGNC-UCL.
DR GO; GO:0021965; P:spinal cord ventral commissure morphogenesis; IEA:Ensembl.
DR CDD; cd19895; DSRM_RED1_rpt1; 1.
DR CDD; cd19898; DSRM_RED1_rpt2; 1.
DR IDEAL; IID00604; -.
DR InterPro; IPR002466; A_deamin.
DR InterPro; IPR044458; ADAR2_DSRM_1.
DR InterPro; IPR044459; ADAR2_DSRM_2.
DR InterPro; IPR014720; dsRBD_dom.
DR InterPro; IPR008996; IL1/FGF.
DR Pfam; PF02137; A_deamin; 1.
DR Pfam; PF00035; dsrm; 2.
DR SMART; SM00552; ADEAMc; 1.
DR SMART; SM00358; DSRM; 2.
DR SUPFAM; SSF50353; SSF50353; 1.
DR PROSITE; PS50141; A_DEAMIN_EDITASE; 1.
DR PROSITE; PS50137; DS_RBD; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative promoter usage; Alternative splicing;
KW Antiviral defense; Disease variant; Hydrolase; Immunity; Innate immunity;
KW Intellectual disability; Metal-binding; mRNA processing; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; RNA-binding; Zinc.
FT CHAIN 1..741
FT /note="Double-stranded RNA-specific editase 1"
FT /id="PRO_0000171779"
FT DOMAIN 78..144
FT /note="DRBM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 231..298
FT /note="DRBM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00266"
FT DOMAIN 370..737
FT /note="A to I editase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00240"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 83..88
FT /note="Interaction with substrate RNA"
FT /evidence="ECO:0000250"
FT REGION 104..105
FT /note="Interaction with substrate RNA"
FT /evidence="ECO:0000250"
FT REGION 237..242
FT /note="Interaction with substrate RNA"
FT /evidence="ECO:0000250"
FT REGION 259
FT /note="Interaction with substrate RNA"
FT /evidence="ECO:0000250"
FT REGION 486..518
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 14..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 489..504
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 396
FT /note="Proton donor"
FT BINDING 394
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 400
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT BINDING 401
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT BINDING 451
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 556
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT BINDING 559
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT BINDING 562
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT BINDING 669
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT BINDING 702
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT BINDING 712
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT BINDING 730
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT MOD_RES 26
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231"
FT MOD_RES 149
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MKIPRMKTPCQPDRNSLRQSRNPQKYFAM (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:12459255"
FT /id="VSP_019597"
FT VAR_SEQ 1
FT /note="M -> MASSTTPPLHMGTFFSVMGRRYKRRRKKRSERKDRNSLRQSRNPQKY
FT FAM (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:19156214"
FT /id="VSP_041421"
FT VAR_SEQ 466..505
FT /note="Missing (in isoform 2, isoform 4 and isoform 6)"
FT /evidence="ECO:0000303|PubMed:12459255,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:16297572,
FT ECO:0000303|PubMed:9111310, ECO:0000303|PubMed:9143496,
FT ECO:0000303|PubMed:9149227"
FT /id="VSP_000865"
FT VAR_SEQ 713..741
FT /note="ARLFTAFIKAGLGAWVEKPTEQDQFSLTP -> VH (in isoform 3
FT and isoform 6)"
FT /evidence="ECO:0000303|PubMed:16297572,
FT ECO:0000303|PubMed:9111310"
FT /id="VSP_000866"
FT VARIANT 127
FT /note="K -> E (in NEDHYMS; unknown pathological
FT significance; mild decreased editing activity)"
FT /evidence="ECO:0000269|PubMed:32220291"
FT /id="VAR_083947"
FT VARIANT 224
FT /note="V -> A (in dbSNP:rs199697177)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_070931"
FT VARIANT 367
FT /note="K -> N (in NEDHYMS; unknown pathological
FT significance; mild decreased editing activity)"
FT /evidence="ECO:0000269|PubMed:32220291"
FT /id="VAR_083948"
FT VARIANT 498
FT /note="T -> A (in NEDHYMS; unknown pathological
FT significance; altered ratio of alternative splicing)"
FT /evidence="ECO:0000269|PubMed:32220291"
FT /id="VAR_083949"
FT VARIANT 603
FT /note="R -> Q (in NEDHYMS; decreased protein stability;
FT strong decreased editing activity)"
FT /evidence="ECO:0000269|PubMed:32220291"
FT /id="VAR_083950"
FT VARIANT 722
FT /note="A -> V (in NEDHYMS; unknown pathological
FT significance; mild decreased editing activity)"
FT /evidence="ECO:0000269|PubMed:32220291"
FT /id="VAR_083951"
FT CONFLICT 30
FT /note="G -> A (in Ref. 4; AAB58300 and 5; AAM83100/
FT AAM97654/AAN10291)"
FT /evidence="ECO:0000305"
FT CONFLICT 423
FT /note="R -> E (in Ref. 4; AAB58300 and 5; AAM83100/
FT AAM97654/AAN10291)"
FT /evidence="ECO:0000305"
FT CONFLICT 475
FT /note="V -> L (in Ref. 5; AAM83100/AAN10291)"
FT /evidence="ECO:0000305"
FT HELIX 237..243
FT /evidence="ECO:0007829|PDB:6VFF"
FT STRAND 250..257
FT /evidence="ECO:0007829|PDB:6VFF"
FT STRAND 262..269
FT /evidence="ECO:0007829|PDB:6VFF"
FT STRAND 272..280
FT /evidence="ECO:0007829|PDB:6VFF"
FT HELIX 281..296
FT /evidence="ECO:0007829|PDB:6VFF"
FT TURN 304..307
FT /evidence="ECO:0007829|PDB:6VFF"
FT STRAND 313..315
FT /evidence="ECO:0007829|PDB:5ED1"
FT HELIX 320..338
FT /evidence="ECO:0007829|PDB:1ZY7"
FT TURN 339..343
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 345..347
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 352..361
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 363..365
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 367..373
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 375..377
FT /evidence="ECO:0007829|PDB:6VFF"
FT HELIX 380..382
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 391..394
FT /evidence="ECO:0007829|PDB:6VFF"
FT HELIX 395..416
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 418..423
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 425..428
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 432..436
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 440..448
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 453..456
FT /evidence="ECO:0007829|PDB:1ZY7"
FT TURN 515..518
FT /evidence="ECO:0007829|PDB:7KFN"
FT STRAND 521..524
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 527..532
FT /evidence="ECO:0007829|PDB:7KFN"
FT STRAND 535..537
FT /evidence="ECO:0007829|PDB:7KFN"
FT HELIX 542..546
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 552..554
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 556..566
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 570..574
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 582..589
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 593..600
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 602..604
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 620..623
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 637..643
FT /evidence="ECO:0007829|PDB:1ZY7"
FT STRAND 650..653
FT /evidence="ECO:0007829|PDB:1ZY7"
FT TURN 654..657
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 669..680
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 685..687
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 698..703
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 706..721
FT /evidence="ECO:0007829|PDB:1ZY7"
FT HELIX 732..735
FT /evidence="ECO:0007829|PDB:1ZY7"
SQ SEQUENCE 741 AA; 80763 MW; 02B583414DD59C20 CRC64;
MDIEDEENMS SSSTDVKENR NLDNVSPKDG STPGPGEGSQ LSNGGGGGPG RKRPLEEGSN
GHSKYRLKKR RKTPGPVLPK NALMQLNEIK PGLQYTLLSQ TGPVHAPLFV MSVEVNGQVF
EGSGPTKKKA KLHAAEKALR SFVQFPNASE AHLAMGRTLS VNTDFTSDQA DFPDTLFNGF
ETPDKAEPPF YVGSNGDDSF SSSGDLSLSA SPVPASLAQP PLPVLPPFPP PSGKNPVMIL
NELRPGLKYD FLSESGESHA KSFVMSVVVD GQFFEGSGRN KKLAKARAAQ SALAAIFNLH
LDQTPSRQPI PSEGLQLHLP QVLADAVSRL VLGKFGDLTD NFSSPHARRK VLAGVVMTTG
TDVKDAKVIS VSTGTKCING EYMSDRGLAL NDCHAEIISR RSLLRFLYTQ LELYLNNKDD
QKRSIFQKSE RGGFRLKENV QFHLYISTSP CGDARIFSPH EPILEGSRSY TQAGVQWCNH
GSLQPRPPGL LSDPSTSTFQ GAGTTEPADR HPNRKARGQL RTKIESGEGT IPVRSNASIQ
TWDGVLQGER LLTMSCSDKI ARWNVVGIQG SLLSIFVEPI YFSSIILGSL YHGDHLSRAM
YQRISNIEDL PPLYTLNKPL LSGISNAEAR QPGKAPNFSV NWTVGDSAIE VINATTGKDE
LGRASRLCKH ALYCRWMRVH GKVPSHLLRS KITKPNVYHE SKLAAKEYQA AKARLFTAFI
KAGLGAWVEK PTEQDQFSLT P
