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 27-MAR-2024, entry version 209. 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 non-specific 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}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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. DR RefSeq; XP_016883737.1; XM_017028248.1. DR RefSeq; XP_016883738.1; XM_017028249.1. DR RefSeq; XP_016883739.1; XM_017028250.1. DR RefSeq; XP_016883740.1; XM_017028251.1. [P78563-1] DR RefSeq; XP_016883743.1; XM_017028254.1. DR RefSeq; XP_016883744.1; XM_017028255.1. 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 PDB; 8E0F; X-ray; 2.70 A; A/B=215-741. DR PDB; 8E4X; X-ray; 2.80 A; A/B=215-741. 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 PDBsum; 8E0F; -. DR PDBsum; 8E4X; -. DR AlphaFoldDB; P78563; -. DR SMR; P78563; -. DR BioGRID; 106618; 505. DR IntAct; P78563; 32. DR MINT; P78563; -. DR STRING; 9606.ENSP00000353920; -. DR iPTMnet; P78563; -. DR PhosphoSitePlus; P78563; -. DR SwissPalm; P78563; -. DR BioMuta; ADARB1; -. DR DMDM; 2829669; -. DR EPD; P78563; -. DR jPOST; P78563; -. DR MassIVE; P78563; -. DR MaxQB; P78563; -. DR PaxDb; 9606-ENSP00000353920; -. DR PeptideAtlas; 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 Pumba; P78563; -. DR Antibodypedia; 10404; 156 antibodies from 27 providers. DR DNASU; 104; -. DR Ensembl; ENST00000348831.9; ENSP00000015877.6; ENSG00000197381.18. [P78563-2] DR Ensembl; ENST00000360697.4; ENSP00000353920.3; ENSG00000197381.18. [P78563-1] DR Ensembl; ENST00000389861.7; ENSP00000516121.1; ENSG00000197381.18. [P78563-2] DR Ensembl; ENST00000389863.8; ENSP00000374513.4; ENSG00000197381.18. [P78563-3] DR Ensembl; ENST00000437626.5; ENSP00000414600.2; ENSG00000197381.18. [P78563-1] DR Ensembl; ENST00000449478.2; ENSP00000387480.2; ENSG00000197381.18. [P78563-1] DR Ensembl; ENST00000492414.5; ENSP00000436367.1; ENSG00000197381.18. [P78563-2] DR Ensembl; ENST00000496664.5; ENSP00000435381.1; ENSG00000197381.18. [P78563-1] 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 AGR; HGNC:226; -. 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; FCMNVSK; -. DR OrthoDB; 118472at2759; -. 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 1155 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 206 other cell types or tissues. DR ExpressionAtlas; P78563; baseline and differential. 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; IDA:HGNC-UCL. 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 Gene3D; 3.30.160.20; -; 2. 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 PANTHER; PTHR10910:SF58; DOUBLE-STRANDED RNA-SPECIFIC EDITASE 1; 1. DR PANTHER; PTHR10910; EUKARYOTE SPECIFIC DSRNA BINDING PROTEIN; 1. DR Pfam; PF02137; A_deamin; 1. DR Pfam; PF00035; dsrm; 2. DR SMART; SM00552; ADEAMc; 1. DR SMART; SM00358; DSRM; 2. DR SUPFAM; SSF50353; Cytokine; 1. DR SUPFAM; SSF54768; dsRNA-binding domain-like; 2. DR PROSITE; PS50141; A_DEAMIN_EDITASE; 1. DR PROSITE; PS50137; DS_RBD; 2. DR Genevisible; P78563; HS. 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; uncertain significance; mild FT 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; uncertain significance; mild FT decreased editing activity)" FT /evidence="ECO:0000269|PubMed:32220291" FT /id="VAR_083948" FT VARIANT 498 FT /note="T -> A (in NEDHYMS; uncertain significance; altered FT 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; uncertain significance; mild FT 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; FT AAM83100/AAM97654/AAN10291)" FT /evidence="ECO:0000305" FT CONFLICT 423 FT /note="R -> E (in Ref. 4; AAB58300 and 5; FT AAM83100/AAM97654/AAN10291)" FT /evidence="ECO:0000305" FT CONFLICT 475 FT /note="V -> L (in Ref. 5; AAM83100/AAN10291)" FT /evidence="ECO:0000305" FT HELIX 236..243 FT /evidence="ECO:0007829|PDB:8E0F" FT STRAND 250..257 FT /evidence="ECO:0007829|PDB:6VFF" FT HELIX 258..260 FT /evidence="ECO:0007829|PDB:8E0F" FT STRAND 262..269 FT /evidence="ECO:0007829|PDB:8E0F" FT STRAND 272..280 FT /evidence="ECO:0007829|PDB:8E0F" FT HELIX 281..296 FT /evidence="ECO:0007829|PDB:8E0F" 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 //