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Overview

Uniprot IDP55265
Protein NameDouble-stranded RNA-specific adenosine deaminase
Gene NameADAR
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
1115 RVSIYDSKRQSGKTK
1196 ARDYETAKNYFKKGL
1200 ETAKNYFKKGLKDMG
1201 TAKNYFKKGLKDMGY
326 AKNIGLTKARDINAV
384 PAAIPETKRNAEFLT
495 PRCSPYKKLTECQLK
637 CEFRLLSKEGPAHEP
665 PSVSAPSKKVAKQMA
666 SVSAPSKKVAKQMAA
669 APSKKVAKQMAAEEA
715 MMPNKVRKIGELVRY
902 KGDSLSLKGETVNDC
936 KYNSQTAKDSIFEPA
944 DSIFEPAKGGEKLQI

Function

Catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA (dsRNA) referred to as A-to-I RNA editing (PubMed:12618436, PubMed:7565688, PubMed:7972084). This may affect gene expression and function in a number of ways that include mRNA translation by changing codons and hence the amino acid sequence of proteins since the translational machinery read the inosine as a guanosine; pre-mRNA splicing by altering splice site recognition sequences; RNA stability by changing sequences involved in nuclease recognition; genetic stability in the case of RNA virus genomes by changing sequences during viral RNA replication; and RNA structure-dependent activities such as microRNA production or targeting or protein-RNA interactions. Can edit both viral and cellular RNAs and can edit RNAs at multiple sites (hyper-editing) or at specific sites (site-specific editing). Its cellular RNA substrates include: bladder cancer-associated protein (BLCAP), neurotransmitter receptors for glutamate (GRIA2) and serotonin (HTR2C) and GABA receptor (GABRA3). Site-specific RNA editing of transcripts encoding these proteins results in amino acid substitutions which consequently alters their functional activities. Exhibits low-level editing at the GRIA2 Q/R site, but edits efficiently at the R/G site and HOTSPOT1. Its viral RNA substrates include: hepatitis C virus (HCV), vesicular stomatitis virus (VSV), measles virus (MV), hepatitis delta virus (HDV), and human immunodeficiency virus type 1 (HIV-1). Exhibits either a proviral (HDV, MV, VSV and HIV-1) or an antiviral effect (HCV) and this can be editing-dependent (HDV and HCV), editing-independent (VSV and MV) or both (HIV-1). Impairs HCV replication via RNA editing at multiple sites. Enhances the replication of MV, VSV and HIV-1 through an editing-independent mechanism via suppression of EIF2AK2/PKR activation and function. Stimulates both the release and infectivity of HIV-1 viral particles by an editing-dependent mechanism where it associates with viral RNAs and edits adenosines in the 5'UTR and the Rev and Tat coding sequence. Can enhance viral replication of HDV via A-to-I editing at a site designated as amber/W, thereby changing an UAG amber stop codon to an UIG tryptophan (W) codon that permits synthesis of the large delta antigen (L-HDAg) which has a key role in the assembly of viral particles. However, high levels of ADAR1 inhibit HDV replication

Protein Sequence

10 MNPRQGYSLS 20 GYYTHPFQGY 30 EHRQLRYQQP 40 GPGSSPSSFL 50 LKQIEFLKGQ 60 LPEAPVIGKQ 70 TPSLPPSLPG 80 LRPRFPVLLA 90 SSTRGRQVDI 100 RGVPRGVHLR 110 SQGLQRGFQH 120 PSPRGRSLPQ 130 RGVDCLSSHF 140 QELSIYQDQE 150 QRILKFLEEL 160 GEGKATTAHD 170 LSGKLGTPKK 180 EINRVLYSLA 190 KKGKLQKEAG 200 TPPLWKIAVS 210 TQAWNQHSGV 220 VRPDGHSQGA 230 PNSDPSLEPE 240 DRNSTSVSED 250 LLEPFIAVSA 260 QAWNQHSGVV 270 RPDSHSQGSP 280 NSDPGLEPED 290 SNSTSALEDP 300 LEFLDMAEIK 310 EKICDYLFNV 320 SDSSALNLAK 330 NIGLTKARDI 340 NAVLIDMERQ 350 GDVYRQGTTP 360 PIWHLTDKKR 370 ERMQIKRNTN 380 SVPETAPAAI 390 PETKRNAEFL 400 TCNIPTSNAS 410 NNMVTTEKVE 420 NGQEPVIKLE 430 NRQEARPEPA 440 RLKPPVHYNG 450 PSKAGYVDFE 460 NGQWATDDIP 470 DDLNSIRAAP 480 GEFRAIMEMP 490 SFYSHGLPRC 500 SPYKKLTECQ 510 LKNPISGLLE 520 YAQFASQTCE 530 FNMIEQSGPP 540 HEPRFKFQVV 550 INGREFPPAE 560 AGSKKVAKQD 570 AAMKAMTILL 580 EEAKAKDSGK 590 SEESSHYSTE 600 KESEKTAESQ 610 TPTPSATSFF 620 SGKSPVTTLL 630 ECMHKLGNSC 640 EFRLLSKEGP 650 AHEPKFQYCV 660 AVGAQTFPSV 670 SAPSKKVAKQ 680 MAAEEAMKAL 690 HGEATNSMAS 700 DNQPEGMISE 710 SLDNLESMMP 720 NKVRKIGELV 730 RYLNTNPVGG 740 LLEYARSHGF 750 AAEFKLVDQS 760 GPPHEPKFVY 770 QAKVGGRWFP 780 AVCAHSKKQG 790 KQEAADAALR 800 VLIGENEKAE 810 RMGFTEVTPV 820 TGASLRRTML 830 LLSRSPEAQP 840 KTLPLTGSTF 850 HDQIAMLSHR 860 CFNTLTNSFQ 870 PSLLGRKILA 880 AIIMKKDSED 890 MGVVVSLGTG 900 NRCVKGDSLS 910 LKGETVNDCH 920 AEIISRRGFI 930 RFLYSELMKY 940 NSQTAKDSIF 950 EPAKGGEKLQ 960 IKKTVSFHLY 970 ISTAPCGDGA 980 LFDKSCSDRA 990 MESTESRHYP 1000 VFENPKQGKL 1010 RTKVENGEGT 1020 IPVESSDIVP 1030 TWDGIRLGER 1040 LRTMSCSDKI 1050 LRWNVLGLQG 1060 ALLTHFLQPI 1070 YLKSVTLGYL 1080 FSQGHLTRAI 1090 CCRVTRDGSA 1100 FEDGLRHPFI 1110 VNHPKVGRVS 1120 IYDSKRQSGK 1130 TKETSVNWCL 1140 ADGYDLEILD 1150 GTRGTVDGPR 1160 NELSRVSKKN 1170 IFLLFKKLCS 1180 FRYRRDLLRL 1190 SYGEAKKAAR 1200 DYETAKNYFK 1210 KGLKDMGYGN 1220 WISKPQEEKN FYLCPV

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005829 cytosol
Cellular Component GO:0016020 membrane
Cellular Component GO:0005739 mitochondrion
Cellular Component GO:0005730 nucleolus
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:0044530 supraspliceosomal complex
Molecular Function GO:0003677 DNA binding
Molecular Function GO:0003726 double-stranded RNA adenosine deaminase activity
Molecular Function GO:0003725 double-stranded RNA binding
Molecular Function GO:0046872 metal ion binding
Molecular Function GO:0003723 RNA binding
Molecular Function GO:0008251 tRNA-specific adenosine deaminase activity
Biological Process GO:0006382 adenosine to inosine editing
Biological Process GO:0016553 base conversion or substitution editing
Biological Process GO:0098586 cellular response to virus
Biological Process GO:0051607 defense response to virus
Biological Process GO:0045087 innate immune response
Biological Process GO:0016556 mRNA modification
Biological Process GO:0006397 mRNA processing
Biological Process GO:0044387 negative regulation of protein kinase activity by regulation of protein phosphorylation
Biological Process GO:0045070 positive regulation of viral genome replication
Biological Process GO:0031054 pre-miRNA processing
Biological Process GO:0006611 protein export from nucleus
Biological Process GO:0006606 protein import into nucleus
Biological Process GO:0035455 response to interferon-alpha
Biological Process GO:0009615 response to virus
Biological Process GO:0070922 RISC complex assembly
Biological Process GO:0006396 RNA processing

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[3] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[4] Yang YH, Wang QC, Kong J, Yang JT, Liu JF. Global profiling of lysine lactylation in human lungs.. Proteomics 23(15):e2200437. 2023 Aug. PMID: 37170646.

[5] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[6] Bao Q, Wan N, He Z, Cao J, Yuan W et al.. Subcellular Proteomic Mapping of Lysine Lactylation.. J Am Soc Mass Spectrom 35(12):3221-3232. 2024 Dec 4. PMID: 39569522.

[7] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[8] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.