CGLR1_DROSI
ID CGLR1_DROSI Reviewed; 393 AA.
AC B4QGZ2;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Cyclic GMP-AMP synthase-like receptor 1 {ECO:0000305};
DE Short=Ds-cGLR1 {ECO:0000303|PubMed:34261127};
DE Short=cGLR1 {ECO:0000303|PubMed:34261127};
DE EC=2.7.7.- {ECO:0000269|PubMed:34261127};
GN ORFNames=GD11141 {ECO:0000312|EMBL:EDX07255.1};
OS Drosophila simulans (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7240;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=17994087; DOI=10.1038/nature06341;
RG Drosophila 12 genomes consortium;
RT "Evolution of genes and genomes on the Drosophila phylogeny.";
RL Nature 450:203-218(2007).
RN [2]
RP FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=34261127; DOI=10.1038/s41586-021-03743-5;
RA Slavik K.M., Morehouse B.R., Ragucci A.E., Zhou W., Ai X., Chen Y., Li L.,
RA Wei Z., Baehre H., Koenig M., Seifert R., Lee A.S.Y., Cai H., Imler J.L.,
RA Kranzusch P.J.;
RT "cGAS-like receptors sense RNA and control 3'2'-cGAMP signaling in
RT Drosophila.";
RL Nature 597:109-113(2021).
CC -!- FUNCTION: Nucleotidyltransferase that catalyzes the formation of cyclic
CC GMP-AMP (3',2'-cGAMP) from ATP and GTP and plays a key role in innate
CC immunity (PubMed:34261127). Synthesizes 3',2'-cGAMP in a two-step
CC reaction through production of the linear intermediate pppA(2'-5')pG
CC (By similarity). Acts as a key sensor of double-stranded RNA (dsRNA),
CC the presence of dsRNA in the cytoplasm being a danger signal that
CC triggers the immune responses (PubMed:34261127). Directly binds dsRNA
CC longer than 35 bp, activating the nucleotidyltransferase activity,
CC leading to synthesis of 3',2'-cGAMP, a second messenger that binds to
CC and activates Sting, thereby triggering the antiviral immune response
CC via activation of the NF-kappa-B transcription factor Rel (Relish)
CC (PubMed:34261127). {ECO:0000250|UniProtKB:A1ZA55,
CC ECO:0000269|PubMed:34261127}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + GTP = 3',2'-cGAMP + 2 diphosphate; Xref=Rhea:RHEA:68344,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:177334; Evidence={ECO:0000250|UniProtKB:A1ZA55};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68345;
CC Evidence={ECO:0000250|UniProtKB:A1ZA55};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:A1ZA55};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:A1ZA55};
CC -!- ACTIVITY REGULATION: The enzyme activity is specifically activated by
CC double-stranded RNA (dsRNA) (PubMed:34261127). Recognizes long dsRNA
CC (>30 bp) with no preference for 5' RNA phosphorylation
CC (PubMed:34261127). {ECO:0000269|PubMed:34261127}.
CC -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EDX07255.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; CM000362; EDX07255.1; ALT_SEQ; Genomic_DNA.
DR HOGENOM; CLU_1469732_0_0_1; -.
DR PhylomeDB; B4QGZ2; -.
DR Proteomes; UP000000304; Chromosome 2r.
DR GO; GO:0140700; F:3',2'-cyclic GMP-AMP synthase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003725; F:double-stranded RNA binding; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:1902615; P:immune response involved in response to exogenous dsRNA; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR InterPro; IPR024810; Mab-21_dom.
DR Pfam; PF03281; Mab-21; 1.
DR SMART; SM01265; Mab-21; 1.
PE 3: Inferred from homology;
KW Antiviral defense; ATP-binding; GTP-binding; Immunity; Innate immunity;
KW Magnesium; Manganese; Metal-binding; Nucleotide-binding;
KW Nucleotidyltransferase; Reference proteome; RNA-binding; Transferase.
FT CHAIN 1..393
FT /note="Cyclic GMP-AMP synthase-like receptor 1"
FT /id="PRO_0000454444"
FT BINDING 89..91
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 89
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 91
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 205
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 205
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 251..258
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 255..258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 276
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 289..293
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
SQ SEQUENCE 393 AA; 44849 MW; 62D67875707F180A CRC64;
MSSIRYHSSA FDDGSFSVMA RNLENMVNRA NAQYVKIDKH REPYTVHYNA LRDKVYSEWK
ESGVLGTLLK GSTLCGGYGD KLKVSMPDEF DLLIHLVFPE NDKIIVKADA SKKGNVILDM
TKVMEIIGSQ EHNKPVFDLL QKIVNKKKQL LEDKLNSLLQ SIMTQTLNKM GNQIEVAGRI
SHLEYKKCGP AHTIFVKGPC EYSVDFVPAI RLSAAQVVLA PEQRRHFGGT LYWDAIPKPM
KPAKTDNASF RASFYEAERS LLLGKQSLKP AIRLLKQNRN VKNKANLKSY HIKTLFLWQV
VQQDASYWSN SPKDIFIEML GKLADSLALT PKKGKLPFFW DPKLDMFAEL TDSQRTDLFN
HFRKCEYTFR KDNGNVNDCT ENNVHSSFSI NTR
