CGLR1_DROER
ID CGLR1_DROER Reviewed; 445 AA.
AC B3NQ14;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 1.
DT 03-AUG-2022, entry version 53.
DE RecName: Full=Cyclic GMP-AMP synthase-like receptor 1 {ECO:0000305};
DE Short=cGLR1 {ECO:0000303|PubMed:34261127};
DE EC=2.7.7.- {ECO:0000269|PubMed:34261127};
GN ORFNames=GG20550;
OS Drosophila erecta (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7220;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tucson 14021-0224.01;
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 activating the nucleotidyltransferase activity, leading to synthesis of
CC 3',2'-cGAMP, a second messenger that binds to and activates Sting,
CC thereby triggering the antiviral immune response via activation of the
CC NF-kappa-B transcription factor Rel (Relish) (By similarity).
CC {ECO:0000250|UniProtKB:A1ZA55, 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). {ECO:0000269|PubMed:34261127}.
CC -!- SIMILARITY: Belongs to the mab-21 family. {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; CH954179; EDV55861.1; -; Genomic_DNA.
DR RefSeq; XP_001975461.1; XM_001975425.1.
DR EnsemblMetazoa; FBtr0140604; FBpp0139096; FBgn0112740.
DR GeneID; 6548847; -.
DR KEGG; der:6548847; -.
DR eggNOG; ENOG502S61H; Eukaryota.
DR HOGENOM; CLU_034978_0_0_1; -.
DR OMA; KLLFFWD; -.
DR OrthoDB; 759341at2759; -.
DR PhylomeDB; B3NQ14; -.
DR Proteomes; UP000008711; Unassembled WGS sequence.
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; RNA-binding; Transferase.
FT CHAIN 1..445
FT /note="Cyclic GMP-AMP synthase-like receptor 1"
FT /id="PRO_0000454445"
FT REGION 357..445
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 360..379
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 380..396
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 397..445
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 70..72
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 70
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 72
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 186
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 186
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 232..239
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 236..239
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 257
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 270..274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
SQ SEQUENCE 445 AA; 50799 MW; 513A10C6E2D4C7D9 CRC64;
MVRNLEDFCN EANAKHIRIE DRERYTGHFN ALKDMVYSYW KKSKGLDKLV KGTTLCGGYG
DNLKVSKPDE YDLLIHLVFP ENDKIIVKAD ASNPGNVLLD MTKVMEIIAK QEHNKPVFDL
LQKIVNNKKQ LLEDKLQSFL HGIMTQTLNK MGNRIEVQGE ISHLSYKKCG PAHNILVKGP
CEYSVDFVPA IKLSAAQLVL APEQRKHFGG TLYWDAVPKP MKPAKPDNPS FRTSFYEAER
SLLHGKQNLK SAIRMIKHIR NEKNKANLKS YHIKTVFLWQ VMEKDASYWE KPKKEILIEM
LGKLADLLAL TPRKGRLPYF WDPKLDMFAD LTDDQRTDMF NCFRKCEYVF RKADGNLNDD
NENSVHSSFK GSGRNGQKME KTSTESEQKK PTETKPNAKV ESTPVKPNPK PSVQEKQAKP
NLADQKKCTK NANGTKSKTT TPKPS
