CGLR_DROEU
ID CGLR_DROEU Reviewed; 372 AA.
AC P0DV11;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 1.
DT 03-AUG-2022, entry version 3.
DE RecName: Full=Cyclic GMP-AMP synthase-like receptor {ECO:0000305};
DE Short=cGLR {ECO:0000303|PubMed:34261127};
DE EC=2.7.7.- {ECO:0000269|PubMed:34261127};
OS Drosophila eugracilis (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=29029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=34279216; DOI=10.7554/elife.66405;
RA Kim B.Y., Wang J.R., Miller D.E., Barmina O., Delaney E., Thompson A.,
RA Comeault A.A., Peede D., D'Agostino E.R., Pelaez J., Aguilar J.M., Haji D.,
RA Matsunaga T., Armstrong E.E., Zych M., Ogawa Y., Stamenkovic-Radak M.,
RA Jelic M., Veselinovic M.S., Tanaskovic M., Eric P., Gao J.J., Katoh T.K.,
RA Toda M.J., Watabe H., Watada M., Davis J.S., Moyle L.C., Manoli G.,
RA Bertolini E., Kostal V., Hawley R.S., Takahashi A., Jones C.D., Price D.K.,
RA Whiteman N., Kopp A., Matute D.R., Petrov D.A.;
RT "Highly contiguous assemblies of 101 drosophilid genomes.";
RL Elife 10:0-0(2021).
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 15 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). {ECO:0000269|PubMed:34261127}.
CC -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
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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..372
FT /note="Cyclic GMP-AMP synthase-like receptor"
FT /id="PRO_0000454446"
FT BINDING 68
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 70
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 82..84
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 82
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 84
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 190
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 190
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 236..243
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 240..243
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 261
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 274..278
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
SQ SEQUENCE 372 AA; 43607 MW; 4BFA5A7568A421CE CRC64;
MENFAEKKIS KPLTFGEGIQ YVLDRISIKP EDRQTFKEDA QQIQNEFVRA ISKQDPYFAS
AFRGLALTGS SLDNVRINLP DEFDMLTKIK MPCKLEPVPI RSHPGYVFLR ASGDNIPIHL
VDRWEDEYCI DRLKVQAWFR DNITAVIPEL SNIRCNDGRS YELVNKTIGD VAHTIQAKCL
SDPDRSISFD FVPAFEFSAS EWPRIFPQHR NEDRSWYAVP SEFKYPNVGD DPLSFLVCAP
YWERMVLTKK QHLKDGYRLM KAMRDANDMP KIYSYTIKSV FLNASNVNKL INWNQSPGRI
LIRAIDLLAM FLRKGKLPSY LVPDRNMLDR LSVDMRQDYR RKLCHIFRRL IRCRDRDCMT
SEDLQFIFGM RY
