CGLR1_DROME
ID CGLR1_DROME Reviewed; 378 AA.
AC A1ZA55;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-2015, sequence version 2.
DT 03-AUG-2022, entry version 101.
DE RecName: Full=Cyclic GMP-AMP synthase-like receptor 1 {ECO:0000305};
DE Short=Dm-cGLR1 {ECO:0000303|PubMed:34261127};
DE Short=cGLR1 {ECO:0000303|PubMed:34261127, ECO:0000303|PubMed:34261128};
DE EC=2.7.7.- {ECO:0000269|PubMed:34261127, ECO:0000269|PubMed:34261128};
GN ORFNames=CG12970 {ECO:0000312|FlyBase:FBgn0034047};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, COFACTOR, AND
RP MUTAGENESIS OF ARG-23; LYS-42; LYS-52; ASP-73; ARG-241 AND LYS-251.
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).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP 71-GLU--ASP-73.
RX PubMed=34261128; DOI=10.1038/s41586-021-03800-z;
RA Holleufer A., Winther K.G., Gad H.H., Ai X., Chen Y., Li L., Wei Z.,
RA Deng H., Liu J., Frederiksen N.A., Simonsen B., Andersen L.L.,
RA Kleigrewe K., Dalskov L., Pichlmair A., Cai H., Imler J.L., Hartmann R.;
RT "Two cGAS-like receptors induce antiviral immunity in Drosophila.";
RL Nature 597:114-118(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
CC antiviral innate immunity (PubMed:34261127, PubMed:34261128).
CC Synthesizes 3',2'-cGAMP in a two-step reaction through production of
CC the linear intermediate pppA(2'-5')pG (PubMed:34261127). Acts as a key
CC sensor of double-stranded RNA (dsRNA), the presence of dsRNA in the
CC cytoplasm being a danger signal that triggers the immune responses
CC (PubMed:34261127). Directly binds dsRNA, activating the
CC nucleotidyltransferase activity, leading to synthesis of 3',2'-cGAMP, a
CC second messenger that binds to and activates Sting, thereby triggering
CC the antiviral immune response via activation of the NF-kappa-B
CC transcription factor Rel (Relish) (PubMed:34261127, PubMed:34261128).
CC 3',2'-cGAMP is protected from poxin cleavage (PubMed:34261127).
CC {ECO:0000269|PubMed:34261127, ECO:0000269|PubMed:34261128}.
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:0000269|PubMed:34261127,
CC ECO:0000269|PubMed:34261128};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68345;
CC Evidence={ECO:0000269|PubMed:34261127};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:34261127};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:34261127};
CC -!- ACTIVITY REGULATION: The enzyme activity is specifically activated by
CC double-stranded RNA (dsRNA) (PubMed:34261127, PubMed:34261128).
CC Recognizes long dsRNA (>30 bp) with no preference for 5' RNA
CC phosphorylation (PubMed:34261127). {ECO:0000269|PubMed:34261127,
CC ECO:0000269|PubMed:34261128}.
CC -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
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DR EMBL; AE013599; AAO41387.2; -; Genomic_DNA.
DR RefSeq; NP_788360.2; NM_176180.2.
DR AlphaFoldDB; A1ZA55; -.
DR SMR; A1ZA55; -.
DR PaxDb; A1ZA55; -.
DR EnsemblMetazoa; FBtr0308816; FBpp0300973; FBgn0034047.
DR GeneID; 36744; -.
DR KEGG; dme:Dmel_CG12970; -.
DR UCSC; CG12970-RB; d. melanogaster.
DR FlyBase; FBgn0034047; CG12970.
DR VEuPathDB; VectorBase:FBgn0034047; -.
DR eggNOG; ENOG502S61H; Eukaryota.
DR HOGENOM; CLU_034978_1_0_1; -.
DR OMA; KLLFFWD; -.
DR OrthoDB; 759341at2759; -.
DR PhylomeDB; A1ZA55; -.
DR BioGRID-ORCS; 36744; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 36744; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0034047; Expressed in midgut and 3 other tissues.
DR Genevisible; A1ZA55; DM.
DR GO; GO:0005829; C:cytosol; IC:FlyBase.
DR GO; GO:0140700; F:3',2'-cyclic GMP-AMP synthase activity; IDA: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; IMP:FlyBase.
DR GO; GO:1902615; P:immune response involved in response to exogenous dsRNA; IMP:FlyBase.
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 1: Evidence at protein level;
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..378
FT /note="Cyclic GMP-AMP synthase-like receptor 1"
FT /id="PRO_0000454441"
FT BINDING 71..73
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 71
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 73
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 187
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 187
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 233..240
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 237..240
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 258
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 271..275
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MUTAGEN 23
FT /note="R->E: Abolished ability to activate Sting."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 42
FT /note="K->E: Abolished ability to activate Sting."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 52
FT /note="K->E: Abolished ability to activate Sting."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 71..73
FT /note="EFD->AFA: Abolished nucleotidyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:34261128"
FT MUTAGEN 73
FT /note="D->A: Abolished ability to activate Sting."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 241
FT /note="R->E: Abolished ability to activate Sting."
FT /evidence="ECO:0000269|PubMed:34261127"
FT MUTAGEN 251
FT /note="K->E: Abolished ability to activate Sting."
FT /evidence="ECO:0000269|PubMed:34261127"
SQ SEQUENCE 378 AA; 43386 MW; C7EA39CB1FB14DBC CRC64;
MAMNLENIVN QATAQYVKIK EHREPYTAHY NALKDKVYSE WKSSAVLGKL LKGSTLCGGY
GDKLKVSIPD EFDLLIHLVF PENDKIIVKA DASKPGNVIL DMTKVMEIIG SQEHNKPVFD
RLQKIVNNKK QLLEDKLNSF LESIMTQTLN KMGNQIEVAG RISHLQYKKC GPAHTIFVKG
SCKYSVDFVP AIRLSAAQVV LAPEQRIHFG ETLYWDAIPK PMKPAKTDNT SFTSSFYEAE
RRLLYGKQFL KPAIRLMKQN RNVKNKANLK SYHIKTLFLW QVIQQDPSYW SNSPKDIFIE
MLGKLADSLA LTPKKGKLPF FWDPKLDMFA QLTDSQRTDL YNHFRKCEYT FRKDNGNVND
CTENNVHSSF SKNTTYKL
