CGLR2_DROME
ID CGLR2_DROME Reviewed; 459 AA.
AC A8DYP7; A0A0B4LGP4; A8DYP8; Q5BIH6;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-FEB-2022, sequence version 2.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Cyclic GMP-AMP synthase-like receptor 2 {ECO:0000303|PubMed:34261128};
DE Short=cGLR2 {ECO:0000303|PubMed:34261128};
DE EC=2.7.7.- {ECO:0000269|PubMed:34261128};
DE EC=2.7.7.86 {ECO:0000269|PubMed:34261128};
GN ORFNames=CG30424 {ECO:0000312|FlyBase:FBgn0050424};
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley; TISSUE=Embryo;
RA Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA Park S., Wan K., Yu C., Rubin G.M., Celniker S.;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF 79-GLU--ASP-81; LYS-256;
RP ARG-267 AND ARG-271.
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 from ATP and GTP and plays a key role in antiviral innate
CC immunity (PubMed:34261128). Directly binds some unknown nucleic acid,
CC activating the nucleotidyltransferase activity, leading to synthesis of
CC both 3',2'-cGAMP and 2',3'-cGAMP second messengers (PubMed:34261128).
CC 3',2'-cGAMP and 2',3'-cGAMP bind to and activate Sting, thereby
CC triggering the antiviral immune response via activation of the NF-
CC kappa-B transcription factor Rel (Relish) (PubMed:34261128).
CC {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:34261128};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + GTP = 2',3'-cGAMP + 2 diphosphate; Xref=Rhea:RHEA:42064,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:143093; EC=2.7.7.86;
CC Evidence={ECO:0000269|PubMed:34261128};
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 some nucleic acid. {ECO:0000269|PubMed:34261128}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=D;
CC IsoId=A8DYP7-1; Sequence=Displayed;
CC Name=E;
CC IsoId=A8DYP7-2; Sequence=VSP_061343;
CC Name=C;
CC IsoId=A8DYP7-3; Sequence=VSP_061341;
CC Name=B;
CC IsoId=A8DYP7-4; Sequence=VSP_061342;
CC -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ABV53908.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE013599; ABV53906.1; -; Genomic_DNA.
DR EMBL; AE013599; ABV53907.1; -; Genomic_DNA.
DR EMBL; AE013599; AHN56662.1; -; Genomic_DNA.
DR EMBL; AE013599; ABV53908.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BT021248; AAX33396.1; -; mRNA.
DR RefSeq; NP_001097455.1; NM_001103985.2.
DR AlphaFoldDB; A8DYP7; -.
DR STRING; 7227.FBpp0112289; -.
DR PaxDb; A8DYP7; -.
DR DNASU; 246606; -.
DR EnsemblMetazoa; FBtr0113375; FBpp0112287; FBgn0050424. [A8DYP7-4]
DR EnsemblMetazoa; FBtr0113376; FBpp0112288; FBgn0050424. [A8DYP7-3]
DR EnsemblMetazoa; FBtr0113377; FBpp0112289; FBgn0050424.
DR EnsemblMetazoa; FBtr0343511; FBpp0310116; FBgn0050424. [A8DYP7-2]
DR GeneID; 246606; -.
DR UCSC; CG30424-RB; d. melanogaster.
DR UCSC; CG30424-RD; d. melanogaster. [A8DYP7-1]
DR FlyBase; FBgn0050424; CG30424.
DR VEuPathDB; VectorBase:FBgn0050424; -.
DR eggNOG; ENOG502S61H; Eukaryota.
DR GeneTree; ENSGT01050000244827; -.
DR HOGENOM; CLU_034978_1_0_1; -.
DR InParanoid; A8DYP7; -.
DR OMA; PELNMLD; -.
DR OrthoDB; 759341at2759; -.
DR PhylomeDB; A8DYP7; -.
DR BioGRID-ORCS; 246606; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 246606; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0050424; Expressed in Malpighian tubule and 15 other tissues.
DR ExpressionAtlas; A8DYP7; baseline and differential.
DR Genevisible; A8DYP7; DM.
DR GO; GO:0005829; C:cytosol; IC:FlyBase.
DR GO; GO:0061501; F:2',3'-cyclic GMP-AMP synthase activity; IDA: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:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003723; F:RNA 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 Alternative splicing; Antiviral defense; ATP-binding; GTP-binding;
KW Immunity; Innate immunity; Magnesium; Manganese; Metal-binding;
KW Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW RNA-binding; Transferase; Zinc.
FT CHAIN 1..459
FT /note="Cyclic GMP-AMP synthase-like receptor 2"
FT /id="PRO_0000454442"
FT BINDING 68
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 79..81
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 79
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 81
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 199
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 199
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 248..255
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 252..255
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 263
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 288..292
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT VAR_SEQ 1..317
FT /note="Missing (in isoform C)"
FT /id="VSP_061341"
FT VAR_SEQ 1..301
FT /note="MKESRNLENFVEKKLYECKKKYVDIPKDEGQRYGGKHYEALTSKIFEILRKE
FT NPELDIIIAEFSLEGSVGMLKIAKPNEFDLVFKLKFPYYKSIAVTRDPKIPGNVLLDMT
FT RVLELLKDDPREDFQRIRELIQGRLVDAQNFFVVDRLRSWLQSLFSQALNRISYRVELV
FT AGVVSHLKYRTCGPAHTIYVYGDYEYSVDYVPAICLAAEQNVLPTKQLECFKRANTSYW
FT EAIPKPLKPLTETSMISFRSSFYAVEKILLQDVHENCRNAIRFMKKFRDVKTNLGNCKS
FT YYIKTLFLWKIIQ -> MNAKRSMLTFQRTRDNDM (in isoform B)"
FT /id="VSP_061342"
FT VAR_SEQ 1..301
FT /note="MKESRNLENFVEKKLYECKKKYVDIPKDEGQRYGGKHYEALTSKIFEILRKE
FT NPELDIIIAEFSLEGSVGMLKIAKPNEFDLVFKLKFPYYKSIAVTRDPKIPGNVLLDMT
FT RVLELLKDDPREDFQRIRELIQGRLVDAQNFFVVDRLRSWLQSLFSQALNRISYRVELV
FT AGVVSHLKYRTCGPAHTIYVYGDYEYSVDYVPAICLAAEQNVLPTKQLECFKRANTSYW
FT EAIPKPLKPLTETSMISFRSSFYAVEKILLQDVHENCRNAIRFMKKFRDVKTNLGNCKS
FT YYIKTLFLWKIIQ -> MNAKRSMLTFQRTRDNDMSWTSLLLSSVWK (in isoform
FT E)"
FT /id="VSP_061343"
FT MUTAGEN 79..81
FT /note="EFD->AFA: Abolished nucleotidyltransferase
FT activity."
FT /evidence="ECO:0000269|PubMed:34261128"
FT MUTAGEN 256
FT /note="K->E: Abolished binding to nucleic acid activator,
FT leading to impaired antiviral immunity; when associated
FT with E-267 or E-271."
FT /evidence="ECO:0000269|PubMed:34261128"
FT MUTAGEN 267
FT /note="R->E: Abolished binding to nucleic acid activator,
FT leading to impaired antiviral immunity; when associated
FT with E-256."
FT /evidence="ECO:0000269|PubMed:34261128"
FT MUTAGEN 271
FT /note="R->E: Abolished binding to nucleic acid activator,
FT leading to impaired antiviral immunity; when associated
FT with E-256."
FT /evidence="ECO:0000269|PubMed:34261128"
SQ SEQUENCE 459 AA; 53811 MW; 630678372FCD013C CRC64;
MKESRNLENF VEKKLYECKK KYVDIPKDEG QRYGGKHYEA LTSKIFEILR KENPELDIII
AEFSLEGSVG MLKIAKPNEF DLVFKLKFPY YKSIAVTRDP KIPGNVLLDM TRVLELLKDD
PREDFQRIRE LIQGRLVDAQ NFFVVDRLRS WLQSLFSQAL NRISYRVELV AGVVSHLKYR
TCGPAHTIYV YGDYEYSVDY VPAICLAAEQ NVLPTKQLEC FKRANTSYWE AIPKPLKPLT
ETSMISFRSS FYAVEKILLQ DVHENCRNAI RFMKKFRDVK TNLGNCKSYY IKTLFLWKII
QEPESYWLNP LSFILADMFD DLAENLRRGV ITFFWDPELN MIDALTRDQV WEMYLCVQRI
PRDLRGAEIS RNKWSFFVLR EFSHKKERNV NLKCSSRRKR NVIKGLKTTS ICKLRNARTN
GTWTAGLWTR PGHAYRGPSE TVSTWDTVKD AAWSEGIVE
