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CGASL_DROME
ID   CGASL_DROME             Reviewed;         346 AA.
AC   Q9VSH0;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-2000, sequence version 1.
DT   03-AUG-2022, entry version 144.
DE   RecName: Full=Cyclic GMP-AMP synthase-like protein {ECO:0000305};
DE            EC=2.7.7.- {ECO:0000250|UniProtKB:Q8N884};
GN   ORFNames=CG7194 {ECO:0000312|FlyBase:FBgn0035868};
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].
RC   STRAIN=Berkeley;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [4]
RP   ACTIVITY REGULATION, AND DISRUPTION PHENOTYPE.
RX   PubMed=29924997; DOI=10.1016/j.celrep.2018.05.029;
RA   Martin M., Hiroyasu A., Guzman R.M., Roberts S.A., Goodman A.G.;
RT   "Analysis of Drosophila STING reveals an evolutionarily conserved
RT   antimicrobial function.";
RL   Cell Rep. 23:3537-3550(2018).
RN   [5]
RP   FUNCTION, AND MUTAGENESIS OF 70-GLU--ASP-72.
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: Probable nucleotidyltransferase that catalyzes the formation
CC       of cyclic dinucleotide second messenger in response to some unknown
CC       stimulus (By similarity). Does not catalyze the formation of cyclic
CC       GMP-AMP from ATP and GTP (PubMed:34261128).
CC       {ECO:0000250|UniProtKB:Q8N884, 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: Activated in response of some unknown stimulus
CC       (PubMed:29924997). Not activated in response to L-monocytogenes
CC       infection (PubMed:29924997). {ECO:0000269|PubMed:29924997}.
CC   -!- DISRUPTION PHENOTYPE: Flies display a normal antiviral immune response.
CC       {ECO:0000269|PubMed:29924997}.
CC   -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
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DR   EMBL; AE014296; AAF50449.1; -; Genomic_DNA.
DR   EMBL; BT022230; AAY54646.1; -; mRNA.
DR   RefSeq; NP_648203.1; NM_139946.2.
DR   AlphaFoldDB; Q9VSH0; -.
DR   SMR; Q9VSH0; -.
DR   STRING; 7227.FBpp0076437; -.
DR   PaxDb; Q9VSH0; -.
DR   PRIDE; Q9VSH0; -.
DR   DNASU; 38933; -.
DR   EnsemblMetazoa; FBtr0076714; FBpp0076437; FBgn0035868.
DR   GeneID; 38933; -.
DR   KEGG; dme:Dmel_CG7194; -.
DR   UCSC; CG7194-RA; d. melanogaster.
DR   FlyBase; FBgn0035868; CG7194.
DR   VEuPathDB; VectorBase:FBgn0035868; -.
DR   eggNOG; KOG3963; Eukaryota.
DR   GeneTree; ENSGT01050000244827; -.
DR   HOGENOM; CLU_068972_0_0_1; -.
DR   InParanoid; Q9VSH0; -.
DR   OMA; TLLVEMW; -.
DR   OrthoDB; 759341at2759; -.
DR   PhylomeDB; Q9VSH0; -.
DR   BioGRID-ORCS; 38933; 1 hit in 1 CRISPR screen.
DR   GenomeRNAi; 38933; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0035868; Expressed in adult midgut (Drosophila) and 23 other tissues.
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:0016779; F:nucleotidyltransferase activity; IEA:UniProtKB-KW.
DR   GO; GO:0055070; P:copper ion homeostasis; IEP:FlyBase.
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   ATP-binding; GTP-binding; Magnesium; Manganese; Metal-binding;
KW   Nucleotide-binding; Nucleotidyltransferase; Reference proteome;
KW   Transferase.
FT   CHAIN           1..346
FT                   /note="Cyclic GMP-AMP synthase-like protein"
FT                   /id="PRO_0000454443"
FT   BINDING         58
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q8N884"
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         165
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:Q8N884"
FT   BINDING         165
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT                   /ligand_note="catalytic"
FT                   /evidence="ECO:0000250|UniProtKB:Q8N884"
FT   BINDING         212..219
FT                   /ligand="GTP"
FT                   /ligand_id="ChEBI:CHEBI:37565"
FT                   /evidence="ECO:0000250|UniProtKB:Q8N884"
FT   BINDING         216..219
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q8N884"
FT   BINDING         237
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q8N884"
FT   BINDING         252..256
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250|UniProtKB:Q8N884"
FT   MUTAGEN         70..72
FT                   /note="EFD->AFA: No effect on antiviral immune response."
FT                   /evidence="ECO:0000269|PubMed:34261128"
SQ   SEQUENCE   346 AA;  40294 MW;  841B6ED5947EAAEE CRC64;
     MSTANHFQRI LEKLSISDNE RAVYTKEAEE IQNYVVDELK RVDKTFRQVF DGLSLGGSYL
     DRVKLNLPDE FDLHMKLKFP FDIRPTRIDQ GFIYLEADLT VINPQRIHRI VLQDWLRNAF
     RKVFRSNQTI ATTSNRVYKL TYTLEGYGCA HTILAVCGSR SISFDLVPAF EFSGSQWPFD
     ICPVPADVSN NWPWFAIPQQ KKKSAKPRTT FMVCAPHWER EIMKGKDNLK NVLRLMKGLR
     DAHARKLPHL SSYMLKTVLL HRLESADWER DLGTLLVEMW SHLVDHLRAR RLEFFLAKDH
     NVFNRMNQNE IKICLENAST LLRKLCIAQT CGGSYHHVAQ LFNIPN
 
 
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