CGLR_LUCCU
ID CGLR_LUCCU Reviewed; 368 AA.
AC P0DV12;
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 Lucilia cuprina (Green bottle fly) (Australian sheep blowfly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Oestroidea;
OC Calliphoridae; Luciliinae; Lucilia.
OX NCBI_TaxID=7375;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=26108605; DOI=10.1038/ncomms8344;
RA Anstead C.A., Korhonen P.K., Young N.D., Hall R.S., Jex A.R., Murali S.C.,
RA Hughes D.S., Lee S.F., Perry T., Stroehlein A.J., Ansell B.R.,
RA Breugelmans B., Hofmann A., Qu J., Dugan S., Lee S.L., Chao H., Dinh H.,
RA Han Y., Doddapaneni H.V., Worley K.C., Muzny D.M., Ioannidis P.,
RA Waterhouse R.M., Zdobnov E.M., James P.J., Bagnall N.H., Kotze A.C.,
RA Gibbs R.A., Richards S., Batterham P., Gasser R.B.;
RT "Lucilia cuprina genome unlocks parasitic fly biology to underpin future
RT interventions.";
RL Nat. Commun. 6:7344-7344(2015).
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}.
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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..368
FT /note="Cyclic GMP-AMP synthase-like receptor"
FT /id="PRO_0000454447"
FT BINDING 60
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 72..74
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
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 74
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 229..236
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 233..236
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 254
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 268..272
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
SQ SEQUENCE 368 AA; 43813 MW; 3E4A06FE7AE2686D CRC64;
MELQANLENV LQKVNNFINI DAKRQIYAAH FDNLKNTIFN ELRKNEVLAY LFNGFQLGGS
YGDNVKVTVP NEYDLVFNIK FPEQPLIIVT ADHELPGNVF LDFTRVIHKI AKEKQHEKIL
QHLKQWLDDE NYLKVEKFQW FLRSCFIDVL TKMNFKITFK GRTSSLRYSR EGPAHTIKVT
ESLNFDYSVD FVPGILLNAN QCVTSNIVGQ WEAIPKPTPT NNHLYKSFRA SFYRQEQKII
KNQQQLKNVY RMMKKFRDSK TNMLKMKSYF IKTLFLWKSS RENVSYWSKP LTEIIIDMFK
DMEKSLREEK LPFYWDRKLN LYDNYQPRLM REMLNCVESA RETLEKAAKE LTLPLQKRVF
CIFCKLKI
