CGAS_PIG
ID CGAS_PIG Reviewed; 495 AA.
AC I3LM39;
DT 24-JUL-2013, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2012, sequence version 1.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Cyclic GMP-AMP synthase {ECO:0000250|UniProtKB:Q8N884};
DE Short=cGAMP synthase {ECO:0000250|UniProtKB:Q8N884};
DE Short=cGAS {ECO:0000250|UniProtKB:Q8N884};
DE EC=2.7.7.86 {ECO:0000269|PubMed:23722159};
DE AltName: Full=2'3'-cGAMP synthase {ECO:0000250|UniProtKB:Q8N884};
DE AltName: Full=Mab-21 domain-containing protein 1 {ECO:0000250|UniProtKB:Q8N884};
GN Name=CGAS {ECO:0000250|UniProtKB:Q8N884};
GN Synonyms=MB21D1 {ECO:0000250|UniProtKB:Q8N884};
OS Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RG Porcine genome sequencing project;
RL Submitted (NOV-2009) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 135-495 IN COMPLEXES WITH
RP MAGNESIUM IONS, ZINC IONS; ATP; GTP; UTP AND DNA, COFACTOR, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVITY REGULATION, DNA-BINDING, AND MUTAGENESIS OF
RP GLU-200 AND ASP-202.
RX PubMed=23722159; DOI=10.1038/nature12305;
RA Civril F., Deimling T., de Oliveira Mann C.C., Ablasser A., Moldt M.,
RA Witte G., Hornung V., Hopfner K.P.;
RT "Structural mechanism of cytosolic DNA sensing by cGAS.";
RL Nature 498:332-337(2013).
CC -!- FUNCTION: Nucleotidyltransferase that catalyzes the formation of cyclic
CC GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate
CC immunity (PubMed:23722159). Catalysis involves both the formation of a
CC 2',5' phosphodiester linkage at the GpA step and the formation of a
CC 3',5' phosphodiester linkage at the ApG step, producing
CC c[G(2',5')pA(3',5')p] (PubMed:23722159). Acts as a key DNA sensor:
CC directly binds double-stranded DNA (dsDNA), inducing the formation of
CC liquid-like droplets in which CGAS is activated, leading to synthesis
CC of 2',3'-cGAMP, a second messenger that binds to and activates STING1,
CC thereby triggering type-I interferon production. Preferentially binds
CC long dsDNA (around 45 bp) and forms ladder-like networks that function
CC cooperatively to stabilize individual cGAS-dsDNA complexes. Acts as a
CC key foreign DNA sensor, the presence of double-stranded DNA (dsDNA) in
CC the cytoplasm being a danger signal that triggers the immune responses.
CC Has antiviral activity by sensing the presence of dsDNA from DNA
CC viruses in the cytoplasm. Also acts as an innate immune sensor of
CC infection by retroviruses by detecting the presence of reverse-
CC transcribed DNA in the cytosol (By similarity). Detection of retroviral
CC reverse-transcribed DNA in the cytosol may be indirect and be mediated
CC via interaction with PQBP1, which directly binds reverse-transcribed
CC retroviral DNA. Also detects the presence of DNA from bacteria (By
CC similarity). 2',3'-cGAMP can be transferred from producing cells to
CC neighboring cells through gap junctions, leading to promote STING1
CC activation and convey immune response to connecting cells. 2',3'-cGAMP
CC can also be transferred between cells by virtue of packaging within
CC viral particles contributing to IFN-induction in newly infected cells
CC in a cGAS-independent but STING1-dependent manner. Also senses the
CC presence of neutrophil extracellular traps (NETs) that are translocated
CC to the cytosol following phagocytosis, leading to synthesis of 2',3'-
CC cGAMP (By similarity). In addition to foreign DNA, can also be
CC activated by endogenous nuclear or mitochondrial DNA (By similarity).
CC When self-DNA leaks into the cytosol during cellular stress (such as
CC mitochondrial stress, DNA damage, mitotic arrest or senescence), or is
CC present in form of cytosolic micronuclei, CGAS is activated leading to
CC a state of sterile inflammation. Acts as a regulator of cellular
CC senescence by binding to cytosolic chromatin fragments that are present
CC in senescent cells, leading to trigger type-I interferon production via
CC STING1 and promote cellular senescence. Also involved in the
CC inflammatory response to genome instability and double-stranded DNA
CC breaks: acts by localizing to micronuclei arising from genome
CC instability. Micronuclei, which are frequently found in cancer cells,
CC consist of chromatin surrounded by their own nuclear membrane:
CC following breakdown of the micronuclear envelope, a process associated
CC with chromothripsis, CGAS binds self-DNA exposed to the cytosol,
CC leading to 2',3'-cGAMP synthesis and subsequent activation of STING1
CC and type-I interferon production (By similarity). In a healthy cell,
CC CGAS is however kept inactive even in cellular events that directly
CC expose it to self-DNA, such as mitosis, when cGAS associates with
CC chromatin directly after nuclear envelope breakdown or remains in the
CC form of postmitotic persistent nuclear cGAS pools bound to chromatin
CC (By similarity). Nuclear CGAS is inactivated by chromatin via direct
CC interaction with nucleosomes, which block CGAS from DNA binding and
CC thus prevent CGAS-induced autoimmunity. Also acts as a suppressor of
CC DNA repair in response to DNA damage: inhibits homologous recombination
CC repair by interacting with PARP1, the CGAS-PARP1 interaction leading to
CC impede the formation of the PARP1-TIMELESS complex (By similarity). In
CC addition to DNA, also sense translation stress: in response to
CC translation stress, translocates to the cytosol and associates with
CC collided ribosomes, promoting its activation and triggering type-I
CC interferon production (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884, ECO:0000269|PubMed:23722159}.
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:23722159};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42065;
CC Evidence={ECO:0000269|PubMed:23722159};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:23722159};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q8C6L5};
CC Note=Binds 1 Mg(2+) per subunit (PubMed:23722159). Is also active with
CC Mn(2+). Mn(2+)-activated enyzme forms an inverted pppGp(2'-5')A
CC intermediate, suggesting a non-canonical but accelerated 2',3'-cGAMP
CC cyclization without substrate flip-over. Mn(2+) ions are coordinated by
CC triphosphate moiety of the inverted substrate, independent of the
CC catalytic triad residues (PubMed:23722159) (By similarity).
CC {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:23722159};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q8C6L5};
CC Note=Undergoes a liquid-like phase transition after binding to DNA,
CC which is dependent on zinc. {ECO:0000250|UniProtKB:Q8N884};
CC -!- ACTIVITY REGULATION: The enzyme activity is strongly increased by
CC double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA
CC (PubMed:23722159). DNA-binding induces the formation of liquid-like
CC droplets in which CGAS is activated. Liquid-like droplets also create a
CC selective environment that restricts entry of negative regulators, such
CC as TREX1 or BANF1/BAF, allowing sensing of DNA (By similarity). A
CC number of mechanisms exist to restrict its activity toward self-DNA.
CC The nucleotidyltransferase activity is inhibited in the nucleus via its
CC association with nucleosomes: interacts with the acidic patch of
CC histones H2A and H2B, thereby blocking DNA-binding and subsequent
CC activation (By similarity). CGAS is also inactive when associated with
CC mitotic chromatin (By similarity). Chromatin-bound CGAS cannot be
CC activated by exogenous DNA in mitotic cells: phosphorylation of the N-
CC terminal disordered part by AURKB during the G2-M transition blocks
CC CGAS liquid phase separation and activation (By similarity). Activity
CC toward self-DNA is inhibited by BANF1/BAF upon acute loss of nuclear
CC membrane integrity: BANF1/BAF acts by outcompeting CGAS for DNA-
CC binding, thereby preventing CGAS activation (By similarity). DNA-
CC induced activation at micronuclei is also limited by TREX1, which
CC degrades micronuclear DNA upon nuclear envelope rupture, thereby
CC preventing CGAS activation. Acetylation at Lys-359, Lys-369 and Lys-389
CC inhibits the cyclic GMP-AMP synthase activity. Acetylation by KAT5
CC increases the cyclic GMP-AMP synthase activity by promoting DNA-binding
CC and subsequent activation (By similarity). Phosphorylation at Ser-278
CC suppresses the nucleotidyltransferase activity. Phosphorylation at Ser-
CC 410 promotes the cyclic GMP-AMP synthase activity (By similarity).
CC Phosphorylation at Ser-188 inhibits its cyclic GMP-AMP synthase
CC activity. Ubiquitination at Lys-359 via 'Lys-27'-linked
CC polyubiquitination enhances the cyclic GMP-AMP synthase activity (By
CC similarity). Monoubiquitination at Lys-322 promotes oligomerization and
CC subsequent activation. Sumoylation at Lys-322, Lys-359 and Lys-369
CC prevents DNA-binding, oligomerization and nucleotidyltransferase
CC activity. The enzyme activity is impaired by the cleavage by CASP1 (By
CC similarity). In addition to DNA, also activated by collided ribosomes
CC upon translation stress: specifically binds collided ribosomes,
CC promoting its activation and triggering type-I interferon production
CC (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884, ECO:0000269|PubMed:23722159}.
CC -!- SUBUNIT: Monomer in the absence of DNA. Homodimer in presence of dsDNA:
CC forms a 2:2 dimer with two enzymes binding to two DNA molecules.
CC Interacts with nucleosomes; interaction is mainly mediated via histones
CC H2A and H2B and inactivates the nucleotidyltransferase activity by
CC blocking DNA-binding and subsequent activation (By similarity).
CC Interacts with PQBP1 (via WW domain). Interacts with TRIM14; this
CC interaction recruits USP14, leading to deubiquitinate and stabilize
CC CGAS and promote type I interferon production. Interacts with ZCCHC3;
CC promoting sensing of dsDNA by CGAS. Interacts with PARP1; interaction
CC takes place in the nucleus and prevents the formation of the PARP1-
CC TIMELESS complex (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8C6L5}.
CC Chromosome {ECO:0000250|UniProtKB:Q8C6L5}. Cell membrane
CC {ECO:0000250|UniProtKB:Q8C6L5}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8C6L5}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:Q8C6L5}. Note=Mainly localizes in the nucleus,
CC and at low level in the cytosol (By similarity). On chromosomes,
CC enriched on centromeric satellite and LINE DNA repeat elements.
CC Exported from the nucleus to the cytosol in a XPO1/CRM1 via the nuclear
CC export signal in response to DNA stimulation (By similarity). Outside
CC the nucleus, localizes at the cell membrane as a peripheral membrane
CC protein in resting conditions: association to the cell membrane is
CC mediated via binding to phosphatidylinositol 4,5-bisphosphate
CC (PtdIns(4,5)P2) (By similarity). Localization at the cell membrane is
CC required to limit the recognition of self-DNA. Following detection of
CC double-stranded DNA (dsDNA), released from the cell membrane into the
CC cytosol in order to signal. Upon transfection with dsDNA forms punctate
CC structures that co-localize with DNA and Beclin-1 (BECN1).
CC Phosphorylation at Tyr-190 promotes cytosolic retention. In response to
CC translation stress, translocates to the cytosol and associates with
CC collided ribosomes (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884}.
CC -!- DOMAIN: The N-terminal disordered part (1-134) binds unspecifically
CC dsDNA and expands the binding and moving range of CGAS on dsDNA (By
CC similarity). The disordered and positively charged residues enhance
CC CGAS-DNA phase separation by increasing the valencies of DNA-binding.
CC The N-terminus is required to sense chromatin and its phosphorylation
CC blocks its activation by chromatin DNA (By similarity). When the N-
CC terminal part (1-134) is missing the protein bound to dsDNA
CC homodimerizes (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884}.
CC -!- DOMAIN: The arginine-anchor tightly binds to the canonical H2A acidic-
CC patch residues. {ECO:0000250|UniProtKB:Q8C6L5}.
CC -!- PTM: The N-terminal disordered part (1-134) is phosphorylated by AURKB
CC during the G2-M transition, blocking CGAS liquid phase separation and
CC preventing activation. Phosphorylation at Tyr-190 by BLK promotes
CC cytosolic retention. Localizes into the nucleus following
CC dephosphorylation at Tyr-190 (By similarity). Phosphorylation at Ser-
CC 410 activates the nucleotidyltransferase activity. Dephosphorylation at
CC Ser-410 by PPP6C impairs its ability to bind GTP, thereby inactivating
CC it (By similarity). Phosphorylation at Ser-188 by PRKDC inhibits its
CC cyclic GMP-AMP synthase activity by impairing homodimerization and
CC activation (By similarity). Phosphorylation at Ser-278 by AKT (AKT1,
CC AKT2 or AKT3) suppresses the nucleotidyltransferase activity.
CC Phosphorylation at Ser-278 by CDK1 during mitosis leads to its
CC inhibition, thereby preventing CGAS activation by self-DNA during
CC mitosis. Dephosphorylated at Ser-278 by protein phosphatase PP1 upon
CC mitotic exit (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884}.
CC -!- PTM: Ubiquitinated at Lys-389 via 'Lys-48'-linked polyubiquitin chains,
CC leading to its SQSTM1-mediated autophagic degradation. Interaction with
CC TRIM14 promotes recruitment of USP14, leading to deubiquitinate Lys-389
CC and stabilize CGAS. Ubiquitinated at Lys-359 by RNF185 via 'Lys-27'-
CC linked polyubiquitination, promoting CGAS cyclic GMP-AMP synthase
CC activity (By similarity). Monoubiquitination at Lys-322 by TRIM56
CC promotes oligomerization and subsequent activation (By similarity).
CC Monoubiquitination by TRIM41 promotes CGAS activation (By similarity).
CC Ubiquitination at Lys-260 via 'Lys-48'-linked polyubiquitination
CC promotes its degradation. Deubiquitination at Lys-260 by USP29 promotes
CC its stabilization. Deubiquitinated by USP27X, promoting its
CC stabilization (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884}.
CC -!- PTM: Sumoylated at Lys-206 by TRIM38 in uninfected cells and during the
CC early phase of viral infection, promoting its stability by preventing
CC ubiquitination at Lys-260 and subsequent degradation. Desumoylated by
CC SENP2 during the late phase of viral infection. Sumoylation at Lys-322,
CC Lys-359 and Lys-369 prevents DNA-binding, oligomerization and
CC nucleotidyltransferase activity. Desumoylation at Lys-322, Lys-359 and
CC Lys-369 by SENP7 relieves inhibition and activates CGAS.
CC {ECO:0000250|UniProtKB:Q8C6L5}.
CC -!- PTM: Polyglutamylated by TTLL6 at Glu-261, leading to impair DNA-
CC binding activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6.
CC {ECO:0000250|UniProtKB:Q8C6L5}.
CC -!- PTM: Acetylation at Lys-359, Lys-369 and Lys-389 inhibits the cyclic
CC GMP-AMP synthase activity. Deacetylated upon cytosolic DNA challenge
CC such as viral infections. Acetylation by KAT5 increases the cyclic GMP-
CC AMP synthase activity by promoting DNA-binding and subsequent
CC activation. {ECO:0000250|UniProtKB:Q8N884}.
CC -!- PTM: Proteolytically cleaved by apoptotic caspases during apoptosis,
CC leading to its inactivation. The damage of the nucleus and the
CC mitochondria during apoptosis leads to leakage of nuclear and
CC mitochondrial DNA, which activate CGAS: cleavage and inactivation
CC during apoptosis in required to prevent cytokine overproduction.
CC Cleaved by CASP7 and CASP3 during virus-induced apoptosis, thereby
CC inactivating it and preventing cytokine overproduction. Cleaved by
CC CASP1 upon DNA virus infection; the cleavage impairs cGAMP production.
CC Also cleaved by the pyroptotic CASP4 during non-canonical inflammasome
CC activation; does not cut at the same sites than CASP1.
CC {ECO:0000250|UniProtKB:Q8C6L5}.
CC -!- SIMILARITY: Belongs to the mab-21 family. {ECO:0000305}.
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DR EMBL; FP102323; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_013840602.1; XM_013985148.1.
DR PDB; 4JLX; X-ray; 2.00 A; A=135-495.
DR PDB; 4JLZ; X-ray; 2.27 A; A/B=135-495.
DR PDB; 4KB6; X-ray; 3.08 A; A=135-495.
DR PDBsum; 4JLX; -.
DR PDBsum; 4JLZ; -.
DR PDBsum; 4KB6; -.
DR AlphaFoldDB; I3LM39; -.
DR SMR; I3LM39; -.
DR STRING; 9823.ENSSSCP00000025159; -.
DR PaxDb; I3LM39; -.
DR PeptideAtlas; I3LM39; -.
DR PRIDE; I3LM39; -.
DR Ensembl; ENSSSCT00000030573; ENSSSCP00000025159; ENSSSCG00000021383.
DR Ensembl; ENSSSCT00015028332; ENSSSCP00015011100; ENSSSCG00015021453.
DR Ensembl; ENSSSCT00025037600; ENSSSCP00025015781; ENSSSCG00025027757.
DR Ensembl; ENSSSCT00030086223; ENSSSCP00030039757; ENSSSCG00030061695.
DR Ensembl; ENSSSCT00035063373; ENSSSCP00035025648; ENSSSCG00035047597.
DR Ensembl; ENSSSCT00040088529; ENSSSCP00040038910; ENSSSCG00040064832.
DR Ensembl; ENSSSCT00045053754; ENSSSCP00045037382; ENSSSCG00045031514.
DR Ensembl; ENSSSCT00050013192; ENSSSCP00050005463; ENSSSCG00050009802.
DR Ensembl; ENSSSCT00055053600; ENSSSCP00055042758; ENSSSCG00055027117.
DR Ensembl; ENSSSCT00060037939; ENSSSCP00060016133; ENSSSCG00060028039.
DR Ensembl; ENSSSCT00065057000; ENSSSCP00065024791; ENSSSCG00065041662.
DR GeneID; 100516408; -.
DR KEGG; ssc:100516408; -.
DR CTD; 115004; -.
DR VGNC; VGNC:86614; CGAS.
DR eggNOG; KOG3963; Eukaryota.
DR GeneTree; ENSGT01050000244827; -.
DR HOGENOM; CLU_040428_2_0_1; -.
DR InParanoid; I3LM39; -.
DR OMA; CLRTEKL; -.
DR OrthoDB; 759341at2759; -.
DR TreeFam; TF331255; -.
DR BRENDA; 2.7.7.86; 6170.
DR Proteomes; UP000008227; Chromosome 1.
DR Proteomes; UP000314985; Unplaced.
DR Bgee; ENSSSCG00000021383; Expressed in tonsil and 29 other tissues.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0061501; F:2',3'-cyclic GMP-AMP synthase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS: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:0031491; F:nucleosome binding; ISS:UniProtKB.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; IBA:GO_Central.
DR GO; GO:0019934; P:cGMP-mediated signaling; IEA:Ensembl.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR GO; GO:2000042; P:negative regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0038001; P:paracrine signaling; ISS:UniProtKB.
DR GO; GO:2000774; P:positive regulation of cellular senescence; ISS:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISS:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
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 3D-structure; Acetylation; Antiviral defense; ATP-binding; Cell membrane;
KW Chromosome; Cytoplasm; DNA damage; DNA repair; DNA-binding; GTP-binding;
KW Immunity; Innate immunity; Isopeptide bond; Lipid-binding; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Nucleotidyltransferase;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Zinc.
FT CHAIN 1..495
FT /note="Cyclic GMP-AMP synthase"
FT /id="PRO_0000423063"
FT REGION 1..134
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 1..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 57..68
FT /note="Required for association with the cell membrane"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 103..134
FT /note="Required for activation upon DNA viral infection"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 147..190
FT /note="DNA-binding"
FT /evidence="ECO:0000269|PubMed:23722159"
FT REGION 316..357
FT /note="Interaction with collided ribosomes"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 359..382
FT /note="DNA-binding"
FT /evidence="ECO:0000269|PubMed:23722159"
FT MOTIF 143..148
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOTIF 268..278
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT COMPBIAS 48..75
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 186
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 188
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 200
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 202
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 202
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 294
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 294
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 294
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 337
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 351..358
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 351
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 358
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 365
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 371
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 372
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 379
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 389
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23722159"
FT BINDING 410..414
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000269|PubMed:23722159"
FT SITE 230
FT /note="Arginine-anchor"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT SITE 294..295
FT /note="Cleavage; by CASP3"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 7
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 56
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 57
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 188
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 190
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 261
FT /note="5-glutamyl polyglutamate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT MOD_RES 278
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 359
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 369
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 389
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT CROSSLNK 206
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 260
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 322
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 322
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 359
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 359
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT CROSSLNK 369
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 389
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MUTAGEN 200
FT /note="E->Q: Abolishes enzyme activity and stimulation of
FT interferon production; when associated with N-202."
FT /evidence="ECO:0000269|PubMed:23722159"
FT MUTAGEN 202
FT /note="D->N: Abolishes enzyme activity and stimulation of
FT interferon production; when associated with Q-200."
FT /evidence="ECO:0000269|PubMed:23722159"
FT HELIX 139..147
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 150..173
FT /evidence="ECO:0007829|PDB:4JLX"
FT TURN 177..180
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 182..184
FT /evidence="ECO:0007829|PDB:4JLX"
FT TURN 188..192
FT /evidence="ECO:0007829|PDB:4JLZ"
FT STRAND 200..208
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 221..227
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 238..240
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 248..262
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 269..271
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 287..289
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 291..301
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 307..309
FT /evidence="ECO:0007829|PDB:4JLX"
FT TURN 316..319
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 321..328
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 332..335
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 339..344
FT /evidence="ECO:0007829|PDB:4JLZ"
FT HELIX 346..348
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 350..353
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 355..363
FT /evidence="ECO:0007829|PDB:4JLX"
FT STRAND 366..368
FT /evidence="ECO:0007829|PDB:4JLZ"
FT TURN 369..372
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 381..398
FT /evidence="ECO:0007829|PDB:4JLX"
FT TURN 399..401
FT /evidence="ECO:0007829|PDB:4JLX"
FT TURN 404..407
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 410..423
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 427..429
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 432..434
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 435..452
FT /evidence="ECO:0007829|PDB:4JLX"
FT TURN 468..470
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 473..488
FT /evidence="ECO:0007829|PDB:4JLX"
FT HELIX 492..494
FT /evidence="ECO:0007829|PDB:4JLX"
SQ SEQUENCE 495 AA; 55809 MW; 13E76296D97E176B CRC64;
MAARRGKSTR TASEVGAAGP RASARSVNGA PTVPEAARPG ARRNGPSRAS GCRREKSGPD
PREKPQVRTR TARAEDQAEG PSAPSERVEP PSAQGASLLR AGSCRAREAR SARELRPQAG
ATELAAPARM EAPPGAWKLQ TVLEKVRLSR HEISEAAEVV NWVVEHLLRR LQGGESEFKG
VALLRTGSYY ERVKISAPNE FDVMFKLEVP RIQLEEYCNS GAHYFVKFKR NPGGNPLEQF
LEKEILSASK MLSKFRKIIK EEIKNIEGVT VERKRRGSPA VTLLISKPKE ISVDIILALE
SKSSWPASTQ KGLPISQWLG AKVKNNLKRQ PFYLVPKHAK EGSGFQEETW RLSFSHIEKD
ILKNHGQSKT CCEIDGVKCC RKECLKLMKY LLEQLKKKFG NRRELAKFCS YHVKTAFFHV
CTQDPHDNQW HLKNLECCFD NCVAYFLQCL KTEQLANYFI PGVNLFSRDL IDKPSKEFLS
KQIEYERNNG FPVFW
