UniProt functional annotation for Q8N884



	UniProt functional annotation for Q8N884

UniProt code: Q8N884.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990, PubMed:29976794, PubMed:30799039). Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed:28363908, PubMed:28214358). Acts as a key cytosolic DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed:28363908). Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production (PubMed:28363908, PubMed:28314590). Preferentially recognizes and binds curved long DNAs (PubMed:30007416). In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less cyclic GMP-AMP (cGAMP), allowing a more fine-tuned response to pathogens (PubMed:30007416). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:28363908). Also acts as an innate immune sensor of infection by retroviruses, such as HIV-1, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:23929945). Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA (PubMed:26046437). Also detects the presence of DNA from bacteria, such as M.tuberculosis (PubMed:26048138). cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote TMEM173/STING activation and convey immune response to connecting cells (PubMed:24077100). cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN- induction in newly infected cells in a cGAS-independent but TMEM173/STING-dependent manner (PubMed:26229115). In addition to antiviral activity, also involved in the response to cellular stresses, such as senescence, DNA damage or genome instability (PubMed:28738408, PubMed:28759889). Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via TMEM173/STING and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability (PubMed:28738408, PubMed:28759889). Micronuclei, which as frequently found in cancer cells, consist of chromatin surrounded by its own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to cGAMP synthesis and subsequent activation of TMEM173/STING and type-I interferon production (PubMed:28738408, PubMed:28759889). Acts as a suppressor of DNA repair in response to DNA damage: translocates to the nucleus following dephosphorylation at Tyr-215 and inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed:30356214). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:21478870, ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:23929945, ECO:0000269|PubMed:24077100, ECO:0000269|PubMed:24116191, ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:26046437, ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:26229115, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:28214358, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28363908, ECO:0000269|PubMed:28738408, ECO:0000269|PubMed:28759889, ECO:0000269|PubMed:29976794, ECO:0000269|PubMed:30007416, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30799039}.

Catalytic activity: Reaction=ATP + GTP = 2',3'-cGAMP + 2 diphosphate; Xref=Rhea:RHEA:42064, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:143093; EC=2.7.7.86; Evidence={ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:28934246, ECO:0000269|PubMed:29976794, ECO:0000269|PubMed:30799039}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42065; Evidence={ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:28934246};

Cofactor: Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269|PubMed:30007416}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269|PubMed:30007416};

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269|PubMed:29976794}; Note=Undergoes a liquid-like phase transition after binding to DNA, which is dependent on zinc. {ECO:0000269|PubMed:29976794};

Activity regulation: The enzyme activity is strongly increased by double-stranded DNA, but not by single-stranded DNA or RNA (PubMed:23258413, PubMed:23707061, PubMed:26300263). Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity (PubMed:30799039). Inhibited by aspirin (acetylsalicylate) drug, which acetylates CGAS (PubMed:30799039). The enzyme activity is impaired by the cleavage at Asp-140 and Asp-157 produced by CASP1 (PubMed:28314590). Strongly inhibited by compound PF-06928215, which is specific for human protein (PubMed:28934246, PubMed:30007416). {ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28934246, ECO:0000269|PubMed:30007416, ECO:0000269|PubMed:30799039}.

Biophysicochemical properties: Kinetic parameters: KM=35 uM for ATP (with 1 mM GTP) {ECO:0000269|PubMed:28934246}; KM=30 uM for GTP (with 1 mM ATP) {ECO:0000269|PubMed:28934246};

Subunit: Monomer in the absence of DNA (PubMed:28363908). Homodimer in presence of dsDNA: forms a 2:2 dimer with two enzymes binding to two DNA molecules (PubMed:30007416, PubMed:30799039). Interacts with PQBP1 (via WW domain) (PubMed:26046437). Interacts with TRIM14; this interaction stabilizes CGAS and promotes type I interferon production (PubMed:27666593, PubMed:32404352). Interacts with ZCCHC3; promoting sensing of dsDNA by CGAS (PubMed:30135424). Interacts with PARP1; interaction takes place in the nucleus and prevents the formation of the PARP1-TIMELESS complex (PubMed:30356214). {ECO:0000269|PubMed:26046437, ECO:0000269|PubMed:27666593, ECO:0000269|PubMed:28363908, ECO:0000269|PubMed:30007416, ECO:0000269|PubMed:30135424, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30799039, ECO:0000269|PubMed:32404352}.

Subunit: (Microbial infection) Interacts with herpes virus 8/HHV-8 protein ORF52; this interaction inhibits cGAS enzymatic activity. {ECO:0000269|PubMed:26320998}.

Subunit: (Microbial infection) Interacts with herpes simplex virus 1 protein UL37; this interaction deaminates CGAS and inhibits its activation. {ECO:0000269|PubMed:30092200}.

Subunit: (Microbial infection) Interacts with cytomegalovirus protein UL31; this interaction promotes dissociation of DNA from CGAS, thereby inhibiting the enzymatic activity of CGAS. {ECO:0000269|PubMed:29937271}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:30827685}; Peripheral membrane protein {ECO:0000269|PubMed:30827685}. Cytoplasm, cytosol {ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:29937271, ECO:0000269|PubMed:30799039, ECO:0000269|PubMed:30827685}. Nucleus {ECO:0000269|PubMed:29937271, ECO:0000269|PubMed:30356214}. Note=In resting conditions, localizes at the cell membrane as a peripheral membrane protein by binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:30827685). Localization at the cell membrane is required to limit the recognition of self-DNA (PubMed:30827685). Following detection of double-stranded DNA (dsDNA), released from the cell membrane into the cytosol in order to signal (PubMed:30827685). Upon transfection with dsDNA forms punctate structures that co-localize with DNA and Beclin-1 (BECN1) (PubMed:26048138). Phosphorylation at Tyr-215 promotes cytosolic retention; translocates into the nucleus following dephosphorylation (PubMed:30356214). {ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30827685}.

Subcellular location: Note=(Microbial infection) Upon infection with virulent M.tuberculosis forms aggregates with dsDNA, non-virulent bacteria (without the ESX-1 locus) do not form these aggregates (PubMed:26048138). {ECO:0000269|PubMed:26048138}.

Tissue specificity: Expressed in the monocytic cell line THP1. {ECO:0000269|PubMed:23258413}.

Induction: By type I interferons. {ECO:0000269|PubMed:21478870}.

Domain: Lys-187 and Leu-195 residues are specific to human and destabilize the interactions with short DNA, shifting the specificity toward the detection of curved long DNAs (PubMed:30007416). Lys-187 and Leu-195 also restrain cGAMP production and, therefore, immune activation, allowing a more fine-tuned response to pathogens (PubMed:30007416). {ECO:0000269|PubMed:30007416}.

Domain: The N-terminal part (1-160) binds unspecifically dsDNA and expand the binding and moving range of CGAS on dsDNA. Enhances the enzyme activity and activation of innate immune signaling upon cytosolic recognition of dsDNA (PubMed:28363908, PubMed:28214358). When the N-terminal part (1-160) is missing the protein bound to dsDNA homodimerizes (By similarity). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:28214358, ECO:0000269|PubMed:28363908}.

Ptm: Phosphorylation at Tyr-215 by BLK promotes cytosolic retention (PubMed:30356214). Translocates into the nucleus following dephosphorylation at Tyr-215 (PubMed:30356214). {ECO:0000269|PubMed:30356214}.

Ptm: (Microbial infection) Deamidated on 'Asn-210' by herpes simplex virus 1 protein UL37. This modification significantly reduces CGAS- dependent cGAMP production and innate immune signaling induced by dsDNA. {ECO:0000269|PubMed:30092200}.

Ptm: Polyglutamylated by TTLL6 at Glu-286, leading to impair DNA- binding activity. Monoglutamylated at Glu-314 by TTLL4, leading to impair the nucleotidyltransferase activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6. {ECO:0000250|UniProtKB:Q8C6L5}.

Ptm: Cleaved by CASP1 at Asp-140 and Asp-157 upon DNA virus infection; the cleavage impairs cGAMP production (PubMed:28314590). Also cleaved by the pyroptotic CASP4 and CASP5 during non-canonical inflammasome activation; they don't cut at the same sites than CASP1 (PubMed:28314590). {ECO:0000269|PubMed:28314590}.

Ptm: Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity (PubMed:30799039). Deacetylated upon cytosolic DNA challenge such as viral infections (PubMed:30799039). Acetylation can be mediated by aspirin (acetylsalicylate) drug, which directly acetylates CGAS (PubMed:30799039). Acetylation by aspirin efficiently inhibits CGAS-mediated immune responses and is able to suppress self-DNA-induced autoimmunity (PubMed:30799039). {ECO:0000269|PubMed:30799039}.

Similarity: Belongs to the mab-21 family. {ECO:0000305}.

Sequence caution: Sequence=AAH12928.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990, PubMed:29976794, PubMed:30799039). Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed:28363908, PubMed:28214358). Acts as a key cytosolic DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed:28363908). Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production (PubMed:28363908, PubMed:28314590). Preferentially recognizes and binds curved long DNAs (PubMed:30007416). In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less cyclic GMP-AMP (cGAMP), allowing a more fine-tuned response to pathogens (PubMed:30007416). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:28363908). Also acts as an innate immune sensor of infection by retroviruses, such as HIV-1, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:23929945). Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA (PubMed:26046437). Also detects the presence of DNA from bacteria, such as M.tuberculosis (PubMed:26048138). cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote TMEM173/STING activation and convey immune response to connecting cells (PubMed:24077100). cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN- induction in newly infected cells in a cGAS-independent but TMEM173/STING-dependent manner (PubMed:26229115). In addition to antiviral activity, also involved in the response to cellular stresses, such as senescence, DNA damage or genome instability (PubMed:28738408, PubMed:28759889). Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via TMEM173/STING and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability (PubMed:28738408, PubMed:28759889). Micronuclei, which as frequently found in cancer cells, consist of chromatin surrounded by its own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to cGAMP synthesis and subsequent activation of TMEM173/STING and type-I interferon production (PubMed:28738408, PubMed:28759889). Acts as a suppressor of DNA repair in response to DNA damage: translocates to the nucleus following dephosphorylation at Tyr-215 and inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed:30356214). {ECO:0000250\|UniProtKB:Q8C6L5, ECO:0000269\|PubMed:21478870, ECO:0000269\|PubMed:23258413, ECO:0000269\|PubMed:23707061, ECO:0000269\|PubMed:23707065, ECO:0000269\|PubMed:23722159, ECO:0000269\|PubMed:23929945, ECO:0000269\|PubMed:24077100, ECO:0000269\|PubMed:24116191, ECO:0000269\|PubMed:24462292, ECO:0000269\|PubMed:25131990, ECO:0000269\|PubMed:26046437, ECO:0000269\|PubMed:26048138, ECO:0000269\|PubMed:26229115, ECO:0000269\|PubMed:26300263, ECO:0000269\|PubMed:28214358, ECO:0000269\|PubMed:28314590, ECO:0000269\|PubMed:28363908, ECO:0000269\|PubMed:28738408, ECO:0000269\|PubMed:28759889, ECO:0000269\|PubMed:29976794, ECO:0000269\|PubMed:30007416, ECO:0000269\|PubMed:30356214, ECO:0000269\|PubMed:30799039}.


Catalytic activity:		Reaction=ATP + GTP = 2',3'-cGAMP + 2 diphosphate; Xref=Rhea:RHEA:42064, ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:37565, ChEBI:CHEBI:143093; EC=2.7.7.86; Evidence={ECO:0000269\|PubMed:23258413, ECO:0000269\|PubMed:23707061, ECO:0000269\|PubMed:23722159, ECO:0000269\|PubMed:25131990, ECO:0000269\|PubMed:28934246, ECO:0000269\|PubMed:29976794, ECO:0000269\|PubMed:30799039}; PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42065; Evidence={ECO:0000269\|PubMed:23258413, ECO:0000269\|PubMed:28934246};
Cofactor:		Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000269\|PubMed:30007416}; Note=Binds 1 Mg(2+) ion per subunit. {ECO:0000269\|PubMed:30007416};
Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000269\|PubMed:29976794}; Note=Undergoes a liquid-like phase transition after binding to DNA, which is dependent on zinc. {ECO:0000269\|PubMed:29976794};
Activity regulation:		The enzyme activity is strongly increased by double-stranded DNA, but not by single-stranded DNA or RNA (PubMed:23258413, PubMed:23707061, PubMed:26300263). Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity (PubMed:30799039). Inhibited by aspirin (acetylsalicylate) drug, which acetylates CGAS (PubMed:30799039). The enzyme activity is impaired by the cleavage at Asp-140 and Asp-157 produced by CASP1 (PubMed:28314590). Strongly inhibited by compound PF-06928215, which is specific for human protein (PubMed:28934246, PubMed:30007416). {ECO:0000269\|PubMed:23258413, ECO:0000269\|PubMed:23707061, ECO:0000269\|PubMed:26300263, ECO:0000269\|PubMed:28314590, ECO:0000269\|PubMed:28934246, ECO:0000269\|PubMed:30007416, ECO:0000269\|PubMed:30799039}.
Biophysicochemical properties:		Kinetic parameters: KM=35 uM for ATP (with 1 mM GTP) {ECO:0000269\|PubMed:28934246}; KM=30 uM for GTP (with 1 mM ATP) {ECO:0000269\|PubMed:28934246};
Subunit:		Monomer in the absence of DNA (PubMed:28363908). Homodimer in presence of dsDNA: forms a 2:2 dimer with two enzymes binding to two DNA molecules (PubMed:30007416, PubMed:30799039). Interacts with PQBP1 (via WW domain) (PubMed:26046437). Interacts with TRIM14; this interaction stabilizes CGAS and promotes type I interferon production (PubMed:27666593, PubMed:32404352). Interacts with ZCCHC3; promoting sensing of dsDNA by CGAS (PubMed:30135424). Interacts with PARP1; interaction takes place in the nucleus and prevents the formation of the PARP1-TIMELESS complex (PubMed:30356214). {ECO:0000269\|PubMed:26046437, ECO:0000269\|PubMed:27666593, ECO:0000269\|PubMed:28363908, ECO:0000269\|PubMed:30007416, ECO:0000269\|PubMed:30135424, ECO:0000269\|PubMed:30356214, ECO:0000269\|PubMed:30799039, ECO:0000269\|PubMed:32404352}.
Subunit:		(Microbial infection) Interacts with herpes virus 8/HHV-8 protein ORF52; this interaction inhibits cGAS enzymatic activity. {ECO:0000269\|PubMed:26320998}.
Subunit:		(Microbial infection) Interacts with herpes simplex virus 1 protein UL37; this interaction deaminates CGAS and inhibits its activation. {ECO:0000269\|PubMed:30092200}.
Subunit:		(Microbial infection) Interacts with cytomegalovirus protein UL31; this interaction promotes dissociation of DNA from CGAS, thereby inhibiting the enzymatic activity of CGAS. {ECO:0000269\|PubMed:29937271}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:30827685}; Peripheral membrane protein {ECO:0000269\|PubMed:30827685}. Cytoplasm, cytosol {ECO:0000269\|PubMed:23258413, ECO:0000269\|PubMed:26048138, ECO:0000269\|PubMed:29937271, ECO:0000269\|PubMed:30799039, ECO:0000269\|PubMed:30827685}. Nucleus {ECO:0000269\|PubMed:29937271, ECO:0000269\|PubMed:30356214}. Note=In resting conditions, localizes at the cell membrane as a peripheral membrane protein by binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:30827685). Localization at the cell membrane is required to limit the recognition of self-DNA (PubMed:30827685). Following detection of double-stranded DNA (dsDNA), released from the cell membrane into the cytosol in order to signal (PubMed:30827685). Upon transfection with dsDNA forms punctate structures that co-localize with DNA and Beclin-1 (BECN1) (PubMed:26048138). Phosphorylation at Tyr-215 promotes cytosolic retention; translocates into the nucleus following dephosphorylation (PubMed:30356214). {ECO:0000269\|PubMed:26048138, ECO:0000269\|PubMed:30356214, ECO:0000269\|PubMed:30827685}.
Subcellular location:		Note=(Microbial infection) Upon infection with virulent M.tuberculosis forms aggregates with dsDNA, non-virulent bacteria (without the ESX-1 locus) do not form these aggregates (PubMed:26048138). {ECO:0000269\|PubMed:26048138}.
Tissue specificity:		Expressed in the monocytic cell line THP1. {ECO:0000269\|PubMed:23258413}.
Induction:		By type I interferons. {ECO:0000269\|PubMed:21478870}.
Domain:		Lys-187 and Leu-195 residues are specific to human and destabilize the interactions with short DNA, shifting the specificity toward the detection of curved long DNAs (PubMed:30007416). Lys-187 and Leu-195 also restrain cGAMP production and, therefore, immune activation, allowing a more fine-tuned response to pathogens (PubMed:30007416). {ECO:0000269\|PubMed:30007416}.
Domain:		The N-terminal part (1-160) binds unspecifically dsDNA and expand the binding and moving range of CGAS on dsDNA. Enhances the enzyme activity and activation of innate immune signaling upon cytosolic recognition of dsDNA (PubMed:28363908, PubMed:28214358). When the N-terminal part (1-160) is missing the protein bound to dsDNA homodimerizes (By similarity). {ECO:0000250\|UniProtKB:Q8C6L5, ECO:0000269\|PubMed:28214358, ECO:0000269\|PubMed:28363908}.
Ptm:		Phosphorylation at Tyr-215 by BLK promotes cytosolic retention (PubMed:30356214). Translocates into the nucleus following dephosphorylation at Tyr-215 (PubMed:30356214). {ECO:0000269\|PubMed:30356214}.
Ptm:		(Microbial infection) Deamidated on 'Asn-210' by herpes simplex virus 1 protein UL37. This modification significantly reduces CGAS- dependent cGAMP production and innate immune signaling induced by dsDNA. {ECO:0000269\|PubMed:30092200}.
Ptm:		Polyglutamylated by TTLL6 at Glu-286, leading to impair DNA- binding activity. Monoglutamylated at Glu-314 by TTLL4, leading to impair the nucleotidyltransferase activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6. {ECO:0000250\|UniProtKB:Q8C6L5}.
Ptm:		Cleaved by CASP1 at Asp-140 and Asp-157 upon DNA virus infection; the cleavage impairs cGAMP production (PubMed:28314590). Also cleaved by the pyroptotic CASP4 and CASP5 during non-canonical inflammasome activation; they don't cut at the same sites than CASP1 (PubMed:28314590). {ECO:0000269\|PubMed:28314590}.
Ptm:		Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity (PubMed:30799039). Deacetylated upon cytosolic DNA challenge such as viral infections (PubMed:30799039). Acetylation can be mediated by aspirin (acetylsalicylate) drug, which directly acetylates CGAS (PubMed:30799039). Acetylation by aspirin efficiently inhibits CGAS-mediated immune responses and is able to suppress self-DNA-induced autoimmunity (PubMed:30799039). {ECO:0000269\|PubMed:30799039}.
Similarity:		Belongs to the mab-21 family. {ECO:0000305}.
Sequence caution:		Sequence=AAH12928.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};