CGAS_BOVIN
ID CGAS_BOVIN Reviewed; 498 AA.
AC E1BGN7;
DT 06-MAR-2013, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 1.
DT 03-AUG-2022, entry version 66.
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:0000250|UniProtKB:Q8C6L5};
DE AltName: Full=2'3'-cGAMP synthase {ECO:0000250|UniProtKB:Q8N884};
GN Name=CGAS {ECO:0000250|UniProtKB:Q8N884};
GN Synonyms=MB21D1 {ECO:0000250|UniProtKB:Q8N884};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Hereford;
RX PubMed=19393038; DOI=10.1186/gb-2009-10-4-r42;
RA Zimin A.V., Delcher A.L., Florea L., Kelley D.R., Schatz M.C., Puiu D.,
RA Hanrahan F., Pertea G., Van Tassell C.P., Sonstegard T.S., Marcais G.,
RA Roberts M., Subramanian P., Yorke J.A., Salzberg S.L.;
RT "A whole-genome assembly of the domestic cow, Bos taurus.";
RL Genome Biol. 10:R42.01-R42.10(2009).
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. Catalysis involves both the formation of a 2',5'
CC phosphodiester linkage at the GpA step and the formation of a 3',5'
CC phosphodiester linkage at the ApG step, producing
CC c[G(2',5')pA(3',5')p]. Acts as a key DNA sensor: directly binds double-
CC stranded DNA (dsDNA), inducing the formation of liquid-like droplets in
CC which CGAS is activated, leading to synthesis of 2',3'-cGAMP, a second
CC messenger that binds to and activates STING1, thereby triggering type-I
CC interferon production. Preferentially binds long dsDNA (around 45 bp)
CC and forms ladder-like networks that function cooperatively to stabilize
CC individual cGAS-dsDNA complexes. Acts as a key foreign DNA sensor, the
CC presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger
CC signal that triggers the immune responses. Has antiviral activity by
CC sensing the presence of dsDNA from DNA viruses in the cytoplasm. Also
CC acts as an innate immune sensor of infection by retroviruses by
CC detecting the presence of reverse-transcribed DNA in the cytosol (By
CC similarity). Detection of retroviral reverse-transcribed DNA in the
CC cytosol may be indirect and be mediated via interaction with PQBP1,
CC which directly binds reverse-transcribed retroviral DNA. Also detects
CC the presence of DNA from bacteria (By similarity). 2',3'-cGAMP can be
CC transferred from producing cells to neighboring cells through gap
CC junctions, leading to promote STING1 activation and convey immune
CC response to connecting cells. 2',3'-cGAMP can also be transferred
CC between cells by virtue of packaging within viral particles
CC contributing to IFN-induction in newly infected cells in a cGAS-
CC independent but STING1-dependent manner. Also senses the presence of
CC neutrophil extracellular traps (NETs) that are translocated to the
CC cytosol following phagocytosis, leading to synthesis of 2',3'-cGAMP (By
CC similarity). In addition to foreign DNA, can also be activated by
CC endogenous nuclear or mitochondrial DNA (By similarity). When self-DNA
CC leaks into the cytosol during cellular stress (such as mitochondrial
CC stress, DNA damage, mitotic arrest or senescence), or is present in
CC form of cytosolic micronuclei, CGAS is activated leading to a state of
CC sterile inflammation. Acts as a regulator of cellular senescence by
CC binding to cytosolic chromatin fragments that are present in senescent
CC cells, leading to trigger type-I interferon production via STING1 and
CC promote cellular senescence. Also involved in the inflammatory response
CC to genome instability and double-stranded DNA breaks: acts by
CC localizing to micronuclei arising from genome instability. Micronuclei,
CC which as frequently found in cancer cells, consist of chromatin
CC surrounded by its own nuclear membrane: following breakdown of the
CC micronuclear envelope, a process associated with chromothripsis, CGAS
CC binds self-DNA exposed to the cytosol, leading to 2',3'-cGAMP synthesis
CC and subsequent activation of STING1 and type-I interferon production
CC (By similarity). In a healthy cell, CGAS is however kept inactive even
CC in cellular events that directly expose it to self-DNA, such as
CC mitosis, when cGAS associates with chromatin directly after nuclear
CC envelope breakdown or remains in the form of postmitotic persistent
CC nuclear cGAS pools bound to chromatin (By similarity). Nuclear CGAS is
CC inactivated by chromatin via direct interaction with nucleosomes, which
CC block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity.
CC Also acts as a suppressor of DNA repair in response to DNA damage:
CC inhibits homologous recombination repair by interacting with PARP1, the
CC CGAS-PARP1 interaction leading to impede the formation of the PARP1-
CC TIMELESS complex (By similarity). In addition to DNA, also sense
CC translation stress: in response to translation stress, translocates to
CC the cytosol and associates with collided ribosomes, promoting its
CC activation and triggering type-I interferon production (By similarity).
CC {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000250|UniProtKB:Q8N884}.
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:0000250|UniProtKB:Q8C6L5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42065;
CC Evidence={ECO:0000250|UniProtKB:Q8C6L5};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q8C6L5};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:Q8C6L5};
CC Note=Binds 1 Mg(2+) per subunit. Is also active with Mn(2+). Mn(2+)-
CC activated enyzme forms an inverted pppGp(2'-5')A intermediate,
CC suggesting a non-canonical but accelerated 2',3'-cGAMP cyclization
CC without substrate flip-over. Mn(2+) ions are coordinated by
CC triphosphate moiety of the inverted substrate, independent of the
CC catalytic triad residues. {ECO:0000250|UniProtKB:Q8C6L5};
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 DNA-binding induces the formation of liquid-like droplets in which CGAS
CC is activated. Liquid-like droplets also create a selective environment
CC that restricts entry of negative regulators, such as TREX1 or
CC BANF1/BAF, allowing sensing of DNA (By similarity). A number of
CC mechanisms exist to restrict its activity toward self-DNA. The
CC 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-375, Lys-385 and Lys-405
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-294
CC suppresses the nucleotidyltransferase activity. Phosphorylation at Ser-
CC 426 promotes the cyclic GMP-AMP synthase activity (By similarity).
CC Phosphorylation at Ser-202 inhibits its cyclic GMP-AMP synthase
CC activity. Ubiquitination at Lys-375 via 'Lys-27'-linked
CC polyubiquitination enhances the cyclic GMP-AMP synthase activity (By
CC similarity). Monoubiquitination at Lys-338 promotes oligomerization and
CC subsequent activation. Sumoylation at Lys-338, Lys-375 and Lys-385
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}.
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-204 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 (1-148) 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 (1-148) 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 (1-146) is phosphorylated by AURKB
CC during the G2-M transition, blocking CGAS liquid phase separation and
CC preventing activation. Phosphorylation at Tyr-204 by BLK promotes
CC cytosolic retention. Localizes into the nucleus following
CC dephosphorylation at Tyr-204 (By similarity). Phosphorylation at Ser-
CC 426 activates the nucleotidyltransferase activity. Dephosphorylation at
CC Ser-426 by PPP6C impairs its ability to bind GTP, thereby inactivating
CC it (By similarity). Phosphorylation at Ser-202 by PRKDC inhibits its
CC cyclic GMP-AMP synthase activity by impairing homodimerization and
CC activation (By similarity). Phosphorylation at Ser-294 by AKT (AKT1,
CC AKT2 or AKT3) suppresses the nucleotidyltransferase activity.
CC Phosphorylation at Ser-294 by CDK1 during mitosis leads to its
CC inhibition, thereby preventing CGAS activation by self-DNA during
CC mitosis. Dephosphorylated at Ser-294 by protein phosphatase PP1 upon
CC mitotic exit (By similarity). {ECO:0000250|UniProtKB:Q8C6L5,
CC ECO:0000250|UniProtKB:Q8N884}.
CC -!- PTM: Ubiquitinated at Lys-405 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-405
CC and stabilize CGAS. Ubiquitinated at Lys-375 by RNF185 via 'Lys-27'-
CC linked polyubiquitination, promoting CGAS cyclic GMP-AMP synthase
CC activity (By similarity). Monoubiquitination at Lys-338 by TRIM56
CC promotes oligomerization and subsequent activation (By similarity).
CC Monoubiquitination by TRIM41 promotes CGAS activation (By similarity).
CC Ubiquitination at Lys-274 via 'Lys-48'-linked polyubiquitination
CC promotes its degradation. Deubiquitination at Lys-274 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 by TRIM38 in uninfected cells and during the early
CC phase of viral infection, promoting its stability by preventing
CC ubiquitination at Lys-274, and subsequent degradation. Desumoylated by
CC SENP2 during the late phase of viral infection. Sumoylation at Lys-338,
CC Lys-375 and Lys-385 prevents DNA-binding, oligomerization and
CC nucleotidyltransferase activity. Desumoylation at Lys-338, Lys-375 and
CC Lys-385 by SENP7 relieves inhibition and activates CGAS.
CC {ECO:0000250|UniProtKB:Q8C6L5}.
CC -!- PTM: Polyglutamylated by TTLL6 at Glu-275, leading to impair DNA-
CC binding activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6.
CC {ECO:0000250|UniProtKB:Q8C6L5}.
CC -!- PTM: Acetylation at Lys-375, Lys-385 and Lys-405 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; DAAA02025231; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR AlphaFoldDB; E1BGN7; -.
DR SMR; E1BGN7; -.
DR STRING; 9913.ENSBTAP00000001184; -.
DR PaxDb; E1BGN7; -.
DR PRIDE; E1BGN7; -.
DR eggNOG; KOG3963; Eukaryota.
DR HOGENOM; CLU_040428_2_0_1; -.
DR InParanoid; E1BGN7; -.
DR TreeFam; TF331255; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
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: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 3: Inferred from homology;
KW Acetylation; Antiviral defense; ATP-binding; Cell membrane; Chromosome;
KW Cytoplasm; DNA damage; DNA repair; DNA-binding; GTP-binding; Immunity;
KW Innate immunity; Isopeptide bond; Lipid-binding; Magnesium; Membrane;
KW Metal-binding; Nucleotide-binding; Nucleotidyltransferase; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation; Zinc.
FT CHAIN 1..498
FT /note="Cyclic GMP-AMP synthase"
FT /id="PRO_0000421763"
FT REGION 1..150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1..148
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 62..73
FT /note="Required for association with the cell membrane"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 108..148
FT /note="Required for activation upon DNA viral infection"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 161..204
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT REGION 332..373
FT /note="Interaction with collided ribosomes"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT REGION 375..398
FT /note="DNA-binding"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT MOTIF 157..162
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOTIF 284..294
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT COMPBIAS 58..80
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 106..120
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 200
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 202
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 214
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 216
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 216
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 310
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 310
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 310
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 353
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 367..374
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 367
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT BINDING 374
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 381
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 388
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 395
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 405
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT BINDING 426..430
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT SITE 244
FT /note="Arginine-anchor"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT SITE 310..311
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 61
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 62
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 204
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 275
FT /note="5-glutamyl polyglutamate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT MOD_RES 294
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 375
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 385
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 405
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT MOD_RES 426
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT CROSSLNK 161
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT CROSSLNK 274
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 338
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 338
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 375
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 375
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
FT CROSSLNK 385
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q8C6L5"
FT CROSSLNK 405
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q8N884"
SQ SEQUENCE 498 AA; 55953 MW; E9B5909E3419030F CRC64;
MAPPRRKATR KASETASGVS APCVEGGLSA EPSEPAAVPE APRPGARRCG AAGASGSRRE
KSRLDPREKP QVRARAARAE DQAEGPAAPT ADAEPPAAPG HSLPRASTRS RGTASSARAR
RPQSGPPEGP GLGPRAPSPH LGRREEAPGA WKPRAVLEKL KLSRQEISVA AEVVNRLGDH
LLRRLNSRES EFKGVDLLRT GSYYERVKIS APNEFDLMFT LEVPRIQLEE YCNSSAHYFV
KFKRNPKGSP LDQFLEGGIL SASKMLFKFR KIIKEEIKHI EDTDVIMERK KRGSPAVTLL
IRKPREISVD IILALESKSS WPASTQKGLP ISNWLGTKVK DNLKRQPFYL VPKHAKEGSL
FQEETWRLSF SHIEKAILTN HGQTKTCCET EGVKCCRKEC LKLMKYLLEQ LKKKFGKQRG
LDKFCSYHVK TAFLHVCTQN PHDSWWLYKD LELCFDNCVT YFLQCLKTEH LEHYFIPDVL
SKQIEYEQNN GFPVFDEF
