Cgas
entrez
214763
canonical
uniprot
Q8C6L5
canonical
ensembl
ENSMUSG00000032344
resolver
ensp
ENSMUSP00000063331
resolver
enst
ENSMUST00000070742
resolver
genesymbol
Cgas
resolver
genesymbol_syn
E330016A19Rik
resolver
genesymbol_syn
Mb21d1
resolver
uniprot
Q3ULW3
resolver
uniprot
Q8BSY1
resolver
uniprot_entry
CGAS_MOUSE
resolver
uniprot_entry
Q8BSY1_MOUSE
resolver
uniprot_sec
Q3ULW3
resolver
activity_regulation
ACTIVITY REGULATION: The enzyme activity is strongly increased by double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA (By similarity). DNA-binding induces the formation of liquid-like droplets in which CGAS is activated (PubMed:39322678). Liquid-like droplets also create a selective environment that restricts entry of negative regulators, such as TREX1 or BANF1/BAF, allowing sensing of DNA (By similarity). A number of mechanisms exist to restrict its activity toward self-DNA (PubMed:32911480, PubMed:32911481, PubMed:32913000). The nucleotidyltransferase activity is inhibited in the nucleus via its association with nucleosomes: interacts with the acidic patch of histones H2A and H2B, thereby blocking DNA-binding and subsequent activation (PubMed:32156810, PubMed:32911480, PubMed:32911481, PubMed:32913000). CGAS is also inactive when associated with mitotic chromatin (By similarity). Chromatin-bound CGAS cannot be activated by exogenous DNA in mitotic cells: phosphorylation of the N-terminal disordered part by AURKB during the G2-M transition blocks CGAS liquid phase separation and activation (By similarity). Activity toward self-DNA is inhibited by BANF1/BAF upon acute loss of nuclear membrane integrity: BANF1/BAF acts by outcompeting CGAS for DNA-binding, thereby preventing CGAS activation (PubMed:32156810). DNA-induced activation at micronuclei is also limited by TREX1, which degrades micronuclear DNA upon nuclear envelope rupture, thereby preventing CGAS activation (By similarity). CGAS can be released from nucleosomes and activated by MRE11 component of the MRN complex, which displaces CGAS from acidic-patch-mediated sequestration (PubMed:38200309). Acetylation at Lys-372, Lys-382 and Lys-402 inhibits the cyclic GMP-AMP synthase activity (By similarity). Acetylation by KAT2A at the plasma membrane activates CGAS (By similarity). Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (By similarity). Phosphorylation at Ser-291 suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-420 promotes the cyclic GMP-AMP synthase activity (PubMed:32474700). Phosphorylation at Thr-52 and Ser-199 inhibits its cyclic GMP-AMP synthase activity (By similarity). Ubiquitination at Lys-372 via 'Lys-27'-linked polyubiquitination enhances the cyclic GMP-AMP synthase activity (By similarity). Monoubiquitination at Lys-335 promotes oligomerization and subsequent activation (PubMed:29426904). Sumoylation at Lys-335, Lys-372 and Lys-382 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (PubMed:28095500). The enzyme activity is impaired by the cleavage by CASP1 (PubMed:28314590). In addition to DNA, also activated by collided ribosomes upon translation stress: specifically binds collided ribosomes, promoting its activation and triggering type-I interferon production (By similarity). In hematopoietic stem cells, binding to circular RNA cia-cGAS inhibits the cyclic GMP-AMP synthase activity (PubMed:29625897). Strongly inhibited by compound RU.521, which is specific for mouse protein (PubMed:28963528, PubMed:30007416). {ECO:0000250|UniProtKB:Q8N884, ECO:0000269|PubMed:26440888, ECO:0000269|PubMed:28095500, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28963528, ECO:0000269|PubMed:29426904, ECO:0000269|PubMed:29625897, ECO:0000269|PubMed:30007416, ECO:0000269|PubMed:32156810, ECO:0000269|PubMed:32474700, ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:32913000, ECO:0000269|PubMed:38200309, ECO:0000269|PubMed:39322678}.
uniprot
proteins
amino_acid_sequence
MEDPRRRTTAPRAKKPSAKRAPTQPSRTRAHAESCGPQRGARSRRAERDGDTTEKPRAPGPRVHPARATELTKDAQPSAMDAAGATARPAVRVPQQQAILDPELPAVREPQPPADPEARKVVRGPSHRRGARSTGQPRAPRGSRKEPDKLKKVLDKLRLKRKDISEAAETVNKVVERLLRRMQKRESEFKGVEQLNTGSYYEHVKISAPNEFDVMFKLEVPRIELQEYYETGAFYLVKFKRIPRGNPLSHFLEGEVLSATKMLSKFRKIIKEEVKEIKDIDVSVEKEKPGSPAVTLLIRNPEEISVDIILALESKGSWPISTKEGLPIQGWLGTKVRTNLRREPFYLVPKNAKDGNSFQGETWRLSFSHTEKYILNNHGIEKTCCESSGAKCCRKECLKLMKYLLEQLKKEFQELDAFCSYHVKTAIFHMWTQDPQDSQWDPRNLSSCFDKLLAFFLECLRTEKLDHYFIPKFNLFSQELIDRKSKEFLSKKIEYERNNGFPIFDKL
uniprot
proteins
ec_number
2.7.7.86
uniprot
proteins
function
FUNCTION: Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (2',3'-cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:23258413, PubMed:23647843, PubMed:23722158, PubMed:26829768, PubMed:28214358, PubMed:29426904, PubMed:29625897, PubMed:32814054, PubMed:38740774). 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:23258413, PubMed:23647843, PubMed:23722158, PubMed:26829768, PubMed:28214358). Acts as a key DNA sensor: directly binds double-stranded DNA (dsDNA), inducing the formation of liquid-like droplets in which CGAS is activated, leading to synthesis of 2',3'-cGAMP, a second messenger that binds to and activates STING1, thereby triggering type-I interferon production (PubMed:23722158, PubMed:28095500, PubMed:28314590, PubMed:28363908, PubMed:39322678). Preferentially binds long dsDNA (around 45 bp) and forms ladder-like networks that function cooperatively to stabilize individual cGAS-dsDNA complexes (PubMed:28902841). Acts as a key foreign DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed:23722158, PubMed:28314590, PubMed:28363908). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:23258413, PubMed:23647843, PubMed:23722158). Also acts as an innate immune sensor of infection by retroviruses 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 (By similarity). Also detects the presence of DNA from bacteria (By similarity). 2',3'-cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote STING1 activation and convey immune response to connecting cells (PubMed:24077100, PubMed:31992625). 2',3'-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 STING1-dependent manner (PubMed:26229117). Also senses the presence of neutrophil extracellular traps (NETs) that are translocated to the cytosol following phagocytosis, leading to synthesis of 2',3'-cGAMP (PubMed:33688080). In addition to foreign DNA, can also be activated by endogenous nuclear or mitochondrial DNA (By similarity). When self-DNA leaks into the cytosol during cellular stress (such as mitochondrial stress, DNA damage, mitotic arrest or senescence), or is present in form of cytosolic micronuclei, CGAS is activated leading to a state of sterile inflammation (PubMed:28738408, PubMed:28759028). 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 STING1 and promote cellular senescence (PubMed:28759028). 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). 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 2',3'-cGAMP synthesis and subsequent activation of STING1 and type-I interferon production (PubMed:28738408). In a healthy cell, CGAS is however kept inactive even in cellular events that directly expose it to self-DNA, such as mitosis, when cGAS associates with chromatin directly after nuclear envelope breakdown or remains in the form of postmitotic persistent nuclear cGAS pools bound to chromatin (By similarity). Nuclear CGAS is inactivated by chromatin via direct interaction with nucleosomes, which block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity (PubMed:31808743, PubMed:32911480, PubMed:32911481, PubMed:32913000). Also acts as a suppressor of DNA repair in response to DNA damage: inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed:30356214, PubMed:31544964, PubMed:35210392). In addition to DNA, also sense translation stress: in response to translation stress, translocates to the cytosol and associates with collided ribosomes, promoting its activation and triggering type-I interferon production (By similarity). {ECO:0000250|UniProtKB:Q8N884, ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23647843, ECO:0000269|PubMed:23722158, ECO:0000269|PubMed:23929945, ECO:0000269|PubMed:24077100, ECO:0000269|PubMed:26229117, ECO:0000269|PubMed:26829768, ECO:0000269|PubMed:28095500, ECO:0000269|PubMed:28214358, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28363908, ECO:0000269|PubMed:28738408, ECO:0000269|PubMed:28759028, ECO:0000269|PubMed:28902841, ECO:0000269|PubMed:29426904, ECO:0000269|PubMed:29625897, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:31992625, ECO:0000269|PubMed:32814054, ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:32913000, ECO:0000269|PubMed:33688080, ECO:0000269|PubMed:35210392, ECO:0000269|PubMed:38740774, ECO:0000269|PubMed:39322678}.
uniprot
proteins
mass_dalton
58194
uniprot
proteins
mutagenesis
MUTAGEN 156; /note="K->Q: Mimics lactylation; knockin mice show higher mortality following HSV-1 infection."; /evidence="ECO:0000269|PubMed:39322678"; MUTAGEN 172; /note="N->K: Induces alteration of the DNA-binding surface and leads to decreased synthesis of cyclic GMP-AMP (cGAMP); when associated with L-180."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 176; /note="E->A: Abolished poly-ADP-ribosylation by PARP1, stimulating interferon production in knockin mice."; /evidence="ECO:0000269|PubMed:35460603"; MUTAGEN 180; /note="R->L: Induces alteration of the DNA-binding surface and leads to decreased synthesis of cyclic GMP-AMP (cGAMP); when associated with K-182."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 198; /note="G->A: Abolishes stimulation of interferon production; when associated with A-199."; /evidence="ECO:0000269|PubMed:26229117"; MUTAGEN 199; /note="S->A: Abolishes stimulation of interferon production; when associated with A-199."; /evidence="ECO:0000269|PubMed:26229117"; MUTAGEN 201; /note="Y->E: Phosphomimetic mutant; reduced translocation to the nucleus following treatment with etoposide."; /evidence="ECO:0000269|PubMed:35210392"; MUTAGEN 211..213; /note="EFD->AFA: Abolished nucleotidyltransferase activity. Does not affect nuclear localization and tethering to chromatin."; /evidence="ECO:0000269|PubMed:31808743"; MUTAGEN 211; /note="E->A: Abolishes ability to promote type-I interferon production."; /evidence="ECO:0000269|PubMed:23258413"; MUTAGEN 213; /note="D->A: Abolishes ability to promote type-I interferon production."; /evidence="ECO:0000269|PubMed:23258413"; MUTAGEN 217; /note="K->R: Reduced sumoylation."; /evidence="ECO:0000269|PubMed:27637147"; MUTAGEN 222; /note="R->E: Impaired tethering to chromatin, leading to constitutive activation in the absence of DNA."; /evidence="ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:32913000"; MUTAGEN 238; /note="K->E: Does not affect interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 240; /note="K->E: Impaired tethering to chromatin, leading to constitutive activation in the absence of DNA."; /evidence="ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:32913000"; MUTAGEN 241; /note="R->E: Abolished tethering to chromatin, leading to strong constitutive activation in the absence of DNA."; /evidence="ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:32913000"; MUTAGEN 242..247; /note="IPRGNP->SGSGSG: Slightly decreased tethering to chromatin, leading to mild constitutive activation in the absence of DNA."; /evidence="ECO:0000269|PubMed:31808743"; MUTAGEN 244..250; /note="RGNPLSH->AGNPLSA: Does not affect ability to bind poly-ADP-ribosylated PARP1."; /evidence="ECO:0000269|PubMed:35210392"; MUTAGEN 244; /note="R->E: Slightly decreased tethering to chromatin. Does not affect interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32911481"; MUTAGEN 271; /note="K->R: Impaired deubiquitination by USP29. Does not affect sumoylation."; /evidence="ECO:0000269|PubMed:27637147, ECO:0000269|PubMed:32457395"; MUTAGEN 272; /note="E->A: Increased DNA-binding activity."; /evidence="ECO:0000269|PubMed:26829768"; MUTAGEN 275..278; /note="KEIK->AEIA: Does not affect ability to bind poly-ADP-ribosylated PARP1."; /evidence="ECO:0000269|PubMed:35210392"; MUTAGEN 278; /note="K->R: Does not affect ubiquitination by TRIM56."; /evidence="ECO:0000269|PubMed:29426904"; MUTAGEN 291; /note="S->A: Enhanced stimulation of interferon production."; /evidence="ECO:0000269|PubMed:26440888"; MUTAGEN 302; /note="E->A: Increased nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:26829768"; MUTAGEN 315; /note="K->E: Slightly decreased interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 323; /note="K->E: Slightly decreased interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 335; /note="K->E: Decreased DNA-binding and subsequent activation. Does not affect nuclear localization and tethering to chromatin."; /evidence="ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32911481"; MUTAGEN 335; /note="K->R: Abolished ubiquitination by TRIM56, leading to impaired homodimerization and activation. Does not affect sumoylation. Strongly reduced sumoylation; when associated with R-372 and R-382."; /evidence="ECO:0000269|PubMed:27637147, ECO:0000269|PubMed:28095500, ECO:0000269|PubMed:29426904"; MUTAGEN 337; /note="R->E: Strongly reduced interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911480"; MUTAGEN 341; /note="R->E: Abolished interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481"; MUTAGEN 342; /note="R->E: Strongly decreased interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481"; MUTAGEN 350; /note="K->R: Does not affect ubiquitination by TRIM56."; /evidence="ECO:0000269|PubMed:29426904"; MUTAGEN 364; /note="R->A: Decreased nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:38740774"; MUTAGEN 372; /note="K->R: Strongly reduced sumoylation; when associated with R-335 and R-382."; /evidence="ECO:0000269|PubMed:28095500"; MUTAGEN 382; /note="K->A: Decreased DNA-binding and abolished homodimerization. Does not affect nuclear localization and tethering to chromatin."; /evidence="ECO:0000269|PubMed:31808743"; MUTAGEN 382; /note="K->E: Slightly decreased interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 382; /note="K->R: Strongly reduced sumoylation; when associated with R-335 and R-372."; /evidence="ECO:0000269|PubMed:28095500"; MUTAGEN 386; /note="E->A: Abolished homodimerization and subsequent activation. Does not affect nuclear localization and tethering to chromatin."; /evidence="ECO:0000269|PubMed:31808743"; MUTAGEN 395..399; /note="KECLK->MECLM: Decreased DNA-binding and subsequent activation. Does not affect nuclear localization and tethering to chromatin."; /evidence="ECO:0000269|PubMed:31808743"; MUTAGEN 399..402; /note="KLMK->ALMA: Does not affect ability to bind poly-ADP-ribosylated PARP1."; /evidence="ECO:0000269|PubMed:35210392"; MUTAGEN 419; /note="C->S: Gains susceptibility to mouse-specific RU.521; when associated with N-467."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 420; /note="S->A: Decreased cyclic GMP-AMP synthase activity."; /evidence="ECO:0000269|PubMed:32474700"; MUTAGEN 420; /note="S->D: Phospho-mimetic mutant; increased cyclic GMP-AMP synthase activity."; /evidence="ECO:0000269|PubMed:32474700"; MUTAGEN 464; /note="K->R: Does not affect deubiquitination by USP29. Reduced sumoylation."; /evidence="ECO:0000269|PubMed:27637147, ECO:0000269|PubMed:32457395"; MUTAGEN 467; /note="H->A: Renders the enzyme more active toward GTP."; /evidence="ECO:0000269|PubMed:38740774"; MUTAGEN 467; /note="H->N: Gains susceptibility to mouse-specific RU.521; when associated with S-419."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 491..497; /note="KKIEYER->AKAEYEA: Impaired ability to bind poly-ADP-ribosylated PARP1."; /evidence="ECO:0000269|PubMed:35210392"; MUTAGEN 491; /note="K->R: Abolished monomethylation, promoting interaction with PARP1."; /evidence="ECO:0000269|PubMed:35210392"; MUTAGEN 498..499; /note="NN->AA: Reduced ubiquitination by the ECS(SPSB3) complex, leading to increased stability in the nucleus."; /evidence="ECO:0000269|PubMed:38418882
uniprot
proteins
post_translational_modification
PTM: The N-terminal disordered part (1-146) is phosphorylated by AURKB during the G2-M transition, blocking CGAS liquid phase separation and preventing activation (By similarity). Phosphorylation at Tyr-201 by BLK promotes cytosolic retention (By similarity). Localizes into the nucleus following dephosphorylation at Tyr-201 (By similarity). Phosphorylation at Ser-420 activates the nucleotidyltransferase activity (PubMed:32474700). Dephosphorylation at Ser-420 by PPP6C impairs its ability to bind GTP, thereby inactivating it (PubMed:32474700). Phosphorylation at Thr-52 and Ser-199 by PRKDC inhibits its cyclic GMP-AMP synthase activity by impairing homodimerization and activation (By similarity). Phosphorylation at Ser-291 by AKT (AKT1, AKT2 or AKT3) suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-291 by CDK1 during mitosis leads to its inhibition, thereby preventing CGAS activation by self-DNA during mitosis (PubMed:32351706). Dephosphorylated at Ser-291 by protein phosphatase PP1 upon mitotic exit (PubMed:32351706). {ECO:0000250|UniProtKB:Q8N884, ECO:0000269|PubMed:26440888, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:32474700}.; PTM: Ubiquitinated at Lys-402 via 'Lys-48'-linked polyubiquitin chains, leading to its SQSTM1-mediated autophagic degradation (By similarity). Interaction with TRIM14 promotes recruitment of USP14, leading to deubiquitinate Lys-402 and stabilize CGAS (By similarity). Ubiquitinated at Lys-372 by RNF185 via 'Lys-27'-linked polyubiquitination, promoting CGAS cyclic GMP-AMP synthase activity (By similarity). Monoubiquitination at Lys-335 by TRIM56 promotes oligomerization and subsequent activation (PubMed:29426904). Monoubiquitination by TRIM41 promotes CGAS activation (By similarity). Ubiquitination at Lys-271 and Lys-464 via 'Lys-48'-linked polyubiquitination promotes its degradation (PubMed:27637147, PubMed:32457395). Deubiquitination at Lys-271 by USP29 promotes its stabilization (PubMed:32457395). Deubiquitinated by USP27X, promoting its stabilization (PubMed:31534008). Ubiquitinated at Lys-399 via 'Lys-63'-linked polyubiquitin chains by MARCHF8, leading to the inhibition of its DNA binding ability (By similarity). In cycling cells, nucleosome-bound CGAS is ubiquitinated at Lys-409 and Lys-410 via 'Lys-48'-linked polyubiquitin chains by the ECS(SPSB3) complex, leading to its degradation: ubiquitination and degradation of nuclear CGAS during G1 and G2 phases is required to promote low intranuclear CGAS abundance before the next mitotic cycle (PubMed:38418882). {ECO:0000250|UniProtKB:Q8N884, ECO:0000269|PubMed:27637147, ECO:0000269|PubMed:29426904, ECO:0000269|PubMed:31534008, ECO:0000269|PubMed:32457395, ECO:0000269|PubMed:38418882}.; PTM: Sumoylated at Lys-217 and Lys-464 by TRIM38 in uninfected cells and during the early phase of viral infection, promoting its stability by preventing ubiquitination at Lys-271 and Lys-464, and subsequent degradation (PubMed:27637147). Desumoylated by SENP2 during the late phase of viral infection (PubMed:27637147). Sumoylation at Lys-335, Lys-372 and Lys-382 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (PubMed:28095500). Desumoylation at Lys-335, Lys-372 and Lys-382 by SENP7 relieves inhibition and activates CGAS (PubMed:28095500). {ECO:0000269|PubMed:27637147, ECO:0000269|PubMed:28095500}.; PTM: ISGylated by HERC5, promoting ability to undergo liquid-liquid phase separation (LLPS), leading to CGAS activation. DeISGylated by USP18. {ECO:0000250|UniProtKB:Q8N884}.; PTM: Polyglutamylated by TTLL6 at Glu-272, leading to impair DNA-binding activity. Monoglutamylated at Glu-302 by TTLL4, leading to impair the nucleotidyltransferase activity. Deglutamylated by AGBL5/CCP5 and AGBL6/CCP6. {ECO:0000269|PubMed:26829768}.; PTM: Acetylation at Lys-372, Lys-382 and Lys-402 inhibits the cyclic GMP-AMP synthase activity. Deacetylated upon cytosolic DNA challenge such as viral infections. Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation. Acetylation at Lys-278 and Lys-409 by KAT2A at the plasma membrane activates CGAS. {ECO:0000250|UniProtKB:Q8N884}.; PTM: Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation (PubMed:25525874, PubMed:30878284). The damage of the nucleus and the mitochondria during apoptosis leads to leakage of nuclear and mitochondrial DNA, which activate CGAS: cleavage and inactivation during apoptosis in required to prevent cytokine overproduction (PubMed:25525874). Cleaved by CASP7 and CASP3 during virus-induced apoptosis, thereby inactivating it and preventing cytokine overproduction (PubMed:30878284). Cleaved by CASP1 upon DNA virus infection; the cleavage impairs cGAMP production (PubMed:28314590). Also cleaved by the pyroptotic CASP4 during non-canonical inflammasome activation; does not cut at the same sites as CASP1 (PubMed:28314590). {ECO:0000269|PubMed:25525874, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:30878284}.; PTM: Degraded via selective autophagy following interaction with Irgm1. Irgm1 promotes CGAS recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagic degradation. {ECO:0000250|UniProtKB:Q8N884}.; PTM: Poly-ADP-ribosylation at Glu-176 by PARP1 impairs DNA-binding, thereby preventing the cyclic GMP-AMP synthase activity. {ECO:0000269|PubMed:35460603}.; PTM: Palmitoylation at Cys-459 by ZDHHC18 impairs DNA-binding, thereby preventing the cyclic GMP-AMP synthase activity (By similarity). Palmitoylation at Cys-392 and Cys-393 by ZDHHC9 promotes homodimerization and cyclic GMP-AMP synthase activity (By similarity). Depalmitoylation at Cys-392 and Cys-393 by LYPLAL1 impairs homodimerization and cyclic GMP-AMP synthase activity (By similarity). {ECO:0000250|UniProtKB:Q8N884}.; PTM: Monomethylated at Lys-491 by SETD7 (PubMed:35210392). Monomethylation promotes interaction with SGF29, preventing interaction between PARP1 nad SGF29 (PubMed:35210392). Demethylation by RIOX1 promotes interaction with PARP1, followed by PARP1 inactivation (PubMed:35210392). {ECO:0000269|PubMed:35210392}.; PTM: Symmetric dimethylation at Arg-129 by PRMT5 prevents DNA-binding and activation. {ECO:0000250|UniProtKB:Q8N884}.; PTM: Lactylation by AARS2 prevents ability to undergo liquid-liquid phase separation (LLPS), thereby inhibiting CGAS activation. {ECO:0000269|PubMed:39322678}.
uniprot
proteins
protein_family
Mab-21 family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
23258413
uniprot
proteins
pubmed
23647843
uniprot
proteins
pubmed
23722158
uniprot
proteins
pubmed
23929945
uniprot
proteins
pubmed
24077100
uniprot
proteins
pubmed
24332030
uniprot
proteins
pubmed
24462292
uniprot
proteins
pubmed
25525874
uniprot
proteins
pubmed
26229117
uniprot
proteins
pubmed
26440888
uniprot
proteins
pubmed
26829768
uniprot
proteins
pubmed
27637147
uniprot
proteins
pubmed
28095500
uniprot
proteins
pubmed
28214358
uniprot
proteins
pubmed
28314590
uniprot
proteins
pubmed
28363908
uniprot
proteins
pubmed
28738408
uniprot
proteins
pubmed
28759028
uniprot
proteins
pubmed
28902841
uniprot
proteins
pubmed
28963528
uniprot
proteins
pubmed
29426904
uniprot
proteins
pubmed
29625897
uniprot
proteins
pubmed
29976794
uniprot
proteins
pubmed
30007416
uniprot
proteins
pubmed
30356214
uniprot
proteins
pubmed
30827685
uniprot
proteins
pubmed
30878284
uniprot
proteins
pubmed
31534008
uniprot
proteins
pubmed
31544964
uniprot
proteins
pubmed
31808743
uniprot
proteins
pubmed
31992625
uniprot
proteins
pubmed
32156810
uniprot
proteins
pubmed
32351706
uniprot
proteins
pubmed
32457395
uniprot
proteins
pubmed
32474700
uniprot
proteins
pubmed
32814054
uniprot
proteins
pubmed
32911480
uniprot
proteins
pubmed
32911481
uniprot
proteins
pubmed
32913000
uniprot
proteins
pubmed
33688080
uniprot
proteins
pubmed
35210392
uniprot
proteins
pubmed
35460603
uniprot
proteins
pubmed
38200309
uniprot
proteins
pubmed
38418882
uniprot
proteins
pubmed
38740774
uniprot
proteins
pubmed
39322678
uniprot
proteins
pubmed
40461475
uniprot
proteins
sequence_length
507
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31808743}. Chromosome {ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:32913000}. Cell membrane {ECO:0000269|PubMed:30827685}; Peripheral membrane protein {ECO:0000269|PubMed:30827685}. Cytoplasm, cytosol {ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31808743}. Note=Mainly localizes in the nucleus, and at low level in the cytosol (PubMed:31544964, PubMed:31808743). On chromosomes, enriched on centromeric satellite and LINE DNA repeat elements (By similarity). Exported from the nucleus to the cytosol in a XPO1/CRM1 via the nuclear export signal in response to DNA stimulation (By similarity). Outside the nucleus, localizes at the cell membrane as a peripheral membrane protein in resting conditions: association to the cell membrane is mediated via 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 (By similarity). Following detection of double-stranded DNA (dsDNA), released from the cell membrane into the cytosol in order to signal (By similarity). Upon transfection with dsDNA forms punctate structures that co-localize with DNA and Beclin-1 (BECN1) (By similarity). Phosphorylation at Tyr-201 promotes cytosolic retention (By similarity). In response to translation stress, translocates to the cytosol and associates with collided ribosomes (By similarity). {ECO:0000250|UniProtKB:Q8N884, ECO:0000269|PubMed:30827685, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31808743}.
uniprot
proteins