CGAS
entrez
115004
canonical
uniprot
Q8N884
canonical
ensembl
ENSG00000164430
resolver
ensp
ENSP00000359339
resolver
ensp
ENSP00000506638
resolver
enst
ENST00000680833
resolver
genesymbol
CGAS
resolver
genesymbol_syn
C6orf150
resolver
genesymbol_syn
MB21D1
resolver
hgnc
HGNC:21367
resolver
uniprot
A0A7P0TBQ3
resolver
uniprot
L0L2J9
resolver
uniprot
Q14CV6
resolver
uniprot
Q32NC9
resolver
uniprot
Q5SWL0
resolver
uniprot
Q5SWL1
resolver
uniprot
Q96E45
resolver
uniprot_entry
A0A7P0TBQ3_HUMAN
resolver
uniprot_entry
CGAS_HUMAN
resolver
uniprot_sec
L0L2J9
resolver
uniprot_sec
Q14CV6
resolver
uniprot_sec
Q32NC9
resolver
uniprot_sec
Q5SWL0
resolver
uniprot_sec
Q5SWL1
resolver
uniprot_sec
Q96E45
resolver
activity_regulation
ACTIVITY REGULATION: The enzyme activity is strongly increased by double-stranded DNA (dsDNA), but not by single-stranded DNA or RNA (PubMed:23258413, PubMed:23707061, PubMed:26300263). DNA-binding induces the formation of liquid-like droplets in which CGAS is activated (PubMed:29976794, PubMed:33606975). Liquid-like droplets also create a selective environment that restricts entry of negative regulators, such as TREX1 or BANF1/BAF, allowing sensing of DNA (PubMed:33606975). A number of mechanisms exist to restrict its activity toward self-DNA (PubMed:31299200, PubMed:32792394, PubMed:32911482, PubMed:32912999, PubMed:33051594, PubMed:33542149). 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:31299200, PubMed:32911482, PubMed:32912999, PubMed:33051594). CGAS is also inactive when associated with mitotic chromatin (PubMed:33542149). 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 (PubMed:33542149). 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:32792394). DNA-induced activation at micronuclei is also limited by TREX1, which degrades micronuclear DNA upon nuclear envelope rupture, thereby preventing CGAS activation (PubMed:33476576). CGAS can be released from nucleosomes and activated by MRE11 component of the MRN complex, which displaces CGAS from acidic-patch-mediated sequestration (By similarity). 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). Acetylation at Lys-131, Lys-292 and Lys-421 by KAT2A at the plasma membrane activates CGAS (PubMed:39694035). Acetylation by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (PubMed:32817552). Phosphorylation at Ser-305 suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-435 promotes the cyclic GMP-AMP synthase activity (PubMed:32474700). Phosphorylation at Thr-68 and Ser-213 inhibits its cyclic GMP-AMP synthase activity (PubMed:33273464). Ubiquitination at Lys-173 and Lys-384 via 'Lys-27'-linked polyubiquitination enhances the cyclic GMP-AMP synthase activity (PubMed:28273161). Monoubiquitination at Lys-347 promotes oligomerization and subsequent activation (PubMed:29426904). Sumoylation at Lys-347, Lys-384 and Lys-394 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (By similarity). The enzyme activity is impaired by the cleavage at Asp-140 and Asp-157 produced 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 (PubMed:34111399). Strongly inhibited by compound PF-06928215, which is specific for human protein (PubMed:28934246, PubMed:30007416, PubMed:32459092). Inhibited by small-molecule inhibitors with a pyridoindole tricyclic core G108, G140 and G150 (PubMed:31113940). Inhibited by small-molecules XL-3156 and XL-3158, which prevent DNA-binding and formation of liquid-like droplets (PubMed:40461475). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:26440888, ECO:0000269|PubMed:28273161, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28934246, ECO:0000269|PubMed:29426904, ECO:0000269|PubMed:29976794, ECO:0000269|PubMed:30007416, ECO:0000269|PubMed:30799039, ECO:0000269|PubMed:31113940, ECO:0000269|PubMed:31299200, ECO:0000269|PubMed:32459092, ECO:0000269|PubMed:32474700, ECO:0000269|PubMed:32792394, ECO:0000269|PubMed:32817552, ECO:0000269|PubMed:32911482, ECO:0000269|PubMed:32912999, ECO:0000269|PubMed:33051594, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33476576, ECO:0000269|PubMed:33542149, ECO:0000269|PubMed:33606975, ECO:0000269|PubMed:34111399, ECO:0000269|PubMed:39694035}.; ACTIVITY REGULATION: (Microbial infection) Nucleotidyltransferase activity is inhibited by different herpesvirus tegument proteins (Herpes simplex virus 1 tegument protein VP22, herpes virus 8 protein ORF52 and herpesvirus 3 tegument protein VP22/ORF9) (PubMed:34015248, PubMed:34387695). Viral tegument proteins act by disrupting liquid-like droplets in which CGAS is activated, thereby preventing CGAS activity (PubMed:34015248, PubMed:34387695). {ECO:0000269|PubMed:34015248, ECO:0000269|PubMed:34387695}.
uniprot
proteins
amino_acid_sequence
MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPSDATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTYFLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF
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:21478870, PubMed:23258413, PubMed:23707061, PubMed:23707065, PubMed:23722159, PubMed:24077100, PubMed:24116191, PubMed:24462292, PubMed:25131990, PubMed:26300263, PubMed:29976794, PubMed:30799039, PubMed:31142647, PubMed:32814054, PubMed:33273464, PubMed:33542149, PubMed:33762328, PubMed:37217469, PubMed:37802025, PubMed:39694035, 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:28214358, PubMed:28363908). 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:28314590, PubMed:28363908, PubMed:29976794, PubMed:32817552, PubMed:33230297, PubMed:33606975, PubMed:33762328, PubMed:35322803, PubMed:35438208, PubMed:35460603, PubMed:35503863, PubMed:38740774, PubMed:40461475). Preferentially recognizes and binds curved long dsDNAs of a minimal length of 40 bp (PubMed:30007416). 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:28363908). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:28363908, PubMed:35613581). Also acts as an innate immune sensor of infection by retroviruses, such as HIV-2, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:23929945, PubMed:24269171, PubMed:30270045, PubMed:32852081). In contrast, HIV-1 is poorly sensed by CGAS, due to its capsid that cloaks viral DNA from CGAS detection (PubMed:24269171, PubMed:30270045, PubMed:32852081). 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). 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:26229115). 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 (PubMed:28738408, PubMed:28759889, PubMed:31299200, PubMed:33031745, PubMed:33230297, PubMed:34648591). When self-DNA leaks into the cytosol during cellular stress (such as mitochondrial stress, SARS-CoV-2 infection causing severe COVID-19 disease, 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:28759889, PubMed:31299200, PubMed:33031745, PubMed:33230297, PubMed:34648591, PubMed:35045565, PubMed:41610251). 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 (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, PubMed:41610251). Micronuclei, which are frequently found in cancer cells, consist of chromatin surrounded by their 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, PubMed:28759889, PubMed:41610251). Activated in response to prolonged mitotic arrest, promoting mitotic cell death (PubMed:31299200). 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 (PubMed:31299200, PubMed:33542149). Nuclear CGAS is inactivated by chromatin via direct interaction with nucleosomes, which block CGAS from DNA binding and thus prevent CGAS-induced autoimmunity (PubMed:31299200, PubMed:32911482, PubMed:32912999, PubMed:33051594, PubMed:33542149). 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). 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 (PubMed:34111399). In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less 2',3'-cGAMP, allowing a more fine-tuned response to pathogens (PubMed:30007416). {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:24269171, 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:30270045, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30799039, ECO:0000269|PubMed:31142647, ECO:0000269|PubMed:31299200, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31992625, ECO:0000269|PubMed:32814054, ECO:0000269|PubMed:32817552, ECO:0000269|PubMed:32852081, ECO:0000269|PubMed:32911482, ECO:0000269|PubMed:32912999, ECO:0000269|PubMed:33031745, ECO:0000269|PubMed:33051594, ECO:0000269|PubMed:33230297, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33542149, ECO:0000269|PubMed:33606975, ECO:0000269|PubMed:33688080, ECO:0000269|PubMed:33762328, ECO:0000269|PubMed:34111399, ECO:0000269|PubMed:34648591, ECO:0000269|PubMed:35045565, ECO:0000269|PubMed:35322803, ECO:0000269|PubMed:35438208, ECO:0000269|PubMed:35460603, ECO:0000269|PubMed:35503863, ECO:0000269|PubMed:35613581, ECO:0000269|PubMed:37217469, ECO:0000269|PubMed:37802025, ECO:0000269|PubMed:38740774, ECO:0000269|PubMed:39694035, ECO:0000269|PubMed:40461475, ECO:0000269|PubMed:41610251}.
uniprot
proteins
mass_dalton
58814
uniprot
proteins
mutagenesis
MUTAGEN 7; /note="K->Q: Acetylation-mimetic mutant; no effect."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 7; /note="K->R: No effect."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 13; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 18; /note="T->E: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 21; /note="K->R: Decreased ISGylation. Abolished ISGylation; when associated with R-187, R-219 and R-458."; /evidence="ECO:0000269|PubMed:38421872"; MUTAGEN 23; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 28; /note="R->K: Does not affect symmetric dimethylation by PRMT5."; /evidence="ECO:0000269|PubMed:33762328"; MUTAGEN 33; /note="D->A: No effect on type IIFN and RSAD2 induction. No effect on cleavage by CASP1. No effect on cleavage by CASP1; when associated with A-67; A-90 and A-95. Highly decreases cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-67; A-90; A-95 and A-140. Abolishes cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-67; A-90; A-95; A-140 and A-157."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 35; /note="T->E: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 37; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 47; /note="K->R: Decreased acetylation by KAT5, leading to decreased stimulation of interferon production."; /evidence="ECO:0000269|PubMed:32817552"; MUTAGEN 50; /note="K->Q: Acetylation-mimetic mutant; no effect."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 50; /note="K->R: No effect."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 56; /note="K->R: Decreased acetylation by KAT5, leading to decreased stimulation of interferon production."; /evidence="ECO:0000269|PubMed:32817552"; MUTAGEN 57; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 59; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 62; /note="K->R: Decreased acetylation by KAT5, leading to decreased stimulation of interferon production."; /evidence="ECO:0000269|PubMed:32817552"; MUTAGEN 64; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 67; /note="D->A: No effect on type IIFN and RSAD2 induction. No effect on cleavage by CASP1; when associated with A-33; A-90 and A-95. Highly decreases cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-90; A-95 and A-140. Abolishes cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-90; A-95; A-140 and A-157."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 68; /note="T->E: Phospho-mimetic mutant; decreased nucleotidyltransferase activity. In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33542149"; MUTAGEN 71..75; /note="RPPVR->EPPVE: Abolished binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and abolished association with the cell membrane."; /evidence="ECO:0000269|PubMed:30827685"; MUTAGEN 77; /note="T->E: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 83; /note="K->R: Decreased acetylation by KAT5, leading to decreased stimulation of interferon production."; /evidence="ECO:0000269|PubMed:32817552"; MUTAGEN 90; /note="D->A: No effect on type IIFN and RSAD2 induction. No effect on cleavage by CASP1; when associated with A-33; A-67 and A-95. Highly decreases cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-95 and A-140. Abolishes cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-95; A-140 and A-157."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 91; /note="T->E: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; D-94; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 94; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; E-97; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 95; /note="D->A: No effect on type IIFN and RSAD2 induction. No effect on cleavage by CASP1; when associated with A-33; A-67 and A-90. Highly decreases cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90 and A-140. Abolishes cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90; A-140 and A-157."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 97; /note="T->E: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; D-98; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 98; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-116; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 116; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-120; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 120; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-129; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 124; /note="R->K: Abolished symmetric dimethylation by PRMT5."; /evidence="ECO:0000269|PubMed:33762328"; MUTAGEN 129; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; E-130; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 130; /note="T->E: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; D-143 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 131; /note="K->R: In K3R mutant; decreased acetylation; when associated with R-292 and R-421."; /evidence="ECO:0000269|PubMed:39694035"; MUTAGEN 140; /note="D->A: Highly decreases cleavage by CASP1 and enhances type IIFN and RSAD2 induction upon DNA virus infection. Abolishes cleavage by CASP1, enhances RSAD2 induction upon DNA virus infection but no effect on cleavage by CASP5; when associated with A-157. Highly decreases cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90 and A-95. Abolishes cleavage by CASP1 and enhances RSAD2 induction upon DNA virus infection; when associated with A-33; A-67; A-90; A-95 and A-157."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 140; /note="D->H: Highly decreases cleavage by CASP1 and enhances type IIFN and RSAD2 induction upon DNA virus infection."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 143; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130 and D-149."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 149; /note="S->D: In 20DE phospho-mimetic mutant; causes inactivation of nucleotidyltransferase activity; when associated with D-13; E-18; D-23; E-35; D-37; D-57; D-59; D-64; E-68; E-77; E-91; D-94; E-97; D-98; D-116; D-120; D-129; E-130 and D-143."; /evidence="ECO:0000269|PubMed:33542149"; MUTAGEN 157; /note="D->A: No effect on type IIFN and RSAD2 induction. Highly decreases cleavage by CASP1 and enhances type IIFN and enhances RSAD2 induction upon DNA virus infection. Abolishes cleavage by CASP1, enhances RSAD2 induction upon DNA virus infection but no effect on cleavage by CASP5; when associated with A-140. Abolishes cleavage by CASP1; when associated with A-33; A-67; A-90; A-95 and A-140."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 157; /note="D->H: Highly decreases cleavage by CASP1 and enhances type IIFN and enhances RSAD2 induction upon DNA virus infection."; /evidence="ECO:0000269|PubMed:28314590"; MUTAGEN 169..174; /note="LEKLKL->AAAAAA: Abolished export from the nucleus to the cytosol in response to DNA stimulation."; /evidence="ECO:0000269|PubMed:33406424"; MUTAGEN 171..174; /note="Missing: Abolishes DNA-binding but does not affect translocation to the nucleus following treatment with etoposide; when associated with A-407."; /evidence="ECO:0000269|PubMed:30356214"; MUTAGEN 171; /note="K->A: No effect on stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061"; MUTAGEN 172; /note="L->A: Impaired type-I interferon production in response to DNA stimulation."; /evidence="ECO:0000269|PubMed:33406424"; MUTAGEN 173; /note="K->A: Strongly reduces enzyme activity and stimulation of interferon production; when associated with A-176. No effect on stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:24116191"; MUTAGEN 173; /note="K->E: Strongly reduces stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23722159"; MUTAGEN 173; /note="K->R: Strongly decreased ubiquitination by RNF185; when associated with R-384."; /evidence="ECO:0000269|PubMed:28273161"; MUTAGEN 174; /note="L->N: Strongly reduces enzyme activity and stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:24116191"; MUTAGEN 176; /note="R->A: Strongly reduces enzyme activity and stimulation of interferon production; when associated with A-173."; /evidence="ECO:0000269|PubMed:23722159"; MUTAGEN 187; /note="K->N: Induces alteration of the DNA-binding surface and leads to increased synthesis of cyclic GMP-AMP (cGAMP); when associated with R-195."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 187; /note="K->R: Decreased ISGylation. Abolished ISGylation; when associated with R-21, R-219 and R-458."; /evidence="ECO:0000269|PubMed:38421872"; MUTAGEN 191; /note="D->A: Abolished poly-ADP-ribosylation by PARP1, stimulating interferon production."; /evidence="ECO:0000269|PubMed:35460603"; MUTAGEN 195; /note="L->R: Induces alteration of the DNA-binding surface and leads to increased synthesis of cyclic GMP-AMP (cGAMP); when associated with N-187."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 204; /note="R->K: Does not affect symmetric dimethylation by PRMT5."; /evidence="ECO:0000269|PubMed:33762328"; MUTAGEN 210..214; /note="NTGSY->ATGSA: Abolishes DNA-binding but does not affect translocation to the nucleus following treatment with etoposide; when associated with A-384."; /evidence="ECO:0000269|PubMed:30356214"; MUTAGEN 210; /note="N->D: More than 75% inhibition of interferon beta production."; /evidence="ECO:0000269|PubMed:30092200"; MUTAGEN 211; /note="T->Q: Abolishes enzyme activity; when associated with I-376 and I-436."; /evidence="ECO:0000269|PubMed:25131990"; MUTAGEN 212..213; /note="GS->AA: Abolishes enzyme activity. Abolishes stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23722159"; MUTAGEN 213; /note="S->D: Phospho-mimetic mutant; decreased nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:33273464"; MUTAGEN 215; /note="Y->A: Strongly reduced tyrosine phosphorylation."; /evidence="ECO:0000269|PubMed:30356214"; MUTAGEN 215; /note="Y->E: Phosphomimetic mutant; reduced translocation to the nucleus following treatment with etoposide."; /evidence="ECO:0000269|PubMed:30356214"; MUTAGEN 219; /note="K->R: Decreased ISGylation. Abolished ISGylation; when associated with R-21, R-187 and R-458."; /evidence="ECO:0000269|PubMed:38421872"; MUTAGEN 225..227; /note="EFD->AFA: Abolishes enzyme activity and stimulation of interferon production. Does not affect subcellular location to the nucleus and cytosol."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:26229115, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:31299200, ECO:0000269|PubMed:31544964"; MUTAGEN 231; /note="K->R: Reduced sumoylation."; /evidence="ECO:0000269|PubMed:27637147"; MUTAGEN 236; /note="R->E: Abolishes stimulation of interferon production; when associated with E-254 and E-327. Strongly decreased interaction with nucleosomes and tethering to chromatin, leading to constitutive activation in the absence of DNA."; /evidence="ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32911480, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:32911482, ECO:0000269|PubMed:33051594"; MUTAGEN 246; /note="R->E: Does not affect interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 252; /note="K->E: Does not affect interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 254; /note="K->A: Strongly decreased interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594"; MUTAGEN 254; /note="K->E: Abolishes stimulation of interferon production; when associated with E-236 and E-327. Abolished interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:32911481"; MUTAGEN 255; /note="R->E: Abolished interaction with nucleosomes and 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:32911482, ECO:0000269|PubMed:32912999, ECO:0000269|PubMed:33051594"; MUTAGEN 258; /note="K->A: Slightly decreased interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594"; MUTAGEN 258; /note="K->E: Does not affect interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 275; /note="K->E: Reduced nucleotidyltransferase activity. Abolished nucleotidyltransferase activity; when associated with E-285."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 279..282; /note="KFRK->EFRE: Strongly reduced nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 279; /note="K->E: Reduced nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 285; /note="K->E: Strongly reduced nucleotidyltransferase activity. Abolished nucleotidyltransferase activity; when associated with E-275."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 292; /note="K->R: In K3R mutant; decreased acetylation; when associated with R-131 and R-421."; /evidence="ECO:0000269|PubMed:39694035"; MUTAGEN 295..305; /note="Missing: Abolished nuclear localization."; /evidence="ECO:0000269|PubMed:30356214"; MUTAGEN 300..301; /note="RK->EE,AA: Abolished nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 300; /note="R->E: Reduced nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 302; /note="R->K: Does not affect symmetric dimethylation by PRMT5."; /evidence="ECO:0000269|PubMed:33762328"; MUTAGEN 305; /note="S->A: Enhanced stimulation of interferon production. Does not affect chromosome localization."; /evidence="ECO:0000269|PubMed:26440888, ECO:0000269|PubMed:32351706"; MUTAGEN 305; /note="S->D: Phospho-mimetic mutant; decreased ability to trigger type-I interferon production."; /evidence="ECO:0000269|PubMed:32351706"; MUTAGEN 319; /note="D->A: Abolishes enzyme activity. Does not affect translocation to the nucleus following treatment with etoposide. Abolished cleavage by CASP3."; /evidence="ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30878284"; MUTAGEN 327; /note="K->A: Slightly decreased interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594"; MUTAGEN 327; /note="K->E: Abolishes stimulation of interferon production; when associated with E-236 and E-254. Does not affect interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:32911481"; MUTAGEN 328; /note="S->A: Slightly decreased interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594"; MUTAGEN 329; /note="S->A: Decreased interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594"; MUTAGEN 347; /note="K->A,E: Impaired association with collided ribosomes in response to translation stress. Abolishes stimulation of interferon production. Decreased interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:34111399"; MUTAGEN 349; /note="R->A: Impaired association with collided ribosomes in response to translation stress. Decreased interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594, ECO:0000269|PubMed:34111399"; MUTAGEN 349; /note="R->E: Impaired association with collided ribosomes in response to translation stress. Decreased interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:34111399"; MUTAGEN 350; /note="K->A: Impaired association with collided ribosomes in response to translation stress. Does not affect interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594, ECO:0000269|PubMed:34111399"; MUTAGEN 350; /note="K->E: Impaired association with collided ribosomes in response to translation stress. Decreased interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481, ECO:0000269|PubMed:34111399"; MUTAGEN 353; /note="R->A,E: Impaired association with collided ribosomes in response to translation stress. Strongly decreased interaction with histones H2A and H2B."; /evidence="ECO:0000269|PubMed:33051594, ECO:0000269|PubMed:34111399"; MUTAGEN 353; /note="R->E: Abolishes stimulation of interferon production."; /evidence="ECO:0000269|PubMed:24462292"; MUTAGEN 355; /note="K->E: Does not affect interaction with nucleosomes."; /evidence="ECO:0000269|PubMed:32911481"; MUTAGEN 376; /note="R->I: Alters enzyme activity, leading to the appearance of 3'-5' linked cGAMP. Abolishes enzyme activity; when associated with Q-211 and I-436."; /evidence="ECO:0000269|PubMed:25131990"; MUTAGEN 384; /note="K->A,E: Abolishes stimulation of interferon production. Abolishes DNA-binding but does not affect translocation to the nucleus following treatment with etoposide; when associated with 210-A--A-214."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:24116191, ECO:0000269|PubMed:30356214"; MUTAGEN 384; /note="K->Q: Acetylation-mimetic mutant; reduced enzyme activity."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 384; /note="K->R: No effect on stimulation of interferon production. Strongly decreased ubiquitination by RNF185; when associated with R-173."; /evidence="ECO:0000269|PubMed:28273161, ECO:0000269|PubMed:30799039"; MUTAGEN 390; /note="H->A: Strongly reduces stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061"; MUTAGEN 392; /note="K->Q: Acetylation-mimetic mutant; no effect."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 392; /note="K->R: No effect."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 394; /note="K->A: Abolishes enzyme activity. No effect on stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:24462292"; MUTAGEN 394; /note="K->E: Abolishes homodimerization and subsequent nucleotidyltransferase activity. Abolishes stimulation of interferon production. Does not affect subcellular location to the nucleus and cytosol."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:32911482"; MUTAGEN 394; /note="K->Q: Acetylation-mimetic mutant; reduced enzyme activity."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 394; /note="K->R: No effect on stimulation of interferon production."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 396..397; /note="CC->AA: Abolishes DNA binding and enzyme activity. Abolishes stimulation of interferon production. Decreased localization to the nucleus."; /evidence="ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:30827685, ECO:0000269|PubMed:31544964"; MUTAGEN 396..397; /note="CC->SS: Does not affect palmitoylation by ZDHHC9."; /evidence="ECO:0000269|PubMed:37802025"; MUTAGEN 396; /note="C->A: Abolishes DNA binding and enzyme activity."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:35438208"; MUTAGEN 397; /note="C->A: Abolishes stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061"; MUTAGEN 400; /note="K->E: Abolishes stimulation of interferon production; when associated with E-403."; /evidence="ECO:0000269|PubMed:24116191"; MUTAGEN 403; /note="K->E: Abolishes stimulation of interferon production; when associated with E-400."; /evidence="ECO:0000269|PubMed:24116191"; MUTAGEN 404..405; /note="CC->SS: Abolished palmitoylation by ZDHHC9, leading to decreased enzyme activity."; /evidence="ECO:0000269|PubMed:37802025"; MUTAGEN 404; /note="C->A: Abolishes stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061"; MUTAGEN 407..411; /note="KDCLK->EDCLA: Prevents activation in response to DNA-binding; leading to abolished enzyme activity and stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:31299200"; MUTAGEN 407; /note="K->A: Abolishes enzyme activity. Abolishes stimulation of interferon production. Abolishes DNA-binding but does not affect translocation to the nucleus following treatment with etoposide; when associated with 171-K--L-174 DEL."; /evidence="ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:30356214"; MUTAGEN 411; /note="K->R: Loss of ubiquitination by MARCHF8."; /evidence="ECO:0000269|PubMed:35503863"; MUTAGEN 414; /note="K->A,E: Abolishes stimulation of interferon production."; /evidence="ECO:0000269|PubMed:23707061"; MUTAGEN 414; /note="K->Q: Acetylation-mimetic mutant; reduced enzyme activity."; /evidence="ECO:0000269|PubMed:30799039"; MUTAGEN 414; /note="K->R: Reduced enzyme activity. Decreased ubiquitination and SQSTM1-mediated autophagic degradation."; /evidence="ECO:0000269|PubMed:27666593, ECO:0000269|PubMed:30799039"; MUTAGEN 421; /note="K->R: In K3R mutant; decreased acetylation; when associated with R-131 and R-292."; /evidence="ECO:0000269|PubMed:39694035"; MUTAGEN 427..428; /note="KK->AA: Reduced nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 427..428; /note="KK->EE: Abolished nucleotidyltransferase activity."; /evidence="ECO:0000269|PubMed:31142647"; MUTAGEN 427..428; /note="KK->RR: Abolished ubiquitination by the ECS(SPSB3) complex."; /evidence="ECO:0000269|PubMed:38418882"; MUTAGEN 434; /note="S->C: Gains susceptibility to mouse-specific RU.521; when associated with H-482."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 435; /note="S->A: Decreased cyclic GMP-AMP synthase activity."; /evidence="ECO:0000269|PubMed:32474700"; MUTAGEN 435; /note="S->D: Phospho-mimetic mutant; increased cyclic GMP-AMP synthase activity."; /evidence="ECO:0000269|PubMed:32474700"; MUTAGEN 436; /note="Y->I: Abolishes enzyme activity; when associated with Q-211 and I-376."; /evidence="ECO:0000269|PubMed:25131990"; MUTAGEN 458; /note="K->R: Decreased ISGylation. Abolished ISGylation; when associated with R-21, R-187 and R-219."; /evidence="ECO:0000269|PubMed:38421872"; MUTAGEN 465; /note="D->A: Reduced interaction with the SPSB3 component of the ECS(SPSB3) complex."; /evidence="ECO:0000269|PubMed:38418882"; MUTAGEN 474; /note="C->S: Abolished palmitoylation by ZDHHC18, leading to increased DNA-binding and enzyme activity."; /evidence="ECO:0000269|PubMed:35460603"; MUTAGEN 479; /note="K->R: Reduced sumoylation."; /evidence="ECO:0000269|PubMed:27637147"; MUTAGEN 482; /note="N->H: Gains susceptibility to mouse-specific RU.521; when associated with C-434."; /evidence="ECO:0000269|PubMed:30007416"; MUTAGEN 509; /note="E->A: Reduced interaction with the SPSB3 component of the ECS(SPSB3) complex."; /evidence="ECO:0000269|PubMed:38418882"; MUTAGEN 510; /note="Y->A: Reduced interaction with the SPSB3 component of the ECS(SPSB3) complex."; /evidence="ECO:0000269|PubMed:38418882"; MUTAGEN 512; /note="R->A: Reduced interaction with the SPSB3 component of the ECS(SPSB3) complex."; /evidence="ECO:0000269|PubMed:38418882"; MUTAGEN 513; /note="N->A: Abollshed interaction with the SPSB3 component of the ECS(SPSB3) complex."; /evidence="ECO:0000269|PubMed:38418882"; MUTAGEN 514; /note="N->A: Abollshed interaction with the SPSB3 component of the ECS(SPSB3) complex."; /evidence="ECO:0000269|PubMed:38418882
uniprot
proteins
post_translational_modification
PTM: The N-terminal disordered part (1-160) is phosphorylated by AURKB during the G2-M transition, blocking CGAS liquid phase separation and preventing activation (PubMed:33542149). Phosphorylation at Tyr-215 by BLK promotes cytosolic retention (PubMed:30356214). Localizes into the nucleus following dephosphorylation at Tyr-215 (PubMed:30356214). Phosphorylation at Ser-435 activates the nucleotidyltransferase activity (PubMed:32474700). Dephosphorylation at Ser-435 by PPP6C impairs its ability to bind GTP, thereby inactivating it (PubMed:32474700). Phosphorylation at Thr-68 and Ser-213 by PRKDC inhibits its cyclic GMP-AMP synthase activity by impairing homodimerization and activation (PubMed:33273464). Phosphorylation at Ser-305 by AKT (AKT1, AKT2 or AKT3) suppresses the nucleotidyltransferase activity (PubMed:26440888). Phosphorylation at Ser-305 by CDK1 during mitosis leads to its inhibition, thereby preventing CGAS activation by self-DNA during mitosis (PubMed:32351706). Dephosphorylated at Ser-305 by protein phosphatase PP1 upon mitotic exit (PubMed:32351706). {ECO:0000269|PubMed:26440888, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:32474700, ECO:0000269|PubMed:33273464, ECO:0000269|PubMed:33542149}.; PTM: Ubiquitinated at Lys-414 via 'Lys-48'-linked polyubiquitin chains, leading to its SQSTM1-mediated autophagic degradation (PubMed:27666593). Interaction with TRIM14 promotes recruitment of USP14, leading to deubiquitinate Lys-414 and stabilize CGAS (PubMed:27666593). Ubiquitinated at Lys-173 and Lys-384 by RNF185 via 'Lys-27'-linked polyubiquitination, promoting CGAS cyclic GMP-AMP synthase activity (PubMed:28273161). Monoubiquitination at Lys-347 by TRIM56 promotes oligomerization and subsequent activation (PubMed:29426904). Monoubiquitination by TRIM41 promotes CGAS activation (PubMed:29760876). Ubiquitination at Lys-285 and Lys-479 via 'Lys-48'-linked polyubiquitination promotes its degradation (By similarity). Deubiquitination at Lys-285 by USP29 promotes its stabilization (By similarity). Deubiquitinated by USP27X, promoting its stabilization (PubMed:31534008). Ubiquitinated at Lys-411 via 'Lys-63'-linked polyubiquitin chains by MARCHF8, leading to the inhibition of its DNA binding ability (PubMed:35503863). In cycling cells, nucleosome-bound CGAS is ubiquitinated at Lys-427 and Lys-428 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:Q8C6L5, ECO:0000269|PubMed:27666593, ECO:0000269|PubMed:28273161, ECO:0000269|PubMed:29426904, ECO:0000269|PubMed:29760876, ECO:0000269|PubMed:31534008, ECO:0000269|PubMed:35503863, ECO:0000269|PubMed:38418882}.; PTM: Sumoylated at Lys-231 and Lys-479 by TRIM38 in uninfected cells and during the early phase of viral infection, promoting its stability by preventing ubiquitination at Lys-285 and Lys-479, and subsequent degradation (By similarity). Desumoylated by SENP2 during the late phase of viral infection (By similarity). Sumoylation at Lys-347, Lys-384 and Lys-394 prevents DNA-binding, oligomerization and nucleotidyltransferase activity (By similarity). Desumoylation at Lys-347, Lys-384 and Lys-394 by SENP7 relieves inhibition and activates CGAS (By similarity). {ECO:0000250|UniProtKB:Q8C6L5}.; PTM: ISGylated by HERC5, promoting ability to undergo liquid-liquid phase separation (LLPS), leading to CGAS activation (PubMed:38421872). DeISGylated by USP18 (PubMed:38421872). {ECO:0000269|PubMed:38421872}.; 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: 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). Acetylation at Lys-47, Lys-56, Lys-62 and Lys-83 by KAT5 increases the cyclic GMP-AMP synthase activity by promoting DNA-binding and subsequent activation (PubMed:32817552). Acetylation at Lys-131, Lys-292 and Lys-421 by KAT2A at the plasma membrane activates CGAS (PubMed:39694035). {ECO:0000269|PubMed:30799039, ECO:0000269|PubMed:32817552, ECO:0000269|PubMed:39694035}.; PTM: Proteolytically cleaved by apoptotic caspases during apoptosis, leading to its inactivation (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 (By similarity). Cleaved by CASP3 at Asp-319 during virus-induced apoptosis, thereby inactivating it and preventing cytokine overproduction (PubMed:30878284). 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 as CASP1 (PubMed:28314590). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:30878284}.; PTM: Degraded via selective autophagy following interaction with IRGM (PubMed:32715615). IRGM promotes CGAS recruitment to autophagosome membranes, promoting its SQSTM1/p62-dependent autophagic degradation (PubMed:32715615). {ECO:0000269|PubMed:32715615}.; PTM: Poly-ADP-ribosylation at Asp-191 by PARP1 impairs DNA-binding, thereby preventing the cyclic GMP-AMP synthase activity. {ECO:0000269|PubMed:35460603}.; PTM: Palmitoylation at Cys-474 by ZDHHC18 impairs DNA-binding, thereby preventing the cyclic GMP-AMP synthase activity (PubMed:35438208). Palmitoylation at Cys-404 and Cys-405 by ZDHHC9 promotes homodimerization and cyclic GMP-AMP synthase activity (PubMed:37802025). Depalmitoylation at Cys-404 and Cys-405 by LYPLAL1 impairs homodimerization and cyclic GMP-AMP synthase activity (PubMed:37802025). {ECO:0000269|PubMed:35438208, ECO:0000269|PubMed:37802025}.; PTM: Monomethylated at Lys-506 by SETD7 (PubMed:35210392). Monomethylation promotes interaction with SGF29, preventing interaction between PARP1 nad SGF29 (By similarity). Demethylation by RIOX1 promotes interaction with PARP1, followed by PARP1 inactivation (By similarity). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:35210392}.; PTM: Symmetric dimethylation at Arg-124 by PRMT5 prevents DNA-binding and activation. {ECO:0000269|PubMed:33762328}.; PTM: Lactylation by AARS2 prevents ability to undergo liquid-liquid phase separation (LLPS), thereby inhibiting CGAS activation. {ECO:0000269|PubMed:39322678}.; 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: (Microbial infection) Degraded by an autophagy-mediated mechanism in presence of Chikungunya virus capsid protein. {ECO:0000269|PubMed:33057424}.
uniprot
proteins
protein_family
Mab-21 family
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19608861
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21478870
uniprot
proteins
pubmed
23258413
uniprot
proteins
pubmed
23707061
uniprot
proteins
pubmed
23707065
uniprot
proteins
pubmed
23722159
uniprot
proteins
pubmed
23929945
uniprot
proteins
pubmed
24077100
uniprot
proteins
pubmed
24116191
uniprot
proteins
pubmed
24269171
uniprot
proteins
pubmed
24332030
uniprot
proteins
pubmed
24462292
uniprot
proteins
pubmed
25131990
uniprot
proteins
pubmed
26046437
uniprot
proteins
pubmed
26048138
uniprot
proteins
pubmed
26229115
uniprot
proteins
pubmed
26300263
uniprot
proteins
pubmed
26320998
uniprot
proteins
pubmed
26440888
uniprot
proteins
pubmed
27637147
uniprot
proteins
pubmed
27666593
uniprot
proteins
pubmed
28214358
uniprot
proteins
pubmed
28273161
uniprot
proteins
pubmed
28314590
uniprot
proteins
pubmed
28363908
uniprot
proteins
pubmed
28738408
uniprot
proteins
pubmed
28759889
uniprot
proteins
pubmed
28934246
uniprot
proteins
pubmed
28940468
uniprot
proteins
pubmed
29263269
uniprot
proteins
pubmed
29426904
uniprot
proteins
pubmed
29760876
uniprot
proteins
pubmed
29793952
uniprot
proteins
pubmed
29937271
uniprot
proteins
pubmed
29976794
uniprot
proteins
pubmed
30007416
uniprot
proteins
pubmed
30092200
uniprot
proteins
pubmed
30135424
uniprot
proteins
pubmed
30270045
uniprot
proteins
pubmed
30356214
uniprot
proteins
pubmed
30799039
uniprot
proteins
pubmed
30811988
uniprot
proteins
pubmed
30827685
uniprot
proteins
pubmed
30878284
uniprot
proteins
pubmed
31107917
uniprot
proteins
pubmed
31113940
uniprot
proteins
pubmed
31142647
uniprot
proteins
pubmed
31299200
uniprot
proteins
pubmed
31534008
uniprot
proteins
pubmed
31544964
uniprot
proteins
pubmed
31808743
uniprot
proteins
pubmed
31992625
uniprot
proteins
pubmed
32351706
uniprot
proteins
pubmed
32404352
uniprot
proteins
pubmed
32459092
uniprot
proteins
pubmed
32474700
uniprot
proteins
pubmed
32715615
uniprot
proteins
pubmed
32792394
uniprot
proteins
pubmed
32814054
uniprot
proteins
pubmed
32817552
uniprot
proteins
pubmed
32852081
uniprot
proteins
pubmed
32911480
uniprot
proteins
pubmed
32911481
uniprot
proteins
pubmed
32911482
uniprot
proteins
pubmed
32912999
uniprot
proteins
pubmed
33031745
uniprot
proteins
pubmed
33051594
uniprot
proteins
pubmed
33057424
uniprot
proteins
pubmed
33230297
uniprot
proteins
pubmed
33273464
uniprot
proteins
pubmed
33406424
uniprot
proteins
pubmed
33476576
uniprot
proteins
pubmed
33542149
uniprot
proteins
pubmed
33606975
uniprot
proteins
pubmed
33688080
uniprot
proteins
pubmed
33762328
uniprot
proteins
pubmed
34015248
uniprot
proteins
pubmed
34111399
uniprot
proteins
pubmed
34387695
uniprot
proteins
pubmed
34648591
uniprot
proteins
pubmed
35045565
uniprot
proteins
pubmed
35210392
uniprot
proteins
pubmed
35322803
uniprot
proteins
pubmed
35438208
uniprot
proteins
pubmed
35460603
uniprot
proteins
pubmed
35503863
uniprot
proteins
pubmed
35613581
uniprot
proteins
pubmed
37217469
uniprot
proteins
pubmed
37802025
uniprot
proteins
pubmed
38418882
uniprot
proteins
pubmed
38421872
uniprot
proteins
pubmed
38740774
uniprot
proteins
pubmed
39322678
uniprot
proteins
pubmed
39694035
uniprot
proteins
pubmed
40461475
uniprot
proteins
pubmed
41073405
uniprot
proteins
pubmed
41610251
uniprot
proteins
sequence_length
522
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:29263269, ECO:0000269|PubMed:29937271, ECO:0000269|PubMed:30270045, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30811988, ECO:0000269|PubMed:31299200, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32792394, ECO:0000269|PubMed:33230297, ECO:0000269|PubMed:33406424, ECO:0000269|PubMed:33476576, ECO:0000269|PubMed:34111399, ECO:0000269|PubMed:35438208, ECO:0000269|PubMed:38418882}. Chromosome {ECO:0000269|PubMed:30811988, ECO:0000269|PubMed:31299200, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:32912999, ECO:0000269|PubMed:33051594}. Cell membrane {ECO:0000269|PubMed:30827685, ECO:0000269|PubMed:32351706, ECO:0000269|PubMed:39694035}; Peripheral membrane protein {ECO:0000269|PubMed:30827685, ECO:0000269|PubMed:39694035}. Cytoplasm, cytosol {ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:29263269, ECO:0000269|PubMed:29937271, ECO:0000269|PubMed:30799039, ECO:0000269|PubMed:30827685, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:32792394, ECO:0000269|PubMed:33406424, ECO:0000269|PubMed:33476576, ECO:0000269|PubMed:34111399, ECO:0000269|PubMed:35438208, ECO:0000269|PubMed:35613581, ECO:0000269|PubMed:37217469}. 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 (PubMed:30811988). Exported from the nucleus to the cytosol in a XPO1/CRM1 via the nuclear export signal in response to DNA stimulation (PubMed:33406424). 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 (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 (PubMed:30356214). In response to translation stress, translocates to the cytosol and associates with collided ribosomes (PubMed:34111399). {ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:30356214, ECO:0000269|PubMed:30811988, ECO:0000269|PubMed:30827685, ECO:0000269|PubMed:31544964, ECO:0000269|PubMed:31808743, ECO:0000269|PubMed:33406424, ECO:0000269|PubMed:34111399}.; 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}.
uniprot
proteins