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Entry version 149 (17 Jun 2020)
Sequence version 2 (05 Jul 2005)
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Protein

Cyclic GMP-AMP synthase

Gene

CGAS

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990, PubMed:29976794, PubMed:30799039). Catalysis involves both the formation of a 2',5' phosphodiester linkage at the GpA step and the formation of a 3',5' phosphodiester linkage at the ApG step, producing c[G(2',5')pA(3',5')p] (PubMed:28363908, PubMed:28214358). Acts as a key cytosolic DNA sensor, the presence of double-stranded DNA (dsDNA) in the cytoplasm being a danger signal that triggers the immune responses (PubMed:28363908). Binds cytosolic DNA directly, leading to activation and synthesis of cGAMP, a second messenger that binds to and activates TMEM173/STING, thereby triggering type-I interferon production (PubMed:28363908, PubMed:28314590). Preferentially recognizes and binds curved long DNAs (PubMed:30007416). In contrast to other mammals, human CGAS displays species-specific mechanisms of DNA recognition and produces less cyclic GMP-AMP (cGAMP), allowing a more fine-tuned response to pathogens (PubMed:30007416). Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm (PubMed:28363908). Also acts as an innate immune sensor of infection by retroviruses, such as HIV-1, by detecting the presence of reverse-transcribed DNA in the cytosol (PubMed:23929945). Detection of retroviral reverse-transcribed DNA in the cytosol may be indirect and be mediated via interaction with PQBP1, which directly binds reverse-transcribed retroviral DNA (PubMed:26046437). Also detects the presence of DNA from bacteria, such as M.tuberculosis (PubMed:26048138). cGAMP can be transferred from producing cells to neighboring cells through gap junctions, leading to promote TMEM173/STING activation and convey immune response to connecting cells (PubMed:24077100). cGAMP can also be transferred between cells by virtue of packaging within viral particles contributing to IFN-induction in newly infected cells in a cGAS-independent but TMEM173/STING-dependent manner (PubMed:26229115). In addition to antiviral activity, also involved in the response to cellular stresses, such as senescence, DNA damage or genome instability (PubMed:28738408, PubMed:28759889). Acts as a regulator of cellular senescence by binding to cytosolic chromatin fragments that are present in senescent cells, leading to trigger type-I interferon production via TMEM173/STING and promote cellular senescence (By similarity). Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability (PubMed:28738408, PubMed:28759889). Micronuclei, which as frequently found in cancer cells, consist of chromatin surrounded by its own nuclear membrane: following breakdown of the micronuclear envelope, a process associated with chromothripsis, CGAS binds self-DNA exposed to the cytosol, leading to cGAMP synthesis and subsequent activation of TMEM173/STING and type-I interferon production (PubMed:28738408, PubMed:28759889). Acts as a suppressor of DNA repair in response to DNA damage: translocates to the nucleus following dephosphorylation at Tyr-215 and inhibits homologous recombination repair by interacting with PARP1, the CGAS-PARP1 interaction leading to impede the formation of the PARP1-TIMELESS complex (PubMed:30356214).By similarity23 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Protein has several cofactor binding sites:

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

The enzyme activity is strongly increased by double-stranded DNA, but not by single-stranded DNA or RNA (PubMed:23258413, PubMed:23707061, PubMed:26300263). Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity (PubMed:30799039). Inhibited by aspirin (acetylsalicylate) drug, which acetylates CGAS (PubMed:30799039). The enzyme activity is impaired by the cleavage at Asp-140 and Asp-157 produced by CASP1 (PubMed:28314590). Strongly inhibited by compound PF-06928215, which is specific for human protein (PubMed:28934246, PubMed:30007416).7 Publications

<p>This subsection of the 'Function' section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

  1. KM=35 µM for ATP (with 1 mM GTP)1 Publication
  2. KM=30 µM for GTP (with 1 mM ATP)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection describes interesting single amino acid sites on the sequence that are not defined in any other subsection. This subsection can be displayed in different sections ('Function', 'PTM / Processing', 'Pathology and Biotech') according to its content.<p><a href='/help/site' target='_top'>More...</a></p>Sitei187Important for preferential detection of curved long DNA1 Publication1
    Sitei195Important for preferential detection of curved long DNA1 Publication1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei211GTPBy similarity1
    Binding sitei213ATPCombined sources1 Publication1
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section indicates at which position the protein binds a given metal ion. The nature of the metal is indicated in the 'Description' field.<p><a href='/help/metal' target='_top'>More...</a></p>Metal bindingi225Magnesium; catalyticCombined sources2 Publications1 Publication1
    Metal bindingi227Magnesium; catalyticCombined sources2 Publications1 Publication1
    Metal bindingi319Magnesium; catalyticCombined sources1 Publication1
    Binding sitei319GTP1 Publication1
    Binding sitei362PF-06928215 inhibitor1 Publication1
    Binding sitei376PF-06928215 inhibitor1 Publication1
    Metal bindingi390Zinc; via tele nitrogenCombined sources6 Publications1
    Metal bindingi396ZincCombined sources6 Publications1
    Metal bindingi397ZincCombined sources6 Publications1
    Metal bindingi404ZincCombined sources6 Publications1
    Binding sitei414ATPCombined sources1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi225 – 227ATPCombined sources1 Publication3
    Nucleotide bindingi376 – 383GTP1 Publication8
    Nucleotide bindingi380 – 383ATPCombined sources1 Publication4
    Nucleotide bindingi435 – 439ATPCombined sources1 Publication1 Publication5

    <p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

    GO - Biological processi

    <p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

    Molecular functionDNA-binding, Nucleotidyltransferase, Transferase
    Biological processAntiviral defense, DNA damage, DNA repair, Host-virus interaction, Immunity, Innate immunity
    LigandATP-binding, GTP-binding, Lipid-binding, Magnesium, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BRENDA Comprehensive Enzyme Information System

    More...
    BRENDAi
    2.7.7.86 2681

    Reactome - a knowledgebase of biological pathways and processes

    More...
    Reactomei
    R-HSA-1834941 STING mediated induction of host immune responses

    SIGNOR Signaling Network Open Resource

    More...
    SIGNORi
    Q8N884

    <p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
    Recommended name:
    Cyclic GMP-AMP synthase1 Publication (EC:2.7.7.867 Publications)
    Short name:
    cGAMP synthase1 Publication
    Short name:
    cGAS1 Publication
    Short name:
    h-cGAS1 Publication
    Alternative name(s):
    2'3'-cGAMP synthase1 Publication
    Mab-21 domain-containing protein 1
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
    Name:CGAS1 PublicationImported
    Synonyms:C6orf150Imported, MB21D1Imported
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    <p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
    • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 6

    Organism-specific databases

    Eukaryotic Pathogen Database Resources

    More...
    EuPathDBi
    HostDB:ENSG00000164430.15

    Human Gene Nomenclature Database

    More...
    HGNCi
    HGNC:21367 CGAS

    Online Mendelian Inheritance in Man (OMIM)

    More...
    MIMi
    613973 gene

    neXtProt; the human protein knowledge platform

    More...
    neXtProti
    NX_Q8N884

    <p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

    Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

    Keywords - Cellular componenti

    Cell membrane, Cytoplasm, Membrane, Nucleus

    <p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi7K → Q: Acetylation-mimetic mutant; no effect. 1 Publication1
    Mutagenesisi7K → R: No effect. 1 Publication1
    Mutagenesisi33D → A: No effect on type I IFN 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. 1 Publication1
    Mutagenesisi50K → Q: Acetylation-mimetic mutant; no effect. 1 Publication1
    Mutagenesisi50K → R: No effect. 1 Publication1
    Mutagenesisi67D → A: No effect on type I IFN 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. 1 Publication1
    Mutagenesisi71 – 75RPPVR → EPPVE: Abolished binding to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) and abolished association with the cell membrane. 1 Publication5
    Mutagenesisi90D → A: No effect on type I IFN 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. 1 Publication1
    Mutagenesisi95D → A: No effect on type I IFN 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. 1 Publication1
    Mutagenesisi140D → A: Highly decreases cleavage by CASP1 and enhances type I IFN 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. 1 Publication1
    Mutagenesisi140D → H: Highly decreases cleavage by CASP1 and enhances type I IFN and RSAD2 induction upon DNA virus infection. 1 Publication1
    Mutagenesisi157D → A: No effect on type I IFN and RSAD2 induction. Highly decreases cleavage by CASP1 and enhances type I IFN 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. 1 Publication1
    Mutagenesisi157D → H: Highly decreases cleavage by CASP1 and enhances type I IFN and enhances RSAD2 induction upon DNA virus infection. 1 Publication1
    Mutagenesisi171 – 174Missing : Abolishes DNA-binding but does not affect translocation to the nucleus following treatment with etoposide; when associated with A-407. 1 Publication4
    Mutagenesisi171K → A: No effect on stimulation of interferon production. 1 Publication1
    Mutagenesisi173K → A: Strongly reduces enzyme activity and stimulation of interferon production; when associated with A-176. No effect on stimulation of interferon production. 3 Publications1
    Mutagenesisi173K → E: Strongly reduces stimulation of interferon production. 2 Publications1
    Mutagenesisi174L → N: Strongly reduces enzyme activity and stimulation of interferon production. 2 Publications1
    Mutagenesisi176R → A: Strongly reduces enzyme activity and stimulation of interferon production; when associated with A-173. 1 Publication1
    Mutagenesisi187K → N: Induces alteration of the DNA-binding surface and leads to increased synthesis of cyclic GMP-AMP (cGAMP); when associated with R-195. 1 Publication1
    Mutagenesisi195L → R: Induces alteration of the DNA-binding surface and leads to increased synthesis of cyclic GMP-AMP (cGAMP); when associated with N-187. 1 Publication1
    Mutagenesisi210 – 214NTGSY → ATGSA: Abolishes DNA-binding but does not affect translocation to the nucleus following treatment with etoposide; when associated with A-384. 1 Publication5
    Mutagenesisi210N → D: More than 75% inhibition of interferon beta production. 1 Publication1
    Mutagenesisi211T → Q: Abolishes enzyme activity; when associated with I-376 and I-436. 1 Publication1
    Mutagenesisi212 – 213GS → AA: Abolishes enzyme activity. Abolishes stimulation of interferon production. 1 Publication2
    Mutagenesisi215Y → A: Strongly reduced tyrosine phosphorylation. 1 Publication1
    Mutagenesisi215Y → E: Phosphomimetic mutant; reduced translocation to the nucleus following treatment with etoposide. 1 Publication1
    Mutagenesisi225 – 227EFD → AFA: Abolishes enzyme activity and stimulation of interferon production. Does not affect translocation to the nucleus following treatment with etoposide. 4 Publications3
    Mutagenesisi236R → E: Abolishes stimulation of interferon production; when associated with E-254 and E-327. 1 Publication1
    Mutagenesisi254K → E: Abolishes stimulation of interferon production; when associated with E-236 and E-327. 1 Publication1
    Mutagenesisi295 – 305Missing : Abolished nuclear localization. 1 PublicationAdd BLAST11
    Mutagenesisi319D → A: Abolishes enzyme activity. Does not affect translocation to the nucleus following treatment with etoposide. 1 Publication1
    Mutagenesisi327K → E: Abolishes stimulation of interferon production; when associated with E-236 and E-254. 1 Publication1
    Mutagenesisi347K → E: Abolishes stimulation of interferon production. 1 Publication1
    Mutagenesisi353R → E: Abolishes stimulation of interferon production. 1 Publication1
    Mutagenesisi376R → I: Alters enzyme activity, leading to the appearance of 3'-5' linked cGAMP. Abolishes enzyme activity; when associated with Q-211 and I-436. 1 Publication1
    Mutagenesisi384K → A or 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. 3 Publications1
    Mutagenesisi384K → Q: Acetylation-mimetic mutant; reduced enzyme activity. 1 Publication1
    Mutagenesisi384K → R: No effect on stimulation of interferon production. 1 Publication1
    Mutagenesisi390H → A: Strongly reduces stimulation of interferon production. 1 Publication1
    Mutagenesisi392K → Q: Acetylation-mimetic mutant; no effect. 1 Publication1
    Mutagenesisi392K → R: No effect. 1 Publication1
    Mutagenesisi394K → A: Abolishes enzyme activity. No effect on stimulation of interferon production. 2 Publications1
    Mutagenesisi394K → E: Abolishes enzyme activity. Abolishes stimulation of interferon production. 1 Publication1
    Mutagenesisi394K → Q: Acetylation-mimetic mutant; reduced enzyme activity. 1 Publication1
    Mutagenesisi394K → R: No effect on stimulation of interferon production. 1 Publication1
    Mutagenesisi396 – 397CC → AA: Abolishes DNA binding and enzyme activity. Abolishes stimulation of interferon production. 2 Publications2
    Mutagenesisi396C → A: Abolishes DNA binding and enzyme activity. 1 Publication1
    Mutagenesisi397C → A: Abolishes stimulation of interferon production. 1 Publication1
    Mutagenesisi400K → E: Abolishes stimulation of interferon production; when associated with E-403. 1 Publication1
    Mutagenesisi403K → E: Abolishes stimulation of interferon production; when associated with E-400. 1 Publication1
    Mutagenesisi404C → A: Abolishes stimulation of interferon production. 1 Publication1
    Mutagenesisi407K → A or E: Abolishes enzyme activity and stimulation of interferon production; when associated with A-411. 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. 3 Publications1
    Mutagenesisi411K → A: Abolishes enzyme activity and stimulation of interferon production; when associated with A-407. 1 Publication1
    Mutagenesisi414K → A or E: Abolishes stimulation of interferon production. 1 Publication1
    Mutagenesisi414K → Q: Acetylation-mimetic mutant; reduced enzyme activity. 1 Publication1
    Mutagenesisi414K → R: Reduced enzyme activity. 1 Publication1
    Mutagenesisi434S → C: Gains susceptibility to mouse-specific RU.521; when associated with H-482. 1 Publication1
    Mutagenesisi436Y → I: Abolishes enzyme activity; when associated with Q-211 and I-376. 1 Publication1
    Mutagenesisi482N → H: Gains susceptibility to mouse-specific RU.521; when associated with C-434. 1 Publication1

    Organism-specific databases

    DisGeNET

    More...
    DisGeNETi
    115004

    Open Targets

    More...
    OpenTargetsi
    ENSG00000164430

    The Pharmacogenetics and Pharmacogenomics Knowledge Base

    More...
    PharmGKBi
    PA134956015

    Miscellaneous databases

    Pharos NIH Druggable Genome Knowledgebase

    More...
    Pharosi
    Q8N884 Tbio

    Chemistry databases

    ChEMBL database of bioactive drug-like small molecules

    More...
    ChEMBLi
    CHEMBL4105728

    Polymorphism and mutation databases

    BioMuta curated single-nucleotide variation and disease association database

    More...
    BioMutai
    MB21D1

    Domain mapping of disease mutations (DMDM)

    More...
    DMDMi
    68565218

    <p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000895431 – 522Cyclic GMP-AMP synthaseAdd BLAST522

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei7N6-acetyllysineCombined sources1 Publication1
    Modified residuei50N6-acetyllysine1 Publication1
    Modified residuei143PhosphoserineCombined sources1
    Modified residuei210(Microbial infection) Deamidated asparagine; by herpes simplex virus 1/HHV-1 UL371 Publication1
    Modified residuei215Phosphotyrosine; by BLK1 Publication1
    Modified residuei2865-glutamyl polyglutamateBy similarity1
    Modified residuei3145-glutamyl glutamateBy similarity1
    Modified residuei384N6-acetyllysine1 Publication1
    Modified residuei389(Microbial infection) Deamidated asparagine; by herpes simplex virus 1/HHV-1 UL371 Publication1
    Modified residuei392N6-acetyllysine1 Publication1
    Modified residuei394N6-acetyllysine1 Publication1
    Modified residuei414N6-acetyllysineCombined sources1 Publication1
    Modified residuei451(Microbial infection) Deamidated glutamine; by herpes simplex virus 1/HHV-1 UL371 Publication1
    Modified residuei454(Microbial infection) Deamidated glutamine; by herpes simplex virus 1/HHV-1 UL371 Publication1

    <p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

    Phosphorylation at Tyr-215 by BLK promotes cytosolic retention (PubMed:30356214). Translocates into the nucleus following dephosphorylation at Tyr-215 (PubMed:30356214).1 Publication
    (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.1 Publication
    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.By similarity
    Cleaved by CASP1 at Asp-140 and Asp-157 upon DNA virus infection; the cleavage impairs cGAMP production (PubMed:28314590). Also cleaved by the pyroptotic CASP4 and CASP5 during non-canonical inflammasome activation; they don't cut at the same sites than CASP1 (PubMed:28314590).1 Publication
    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).1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Sitei140 – 141Cleavage; by CASP11 Publication2
    Sitei157 – 158Cleavage; by CASP11 Publication2

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein

    Proteomic databases

    Encyclopedia of Proteome Dynamics

    More...
    EPDi
    Q8N884

    jPOST - Japan Proteome Standard Repository/Database

    More...
    jPOSTi
    Q8N884

    MassIVE - Mass Spectrometry Interactive Virtual Environment

    More...
    MassIVEi
    Q8N884

    MaxQB - The MaxQuant DataBase

    More...
    MaxQBi
    Q8N884

    PaxDb, a database of protein abundance averages across all three domains of life

    More...
    PaxDbi
    Q8N884

    PeptideAtlas

    More...
    PeptideAtlasi
    Q8N884

    PRoteomics IDEntifications database

    More...
    PRIDEi
    Q8N884

    ProteomicsDB: a multi-organism proteome resource

    More...
    ProteomicsDBi
    72382 [Q8N884-1]
    72383 [Q8N884-2]

    PTM databases

    iPTMnet integrated resource for PTMs in systems biology context

    More...
    iPTMneti
    Q8N884

    Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

    More...
    PhosphoSitePlusi
    Q8N884

    <p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

    <p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

    Expressed in the monocytic cell line THP1.1 Publication

    <p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

    By type I interferons.1 Publication

    Gene expression databases

    Bgee dataBase for Gene Expression Evolution

    More...
    Bgeei
    ENSG00000164430 Expressed in sperm and 192 other tissues

    Genevisible search portal to normalized and curated expression data from Genevestigator

    More...
    Genevisiblei
    Q8N884 HS

    Organism-specific databases

    Human Protein Atlas

    More...
    HPAi
    ENSG00000164430 Tissue enhanced (vagina)

    <p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

    <p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

    Monomer in the absence of DNA (PubMed:28363908). Homodimer in presence of dsDNA: forms a 2:2 dimer with two enzymes binding to two DNA molecules (PubMed:30007416, PubMed:30799039).

    Interacts with PQBP1 (via WW domain) (PubMed:26046437).

    Interacts with TRIM14; this interaction stabilizes CGAS and promotes type I interferon production (PubMed:27666593).

    Interacts with ZCCHC3; promoting sensing of dsDNA by CGAS (PubMed:30135424).

    Interacts with PARP1; interaction takes place in the nucleus and prevents the formation of the PARP1-TIMELESS complex (PubMed:30356214).

    7 Publications

    (Microbial infection) Interacts with herpes virus 8/HHV-8 protein ORF52; this interaction inhibits cGAS enzymatic activity.

    1 Publication

    (Microbial infection) Interacts with herpes simplex virus 1 protein UL37; this interaction deaminates CGAS and inhibits its activation.

    1 Publication

    (Microbial infection) Interacts with cytomegalovirus protein UL31; this interaction promotes dissociation of DNA from CGAS, thereby inhibiting the enzymatic activity of CGAS.

    1 Publication

    Protein-protein interaction databases

    The Biological General Repository for Interaction Datasets (BioGRID)

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    BioGRIDi
    125408, 265 interactors

    Protein interaction database and analysis system

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    IntActi
    Q8N884, 12 interactors

    Molecular INTeraction database

    More...
    MINTi
    Q8N884

    STRING: functional protein association networks

    More...
    STRINGi
    9606.ENSP00000359339

    Chemistry databases

    BindingDB database of measured binding affinities

    More...
    BindingDBi
    Q8N884

    Miscellaneous databases

    RNAct, Protein-RNA interaction predictions for model organisms.

    More...
    RNActi
    Q8N884 protein

    <p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

    Secondary structure

    1522
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details

    3D structure databases

    SWISS-MODEL Repository - a database of annotated 3D protein structure models

    More...
    SMRi
    Q8N884

    Database of comparative protein structure models

    More...
    ModBasei
    Search...

    Protein Data Bank in Europe - Knowledge Base

    More...
    PDBe-KBi
    Search...

    <p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni1 – 160DNA-binding1 PublicationAdd BLAST160
    Regioni64 – 75Required for association with the cell membrane1 PublicationAdd BLAST12
    Regioni120 – 160Required for activation upon DNA viral infection1 PublicationAdd BLAST41
    Regioni173 – 215DNA-bindingCombined sources1 Publication1 PublicationAdd BLAST43
    Regioni384 – 407DNA-binding1 PublicationAdd BLAST24

    Motif

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi295 – 305Nuclear localization signal1 PublicationAdd BLAST11

    <p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

    Lys-187 and Leu-195 residues are specific to human and destabilize the interactions with short DNA, shifting the specificity toward the detection of curved long DNAs (PubMed:30007416). Lys-187 and Leu-195 also restrain cGAMP production and, therefore, immune activation, allowing a more fine-tuned response to pathogens (PubMed:30007416).1 Publication
    The N-terminal part (1-160) binds unspecifically dsDNA and expand the binding and moving range of CGAS on dsDNA. Enhances the enzyme activity and activation of innate immune signaling upon cytosolic recognition of dsDNA (PubMed:28363908, PubMed:28214358). When the N-terminal part (1-160) is missing the protein bound to dsDNA homodimerizes (By similarity).By similarity2 Publications

    <p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

    Belongs to the mab-21 family.Curated

    Phylogenomic databases

    evolutionary genealogy of genes: Non-supervised Orthologous Groups

    More...
    eggNOGi
    ENOG410IE27 Eukaryota
    ENOG410XTKD LUCA

    Ensembl GeneTree

    More...
    GeneTreei
    ENSGT00980000198551

    The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

    More...
    HOGENOMi
    CLU_040428_2_0_1

    InParanoid: Eukaryotic Ortholog Groups

    More...
    InParanoidi
    Q8N884

    KEGG Orthology (KO)

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    KOi
    K17834

    Identification of Orthologs from Complete Genome Data

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    OMAi
    VKCCRKE

    Database of Orthologous Groups

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    OrthoDBi
    759341at2759

    Database for complete collections of gene phylogenies

    More...
    PhylomeDBi
    Q8N884

    TreeFam database of animal gene trees

    More...
    TreeFami
    TF331255

    Family and domain databases

    Integrated resource of protein families, domains and functional sites

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    InterProi
    View protein in InterPro
    IPR024810 Mab-21_dom

    Pfam protein domain database

    More...
    Pfami
    View protein in Pfam
    PF03281 Mab-21, 1 hit

    Simple Modular Architecture Research Tool; a protein domain database

    More...
    SMARTi
    View protein in SMART
    SM01265 Mab-21, 1 hit

    <p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2)i

    <p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

    This entry describes 2 <p>This subsection of the 'Sequence' section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform. This section is only present in reviewed entries, i.e. in UniProtKB/Swiss-Prot.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
    Isoform 1 (identifier: Q8N884-1) [UniParc]FASTAAdd to basket

    This isoform has been chosen as the <div> <p><b>What is the canonical sequence?</b><p><a href='/help/canonical_and_isoforms' target='_top'>More...</a></p>canonicali sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide
            10         20         30         40         50
    MQPWHGKAMQ RASEAGATAP KASARNARGA PMDPTESPAA PEAALPKAGK
    60 70 80 90 100
    FGPARKSGSR QKKSAPDTQE RPPVRATGAR AKKAPQRAQD TQPSDATSAP
    110 120 130 140 150
    GAEGLEPPAA REPALSRAGS CRQRGARCST KPRPPPGPWD VPSPGLPVSA
    160 170 180 190 200
    PILVRRDAAP GASKLRAVLE KLKLSRDDIS TAAGMVKGVV DHLLLRLKCD
    210 220 230 240 250
    SAFRGVGLLN TGSYYEHVKI SAPNEFDVMF KLEVPRIQLE EYSNTRAYYF
    260 270 280 290 300
    VKFKRNPKEN PLSQFLEGEI LSASKMLSKF RKIIKEEIND IKDTDVIMKR
    310 320 330 340 350
    KRGGSPAVTL LISEKISVDI TLALESKSSW PASTQEGLRI QNWLSAKVRK
    360 370 380 390 400
    QLRLKPFYLV PKHAKEGNGF QEETWRLSFS HIEKEILNNH GKSKTCCENK
    410 420 430 440 450
    EEKCCRKDCL KLMKYLLEQL KERFKDKKHL DKFSSYHVKT AFFHVCTQNP
    460 470 480 490 500
    QDSQWDRKDL GLCFDNCVTY FLQCLRTEKL ENYFIPEFNL FSSNLIDKRS
    510 520
    KEFLTKQIEY ERNNEFPVFD EF
    Length:522
    Mass (Da):58,814
    Last modified:July 5, 2005 - v2
    <p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i808FF6F9F3BF8C50
    GO
    Isoform 2 (identifier: Q8N884-2) [UniParc]FASTAAdd to basket

    The sequence of this isoform differs from the canonical sequence as follows:
         445-447: VCT → RLY
         448-522: Missing.

    Show »
    Length:447
    Mass (Da):49,762
    Checksum:i61504BFBBB6FD338
    GO

    <p>This subsection of the 'Sequence' section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

    The sequence AAH12928 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    <p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_05081135T → N2 Publications