Tchem CGAS Cyclic GMP-AMP synthase

Protein Summary

Description

Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP (PubMed:23258413, PubMed:23707061, PubMed:23722159, PubMed:24077100, PubMed:25131990). 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). 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).

Uniprot Accession IDs

• Q8N884
• L0L2J9
• Q14CV6
• Q32NC9
• Q5SWL0
• Q5SWL1
• Q96E45
• cGAMP synthase

Gene Name

• CGAS

Ensembl ID

• ENST00000370315
• ENSP00000359339
• ENSG00000164430
• ENST00000370318
• ENSP00000359342

Symbol

• C6orf150
• MB21D1
• MB21D1
• h-cGAS
• C6orf150

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
biological process	0
biological term	0
cell line	0
cell type or tissue	0
cellular component	0

Protein Classes

No PANTHER Classes or DTO Classes found

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 591.76   (req: < 5)

Gene RIFs: 64   (req: <= 3)

Antibodies: 189   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 591.76   (req: >= 5)

Gene RIFs: 64   (req: > 3)

Antibodies: 189   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 18

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 61

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (2)

GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (0)

No approved drugs found

Active Ligands (61)

Explore Active Ligands

1 – 10 of 61

BX-795

CGASTchem Enzyme

pKd : 7.7

alpha-mangostin

CGASTchem Enzyme

pIC50 : 8.4

CHEMBL4448176

CGASTchem Enzyme

pIC50 : 7.99

CHEMBL4096573

CGASTchem Enzyme

pKd : 6.7

5-(pyridin-4-ylmethylene)imidazolidine-2,4-dione

CGASTchem Enzyme

pIC50 : 6.3

CHEMBL4483323

CGASTchem Enzyme

pIC50 : 6.3

CHEMBL4474744

CGASTchem Enzyme

pIC50 : 6.3

CHEMBL4553894

CGASTchem Enzyme

pIC50 : 6.3

CHEMBL4573520

CGASTchem Enzyme

pIC50 : 6.3

CHEMBL4528559

CGASTchem Enzyme

pIC50 : 6.3

Protein-Protein Interactions (102)

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1 – 10 of 102

• See Interactions on String-DB

ZNF593

Tbio

Novelty:  0.45276787

p_int:  0.774754208

p_ni:  0.225244676

p_wrong:  0.000001116

Score:  0.359

Data Source:  BioPlex,STRINGDB

TMEM173

Tchem

Novelty:  0.0070581

Score:  0.973

Data Source:  STRINGDB

IFI16

Tbio

Novelty:  0.00739446

Score:  0.89

Data Source:  STRINGDB

TBK1

Tchem

Family:  Kinase

Novelty:  0.00194753

Score:  0.802

Data Source:  STRINGDB

IRF3

Tbio

Family:  TF

Novelty:  0.00099474

Score:  0.789

Data Source:  STRINGDB

IFNB1

Tbio

Novelty:  0.00011797

Score:  0.776

Data Source:  STRINGDB

DDX58

Tbio

Family:  Enzyme

Novelty:  0.00080099

Score:  0.765

Data Source:  STRINGDB

RNF185

Tbio

Family:  Enzyme

Novelty:  0.23911257

Score:  0.762

Data Source:  STRINGDB

AIM2

Tbio

Novelty:  0.00360474

Score:  0.743

Data Source:  STRINGDB

DDX41

Tbio

Family:  Enzyme

Novelty:  0.01658581

Score:  0.717

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (31)

Reactome (4)

KEGG (4)

WikiPathways (23)

Cytosolic sensors of pathogen-associated DNA (R-HSA-1834949)

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Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Cytosolic sensors of pathogen-associated DNA	64 targets	R-HSA-1834949
Reactome	Immune System	2246 targets	R-HSA-168256
Reactome	Innate Immune System	1188 targets	R-HSA-168249
Reactome	STING mediated induction of host immune responses	16 targets	R-HSA-1834941

Name	Explore in Pharos	Explore in Source
Cytosolic sensors of pathogen-associated DNA	64 targets	R-HSA-1834949
Immune System	2246 targets	R-HSA-168256
Innate Immune System	1188 targets	R-HSA-168249
STING mediated induction of host immune responses	16 targets	R-HSA-1834941

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (19)

Functions (7)

Components (1)

Processes (11)

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1 – 7 of 7

GO Term	Evidence	Assigned by
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
cyclic-GMP-AMP synthase activity	Inferred from Direct Assay (IDA)	UniProtKB
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
double-stranded DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
ATP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
GTP binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW
metal ion binding	Inferred from Electronic Annotation (IEA)	UniProtKB-KW

Disease Associations (null)

No disease associations found

GWAS Traits (0)

No GWAS traits found

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Alternative splicing
Antiviral defense
ATP-binding
Complete proteome
Cytoplasm
DNA-binding
GTP-binding
Immunity

MGI Phenotype Find Similar Targets

No Header	No Header
behavior/neurological phenotype
hematopoietic system phenotype
homeostasis/metabolism phenotype
immune system phenotype
mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (10)

1 – 5 of 10

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	cyclic GMP-AMP synthase	VGNC:7205	462822
Macaque	cyclic GMP-AMP synthase		717665
Mouse	Mab-21 domain containing 1	MGI:2442261	214763
Rat	cyclic GMP-AMP synthase	RGD:1586939	682147
Dog	cyclic GMP-AMP synthase	VGNC:43047	611033

Species	Name	OMA	EggNOG	Inparanoid
Chimp	cyclic GMP-AMP synthase
Macaque	cyclic GMP-AMP synthase
Mouse	Mab-21 domain containing 1
Rat	cyclic GMP-AMP synthase
Dog	cyclic GMP-AMP synthase

Publication Statistics

PubMed Score 591.76

PubMed score by year

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PubTator Score 94.18

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Related Publications

Text Mined References (77)

GeneRif Annotations (64)

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PMID	Year	Title