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: 816.03   (req: < 5)

Gene RIFs: 218   (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: 816.03   (req: >= 5)

Gene RIFs: 218   (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