Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

MB21D1

Uniprot No.

Q8N884

Research Area

Others

Alternative Names

C6orf150; cGAMP synthase; cGAS; CGAS_HUMAN; cGMP Synthase; Chromosome 6 open reading frame 150; Cyclic GMP-AMP synthase; h-cGAS; Hypothetical protein LOC115004; Mab 21 domain containing 1; Mab-21 domain-containing protein 1; MB21D1; MGC131892; MGC142166; MGC142168; OTTHUMP00000016743; OTTHUMP00000039330; protein MB21D1; Uncharacterized protein C6orf150

Species

Homo sapiens (Human)

Source

E.coli

Expression Region

161-522aa

Target Protein Sequence

GASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTYFLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Mol. Weight

58.3kDa

Protein Length

Partial

Tag Info

N-terminal 6xHis-SUMO-tagged

Form

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

3-7 business days

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet & COA

Please contact us to get it.

Description

The recombinant 6xHis-SUMO-tagged cyclic GMP-AMP synthase (CGAS) protein was expressed in E.coli. Amino acid residues Gly161-Phe522 of human CGAS protein are contained in this recombinant protein. The SDS-PAGE measured its purity of over 90%, and the CGAS protein migrated to the molecular mass of about 50-61 kDa on the gel. And It was also validated by the LC-MS/MS analysis. In addition to generating specific anti-CGAS antibodies, this recombinant CGAS protein may be also used in the studies of the CGAS-STING signaling pathway.

CGAS is an enzyme that synthesizes second messenger GAMP, which is activated upon binding of CGAS to DNA or RNA-DNA hybrids in the cytoplasm. As a DNA damage sensor, CGAS detects pathogenic DNA to trigger an innate immune reaction involving a strong type I interferon response against microbial infections through the CGAS-STING signaling pathway. CGAS also plays a major role in modulating autophagy. It is involved in cancer, diabetes, and immune disorders. Manish Sharma etc. demonstrated that CGAS is up-regulated in Huntington disease (HD) and mediates inflammatory and autophagy responses and suggested that the CGAS pathway may be the therapeutic target for HD.

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Target Background

Function

Nucleotidyltransferase that catalyzes the formation of cyclic GMP-AMP (cGAMP) from ATP and GTP and plays a key role in innate immunity. 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]. 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. 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. Preferentially recognizes and binds curved long DNAs. 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. Has antiviral activity by sensing the presence of dsDNA from DNA viruses in the cytoplasm. 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. 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. Also detects the presence of DNA from bacteria, such as M.tuberculosis. 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. 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. In addition to antiviral activity, also involved in the response to cellular stresses, such as senescence, DNA damage or genome instability. 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. Also involved in the inflammatory response to genome instability and double-stranded DNA breaks: acts by localizing to micronuclei arising from genome instability. 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. 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.

Gene References into Functions

STAG2 deficiency induces interferon responses via cGAS-STING pathway and restricts virus infection. PMID: 29662124
Data show that both cyclic GMP-AMP synthase (cGAS) and interferon-gamma inducible protein 16 (IFI16) are required for the activation of membrane protein STING (STING) and an innate immune response to exogenous DNA and DNA viruses. PMID: 28194029
duration of LVAD support negatively correlated with expression differences of PKG I, PDE5, and sGC in ICM, but not in DCM. Originating from the same activation level at LVAD implantation, cardiac unloading significantly alters key components of the cGMP-PKG pathway in DCM, but not in ICM patients. PMID: 29546540
cGAS and STING mediated detection of pneumococcal DNA in mouse macrophages to primarily stimulate type I interferon responses. PMID: 29263110
These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling. PMID: 29976794
Thus, the intracellular level of TREX1 pivotally modulates innate immune induction by HIV-1. Partial HIV-1 genomes are the TREX1 target and are sensed by cGAS. PMID: 29769349
This study demonstrated that HSV-1 tegument protein VP22 counteracts the cGAS/STING-mediated DNA-sensing antiviral innate immunity signaling pathway by inhibiting the enzymatic activity of cGAS. PMID: 29793952
study reports that the DENV NS2B protease cofactor targets the DNA sensor cyclic GMP-AMP synthase (cGAS) for lysosomal degradation to avoid the detection of mitochondrial DNA during infection. PMID: 28346446
This work identifies long DNA as the molecular entity stimulating the cGAS pathway upon cytosolic DNA challenge such as viral infections. PMID: 28801534
DNA damage leads to accumulation of damaged DNA in cytoplasmic foci that contain cGAS. In lung adenocarcinoma patients, low expression of cGAS is correlated with poor survival. PMID: 28533362
This study demonstrates that the HCMV tegument protein pp65 inhibits IFN-beta production by binding and inactivating cGAS early during infection. In addition, this inhibitory activity specifically targets cGAS, since it can be bypassed via the addition of exogenous cGAMP, even in the presence of pp65. Notably, STING proteasome-mediated degradation was observed in both the presence and absence of pp65. PMID: 29263269
Results indicate that the rs311678 polymorphism in the cyclic GMP-AMP synthase (cGAS) gene confers genetic susceptibility to cervical precancerous lesions. PMID: 27705945
results suggest a nucleation-cooperativity-based mechanism for sensitive detection of mitochondrial DNA and pathogen genomes, and identify HMGB/TFAM proteins as DNA-structuring host factors; they provide an explanation for the peculiar cGAS dimer structure and suggest that cGAS preferentially binds incomplete nucleoid-like structures or bent DNA PMID: 28902841
cGAS localizes to micronuclei arising from genome instability in a mouse model of monogenic autoinflammation, after exogenous DNA damage and spontaneously in human cancer cells PMID: 28738408
Study and report of the structure and catalytic mechanism of Cyclic GMP-AMP synthase (cGAS). PMID: 28940468
Our results identify cGAS as mediator of an IFN-I response to HIV-1 infection in CD4(+) T cells and demonstrate that this response is modulated by the viral accessory proteins Vpr and Vpu. Thus, viral innate immune evasion is incomplete in the main target cells of HIV-1 PMID: 27705790
miR-25/93 targets NCOA3, an epigenetic factor that maintains basal levels of cGAS expression, leading to repression of cGAS during hypoxia. This allows hypoxic tumour cells to escape immunological responses induced by damage-associated molecular pattern molecules, specifically the release of mitochondrial DNA. PMID: 28920955
IN this review, we highlight our current understanding of DNA sensing by cGAS and its involvement in human disease PMID: 27154323
study identifies the AIM2 inflammasome and cGAS/IFI16-STING-type I IFN pathway as a novel mechanism for host innate immunity to the ALVAC vaccine vector. PMID: 28947539
NEMO was critically involved in the cGAS-STING pathway. PMID: 28939760
Type I IFN is detrimental to the host, and dysregulation of iron homeostasis genes may explain lower bacteria survival in cGAS(-/-) and TLR4(-/-) cells. PMID: 27264171
Decreased expression of cGAS in neonatal cells can be rescued by DNA demethylation. PMID: 28412547
Essential roles of the cGAS-cGAMP-STING pathway. [review] PMID: 27706894
the current study demonstrated that the DNA sensor cGAS is dynamically modified by SUMO PMID: 28095500
while IFI16 induces cytokines, only cGAS activates STING/TBK-1/IRF3 and apoptotic responses upon herpes simplex virus 1 and human cytomegalovirus infections; findings show that IFI16, not cGAS or PML, represses HSV-1 gene expression, reducing virus PMID: 27935834
These results suggest that pDCs sense cytosolic DNA and cyclic dinucleotides via the cGAS-STING pathway and that targeting this pathway could be of therapeutic interest. PMID: 27125983
cGAs recognizes bacterial/viral DNA, and is a strong activator of STING that can further activate IRF3 and subsequent type I interferon production. (Review) PMID: 27696330
Data suggest that the N terminus enhanced the activity of core-cyclic GMP-AMP synthase (cGAS) by facilitating formation of a monomeric complex of cGAS and DNA. PMID: 28214358
In the present study, the authors found that herpes simplex virus 1 tegument protein UL41 was involved in counteracting the cGAS/STING-mediated DNA-sensing pathway. PMID: 28077645
cGAS-STING pathway plays a role in the surveillance of hepatitis B virus infection. PMID: 27902332
Primary human endothelial cells mount robust type I interferon responses to human cytomegalovirus that are dependent upon cyclic GMP-AMP synthase (cGAS), STING, and interferon regulatory factor 3 (IRF3) signaling. PMID: 27334590
this study shows the N-terminal domain of cGAS plays an important role in enhancing its function PMID: 28363908
cGAS and STING are intracellular sensors that activate the interferon pathway in response to virus infection. [review] PMID: 26867174
cGAS silencing inhibited production of proinflammatory cytokines and matrix metalloproteinases (MMPs) as well as AKT and ERK phosphorylation in TNFalpha-stimulated fibroblast-like synoviocytes PMID: 26819496
A STING-dependent, cGAS-independent pathway important for full interferon production and antiviral control of enveloped RNA viruses. PMID: 26893169
By directly binding to cGAS, LANA, and particularly, a cytoplasmic isoform, inhibit the cGAS-STING-dependent phosphorylation of TBK1 and IRF3 and thereby antagonize the cGAS-mediated restriction of KSHV lytic replication. PMID: 26811480
Kaposi's sarcoma-associated herpesvirus ORF52 subverts cytosolic DNA sensing by directly inhibiting cGAS enzymatic activity through a mechanism involving both cGAS binding and DNA binding. PMID: 26320998
TRIM21-induced exposure of the viral genome promotes sensing of DNA and RNA viruses by cGAS and RIG-I PMID: 26506431
M. tuberculosis infection induces cGAS in macrophages and human lung tissue. PMID: 26048137
cGAS is an innate sensor of Mycobacterium tuberculosis.Mycobacterium tuberculosis differentially activates cGAS- and inflammasome-dependent intracellular immune responses through ESX-1. PMID: 26048138
Knockout of cGAS and STING Rescues Virus Infection of Plasmid DNA-Transfected Cells. PMID: 26311870
Gammaherpesviruses encode inhibitors that block cGAS-STING-mediated antiviral immunity. PMID: 26199418
Study found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. PMID: 26046437
The mechanism of double-stranded DNA sensing through the cGAS-STING pathway. PMID: 25007740
Studies in THP-1 knockout cells revealed that the recognition of RNA:DNA hybrids is completely attributable to the cGAS-STING pathway. PMID: 25425575
IFI16 and cGAS cooperate in a novel way to sense nuclear herpesviral DNA and initiate innate signaling PMID: 25831530
our study not only provides a novel mechanism of modulating cGAS expression, but also adds another layer of regulation in DNA-triggered IFN-I production by induction of cGAS. PMID: 25609843
The cGAS/STING/TBK1/IRF3 cascade was not a direct target of viral antihost strategies, and authors found no evidence that adenovirus stimulation of the cGAS/STING DNA response had an impact on viral replication efficiency. PMID: 25297994
cGAS localized in punctate regions on the cytosolic side of the chlamydial inclusion membrane in association with STING, indicating that chlamydial DNA is most likely recognized outside the inclusion as infection progresses. PMID: 25070851
The crystal structures of human cGAS in its apo form, representing its autoinhibited conformation as well as in its cGAMP- and sulfate-bound forms, are reported. PMID: 24462292

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Subcellular Location

Cell membrane; Peripheral membrane protein. Cytoplasm, cytosol. Nucleus.;

Protein Families

Mab-21 family

Tissue Specificity

Expressed in the monocytic cell line THP1.

Database Links

HGNC: 21367

OMIM: 613973

KEGG: hsa:115004

STRING: 9606.ENSP00000359339

UniGene: Hs.658405

Code	CSB-EP822726HU
Abbreviation	Recombinant Human CGAS protein, partial
MSDS	MSDS Datasheet
Size	$224
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Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel. Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP822726HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) MB21D1. Based on the SEQUEST from database of E.coli host and target protein, the LC-MS/MS Analysis result of CSB-EP822726HU could indicate that this peptide derived from E.coli-expressed Homo sapiens (Human) MB21D1.
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Recombinant Human Cyclic GMP-AMP synthase (CGAS), partial

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