Product: C6orf150 Antibody
Catalog: DF12574
Description: Rabbit polyclonal antibody to C6orf150
Application: WB
Reactivity: Human
Mol.Wt.: 54 kDa; 59kD(Calculated).
Uniprot: Q8N884
RRID: AB_2845536

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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human
Clonality:
Polyclonal
Specificity:
C6orf150 Antibody detects endogenous levels of total C6orf150.
RRID:
AB_2845536
Cite Format: Affinity Biosciences Cat# DF12574, RRID:AB_2845536.
Conjugate:
Unconjugated.
Purification:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

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;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
Q8N884 CGAS_HUMAN:

Expressed in the monocytic cell line THP1.

Sequence:
MQPWHGKAMQRASEAGATAPKASARNARGAPMDPTESPAAPEAALPKAGKFGPARKSGSRQKKSAPDTQERPPVRATGARAKKAPQRAQDTQPSDATSAPGAEGLEPPAAREPALSRAGSCRQRGARCSTKPRPPPGPWDVPSPGLPVSAPILVRRDAAPGASKLRAVLEKLKLSRDDISTAAGMVKGVVDHLLLRLKCDSAFRGVGLLNTGSYYEHVKISAPNEFDVMFKLEVPRIQLEEYSNTRAYYFVKFKRNPKENPLSQFLEGEILSASKMLSKFRKIIKEEINDIKDTDVIMKRKRGGSPAVTLLISEKISVDITLALESKSSWPASTQEGLRIQNWLSAKVRKQLRLKPFYLVPKHAKEGNGFQEETWRLSFSHIEKEILNNHGKSKTCCENKEEKCCRKDCLKLMKYLLEQLKERFKDKKHLDKFSSYHVKTAFFHVCTQNPQDSQWDRKDLGLCFDNCVTYFLQCLRTEKLENYFIPEFNLFSSNLIDKRSKEFLTKQIEYERNNEFPVFDEF

PTMs - Q8N884 As Substrate

Site PTM Type Enzyme
K7 Acetylation
K7 Methylation
S13 Phosphorylation
K50 Acetylation
S64 Phosphorylation
T68 Phosphorylation
K82 Methylation
T91 Phosphorylation
S116 Phosphorylation
S120 Phosphorylation
S129 Phosphorylation
S143 Phosphorylation
K164 Ubiquitination
K173 Ubiquitination
S175 Phosphorylation
T181 Phosphorylation
K198 Ubiquitination
Y215 Phosphorylation
K231 Sumoylation
Y248 Phosphorylation
K282 Ubiquitination
K285 Sumoylation
K285 Ubiquitination
K292 Ubiquitination
T294 Phosphorylation
K301 Methylation
S305 Phosphorylation
K347 Ubiquitination
K355 Ubiquitination
K362 Methylation
K365 Ubiquitination
K384 Acetylation
K384 Sumoylation
K384 Ubiquitination
K392 Acetylation
K392 Ubiquitination
K394 Acetylation
K394 Sumoylation
K414 Acetylation
K414 Ubiquitination
Y415 Phosphorylation
K421 Ubiquitination
K432 Ubiquitination
K479 Sumoylation
K501 Ubiquitination
K506 Ubiquitination

Research Backgrounds

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 (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. 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.

PTMs:

Phosphorylation at Tyr-215 by BLK promotes cytosolic retention. Translocates into the nucleus following dephosphorylation at Tyr-215.

(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.

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.

Cleaved by CASP1 at Asp-140 and Asp-157 upon DNA virus infection; the cleavage impairs cGAMP production. Also cleaved by the pyroptotic CASP4 and CASP5 during non-canonical inflammasome activation; they don't cut at the same sites than CASP1.

Acetylation at Lys-384, Lys-394 and Lys-414 inhibits the cyclic GMP-AMP synthase activity. Deacetylated upon cytosolic DNA challenge such as viral infections. Acetylation can be mediated by aspirin (acetylsalicylate) drug, which directly acetylates CGAS. Acetylation by aspirin efficiently inhibits CGAS-mediated immune responses and is able to suppress self-DNA-induced autoimmunity.

Subcellular Location:

Cell membrane>Peripheral membrane protein. Cytoplasm>Cytosol. Nucleus.
Note: In resting conditions, localizes at the cell membrane as a peripheral membrane protein by 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; translocates into the nucleus following dephosphorylation (PubMed:30356214).


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).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Expressed in the monocytic cell line THP1.

Subunit Structure:

Monomer in the absence of DNA. Homodimer in presence of dsDNA: forms a 2:2 dimer with two enzymes binding to two DNA molecules. Interacts with PQBP1 (via WW domain). Interacts with TRIM14; this interaction stabilizes CGAS and promotes type I interferon production. Interacts with ZCCHC3; promoting sensing of dsDNA by CGAS. Interacts with PARP1; interaction takes place in the nucleus and prevents the formation of the PARP1-TIMELESS complex.

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

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

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

Family&Domains:

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).

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).

Belongs to the mab-21 family.

Research Fields

· Organismal Systems > Immune system > Cytosolic DNA-sensing pathway.   (View pathway)

References

1). Palmitic acid promotes endothelial-to-mesenchymal transition via activation of the cytosolic DNA-sensing cGAS-STING pathway. ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS, 2022 (PubMed: 35697075) [IF=3.9]

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