Q8C6L5

PR
Gene name
Cgas
Protein name
Cyclic GMP-AMP synthase
Names
cGAMP synthase, cGAS, m-cGAS, 2'3'-cGAMP synthase, Mab-21 domain-containing protein 1
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:214763
EC number
2.7.7.86: Nucleotidyltransferases
Protein Class

Descriptions

The autoinhibited protein was predicted that may have potential autoinhibitory elements via cis-regPred.

Autoinhibitory domains (AIDs)

1-169 (Predicted disordered autoinhibitory region) PR

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

36 structures for Q8C6L5

Entry ID Method Resolution Chain Position Source
4K8V X-ray 200 A A/B/C/D 147-507 PDB
4K96 X-ray 208 A A/B 147-507 PDB
4K97 X-ray 241 A A 147-507 PDB
4K98 X-ray 194 A A 147-507 PDB
4K99 X-ray 195 A A 147-507 PDB
4K9A X-ray 226 A A 147-507 PDB
4K9B X-ray 226 A A 147-507 PDB
4LEY X-ray 250 A A/B/C/D 142-507 PDB
4LEZ X-ray 236 A A/C 142-507 PDB
4O6A X-ray 186 A A/B 147-507 PDB
5N6I X-ray 360 A A/B/C/D/E/F 139-507 PDB
5XZB X-ray 213 A A 149-505 PDB
5XZE X-ray 218 A A 147-507 PDB
5XZG X-ray 183 A A 147-507 PDB
6X59 EM 298 A K 142-507 PDB
6X5A EM 436 A K 142-507 PDB
6XJD EM 680 A K/L 142-507 PDB
7A08 EM 311 A a 139-507 PDB
7BUJ X-ray 213 A A/B 61-507 PDB
7BUM X-ray 305 A A/B 1-507 PDB
7BUQ X-ray 309 A A/B 1-507 PDB
7JO9 EM 330 A K 142-507 PDB
7JOA EM 330 A K 142-507 PDB
7KXS X-ray 260 A A/B 147-507 PDB
7UTT X-ray 204 A A/C 147-507 PDB
7UUX X-ray 226 A A/C 147-507 PDB
7UXW X-ray 257 A A/C 147-507 PDB
7UYQ X-ray 257 A A/C 147-507 PDB
7UYZ X-ray 249 A A/C 147-507 PDB
7UZR X-ray 270 A A/C 147-507 PDB
7V0C X-ray 257 A A/C 147-507 PDB
7V0R X-ray 251 A A/C 147-507 PDB
7V0W X-ray 266 A A/C 147-507 PDB
8EAE X-ray 256 A A/C 147-507 PDB
8ECC X-ray 244 A A/C 147-507 PDB
AF-Q8C6L5-F1 Predicted AlphaFoldDB

16 variants for Q8C6L5

Variant ID(s) Position Change Description Diseaes Association Provenance
rs233690332 9 T>A No EVA
rs241013452 64 H>R No EVA
rs220987275 92 R>P No EVA
rs3399820834 125 P>L No EVA
rs243131043 163 D>A No EVA
rs3389068006 245 G>* No EVA
rs3389053770 283 S>DG* No EVA
rs3399820810 349 P>H No EVA
rs3389067957 421 Y>N No EVA
rs3389062773 422 H>L No EVA
rs3400185560 425 T>A No EVA
rs3400378492 425 T>N No EVA
rs3400512748 426 A>G No EVA
rs3413070844 427 I>S No EVA
rs265245495 454 A>V No EVA
rs248304713 483 R>Q No EVA

No associated diseases with Q8C6L5

2 regional properties for Q8C6L5

Type Name Position InterPro Accession
domain Mab-21-like, nucleotidyltransferase domain 200 - 377 IPR046903
domain Mab-21-like, HhH/H2TH-like domain 393 - 494 IPR046906

Functions

Description
EC Number 2.7.7.86 Nucleotidyltransferases
Subcellular Localization
  • Nucleus
  • Chromosome
  • Cell membrane ; Peripheral membrane protein
  • Cytoplasm, cytosol
  • Mainly localizes in the nucleus, and at low level in the cytosol (PubMed:31544964, PubMed:31808743)
  • On chromosomes, enriched on centromeric satellite and LINE DNA repeat elements (By similarity)
  • Exported from the nucleus to the cytosol in a XPO1/CRM1 via the nuclear export signal in response to DNA stimulation (By similarity)
  • Outside the nucleus, localizes at the cell membrane as a peripheral membrane protein in resting conditions: association to the cell membrane is mediated via 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 (By similarity)
  • Following detection of double-stranded DNA (dsDNA), released from the cell membrane into the cytosol in order to signal (By similarity)
  • Upon transfection with dsDNA forms punctate structures that co-localize with DNA and Beclin-1 (BECN1) (By similarity)
  • Phosphorylation at Tyr-201 promotes cytosolic retention (By similarity)
  • In response to translation stress, translocates to the cytosol and associates with collided ribosomes (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

5 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
site of double-strand break A region of a chromosome at which a DNA double-strand break has occurred. DNA damage signaling and repair proteins accumulate at the lesion to respond to the damage and repair the DNA to form a continuous DNA helix.

12 GO annotations of molecular function

Name Definition
2',3'-cyclic GMP-AMP synthase activity Catalysis of the reaction: ATP + GTP = 2 diphosphate + cyclic G-P(2'-5')A-P(3'-5') (cyclic 2',3' GAMP).
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
chromatin binding Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
DNA binding Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
double-stranded DNA binding Binding to double-stranded DNA.
GTP binding Binding to GTP, guanosine triphosphate.
metal ion binding Binding to a metal ion.
molecular condensate scaffold activity Binding and bringing together two or more macromolecules in contact, permitting those molecules to organize as a molecular condensate.
nucleosome binding Binding to a nucleosome, a complex comprised of DNA wound around a multisubunit core and associated proteins, which forms the primary packing unit of DNA into higher order structures.
phosphatidylinositol-4,5-bisphosphate binding Binding to phosphatidylinositol-4,5-bisphosphate, a derivative of phosphatidylinositol in which the inositol ring is phosphorylated at the 4' and 5' positions.
poly-ADP-D-ribose modification-dependent protein binding Binding to a protein upon poly-ADP-ribosylation of the target protein.
protein homodimerization activity Binding to an identical protein to form a homodimer.

18 GO annotations of biological process

Name Definition
activation of innate immune response Any process that initiates an innate immune response. Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens. Examples of this process include activation of the hypersensitive response of Arabidopsis thaliana and activation of any NOD or TLR signaling pathway in vertebrate species.
cAMP-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell via cyclic AMP (cAMP). Includes production of cAMP, and downstream effectors that further transmit the signal within the cell.
cellular response to DNA damage stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating damage to its DNA from environmental insults or errors during metabolism.
cellular response to exogenous dsRNA Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an exogenous double-stranded RNA stimulus.
cGMP-mediated signaling Any intracellular signal transduction in which the signal is passed on within the cell via cyclic GMP (cGMP). Includes production of cGMP, and downstream effectors that further transmit the signal within the cell.
defense response to virus Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
determination of adult lifespan The pathways that regulate the duration of the adult phase of the life-cycle of an animal.
DNA repair The process of restoring DNA after damage. Genomes are subject to damage by chemical and physical agents in the environment (e.g. UV and ionizing radiations, chemical mutagens, fungal and bacterial toxins, etc.) and by free radicals or alkylating agents endogenously generated in metabolism. DNA is also damaged because of errors during its replication. A variety of different DNA repair pathways have been reported that include direct reversal, base excision repair, nucleotide excision repair, photoreactivation, bypass, double-strand break repair pathway, and mismatch repair pathway.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
negative regulation of double-strand break repair via homologous recombination Any process that stops, prevents, or reduces the frequency, rate or extent of double-strand break repair via homologous recombination.
paracrine signaling The transfer of information from one cell to another, where the signal travels from the signal-producing cell to the receiving cell by passive diffusion or bulk flow in intercellular fluid. The signaling cell and the receiving cell are usually in the vicinity of each other.
positive regulation of cellular senescence Any process that activates or increases the frequency, rate or extent of cellular senescence.
positive regulation of defense response to virus by host Any host process that results in the promotion of antiviral immune response mechanisms, thereby limiting viral replication.
positive regulation of type I interferon production Any process that activates or increases the frequency, rate, or extent of type I interferon production. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.
regulation of immune response Any process that modulates the frequency, rate or extent of the immune response, the immunological reaction of an organism to an immunogenic stimulus.
regulation of immunoglobulin production Any process that modulates the frequency, rate, or extent of immunoglobulin production.
regulation of T cell activation Any process that modulates the frequency, rate or extent of T cell activation.
regulation of type I interferon production Any process that modulates the frequency, rate, or extent of interferon type I production. Type I interferons include the interferon-alpha, beta, delta, episilon, zeta, kappa, tau, and omega gene families.

4 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
E1BGN7 CGAS Cyclic GMP-AMP synthase Bos taurus (Bovine) PR
Q8N884 CGAS Cyclic GMP-AMP synthase Homo sapiens (Human) PR
Q8C525 Mb21d2 Nucleotidyltransferase MB21D2 Mus musculus (Mouse) PR
I3LM39 CGAS Cyclic GMP-AMP synthase Sus scrofa (Pig) PR
10 20 30 40 50 60
MEDPRRRTTA PRAKKPSAKR APTQPSRTRA HAESCGPQRG ARSRRAERDG DTTEKPRAPG
70 80 90 100 110 120
PRVHPARATE LTKDAQPSAM DAAGATARPA VRVPQQQAIL DPELPAVREP QPPADPEARK
130 140 150 160 170 180
VVRGPSHRRG ARSTGQPRAP RGSRKEPDKL KKVLDKLRLK RKDISEAAET VNKVVERLLR
190 200 210 220 230 240
RMQKRESEFK GVEQLNTGSY YEHVKISAPN EFDVMFKLEV PRIELQEYYE TGAFYLVKFK
250 260 270 280 290 300
RIPRGNPLSH FLEGEVLSAT KMLSKFRKII KEEVKEIKDI DVSVEKEKPG SPAVTLLIRN
310 320 330 340 350 360
PEEISVDIIL ALESKGSWPI STKEGLPIQG WLGTKVRTNL RREPFYLVPK NAKDGNSFQG
370 380 390 400 410 420
ETWRLSFSHT EKYILNNHGI EKTCCESSGA KCCRKECLKL MKYLLEQLKK EFQELDAFCS
430 440 450 460 470 480
YHVKTAIFHM WTQDPQDSQW DPRNLSSCFD KLLAFFLECL RTEKLDHYFI PKFNLFSQEL
490 500
IDRKSKEFLS KKIEYERNNG FPIFDKL