MB21D1 [The Human Chemical-Genetic Interaction Map Project]

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======= MB21D1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: CGAS
  * **<color #00a2e8>Official Name</color>**: cyclic GMP-AMP synthase
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=115004|115004]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q8N884|Q8N884]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=MB21D1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20MB21D1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/613973|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000250|UniProtKB:Q8C6L5, ECO:0000269|PubMed:21478870, ECO:0000269|PubMed:23258413, ECO:0000269|PubMed:23707061, ECO:0000269|PubMed:23707065, ECO:0000269|PubMed:23722159, ECO:0000269|PubMed:23929945, ECO:0000269|PubMed:24077100, ECO:0000269|PubMed:24116191, ECO:0000269|PubMed:24462292, ECO:0000269|PubMed:25131990, ECO:0000269|PubMed:26046437, ECO:0000269|PubMed:26048138, ECO:0000269|PubMed:26229115, ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:28214358, ECO:0000269|PubMed:28314590, ECO:0000269|PubMed:28363908, ECO:0000269|PubMed:28738408, ECO:0000269|PubMed:28759889}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Mab-21|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|cyclic-GMP-AMP synthase activity|
|positive regulation of cGMP-mediated signaling|
|paracrine signaling|
|positive regulation of cellular senescence|
|regulation of cGMP-mediated signaling|
|positive regulation of cell aging|
|cellular response to exogenous dsRNA|
|determination of adult lifespan|
|negative regulation of double-strand break repair via homologous recombination|
|cellular response to dsRNA|
|positive regulation of cAMP-mediated signaling|
|positive regulation of defense response to virus by host|
|negative regulation of double-strand break repair|
|negative regulation of DNA repair|
|multicellular organism aging|
|regulation of defense response to virus by host|
|regulation of cellular senescence|
|response to exogenous dsRNA|
|negative regulation of DNA recombination|
|regulation of double-strand break repair via homologous recombination|
|regulation of cell aging|
|regulation of cAMP-mediated signaling|
|response to dsRNA|
|site of double-strand break|
|regulation of immunoglobulin production|
|regulation of defense response to virus|
|phosphatidylinositol-4,5-bisphosphate binding|
|regulation of double-strand break repair|
|positive regulation of type I interferon production|
|negative regulation of response to DNA damage stimulus|
|double-stranded DNA binding|
|regulation of DNA recombination|
|negative regulation of DNA metabolic process|
|regulation of DNA repair|
|regulation of type I interferon production|
|regulation of production of molecular mediator of immune response|
|defense response to virus|
|regulation of response to DNA damage stimulus|
|activation of innate immune response|
|aging|
|response to virus|
|regulation of T cell activation|
|positive regulation of innate immune response|
|regulation of DNA metabolic process|
|positive regulation of response to biotic stimulus|
|GTP binding|
|chromatin binding|
|positive regulation of cytokine production|
|regulation of innate immune response|
|regulation of immune effector process|
|positive regulation of defense response|
|DNA repair|
|positive regulation of multi-organism process|
|regulation of lymphocyte activation|
|regulation of response to biotic stimulus|
|cellular response to organic cyclic compound|
|regulation of leukocyte activation|
|positive regulation of response to external stimulus|
|activation of immune response|
|regulation of cell activation|
|cellular response to nitrogen compound|
|regulation of cytokine production|
|viral process|
|regulation of cellular response to stress|
|DNA metabolic process|
|regulation of defense response|
|innate immune response|
|regulation of multi-organism process|
|cellular response to DNA damage stimulus|
|symbiotic process|
|interspecies interaction between organisms|
|positive regulation of immune response|
|response to organic cyclic compound|
|defense response to other organism|
|positive regulation of intracellular signal transduction|
|response to nitrogen compound|
|immune effector process|
|regulation of response to external stimulus|
|cell-cell signaling|
|positive regulation of immune system process|
|regulation of immune response|
|response to other organism|
|response to external biotic stimulus|
|response to biotic stimulus|
|defense response|
|positive regulation of developmental process|
|negative regulation of nucleobase-containing compound metabolic process|
|DNA binding|
|regulation of response to stress|
|ATP binding|
|negative regulation of response to stimulus|
|regulation of immune system process|
|positive regulation of signal transduction|
|cellular response to stress|
|positive regulation of multicellular organismal process|
|positive regulation of cell communication|
|positive regulation of signaling|
|regulation of intracellular signal transduction|
|immune response|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='default' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp36|TRAIL 50ng/ml R00 exp36]]|1.78|
|[[:results:exp28|Pimelic-diphenylamide-106 5μM R00 exp28]]|1.85|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
No correlation found to any other genes in chemogenomics.
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 9574
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 3.92 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='MB21D1 Expression in NALM6 Cells: 3.92'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>