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Showing Protein Stimulator of interferon genes protein (HMDBP12695)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP12695
Secondary Accession Numbers None
Name Stimulator of interferon genes protein
Synonyms
  1. hSTING
  2. Endoplasmic reticulum interferon stimulator
  3. Mediator of IRF3 activation
  4. Transmembrane protein 173
  5. ERIS
  6. hMITA
Gene Name STING1
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Facilitator of innate immune signaling that acts as a sensor of cytosolic DNA from bacteria and viruses and promotes the production of type I interferon (IFN-alpha and IFN-beta) (PubMed:18724357, PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, PubMed:23910378, PubMed:23747010, PubMed:30842659). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:26300263). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:21947006, PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:26229117, PubMed:23910378, PubMed:23747010, PubMed:30842659). Upon binding of c-di-GMP or cGAMP, STING1 oligomerizes, translocates from the endoplasmic reticulum and is phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and subsequent activation of the transcription factor IRF3 to induce expression of type I interferon and exert a potent anti-viral state (PubMed:22394562, PubMed:25636800, PubMed:30842653). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238, PubMed:30842662). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (PubMed:30842662). The ERGIC serves as the membrane source for WIPI2 recruitment and LC3 lipidation, leading to formation of autophagosomes that target cytosolic DNA or DNA viruses for degradation by the lysosome (PubMed:30842662). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (By similarity). Exhibits 2',3' phosphodiester linkage-specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:26300263, PubMed:23910378, PubMed:23747010). The preference for 2'-3'-cGAMP, compared to other linkage isomers is probably due to the ligand itself, whichs adopts an organized free-ligand conformation that resembles the STING1-bound conformation and pays low energy costs in changing into the active conformation (PubMed:26150511). May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (PubMed:18724357). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (By similarity).(Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein (PubMed:26405230). Such oncoproteins prevent the ability to sense cytosolic DNA (PubMed:26405230).
Pathways
  • Coronavirus disease - COVID-19
  • Cytosolic DNA-sensing pathway
  • Herpes simplex virus 1 infection
  • Human cytomegalovirus infection
  • Human immunodeficiency virus 1 infection
  • NOD-like receptor signaling pathway
  • RIG-I-like receptor signaling pathway
  • Shigellosis
Reactions Not Available
GO Classification
Biological Process
regulation of inflammatory response
neutrophil degranulation
activation of innate immune response
autophagosome assembly
cellular response to exogenous dsRNA
reticulophagy
regulation of type I interferon production
positive regulation of protein binding
positive regulation of macroautophagy
positive regulation of interferon-beta production
cellular response to interferon-beta
protein oligomerization
cellular response to organic cyclic compound
positive regulation of sequence-specific DNA binding transcription factor activity
defense response to virus
innate immune response
positive regulation of defense response to virus by host
viral reproduction
positive regulation of transcription from RNA polymerase II promoter
positive regulation of type I interferon production
Cellular Component
endoplasmic reticulum membrane
cytosol
integral to endoplasmic reticulum membrane
plasma membrane
Golgi apparatus
perinuclear region of cytoplasm
cytoplasmic vesicle membrane
autophagic vacuole membrane
autophagosome
integral component of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane
nucleoplasm
mitochondrial outer membrane
peroxisome
secretory granule membrane
endosome
Molecular Function
protein kinase binding
cyclic-di-GMP binding
cyclic-GMP-AMP binding
ubiquitin protein ligase binding
transcription factor binding
protein homodimerization activity
identical protein binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 379
Molecular Weight 42192.08
Theoretical pI 7.054
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 18-34;45-69;92-106;117-134;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q86WV6
UniProtKB/Swiss-Prot Entry Name STING_HUMAN
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
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