Q3TBT3

SS
Gene name
Sting1
Protein name
Stimulator of interferon genes protein
Names
mSTING, Endoplasmic reticulum interferon stimulator, ERIS, Mediator of IRF3 activation, MMITA, Transmembrane protein 173
Species
Mus musculus (Mouse)
KEGG Pathway
mmu:72512
EC number
Protein Class

Descriptions

Stimulator of interferon genes (STING) plays a role as a sensor to directly bind cyclic diguanylate monophosphate (c-di-GMP), the abacterial second message, facilitates innate immune signalling and promotes the production of type I interferon for the first line of defence immune. In human STRING1 (Q86WV6), the autoinhibitory conformation of cytosolic c-di-GMP binding domain (CBD) is formed via the intramolecular interaction with the C-terminal tail (CTT), which hinders the binding of c-di-GMP on STING.

Autoinhibitory domains (AIDs)

339-378 (C-terminal regulatory region) SS

Target domain

153-336 (Cytosolic c-di-GMP binding domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

9 structures for Q3TBT3

Entry ID Method Resolution Chain Position Source
4JC5 X-ray 275 A A/B 149-348 PDB
4KBY X-ray 236 A A/B 138-344 PDB
4KC0 X-ray 220 A A/B 138-344 PDB
4LOJ X-ray 177 A A/B 154-340 PDB
4LOK X-ray 207 A A/B 154-340 PDB
4LOL X-ray 243 A A/B 154-340 PDB
4YP1 X-ray 265 A A/B 138-344 PDB
6XNN X-ray 249 A A/B 154-340 PDB
AF-Q3TBT3-F1 Predicted AlphaFoldDB

16 variants for Q3TBT3

Variant ID(s) Position Change Description Diseaes Association Provenance
rs216870905 37 K>E No Ensembl
rs584537956 95 C>Y No Ensembl
rs244124397 98 M>T No Ensembl
rs578374977 99 I>V No Ensembl
rs230125334 103 S>F No Ensembl
rs257761261 108 L>R No Ensembl
rs238915886 111 T>I No Ensembl
rs31809050 114 I>M No Ensembl
rs222376615 114 I>V No Ensembl
rs244737939 115 Y>C No Ensembl
rs220800831 120 F>L No Ensembl
rs262587515 125 L>F No Ensembl
rs236561144 126 Y>S No Ensembl
rs233698066 210 N>D No Ensembl
rs219976114 305 R>Q No Ensembl
rs262068172 324 L>V No Ensembl

No associated diseases with Q3TBT3

13 regional properties for Q3TBT3

Type Name Position InterPro Accession
domain Protein kinase domain 505 - 776 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 506 - 773 IPR001245
domain Immunoglobulin subtype 2 43 - 112 IPR003598
domain Immunoglobulin subtype 37 - 124 IPR003599-1
domain Immunoglobulin subtype 133 - 210 IPR003599-2
domain Fibronectin type III 213 - 308 IPR003961-1
domain Fibronectin type III 310 - 403 IPR003961-2
domain Immunoglobulin-like domain 10 - 122 IPR007110-1
domain Immunoglobulin-like domain 127 - 208 IPR007110-2
active_site Tyrosine-protein kinase, active site 638 - 650 IPR008266
domain Immunoglobulin I-set 32 - 116 IPR013098
binding_site Protein kinase, ATP binding site 511 - 537 IPR017441
domain Tyrosine-protein kinase, catalytic domain 505 - 773 IPR020635

Functions

Description
EC Number
Subcellular Localization
  • Endoplasmic reticulum membrane ; Multi-pass membrane protein
  • Cytoplasm, perinuclear region
  • Endoplasmic reticulum-Golgi intermediate compartment membrane ; Multi-pass membrane protein
  • Golgi apparatus membrane ; Multi-pass membrane protein
  • Cytoplasmic vesicle, autophagosome membrane ; Multi-pass membrane protein
  • Mitochondrion outer membrane ; Multi-pass membrane protein
  • Cell membrane ; Multi-pass membrane protein
  • Lysosome membrane ; Multi-pass membrane protein
  • In response to double-stranded DNA stimulation, translocates from the endoplasmic reticulum through the endoplasmic reticulum-Golgi intermediate compartment and Golgi to post-Golgi vesicles, where the kinase TBK1 is recruited
  • Upon cGAMP-binding, translocates to the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) in a process that is dependent on COPII vesicles; STING1-containing ERGIC serves as a membrane source for LC3 lipidation, which is a key step in autophagosome biogenesis (By similarity)
  • Localizes in the lysosome membrane in a TMEM203-dependent manner (PubMed:31346090)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

16 GO annotations of cellular component

Name Definition
autophagosome A double-membrane-bounded compartment that engulfs endogenous cellular material as well as invading microorganisms to target them to the lytic vacuole/lysosome for degradation as part of macroautophagy.
autophagosome membrane The lipid bilayer surrounding an autophagosome, a double-membrane-bounded vesicle in which endogenous cellular material is sequestered.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
endoplasmic reticulum The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached).
endoplasmic reticulum membrane The lipid bilayer surrounding the endoplasmic reticulum.
endosome A vacuole to which materials ingested by endocytosis are delivered.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
integral component of endoplasmic reticulum membrane The component of the endoplasmic reticulum membrane consisting of the gene products and protein complexes having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
integral component of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane The component of the ERGIC membrane consisting of the gene products having at least some part of their peptide sequence embedded in the hydrophobic region of the membrane.
mitochondrial outer membrane The outer, i.e. cytoplasm-facing, lipid bilayer of the mitochondrial envelope.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
perinuclear region of cytoplasm Cytoplasm situated near, or occurring around, the nucleus.
peroxisome A small organelle enclosed by a single membrane, and found in most eukaryotic cells. Contains peroxidases and other enzymes involved in a variety of metabolic processes including free radical detoxification, lipid catabolism and biosynthesis, and hydrogen peroxide metabolism.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
STING complex A protein dimer containing two STING monomers. It binds cyclic purine di-nucleotides. Activation of the sting complex by 2',5'-3'-5'-cyclic GMP-AMP activates nuclear transcription factor kB (NF-kB) and interferon regulatory factor 3 (IRF3) which then induce transcription of the genes encoding type I IFN and cytokines active in the innate immune response.

7 GO annotations of molecular function

Name Definition
2',3'-cyclic GMP-AMP binding Binding to 2',3' cyclic GMP-AMP (cGAMP) nucleotide, a cyclic purine dinucleotide that consists of AMP and GMP units cyclized via 2',5' and 3',5' linkages.
cyclic-di-GMP binding Binding to cyclic-di-GMP, cyclic dimeric guanosine monophosphate.
identical protein binding Binding to an identical protein or proteins.
protein homodimerization activity Binding to an identical protein to form a homodimer.
protein kinase binding Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate.
RNA polymerase II-specific DNA-binding transcription factor binding Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription.
ubiquitin protein ligase binding Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

19 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.
autophagosome assembly The formation of a double membrane-bounded structure, the autophagosome, that occurs when a specialized membrane sac, called the isolation membrane, starts to enclose a portion of the cytoplasm.
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.
cellular response to interferon-beta 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 interferon-beta stimulus. Interferon-beta is a type I interferon.
cellular response to organic cyclic compound 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 organic cyclic compound stimulus.
defense response to virus Reactions triggered in response to the presence of a virus that act to protect the cell or organism.
innate immune response Innate immune responses are defense responses mediated by germline encoded components that directly recognize components of potential pathogens.
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 DNA-binding transcription factor activity Any process that activates or increases the frequency, rate or extent of activity of a transcription factor, any factor involved in the initiation or regulation of transcription.
positive regulation of interferon-beta production Any process that activates or increases the frequency, rate, or extent of interferon-beta production.
positive regulation of macroautophagy Any process, such as recognition of nutrient depletion, that activates or increases the rate of macroautophagy to bring cytosolic macromolecules to the vacuole/lysosome for degradation.
positive regulation of protein binding Any process that activates or increases the frequency, rate or extent of protein binding.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
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.
positive regulation of type I interferon-mediated signaling pathway Any process that increases the rate, frequency or extent of a type I interferon-mediated signaling pathway.
protein complex oligomerization The process of creating protein oligomers, compounds composed of a small number, usually between three and ten, of component monomers; protein oligomers may be composed of different or identical monomers. Oligomers may be formed by the polymerization of a number of monomers or the depolymerization of a large protein polymer.
regulation of gene expression Any process that modulates the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
regulation of inflammatory response Any process that modulates the frequency, rate or extent of the inflammatory response, the immediate defensive reaction (by vertebrate tissue) to infection or injury caused by chemical or physical agents.
reticulophagy The selective autohagy process in which parts of the endoplasmic reticulum are loaded into autophagosomes, delivered to the vacuole, and degraded in response to changing cellular conditions.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q2KI99 STING1 Stimulator of interferon genes protein Bos taurus (Bovine) SS
E1C7U0 STING1 Stimulator of interferon genes protein Gallus gallus (Chicken) SS
Q86WV6 STING1 Stimulator of interferon genes protein Homo sapiens (Human) EV
B8XX90 STING1 Stimulator of interferon genes protein Sus scrofa (Pig) SS
F1M391 Sting1 Stimulator of interferon genes protein Rattus norvegicus (Rat) SS
10 20 30 40 50 60
MPYSNLHPAI PRPRGHRSKY VALIFLVASL MILWVAKDPP NHTLKYLALH LASHELGLLL
70 80 90 100 110 120
KNLCCLAEEL CHVQSRYQGS YWKAVRACLG CPIHCMAMIL LSSYFYFLQN TADIYLSWMF
130 140 150 160 170 180
GLLVLYKSLS MLLGLQSLTP AEVSAVCEEK KLNVAHGLAW SYYIGYLRLI LPGLQARIRM
190 200 210 220 230 240
FNQLHNNMLS GAGSRRLYIL FPLDCGVPDN LSVVDPNIRF RDMLPQQNID RAGIKNRVYS
250 260 270 280 290 300
NSVYEILENG QPAGVCILEY ATPLQTLFAM SQDAKAGFSR EDRLEQAKLF CRTLEEILED
310 320 330 340 350 360
VPESRNNCRL IVYQEPTDGN SFSLSQEVLR HIRQEEKEEV TMNAPMTSVA PPPSVLSQEP
370
RLLISGMDQP LPLRTDLI