Q2KI99

SS
Gene name
STING1
Protein name
Stimulator of interferon genes protein
Names
STING, Transmembrane protein 173
Species
Bos taurus (Bovine)
KEGG Pathway
bta:533661
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

154-337 (Cytosolic c-di-GMP binding domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

References

Autoinhibited structure

Activated structure

1 structures for Q2KI99

Entry ID Method Resolution Chain Position Source
AF-Q2KI99-F1 Predicted AlphaFoldDB

77 variants for Q2KI99

Variant ID(s) Position Change Description Diseaes Association Provenance
rs434319677 3 H>L No Ensembl
rs434319677 3 H>P No Ensembl
rs467116756 3 H>Q No Ensembl
rs447056038 4 S>A No Ensembl
rs481765811 5 S>C No Ensembl
rs467984374 5 S>R No Ensembl
rs451062497 8 P>S No Ensembl
rs445275021 10 I>M No Ensembl
rs459007312 10 I>S No Ensembl
rs482409037 10 I>V No Ensembl
rs479765406 14 R>M No Ensembl
rs459641099 14 R>S No Ensembl
rs442738592 15 G>C No Ensembl
rs463555315 18 A>T No Ensembl
rs443393478 20 K>M No Ensembl
rs471333875 21 A>S No Ensembl
rs451264538 24 V>F No Ensembl
rs434350562 26 L>V No Ensembl
rs472050353 29 C>G No Ensembl
rs455315460 33 L>F No Ensembl
rs468069892 38 E>* No Ensembl
rs451013757 38 E>A No Ensembl
rs437354419 42 Y>S No Ensembl
rs445313667 47 L>F No Ensembl
rs465471198 47 L>M No Ensembl
rs451643109 49 L>I No Ensembl
rs449254328 54 Q>L No Ensembl
rs463639429 60 I>N No Ensembl
rs443413237 61 K>N No Ensembl
rs471369642 68 E>K No Ensembl
rs457776461 69 E>D No Ensembl
rs440907209 70 L>Q No Ensembl
rs472087269 72 H>P No Ensembl
rs455273248 73 V>F No Ensembl
rs801374840 86 R>W No Ensembl
rs480617132 139 L>V No Ensembl
rs470078737 140 A>S No Ensembl
rs477897853 141 P>A No Ensembl
rs457813325 157 H>R No Ensembl
rs440945702 162 S>* No Ensembl
rs478531582 165 I>V No Ensembl
rs433906802 176 P>A No Ensembl
rs468425829 187 N>K No Ensembl
rs520476700 201 L>I No Ensembl
rs448293302 202 F>L No Ensembl
rs437752266 205 D>H No Ensembl
rs469081634 247 L>F No Ensembl
rs469081634 247 L>V No Ensembl
rs445716492 249 E>* No Ensembl
rs477096221 249 E>G No Ensembl
rs460168453 250 N>K No Ensembl
rs481556840 263 T>P No Ensembl
rs461341897 272 S>P No Ensembl
rs444417140 277 A>T No Ensembl
rs452382673 284 R>P No Ensembl
rs473229399 286 E>G No Ensembl
rs436116660 287 Q>* No Ensembl
rs473902954 288 A>G No Ensembl
rs456902714 308 N>Y No Ensembl
rs436727997 312 I>S No Ensembl
rs449172952 317 P>T No Ensembl
rs480351112 325 L>W No Ensembl
rs449800604 335 Q>* No Ensembl
rs477758776 336 E>K No Ensembl
rs447379082 341 T>S No Ensembl
rs461782305 342 M>I No Ensembl
rs439835023 343 G>C No Ensembl
rs441562968 344 S>R No Ensembl
rs474510534 348 S>* No Ensembl
rs464015420 349 V>L No Ensembl
rs472037752 351 P>H No Ensembl
rs443847049 351 P>T No Ensembl
rs434911974 357 S>Y No Ensembl
rs472658432 360 P>T No Ensembl
rs435522271 363 L>R No Ensembl
rs469911580 367 L>M No Ensembl
rs449939309 377 V>F No Ensembl

No associated diseases with Q2KI99

4 regional properties for Q2KI99

Type Name Position InterPro Accession
ptm P-type ATPase, phosphorylation site 438 - 444 IPR018303
domain P-type ATPase, C-terminal 1082 - 1327 IPR032630
domain P-type ATPase, N-terminal 68 - 123 IPR032631
domain P-type ATPase, haloacid dehalogenase domain 419 - 1105 IPR044492

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
  • 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
  • Localizes in the lysosome membrane in a TMEM203-dependent manner
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

15 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 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.

6 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.
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.

17 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.
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 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
E1C7U0 STING1 Stimulator of interferon genes protein Gallus gallus (Chicken) SS
Q86WV6 STING1 Stimulator of interferon genes protein Homo sapiens (Human) EV
Q3TBT3 Sting1 Stimulator of interferon genes protein Mus musculus (Mouse) SS
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
MPHSSLHPSI PQPRGLRAQK AALVLLSACL VALWGLGEPP DYTLKWLVLH LASQQMGLLI
70 80 90 100 110 120
KGICSLAEEL CHVHSRYHGS YWRAVRACLC SSMRCGALLL LSCYFYCSLP NMADLPFTWM
130 140 150 160 170 180
LALLGLSQAL NILLGLQGLA PAEVSAICEK RNFNVAHGLA WSYYIGYLRL ILPGLPARIQ
190 200 210 220 230 240
IYNQFHNNTL QGAGSHRLHI LFPLDCGVPD DLNVADPNIR FLHELPQQSA DRAGIKGRVY
250 260 270 280 290 300
TNSIYELLEN GQRAGVCVLE YATPLQTLFA MSQDGRAGFS REDRLEQAKL FCRTLEDILA
310 320 330 340 350 360
NAPESQNNCR LIVYQEPAEG SSFSLSQEIL QHLRQEEREV TMGSTETSVM PGSSVLSQEP
370
ELLISGLEKP LPLRSDVF