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, 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)

Target domain

159-342 (Cytosolic c-di-GMP binding domain)

Relief mechanism

Ligand binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

6 structures for E1C7U0

Entry ID Method Resolution Chain Position Source
6NT6 EM 400 A A/B 1-379 PDB
6NT7 EM 400 A A/B 1-379 PDB
6NT8 EM 650 A A/B/D/E 1-379 PDB
6NT9 EM 330 A C/D 1-379 PDB
8IK0 EM 330 A A/B/C/D/E/F/G/H 1-342 PDB
AF-E1C7U0-F1 Predicted AlphaFoldDB

19 variants for E1C7U0

Variant ID(s) Position Change Description Diseaes Association Provenance
rs738348950 25 R>Q No Ensembl
rs736682813 38 V>G No Ensembl
rs1059026384 45 P>S No Ensembl
rs734866541 50 I>T No Ensembl
rs741027654 52 S>R No Ensembl
rs741441648 83 H>P No Ensembl
rs1058396939 98 R>C No Ensembl
rs313275578 100 Y>H No Ensembl
rs733624988 115 P>L No Ensembl
rs1059431429 123 R>H No Ensembl
rs740652568 124 L>P No Ensembl
rs734095987 125 A>P No Ensembl
rs733393697 127 T>P No Ensembl
rs736757845 128 L>P No Ensembl
rs739213533 150 S>A No Ensembl
rs15676079 187 L>I No Ensembl
rs15676075 246 K>R No Ensembl
rs316454179 357 S>G No Ensembl
rs736224875 377 D>A No Ensembl

No associated diseases with E1C7U0

3 regional properties for E1C7U0

Type Name Position InterPro Accession
domain Transcription factor, MADS-box 1 - 61 IPR002100
domain Transcription factor, K-box 82 - 174 IPR002487
domain MADS MEF2-like 2 - 80 IPR033896

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
  • 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
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

12 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.
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.
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.

5 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.

15 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.
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.
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
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
MPQDPSTRSS PARLLIPEPR AGRARHAACV LLAVCFVVLF LSGEPLAPII RSVCTQLAAL
70 80 90 100 110 120
QLGVLLKGCC CLAEEIFHLH SRHHGSLWQV LCSCFPPRWY LALLLVGGSA YLDPPEDNGH
130 140 150 160 170 180
SPRLALTLSC LCQLLVLALG LQKLSAVEVS ELTESSKKNV AHGLAWSYYI GYLKVVLPRL
190 200 210 220 230 240
KECMEELSRT NPMLRAHRDT WKLHILVPLG CDIWDDLEKA DSNIQYLADL PETILTRAGI
250 260 270 280 290 300
KRRVYKHSLY VIRDKDNKLR PCVLEFASPL QTLCAMSQDD CAAFSREQRL EQARLFYRSL
310 320 330 340 350 360
RDILGSSKEC AGLYRLIAYE EPAEPESHFL SGLILWHLQQ QQREEYMVQE ELPLGTSSVE
370
LSLQVSSSDL PQPLRSDCP