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Entry version 117 (08 May 2019)
Sequence version 2 (25 Nov 2008)
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Protein

Stimulator of interferon genes protein

Gene

Tmem173

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the ‘correct annotation’ for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the ‘protein existence’ evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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:18818105, PubMed:19433799, PubMed:19776740, PubMed:26229117, PubMed:26669264). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:26229117, PubMed:26669264). 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:23722158, PubMed:23258412, PubMed:23519410, PubMed:23910378). Upon binding of c-di-GMP or cGAMP, TMEM173/STING 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:25636800). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238). Following cGAMP-binding, TMEM173/STING buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By similarity). 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 (By similarity). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (By similarity). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (PubMed:29056340). 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). 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 TMEM173/STING-bound conformation and pays low energy costs in changing into the active conformation (By similarity). May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (By similarity). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (PubMed:18559423).By similarity15 Publications

Miscellaneous

Was named MPYS because the protein sequence begins by Met-Pro-Tyr-Ser residues.1 Publication

<p>This subsection of the ‘Function’ section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by anticancer drug 5,6-dimethylxanthenone 4-acetic acid (DMXAA).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Function’ section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei2375,6-dimethylxanthenone 4-acetic acid (DMXAA) activatorCombined sources1 Publication1
Binding sitei2625,6-dimethylxanthenone 4-acetic acid (DMXAA) activatorCombined sources1 Publication1
Binding sitei262Cyclic dinucleotideCombined sources2 Publications1

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Biological processAutophagy, Immunity, Innate immunity
LigandNucleotide-binding

Enzyme and pathway databases

Reactome - a knowledgebase of biological pathways and processes

More...
Reactomei
R-MMU-1834941 STING mediated induction of host immune responses
R-MMU-3134975 Regulation of innate immune responses to cytosolic DNA
R-MMU-3249367 STAT6-mediated induction of chemokines
R-MMU-3270619 IRF3-mediated induction of type I IFN
R-MMU-6798695 Neutrophil degranulation

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Stimulator of interferon genes protein2 Publications
Short name:
mSTING3 Publications
Alternative name(s):
Endoplasmic reticulum interferon stimulator1 Publication
Short name:
ERIS1 Publication
Mediator of IRF3 activation1 Publication
Short name:
MMITA1 Publication
Transmembrane protein 173
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: ‘Name’, ‘Synonyms’, ‘Ordered locus names’ and ‘ORF names’.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:Tmem173Imported
Synonyms:Eris1 Publication, Mita1 Publication, Mpys1 Publication, Sting2 Publications
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiMus musculus (Mouse)
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the ‘taxonomic identifier’ or ‘taxid’.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri10090 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
<p>This subsection of the <a href="http://www.uniprot.org/help/names_and_taxonomy_section">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000000589 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes_manual">proteome</a> can consist of several components. <br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 18

Organism-specific databases

Mouse genome database (MGD) from Mouse Genome Informatics (MGI)

More...
MGIi
MGI:1919762 Tmem173

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini1 – 17CytoplasmicBy similarityAdd BLAST17
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular_location_section">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei18 – 34Helical; Name=1By similarityAdd BLAST17
Topological domaini35 – 44LumenalBy similarity10
Transmembranei45 – 69Helical; Name=2By similarityAdd BLAST25
Topological domaini70 – 91CytoplasmicBy similarityAdd BLAST22
Transmembranei92 – 106Helical; Name=3By similarityAdd BLAST15
Topological domaini107 – 115LumenalBy similarity9
Transmembranei116 – 133Helical; Name=4By similarityAdd BLAST18
Topological domaini134 – 378CytoplasmicBy similarityAdd BLAST245

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoplasmic vesicle, Endoplasmic reticulum, Membrane, Mitochondrion, Mitochondrion outer membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the ‘Pathology and Biotech’ section describes the in vivo effects caused by ablation of the gene (or one or more transcripts) coding for the protein described in the entry. This includes gene knockout and knockdown, provided experiments have been performed in the context of a whole organism or a specific tissue, and not at the single-cell level.<p><a href='/help/disruption_phenotype' target='_top'>More...</a></p>Disruption phenotypei

Defects in innate immunity. Death within 7 days of herpes simplex virus 1 (HSV-1) infection. In addition, mice show a remarkable reduction in cytotoxic T-cell responses after plasmid DNA vaccination. Cells fail to induce type I interferon production in response to dsDNA and infection with herpes simplex virus 1 (HSV-1) and L.monocytogenes that deliver DNA to the host cytosol.1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology_and_biotech_section">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi161S → A: Decrease in cGAMP-binding. 1 Publication1
Mutagenesisi229I → A, G or T: Strongly decreases affinity for the synthetic compound 5,6-dimethylxanthenone 4-acetic acid (DMXAA). 1 Publication1
Mutagenesisi239Y → S: Strong decrease in cGAMP-binding. 1 Publication1
Mutagenesisi241N → A: Strong decrease in cGAMP-binding. 1 Publication1
Mutagenesisi365S → A: Abolished ability to activate IRF3. 1 Publication1

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘PTM / Processing’ section describes the extent of a polypeptide chain in the mature protein following processing.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00002711171 – 378Stimulator of interferon genes proteinAdd BLAST378

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki150Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
<p>This subsection of the ‘PTM / Processing’ section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei357Phosphoserine; by TBK1By similarity1
Modified residuei365Phosphoserine; by TBK11 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm_processing_section">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

Phosphorylation by TBK1 leads to activation and production of IFN-beta (By similarity). Following cyclic nucleotide (c-di-GMP or cGAMP)-binding, activation and translocation from the endoplasmic reticulum, TMEM173/STING is phosphorylated by TBK1 at Ser-365 in the pLxIS motif. The phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading to recruitment of the transcription factor IRF3 to induce type-I interferons and other cytokines (By similarity). Phosphorylated on tyrosine residues upon MHC-II aggregation (PubMed:18559423).By similarity1 Publication
Ubiquitinated (PubMed:29496741). Ubiquitinated via 'Lys-63'-linked ubiquitin chains in response to double-stranded DNA treatment, leading to relocalization to autophagosomes and subsequent degradation; this process is dependent on SQSTM1 (PubMed:29496741). 'Lys-63'-linked ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization and recruitment of the antiviral kinase TBK1 and subsequent production of IFN-beta (By similarity). 'Lys-48'-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation (By similarity). 'Lys-11'-linked polyubiquitination at Lys-150 by RNF26 leads to stabilize TMEM173/STING: it protects TMEM173/STING from RNF5-mediated 'Lys-48'-linked polyubiquitination (By similarity).By similarity1 Publication

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

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EPDi
Q3TBT3

MaxQB - The MaxQuant DataBase

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MaxQBi
Q3TBT3

PaxDb, a database of protein abundance averages across all three domains of life

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PaxDbi
Q3TBT3

PeptideAtlas

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PeptideAtlasi
Q3TBT3

PRoteomics IDEntifications database

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PRIDEi
Q3TBT3

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

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iPTMneti
Q3TBT3

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

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PhosphoSitePlusi
Q3TBT3

SwissPalm database of S-palmitoylation events

More...
SwissPalmi
Q3TBT3

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the ‘Expression’ section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified ‘at protein level’. <br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Present in spleen and thymus tissue. Also present in dendritic cells (at protein level).1 Publication

<p>This subsection of the ‘Expression’ section provides information on the expression of the gene product at various stages of a cell, tissue or organism development. By default, the information is derived from experiments at the mRNA level, unless specified ‘at the protein level’.<p><a href='/help/developmental_stage' target='_top'>More...</a></p>Developmental stagei

Expressed throughout the B-cell lineage prior to the plasma cell stage but occurs at highest levels in mature B-cells. Highly expressed in cells representing mature stages of B-cells but weakly expressed in pre-B cells, immature B-cells, and memory B-cell stages. Not detected in plasma cells.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

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Bgeei
ENSMUSG00000024349 Expressed in 190 organ(s), highest expression level in mesenteric lymph node

ExpressionAtlas, Differential and Baseline Expression

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ExpressionAtlasi
Q3TBT3 baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

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Genevisiblei
Q3TBT3 MM

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction_section">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function_section">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Homodimer; forms a homodimer in absence of cyclic nucleotide (c-di-GMP or cGAMP); 'Lys-63'-linked ubiquitination at Lys-150 is required for homodimerization (PubMed:18559423). Homotetramer; in presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order oligomers through side-by-side packing (By similarity). Interacts (when phosphorylated) with IRF3; following activation and phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By similarity). Interacts with DDX58/RIG-I, MAVS and SSR2 (By similarity). Interacts with RNF5 and TRIM56 (By similarity). Interacts with TBK1; when homodimer, leading to subsequent production of IFN-beta (By similarity). Interacts with IFIT1 and IFIT2 (By similarity). Interacts with TRIM29; this interaction induces TMEM173/STING ubiquitination and subsequent degradation (By similarity). Associates with the MHC-II complex (PubMed:18559423). Interacts with SEC24C; promoting translocation to the COPII vesicles (By similarity). Interacts (when ubiquitinated) with SQSTM1; leading to relocalization to autophagosomes (PubMed:29496741).By similarity2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction_section%27">Interaction</a> section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="http://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated on a monthly basis. Each binary interaction is displayed on a separate line.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGrid)

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BioGridi
215410, 6 interactors

ComplexPortal: manually curated resource of macromolecular complexes

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ComplexPortali
CPX-2128 Sting complex

Database of interacting proteins

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DIPi
DIP-59959N

Protein interaction database and analysis system

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IntActi
Q3TBT3, 105 interactors

STRING: functional protein association networks

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STRINGi
10090.ENSMUSP00000111393

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

1378
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

Select the link destinations:

Protein Data Bank Europe

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PDBei

Protein Data Bank RCSB

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RCSB PDBi

Protein Data Bank Japan

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PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4JC5X-ray2.75A/B149-348[»]
4KBYX-ray2.36A/B138-344[»]
4KC0X-ray2.20A/B138-344[»]
4LOJX-ray1.77A/B154-340[»]
4LOKX-ray2.07A/B154-340[»]
4LOLX-ray2.43A/B154-340[»]
4YP1X-ray2.65A/B138-344[»]

SWISS-MODEL Repository - a database of annotated 3D protein structure models

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SMRi
Q3TBT3

Database of comparative protein structure models

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ModBasei
Search...

MobiDB: a database of protein disorder and mobility annotations

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MobiDBi
Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni152 – 339Cyclic dinucleotide-binding domain (CBD)1 PublicationAdd BLAST188
Regioni161 – 166Cyclic dinucleotide bindingCombined sources2 Publications6
Regioni237 – 240Cyclic dinucleotide bindingCombined sources2 Publications4
Regioni339 – 378C-terminal tail (CTT)By similarityAdd BLAST40

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Family and Domains’ section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi362 – 365pLxIS motifBy similarity4

<p>This subsection of the ‘Family and domains’ section provides general information on the biological role of a domain. The term ‘domain’ is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

In absence of cGAMP, the transmembrane and cytoplasmic regions interact to form an integrated, domain-swapped dimeric assembly (By similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the protein is autoinhibited by an intramolecular interaction between the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT) (By similarity). Following cGAMP-binding, the cyclic dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees rotation of the CBD domain relative to the transmembrane domain. This rotation is coupled to a conformational change in a loop on the side of the CBD dimer, which leads to the formation of the TMEM173/STING tetramer and higher-order oligomers through side-by-side packing (By similarity). The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (By similarity).By similarity
The pLxIS motif constitutes an IRF3-binding motif: following phosphorylation by TBK1, the phosphorylated pLxIS motif of TMEM173/STING recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to induce type-I interferons and other cytokines.By similarity

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the TMEM173 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

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eggNOGi
ENOG410IH2R Eukaryota
ENOG4111M85 LUCA

Ensembl GeneTree

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GeneTreei
ENSGT00390000008582

InParanoid: Eukaryotic Ortholog Groups

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InParanoidi
Q3TBT3

KEGG Orthology (KO)

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KOi
K12654

Identification of Orthologs from Complete Genome Data

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OMAi
YSNSVYE

Database of Orthologous Groups

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OrthoDBi
865174at2759

Database for complete collections of gene phylogenies

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PhylomeDBi
Q3TBT3

TreeFam database of animal gene trees

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TreeFami
TF324444

Family and domain databases

Conserved Domains Database

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CDDi
cd12146 STING_C, 1 hit

Gene3D Structural and Functional Annotation of Protein Families

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Gene3Di
3.40.50.12100, 1 hit

Integrated resource of protein families, domains and functional sites

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InterProi
View protein in InterPro
IPR029158 STING
IPR033952 STING_C
IPR038623 STING_C_sf

The PANTHER Classification System

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PANTHERi
PTHR34339 PTHR34339, 1 hit

Pfam protein domain database

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Pfami
View protein in Pfam
PF15009 TMEM173, 1 hit

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence_length">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>.<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (3)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences_section">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry describes 3 <p>This subsection of the ‘Sequence’ section lists the alternative protein sequences (isoforms) that can be generated from the same gene by a single or by the combination of up to four biological events (alternative promoter usage, alternative splicing, alternative initiation and ribosomal frameshifting). Additionally, this section gives relevant information on each alternative protein isoform.<p><a href='/help/alternative_products' target='_top'>More...</a></p> isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q3TBT3-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

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        10         20         30         40         50
MPYSNLHPAI PRPRGHRSKY VALIFLVASL MILWVAKDPP NHTLKYLALH
60 70 80 90 100
LASHELGLLL KNLCCLAEEL CHVQSRYQGS YWKAVRACLG CPIHCMAMIL
110 120 130 140 150
LSSYFYFLQN TADIYLSWMF GLLVLYKSLS MLLGLQSLTP AEVSAVCEEK
160 170 180 190 200
KLNVAHGLAW SYYIGYLRLI LPGLQARIRM FNQLHNNMLS GAGSRRLYIL
210 220 230 240 250
FPLDCGVPDN LSVVDPNIRF RDMLPQQNID RAGIKNRVYS NSVYEILENG
260 270 280 290 300
QPAGVCILEY ATPLQTLFAM SQDAKAGFSR EDRLEQAKLF CRTLEEILED
310 320 330 340 350
VPESRNNCRL IVYQEPTDGN SFSLSQEVLR HIRQEEKEEV TMNAPMTSVA
360 370
PPPSVLSQEP RLLISGMDQP LPLRTDLI
Length:378
Mass (Da):42,830
Last modified:November 25, 2008 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i656ED19097ACE4C8
GO
Isoform 2 (identifier: Q3TBT3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MIVESFGASGNPVGPCHFWSLYGVLLGVHWSVLHLGTFRGIRSAGLWLLM

Note: No experimental confirmation available.
Show »
Length:427
Mass (Da):48,151
Checksum:iCC362C808C035BE9
GO
Isoform 3 (identifier: Q3TBT3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-116: Missing.

Note: No experimental confirmation available.
Show »
Length:337
Mass (Da):38,036
Checksum:i9F25E302E7E0FCE8
GO

<p>This subsection of the ‘Sequence’ section reports difference(s) between the protein sequence shown in the UniProtKB entry and other available protein sequences derived from the same gene.<p><a href='/help/sequence_caution' target='_top'>More...</a></p>Sequence cautioni

The sequence AAH27757 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence BAC37010 differs from that shown. Reason: Erroneous termination at position 203. Translated as Leu.Curated
The sequence BAE42563 differs from that shown. Reason: Frameshift at position 377.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti11P → Q in BAE27042 (PubMed:16141072).Curated1
Sequence conflicti39P → S in BAB27972 (PubMed:16141072).Curated1
Sequence conflicti98M → V in BAE42563 (PubMed:16141072).Curated1
Sequence conflicti111T → N in BAC37010 (PubMed:16141072).Curated1
Sequence conflicti210N → D in BAE34068 (PubMed:16141072).Curated1
Sequence conflicti210N → D in BAE42310 (PubMed:16141072).Curated1
Sequence conflicti210N → D in BAE42224 (PubMed:16141072).Curated1
Sequence conflicti210N → D in BAE32222 (PubMed:16141072).Curated1
Sequence conflicti210N → D in BAE34517 (PubMed:16141072).Curated1
Sequence conflicti315E → K in BAC37010 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the ‘Sequence’ section describes the sequence of naturally occurring alternative protein isoform(s). The changes in the amino acid sequence may be due to alternative splicing, alternative promoter usage, alternative initiation, or ribosomal frameshifting.<p><a href='/help/var_seq' target='_top'>More...</a></p>Alternative sequenceiVSP_0222841M → MIVESFGASGNPVGPCHFWS LYGVLLGVHWSVLHLGTFRG IRSAGLWLLM in isoform 2. 1 Publication1
Alternative sequenceiVSP_02228576 – 116Missing in isoform 3. 1 PublicationAdd BLAST41

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

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EMBLi

GenBank nucleotide sequence database

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GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

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DDBJi
Links Updated
FJ222242 mRNA Translation: ACI46649.1
DQ910493 mRNA Translation: ABI78935.1
AK012006 mRNA Translation: BAB27972.1
AK077788 mRNA Translation: BAC37010.1 Sequence problems.
AK089405 mRNA Translation: BAC40870.1
AK146284 mRNA Translation: BAE27042.1
AK153868 mRNA Translation: BAE32222.1
AK157370 mRNA Translation: BAE34068.1
AK158458 mRNA Translation: BAE34517.1
AK170724 mRNA Translation: BAE41981.1
AK171065 mRNA Translation: BAE42224.1
AK171203 mRNA Translation: BAE42310.1
AK171612 mRNA Translation: BAE42563.1 Frameshift.
CH466557 Genomic DNA Translation: EDK97142.1
BC027757 mRNA Translation: AAH27757.1 Different initiation.
BC046640 mRNA Translation: AAH46640.1

The Consensus CDS (CCDS) project

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CCDSi
CCDS50253.1 [Q3TBT3-1]

NCBI Reference Sequences

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RefSeqi
NP_001276520.1, NM_001289591.1 [Q3TBT3-2]
NP_001276521.1, NM_001289592.1 [Q3TBT3-3]
NP_082537.1, NM_028261.1 [Q3TBT3-1]

Genome annotation databases

Ensembl eukaryotic genome annotation project

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Ensembli
ENSMUST00000115728; ENSMUSP00000111393; ENSMUSG00000024349 [Q3TBT3-1]

Database of genes from NCBI RefSeq genomes

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GeneIDi
72512

KEGG: Kyoto Encyclopedia of Genes and Genomes

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KEGGi
mmu:72512

UCSC genome browser

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UCSCi
uc008emt.3 mouse [Q3TBT3-1]
uc008emu.3 mouse [Q3TBT3-3]
uc008emv.3 mouse [Q3TBT3-2]

Keywords - Coding sequence diversityi

Alternative splicing

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FJ222242 mRNA Translation: ACI46649.1
DQ910493 mRNA Translation: ABI78935.1
AK012006 mRNA Translation: BAB27972.1
AK077788 mRNA Translation: BAC37010.1 Sequence problems.
AK089405 mRNA Translation: BAC40870.1
AK146284 mRNA Translation: BAE27042.1
AK153868 mRNA Translation: BAE32222.1
AK157370 mRNA Translation: BAE34068.1
AK158458 mRNA Translation: BAE34517.1
AK170724 mRNA Translation: BAE41981.1
AK171065 mRNA Translation: BAE42224.1
AK171203 mRNA Translation: BAE42310.1
AK171612 mRNA Translation: BAE42563.1 Frameshift.
CH466557 Genomic DNA Translation: EDK97142.1
BC027757 mRNA Translation: AAH27757.1 Different initiation.
BC046640 mRNA Translation: AAH46640.1
CCDSiCCDS50253.1 [Q3TBT3-1]
RefSeqiNP_001276520.1, NM_001289591.1 [Q3TBT3-2]
NP_001276521.1, NM_001289592.1 [Q3TBT3-3]
NP_082537.1, NM_028261.1 [Q3TBT3-1]

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4JC5X-ray2.75A/B149-348[»]
4KBYX-ray2.36A/B138-344[»]
4KC0X-ray2.20A/B138-344[»]
4LOJX-ray1.77A/B154-340[»]
4LOKX-ray2.07A/B154-340[»]
4LOLX-ray2.43A/B154-340[»]
4YP1X-ray2.65A/B138-344[»]
SMRiQ3TBT3
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi215410, 6 interactors
ComplexPortaliCPX-2128 Sting complex
DIPiDIP-59959N
IntActiQ3TBT3, 105 interactors
STRINGi10090.ENSMUSP00000111393

PTM databases

iPTMnetiQ3TBT3
PhosphoSitePlusiQ3TBT3
SwissPalmiQ3TBT3

Proteomic databases

EPDiQ3TBT3
MaxQBiQ3TBT3
PaxDbiQ3TBT3
PeptideAtlasiQ3TBT3
PRIDEiQ3TBT3

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000115728; ENSMUSP00000111393; ENSMUSG00000024349 [Q3TBT3-1]
GeneIDi72512
KEGGimmu:72512
UCSCiuc008emt.3 mouse [Q3TBT3-1]
uc008emu.3 mouse [Q3TBT3-3]
uc008emv.3 mouse [Q3TBT3-2]

Organism-specific databases

Comparative Toxicogenomics Database

More...
CTDi
340061
MGIiMGI:1919762 Tmem173

Phylogenomic databases

eggNOGiENOG410IH2R Eukaryota
ENOG4111M85 LUCA
GeneTreeiENSGT00390000008582
InParanoidiQ3TBT3
KOiK12654
OMAiYSNSVYE
OrthoDBi865174at2759
PhylomeDBiQ3TBT3
TreeFamiTF324444

Enzyme and pathway databases

ReactomeiR-MMU-1834941 STING mediated induction of host immune responses
R-MMU-3134975 Regulation of innate immune responses to cytosolic DNA
R-MMU-3249367 STAT6-mediated induction of chemokines
R-MMU-3270619 IRF3-mediated induction of type I IFN
R-MMU-6798695 Neutrophil degranulation

Miscellaneous databases

Protein Ontology

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PROi
PR:Q3TBT3

The Stanford Online Universal Resource for Clones and ESTs

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SOURCEi
Search...

Gene expression databases

BgeeiENSMUSG00000024349 Expressed in 190 organ(s), highest expression level in mesenteric lymph node
ExpressionAtlasiQ3TBT3 baseline and differential
GenevisibleiQ3TBT3 MM

Family and domain databases

CDDicd12146 STING_C, 1 hit
Gene3Di3.40.50.12100, 1 hit
InterProiView protein in InterPro
IPR029158 STING
IPR033952 STING_C
IPR038623 STING_C_sf
PANTHERiPTHR34339 PTHR34339, 1 hit
PfamiView protein in Pfam
PF15009 TMEM173, 1 hit

ProtoNet; Automatic hierarchical classification of proteins

More...
ProtoNeti
Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the ‘Entry information’ section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSTING_MOUSE
<p>This subsection of the ‘Entry information’ section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called ‘Primary (citable) accession number’.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: Q3TBT3
Secondary accession number(s): A7YGY9
, Q3TAV5, Q3TYP5, Q3TZY8, Q3UJW3, Q8C227, Q8C5Q3, Q8K393, Q9CZY7
<p>This subsection of the ‘Entry information’ section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification (‘Last modified’). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical_and_isoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 9, 2007
Last sequence update: November 25, 2008
Last modified: May 8, 2019
This is version 117 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the ‘Entry information’ section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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