STING_RAT
ID STING_RAT Reviewed; 379 AA.
AC F1M391;
DT 05-OCT-2016, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2013, sequence version 2.
DT 03-AUG-2022, entry version 79.
DE RecName: Full=Stimulator of interferon genes protein {ECO:0000303|PubMed:26669264};
DE Short=rSTING {ECO:0000303|PubMed:26669264};
DE AltName: Full=Transmembrane protein 173 {ECO:0000305};
GN Name=Sting1 {ECO:0000250|UniProtKB:Q86WV6};
GN Synonyms=Sting {ECO:0000303|PubMed:26669264},
GN Tmem173 {ECO:0000312|RGD:1562552};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, X-RAY CRYSTALLOGRAPHY (1.55 ANGSTROMS) OF 140-337 OF APOPROTEIN
RP AND IN COMPLEX WITH 2'-3' LINKED CGAMP, SUBUNIT, MUTAGENESIS OF PRO-141;
RP GLU-143; VAL-144; SER-145; GLU-149; GLU-150; LYS-151 AND THR-230, AND
RP ACTIVITY REGULATION.
RX PubMed=26669264; DOI=10.1038/srep18035;
RA Zhang H., Han M.J., Tao J., Ye Z.Y., Du X.X., Deng M.J., Zhang X.Y.,
RA Li L.F., Jiang Z.F., Su X.D.;
RT "Rat and human STINGs profile similarly towards anticancer/antiviral
RT compounds.";
RL Sci. Rep. 5:18035-18035(2015).
CC -!- FUNCTION: Facilitator of innate immune signaling that acts as a sensor
CC of cytosolic DNA from bacteria and viruses and promotes the production
CC of type I interferon (IFN-alpha and IFN-beta) (PubMed:26669264). Innate
CC immune response is triggered in response to non-CpG double-stranded DNA
CC from viruses and bacteria delivered to the cytoplasm (By similarity).
CC Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-
CC GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic
CC GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus
CC in the cytosol (By similarity). Upon binding of c-di-GMP or cGAMP,
CC STING1 oligomerizes, translocates from the endoplasmic reticulum and is
CC phosphorylated by TBK1 on the pLxIS motif, leading to recruitment and
CC subsequent activation of the transcription factor IRF3 to induce
CC expression of type I interferon and exert a potent anti-viral state
CC (PubMed:26669264). In addition to promote the production of type I
CC interferons, plays a direct role in autophagy (By similarity).
CC Following cGAMP-binding, STING1 buds from the endoplasmic reticulum
CC into COPII vesicles, which then form the endoplasmic reticulum-Golgi
CC intermediate compartment (ERGIC) (By similarity). The ERGIC serves as
CC the membrane source for WIPI2 recruitment and LC3 lipidation, leading
CC to formation of autophagosomes that target cytosolic DNA or DNA viruses
CC for degradation by the lysosome (By similarity). The autophagy- and
CC interferon-inducing activities can be uncoupled and autophagy induction
CC is independent of TBK1 phosphorylation (By similarity). Autophagy is
CC also triggered upon infection by bacteria: following c-di-GMP-binding,
CC which is produced by live Gram-positive bacteria, promotes
CC reticulophagy (By similarity). Exhibits 2',3' phosphodiester linkage-
CC specific ligand recognition: can bind both 2'-3' linked cGAMP (2'-3'-
CC cGAMP) and 3'-3' linked cGAMP but is preferentially activated by 2'-3'
CC linked cGAMP (PubMed:26669264). The preference for 2'-3'-cGAMP,
CC compared to other linkage isomers is probably due to the ligand itself,
CC whichs adopts an organized free-ligand conformation that resembles the
CC STING1-bound conformation and pays low energy costs in changing into
CC the active conformation (By similarity). May be involved in translocon
CC function, the translocon possibly being able to influence the induction
CC of type I interferons (By similarity). May be involved in transduction
CC of apoptotic signals via its association with the major
CC histocompatibility complex class II (MHC-II) (By similarity).
CC {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000250|UniProtKB:Q86WV6,
CC ECO:0000269|PubMed:26669264}.
CC -!- ACTIVITY REGULATION: In contrast to mouse protein, not activated by
CC anticancer molecule 5,6-dimethylxanthenone 4-acetic acid (DMXAA).
CC {ECO:0000269|PubMed:26669264}.
CC -!- SUBUNIT: Homodimer; forms a homodimer in absence of cyclic nucleotide
CC (c-di-GMP or cGAMP); 'Lys-63'-linked ubiquitination at Lys-151 is
CC required for homodimerization (PubMed:26669264). Homotetramer; in
CC presence of cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and
CC higher-order oligomers through side-by-side packing (By similarity).
CC Interacts (when phosphorylated) with IRF3; following activation and
CC phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By
CC similarity). Interacts with DDX58/RIG-I, MAVS and SSR2 (By similarity).
CC Interacts with RNF5 and TRIM56 (By similarity). Interacts with TBK1;
CC when homodimer, leading to subsequent production of IFN-beta (By
CC similarity). Interacts with IFIT1 and IFIT2 (By similarity). Interacts
CC with TRIM29; this interaction induces STING1 ubiquitination and
CC subsequent degradation (By similarity). Associates with the MHC-II
CC complex (By similarity).Interacts with STEEP; the interaction is
CC increased upon cGAMP binding and promotes STING1 translocation to COPII
CC vesicles (By similarity). Interacts with SEC24A, SEC24B and SEC24C;
CC promoting translocation to COPII vesicles (By similarity). Interacts
CC (when ubiquitinated) with SQSTM1; leading to relocalization to
CC autophagosomes (By similarity). Interacts with SURF4 (By similarity).
CC Interacts with HNRNPA2B1 (By similarity). Interacts with ZDHHC1; ZDHHC1
CC constitutively interacts with STING1 and in presence of DNA viruses
CC activates it by promoting its cGAMP-induced oligomerization and the
CC recruitment of downstream signaling components (By similarity).
CC Interacts with ZDHHC11; in presence of DNA viruses promotes the
CC recruitment of IRF3 to STING1 (By similarity). Interacts with TOMM70
CC (By similarity). {ECO:0000250|UniProtKB:Q3TBT3,
CC ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:26669264}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q86WV6, ECO:0000255}. Cytoplasm, perinuclear
CC region {ECO:0000250|UniProtKB:Q86WV6}. Endoplasmic reticulum-Golgi
CC intermediate compartment membrane {ECO:0000250|UniProtKB:Q86WV6};
CC Multi-pass membrane protein {ECO:0000255}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasmic vesicle, autophagosome membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein
CC {ECO:0000255}. Mitochondrion outer membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000250|UniProtKB:Q3TBT3}; Multi-pass
CC membrane protein {ECO:0000255}. Note=In response to double-stranded DNA
CC stimulation, translocates from the endoplasmic reticulum through the
CC endoplasmic reticulum-Golgi intermediate compartment and Golgi to post-
CC Golgi vesicles, where the kinase TBK1 is recruited. Upon cGAMP-binding,
CC translocates to the endoplasmic reticulum-Golgi intermediate
CC compartment (ERGIC) in a process that is dependent on COPII vesicles;
CC STING1-containing ERGIC serves as a membrane source for LC3 lipidation,
CC which is a key step in autophagosome biogenesis.
CC {ECO:0000250|UniProtKB:Q86WV6}.
CC -!- DOMAIN: In absence of cGAMP, the transmembrane and cytoplasmic regions
CC interact to form an integrated, domain-swapped dimeric assembly (By
CC similarity). In absence of cyclic nucleotide (c-di-GMP or cGAMP), the
CC protein is autoinhibited by an intramolecular interaction between the
CC cyclic dinucleotide-binding domain (CBD) and the C-terminal tail (CTT)
CC (By similarity). Following cGAMP-binding, the cyclic dinucleotide-
CC binding domain (CBD) is closed, leading to a 180 degrees rotation of
CC the CBD domain relative to the transmembrane domain. This rotation is
CC coupled to a conformational change in a loop on the side of the CBD
CC dimer, which leads to the formation of the STING1 tetramer and higher-
CC order oligomers through side-by-side packing (By similarity). The N-
CC terminal part of the CBD region was initially though to contain a fifth
CC transmembrane region (TM5) but is part of the folded, soluble CBD (By
CC similarity). {ECO:0000250|UniProtKB:E1C7U0,
CC ECO:0000250|UniProtKB:Q86WV6}.
CC -!- DOMAIN: The pLxIS motif constitutes an IRF3-binding motif: following
CC phosphorylation by TBK1, the phosphorylated pLxIS motif of STING1
CC recruits IRF3. IRF3 is then phosphorylated and activated by TBK1 to
CC induce type-I interferons and other cytokines.
CC {ECO:0000250|UniProtKB:Q86WV6}.
CC -!- DOMAIN: The N-terminal domain interacts with glycerophospholipids and
CC phospholipids. {ECO:0000250|UniProtKB:Q86WV6}.
CC -!- PTM: Phosphorylation by TBK1 leads to activation and production of IFN-
CC beta. Following cyclic nucleotide (c-di-GMP or cGAMP)-binding,
CC activation and translocation from the endoplasmic reticulum, STING1 is
CC phosphorylated by TBK1 at Ser-366 in the pLxIS motif. The
CC phosphorylated pLxIS motif constitutes an IRF3-binding motif, leading
CC to recruitment of the transcription factor IRF3 to induce type-I
CC interferons and other cytokines (By similarity). Phosphorylated on
CC tyrosine residues upon MHC-II aggregation (By similarity).
CC Dephosphorylation by PPP6C leads to inactivation and decreased
CC production of IFN-beta (By similarity). Phosphorylation at Ser-358 is
CC also required to activate IRF3 (By similarity).
CC {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000250|UniProtKB:Q86WV6}.
CC -!- PTM: Ubiquitinated (By similarity). Ubiquitinated via 'Lys-63'-linked
CC ubiquitin chains in response to double-stranded DNA treatment, leading
CC to relocalization to autophagosomes and subsequent degradation; this
CC process is dependent on SQSTM1 (By similarity). 'Lys-63'-linked
CC ubiquitination mediated by TRIM56 at Lys-151 promotes homodimerization
CC and recruitment of the antiviral kinase TBK1 and subsequent production
CC of IFN-beta. 'Lys-48'-linked polyubiquitination at Lys-151 occurring
CC after viral infection is mediated by RNF5 and leads to proteasomal
CC degradation. 'Lys-11'-linked polyubiquitination at Lys-151 by RNF26
CC leads to stabilize STING1: it protects STING1 from RNF5-mediated 'Lys-
CC 48'-linked polyubiquitination (By similarity).
CC {ECO:0000250|UniProtKB:Q3TBT3, ECO:0000250|UniProtKB:Q86WV6}.
CC -!- PTM: Sumoylated at Lys-338 by TRIM38 during the early phase of viral
CC infection, promoting its stability by preventing its relocalization to
CC autophagosomes and subsequent degradation. Desumoylated by SENP2 during
CC the late phase of viral infection. {ECO:0000250|UniProtKB:Q3TBT3}.
CC -!- PTM: Palmitoylation takes place in the Golgi apparatus and creates a
CC platform for the recruitment of TBK1. {ECO:0000250|UniProtKB:Q3TBT3}.
CC -!- SIMILARITY: Belongs to the STING family. {ECO:0000305}.
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DR EMBL; AABR07072583; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC135285; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH473974; EDL76277.1; -; Genomic_DNA.
DR RefSeq; NP_001102592.1; NM_001109122.1.
DR PDB; 5GRM; X-ray; 1.55 A; A/B=155-341.
DR PDB; 5GS5; X-ray; 1.84 A; A/B/C/D=140-337.
DR PDBsum; 5GRM; -.
DR PDBsum; 5GS5; -.
DR AlphaFoldDB; F1M391; -.
DR SMR; F1M391; -.
DR STRING; 10116.ENSRNOP00000063348; -.
DR PhosphoSitePlus; F1M391; -.
DR PaxDb; F1M391; -.
DR GeneID; 498840; -.
DR KEGG; rno:498840; -.
DR CTD; 340061; -.
DR RGD; 1562552; Tmem173.
DR VEuPathDB; HostDB:ENSRNOG00000042137; -.
DR eggNOG; ENOG502R15M; Eukaryota.
DR HOGENOM; CLU_062449_0_0_1; -.
DR InParanoid; F1M391; -.
DR OMA; FAMSQYG; -.
DR OrthoDB; 865174at2759; -.
DR TreeFam; TF324444; -.
DR Reactome; R-RNO-1834941; STING mediated induction of host immune responses.
DR Reactome; R-RNO-3134975; Regulation of innate immune responses to cytosolic DNA.
DR Reactome; R-RNO-3249367; STAT6-mediated induction of chemokines.
DR Reactome; R-RNO-3270619; IRF3-mediated induction of type I IFN.
DR Reactome; R-RNO-6798695; Neutrophil degranulation.
DR PRO; PR:F1M391; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Proteomes; UP000234681; Chromosome 18.
DR Bgee; ENSRNOG00000042137; Expressed in spleen and 20 other tissues.
DR GO; GO:0005776; C:autophagosome; ISO:RGD.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0000139; C:Golgi membrane; ISO:RGD.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:1990701; C:integral component of endoplasmic reticulum-Golgi intermediate compartment (ERGIC) membrane; ISO:RGD.
DR GO; GO:0005741; C:mitochondrial outer membrane; ISO:RGD.
DR GO; GO:0005654; C:nucleoplasm; IEA:Ensembl.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:RGD.
DR GO; GO:0005777; C:peroxisome; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1990231; C:STING complex; ISO:RGD.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IDA:UniProtKB.
DR GO; GO:0035438; F:cyclic-di-GMP binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:RGD.
DR GO; GO:0019901; F:protein kinase binding; ISO:RGD.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0002218; P:activation of innate immune response; ISO:RGD.
DR GO; GO:0000045; P:autophagosome assembly; ISS:UniProtKB.
DR GO; GO:0071360; P:cellular response to exogenous dsRNA; ISO:RGD.
DR GO; GO:0035458; P:cellular response to interferon-beta; ISO:RGD.
DR GO; GO:0071407; P:cellular response to organic cyclic compound; IDA:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0002230; P:positive regulation of defense response to virus by host; ISO:RGD.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0032092; P:positive regulation of protein binding; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IDA:UniProtKB.
DR GO; GO:0060340; P:positive regulation of type I interferon-mediated signaling pathway; ISO:RGD.
DR GO; GO:0051259; P:protein complex oligomerization; ISO:RGD.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:0050727; P:regulation of inflammatory response; ISO:RGD.
DR GO; GO:0061709; P:reticulophagy; ISS:UniProtKB.
DR CDD; cd12146; STING_C; 1.
DR Gene3D; 3.40.50.12100; -; 1.
DR InterPro; IPR029158; STING.
DR InterPro; IPR033952; STING_C.
DR InterPro; IPR038623; STING_C_sf.
DR PANTHER; PTHR34339; PTHR34339; 1.
DR Pfam; PF15009; TMEM173; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Cell membrane; Cytoplasm; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Golgi apparatus; Immunity; Innate immunity;
KW Isopeptide bond; Lipoprotein; Membrane; Mitochondrion;
KW Mitochondrion outer membrane; Nucleotide-binding; Palmitate;
KW Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT CHAIN 1..379
FT /note="Stimulator of interferon genes protein"
FT /id="PRO_0000437256"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 18..34
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT TOPO_DOM 35..44
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 45..69
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT TOPO_DOM 70..91
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 92..106
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT TOPO_DOM 107..116
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 117..134
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT TOPO_DOM 135..379
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..190
FT /note="Mediates interaction with ZDHHC1 and ZDHHC11"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT REGION 153..340
FT /note="Cyclic dinucleotide-binding domain (CBD)"
FT /evidence="ECO:0000269|PubMed:26669264"
FT REGION 340..379
FT /note="C-terminal tail (CTT)"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT MOTIF 363..366
FT /note="pLxIS motif"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 162..167
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000305|PubMed:26669264"
FT BINDING 166
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q3TBT3"
FT BINDING 238..241
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000305|PubMed:26669264"
FT BINDING 238..241
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q3TBT3"
FT BINDING 263
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000305|PubMed:26669264"
FT BINDING 263
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q3TBT3"
FT MOD_RES 358
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT MOD_RES 366
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT LIPID 88
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q3TBT3"
FT CROSSLNK 151
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q3TBT3"
FT CROSSLNK 338
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO)"
FT /evidence="ECO:0000250|UniProtKB:Q3TBT3"
FT MUTAGEN 141
FT /note="P->A: Abolishes response to 2'-3' linked cGAMP and
FT 3'-3' linked cGAMP and production of interferon IFNB1."
FT /evidence="ECO:0000269|PubMed:26669264"
FT MUTAGEN 143
FT /note="E->A: Abolishes response to 2'-3' linked cGAMP and
FT 3'-3' linked cGAMP and production of interferon IFNB1."
FT /evidence="ECO:0000269|PubMed:26669264"
FT MUTAGEN 144
FT /note="V->A: Decreases response to 2'-3' linked cGAMP and
FT 3'-3' linked cGAMP and production of interferon IFNB1."
FT /evidence="ECO:0000269|PubMed:26669264"
FT MUTAGEN 145
FT /note="S->A: Abolishes response to 2'-3' linked cGAMP and
FT 3'-3' linked cGAMP and production of interferon IFNB1."
FT /evidence="ECO:0000269|PubMed:26669264"
FT MUTAGEN 149
FT /note="E->A,R: Abolishes response to 2'-3' linked cGAMP and
FT 3'-3' linked cGAMP and production of interferon IFNB1."
FT /evidence="ECO:0000269|PubMed:26669264"
FT MUTAGEN 150
FT /note="E->A: Abolishes response to 2'-3' linked cGAMP and
FT 3'-3' linked cGAMP and production of interferon IFNB1."
FT /evidence="ECO:0000269|PubMed:26669264"
FT MUTAGEN 151
FT /note="K->R: Abolishes response to 2'-3' linked cGAMP and
FT 3'-3' linked cGAMP and production of interferon IFNB1."
FT /evidence="ECO:0000269|PubMed:26669264"
FT MUTAGEN 230
FT /note="T->I,L,M,V: No effect on response to 2'-3' linked
FT cGAMP and production of interferon IFNB1. Strongly
FT increases affinity for the synthetic compound 5,6-
FT dimethylxanthenone 4-acetic acid (DMXAA)."
FT /evidence="ECO:0000269|PubMed:26669264"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 168..171
FT /evidence="ECO:0007829|PDB:5GRM"
FT TURN 172..174
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 175..185
FT /evidence="ECO:0007829|PDB:5GRM"
FT TURN 186..188
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 193..195
FT /evidence="ECO:0007829|PDB:5GRM"
FT STRAND 196..203
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 212..214
FT /evidence="ECO:0007829|PDB:5GRM"
FT STRAND 219..224
FT /evidence="ECO:0007829|PDB:5GRM"
FT STRAND 228..232
FT /evidence="ECO:0007829|PDB:5GRM"
FT STRAND 235..240
FT /evidence="ECO:0007829|PDB:5GRM"
FT STRAND 243..249
FT /evidence="ECO:0007829|PDB:5GRM"
FT STRAND 252..261
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 264..273
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 275..277
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 281..299
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 304..306
FT /evidence="ECO:0007829|PDB:5GRM"
FT STRAND 309..314
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 316..318
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 325..334
FT /evidence="ECO:0007829|PDB:5GRM"
FT HELIX 336..339
FT /evidence="ECO:0007829|PDB:5GRM"
SQ SEQUENCE 379 AA; 42655 MW; 69AB884C9DA209EC CRC64;
MPYSNLHPSI PRPRSYRFKL AAFVLLVGSL MSLWMTGEPP SHTLHYLALH VASQQLGLLL
KKLCCLAEEL CHVQSRYQGS YWKAVRACVG SPICFMALIL LSFYFYCSLE NTSDLRLAWH
LGILVLSKSL SMTLDLQSLA PAEVSAVCEE KNFNVAHGLA WSYYIGYLKL ILPGLQARIR
MFNQLHNNML SGAGSRRLYI LFPLDCGVPD DLSVADPNIR FRDMLPQQNT DRAGVKNRAY
SNSVYELLEN GQPAGACILE YATPLQTLFA MSQDGKAGFS REDRLEQAKL FCRTLEEILA
DVPESRNHCR LIVYQESEEG NSFSLSQEVL RHIRQEEKEE VTMSGPPTSV APRPSLLSQE
PRLLISGMEQ PLPLRTDLI
