STING_CHICK
ID STING_CHICK Reviewed; 379 AA.
AC E1C7U0; A0A1D5P7Q9;
DT 08-FEB-2011, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 2.
DT 03-AUG-2022, entry version 60.
DE RecName: Full=Stimulator of interferon genes protein {ECO:0000303|PubMed:30842659};
DE Short=STING {ECO:0000303|PubMed:30842659};
DE AltName: Full=Transmembrane protein 173 {ECO:0000250|UniProtKB:Q86WV6};
GN Name=STING1 {ECO:0000250|UniProtKB:Q86WV6};
GN Synonyms=STING {ECO:0000303|PubMed:30842659},
GN TMEM173 {ECO:0000250|UniProtKB:Q86WV6};
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [2]
RP STRUCTURE BY ELECTRON MICROSCOPY (4.0 ANGSTROMS) OF 1-379 IN COMPLEX WITH
RP CGAMP, AND DOMAIN.
RX PubMed=30842659; DOI=10.1038/s41586-019-0998-5;
RA Shang G., Zhang C., Chen Z.J., Bai X.C., Zhang X.;
RT "Cryo-EM structures of STING reveal its mechanism of activation by cyclic
RT GMP-AMP.";
RL Nature 567:389-393(2019).
RN [3]
RP STRUCTURE BY ELECTRON MICROSCOPY (3.3 ANGSTROMS) OF 1-379 IN COMPLEX WITH
RP CGAMP AND TBK1, AND PHOSPHORYLATION AT SER-366.
RX PubMed=30842653; DOI=10.1038/s41586-019-1000-2;
RA Zhang C., Shang G., Gui X., Zhang X., Bai X.C., Chen Z.J.;
RT "Structural basis of STING binding with and phosphorylation by TBK1.";
RL Nature 567:394-398(2019).
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) (By similarity). 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 (PubMed:30842659). Upon binding of c-di-GMP or cGAMP,
CC STING1 oligomerizes and is able to activate both NF-kappa-B and IRF3
CC transcription pathways to induce expression of type I interferon and
CC exert a potent anti-viral state (PubMed:30842659). In addition to
CC promote the production of type I interferons, plays a direct role in
CC autophagy (By similarity). Following cGAMP-binding, STING1 buds from
CC the endoplasmic reticulum into COPII vesicles, which then form the
CC endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (By
CC similarity). The ERGIC serves as the membrane source for LC3
CC lipidation, leading to formation of autophagosomes that target
CC cytosolic DNA or DNA viruses for degradation by the lysosome (By
CC similarity). The autophagy- and interferon-inducing activities can be
CC uncoupled and autophagy induction is independent of TBK1
CC phosphorylation (By similarity). Exhibits 2',3' phosphodiester linkage-
CC specific ligand recognition: can bind both 2'-3' linked cGAMP and 3'-3'
CC linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (By
CC similarity). {ECO:0000250|UniProtKB:Q86WV6,
CC ECO:0000269|PubMed:30842659}.
CC -!- SUBUNIT: Homodimer; forms a homodimer in absence of cyclic nucleotide
CC (c-di-GMP or cGAMP) (PubMed:30842659). Homotetramer; in presence of
CC cyclic nucleotide (c-di-GMP or cGAMP), forms tetramers and higher-order
CC oligomers through side-by-side packing (PubMed:30842659). Interacts
CC (when phosphorylated) with IRF3; following activation and
CC phosphorylation on the pLxIS motif by TBK1, recruits IRF3 (By
CC similarity). {ECO:0000250|UniProtKB:Q86WV6,
CC ECO:0000269|PubMed:30842659}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein
CC {ECO:0000255}. Cytoplasm, perinuclear region
CC {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}. Note=In response to double-stranded DNA stimulation,
CC translocates from the endoplasmic reticulum through the endoplasmic
CC reticulum-Golgi intermediate compartment and Golgi to post-Golgi
CC 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
CC (PubMed:30842659). In absence of cyclic nucleotide (c-di-GMP or cGAMP),
CC the protein is autoinhibited by an intramolecular interaction between
CC the cyclic dinucleotide-binding domain (CBD) and the C-terminal tail
CC (CTT) (By similarity). Following cGAMP-binding, the cyclic
CC dinucleotide-binding domain (CBD) is closed, leading to a 180 degrees
CC rotation of the CBD domain relative to the transmembrane domain
CC (PubMed:30842659). This rotation is coupled to a conformational change
CC in a loop on the side of the CBD dimer, which leads to the formation of
CC the STING1 tetramer and higher-order oligomers through side-by-side
CC packing (PubMed:30842659). The N-terminal part of the CBD region was
CC initially though to contain a fifth transmembrane region (TM5) but is
CC part of the folded, soluble CBD (By similarity).
CC {ECO:0000250|UniProtKB:Q86WV6, ECO:0000269|PubMed:30842659}.
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 (Probable). Following cyclic nucleotide (c-di-GMP or cGAMP)-
CC binding, activation and translocation from the endoplasmic reticulum,
CC STING1 is phosphorylated by TBK1 at Ser-366 in the pLxIS motif
CC (Probable). The phosphorylated pLxIS motif constitutes an IRF3-binding
CC motif, leading to recruitment of the transcription factor IRF3 to
CC induce type-I interferons and other cytokines (Probable).
CC {ECO:0000305|PubMed:30842653}.
CC -!- SIMILARITY: Belongs to the STING family. {ECO:0000305}.
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DR EMBL; AADN02063745; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AADN02063746; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AADN04000430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_001232171.2; XM_001232170.4.
DR RefSeq; XP_015149009.1; XM_015293523.1.
DR RefSeq; XP_015149010.1; XM_015293524.1.
DR RefSeq; XP_015149011.1; XM_015293525.1.
DR RefSeq; XP_015149012.1; XM_015293526.1.
DR RefSeq; XP_015149013.1; XM_015293527.1.
DR RefSeq; XP_015149014.1; XM_015293528.1.
DR RefSeq; XP_015149015.1; XM_015293529.1.
DR RefSeq; XP_015149016.1; XM_015293530.1.
DR PDB; 6NT6; EM; 4.00 A; A/B=1-379.
DR PDB; 6NT7; EM; 4.00 A; A/B=1-379.
DR PDB; 6NT8; EM; 6.50 A; A/B/D/E=1-379.
DR PDB; 6NT9; EM; 3.30 A; C/D=1-379.
DR PDBsum; 6NT6; -.
DR PDBsum; 6NT7; -.
DR PDBsum; 6NT8; -.
DR PDBsum; 6NT9; -.
DR AlphaFoldDB; E1C7U0; -.
DR SMR; E1C7U0; -.
DR STRING; 9031.ENSGALP00000001248; -.
DR iPTMnet; E1C7U0; -.
DR PaxDb; E1C7U0; -.
DR Ensembl; ENSGALT00000071854; ENSGALP00000048751; ENSGALG00000041129.
DR GeneID; 768990; -.
DR CTD; 768990; -.
DR VEuPathDB; HostDB:geneid_768990; -.
DR eggNOG; ENOG502R15M; Eukaryota.
DR GeneTree; ENSGT00390000008582; -.
DR InParanoid; E1C7U0; -.
DR OMA; FAMSQYG; -.
DR OrthoDB; 865174at2759; -.
DR PhylomeDB; E1C7U0; -.
DR TreeFam; TF324444; -.
DR PRO; PR:E1C7U0; -.
DR Proteomes; UP000000539; Chromosome 13.
DR Bgee; ENSGALG00000041129; Expressed in ovary and 13 other tissues.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0000421; C:autophagosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0033116; C:endoplasmic reticulum-Golgi intermediate compartment membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:UniProtKB.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IDA:UniProtKB.
DR GO; GO:0035438; F:cyclic-di-GMP binding; ISS:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; ISS:UniProtKB.
DR GO; GO:0000045; P:autophagosome assembly; ISS: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:0032728; P:positive regulation of interferon-beta production; ISS:UniProtKB.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISS:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; ISS:UniProtKB.
DR GO; GO:0051259; P:protein complex oligomerization; IDA:UniProtKB.
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; Cytoplasm; Cytoplasmic vesicle;
KW Endoplasmic reticulum; Golgi apparatus; Immunity; Innate immunity;
KW Membrane; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..379
FT /note="Stimulator of interferon genes protein"
FT /id="PRO_0000404588"
FT TOPO_DOM 1..23
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TRANSMEM 24..40
FT /note="Helical; Name=1"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TOPO_DOM 41..50
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TRANSMEM 51..75
FT /note="Helical; Name=2"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TOPO_DOM 76..97
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TRANSMEM 98..111
FT /note="Helical; Name=3"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TOPO_DOM 112..121
FT /note="Lumenal"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TRANSMEM 122..139
FT /note="Helical; Name=4"
FT /evidence="ECO:0000269|PubMed:30842659"
FT TOPO_DOM 140..379
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:30842659"
FT REGION 158..345
FT /note="Cyclic dinucleotide-binding domain (CBD)"
FT /evidence="ECO:0000269|PubMed:30842659"
FT MOTIF 363..366
FT /note="pLxIS motif"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 167..172
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000269|PubMed:30842659,
FT ECO:0007744|PDB:6NT7"
FT BINDING 167
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 172
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 243..246
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000269|PubMed:30842659,
FT ECO:0007744|PDB:6NT7"
FT BINDING 243..246
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT BINDING 268
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000269|PubMed:30842659,
FT ECO:0007744|PDB:6NT7"
FT BINDING 268
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6"
FT MOD_RES 366
FT /note="Phosphoserine; by TBK1"
FT /evidence="ECO:0000305|PubMed:30842653"
SQ SEQUENCE 379 AA; 42596 MW; 41E0232AE90E0D47 CRC64;
MPQDPSTRSS PARLLIPEPR AGRARHAACV LLAVCFVVLF LSGEPLAPII RSVCTQLAAL
QLGVLLKGCC CLAEEIFHLH SRHHGSLWQV LCSCFPPRWY LALLLVGGSA YLDPPEDNGH
SPRLALTLSC LCQLLVLALG LQKLSAVEVS ELTESSKKNV AHGLAWSYYI GYLKVVLPRL
KECMEELSRT NPMLRAHRDT WKLHILVPLG CDIWDDLEKA DSNIQYLADL PETILTRAGI
KRRVYKHSLY VIRDKDNKLR PCVLEFASPL QTLCAMSQDD CAAFSREQRL EQARLFYRSL
RDILGSSKEC AGLYRLIAYE EPAEPESHFL SGLILWHLQQ QQREEYMVQE ELPLGTSSVE
LSLQVSSSDL PQPLRSDCP
