STING_NEMVE
ID STING_NEMVE Reviewed; 377 AA.
AC A7SLZ2;
DT 09-DEC-2015, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 58.
DE RecName: Full=Stimulator of interferon genes protein {ECO:0000303|PubMed:26300263};
DE Short=NvSTING {ECO:0000303|PubMed:30842662};
DE Short=STING {ECO:0000303|PubMed:26300263};
GN ORFNames=v1g246111;
OS Nematostella vectensis (Starlet sea anemone).
OC Eukaryota; Metazoa; Cnidaria; Anthozoa; Hexacorallia; Actiniaria;
OC Edwardsiidae; Nematostella.
OX NCBI_TaxID=45351;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CH2 X CH6;
RX PubMed=17615350; DOI=10.1126/science.1139158;
RA Putnam N.H., Srivastava M., Hellsten U., Dirks B., Chapman J., Salamov A.,
RA Terry A., Shapiro H., Lindquist E., Kapitonov V.V., Jurka J.,
RA Genikhovich G., Grigoriev I.V., Lucas S.M., Steele R.E., Finnerty J.R.,
RA Technau U., Martindale M.Q., Rokhsar D.S.;
RT "Sea anemone genome reveals ancestral eumetazoan gene repertoire and
RT genomic organization.";
RL Science 317:86-94(2007).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS) OF 178-377 IN COMPLEXES WITH
RP 2'3'-CGAMP AND C-DI-GMP, SUBUNIT, FUNCTION, AND MUTAGENESIS OF PHE-276.
RX PubMed=26300263; DOI=10.1016/j.molcel.2015.07.022;
RA Kranzusch P.J., Wilson S.C., Lee A.S., Berger J.M., Doudna J.A.,
RA Vance R.E.;
RT "Ancient origin of cGAS-STING reveals mechanism of universal 2',3' cGAMP
RT signaling.";
RL Mol. Cell 59:891-903(2015).
RN [3]
RP FUNCTION.
RX PubMed=30842662; DOI=10.1038/s41586-019-1006-9;
RA Gui X., Yang H., Li T., Tan X., Shi P., Li M., Du F., Chen Z.J.;
RT "Autophagy induction via STING trafficking is a primordial function of the
RT cGAS pathway.";
RL Nature 567:262-266(2019).
CC -!- FUNCTION: Sensor of cytosolic DNA from bacteria and viruses that
CC promotes autophagy (PubMed:30842662). Acts by recognizing and binding
CC cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA
CC in the cytosol (PubMed:26300263, PubMed:30842662). Following cGAMP-
CC binding, promotes the formation of autophagosomes, leading to target
CC cytosolic DNA for degradation by the lysosome (PubMed:30842662).
CC Exhibits guanine base-specific ligand recognition. Binds 3'-3'linked
CC cGAMP, 2'-3' linked cGAMP and 3'-3' linked c-di-GMP with much greater
CC affinity as compared to 3'-3' linked c-di-AMP (PubMed:26300263). Lacks
CC the C-terminal tail (CTT) found in mammalian orthologs which is
CC essential for interferon signaling (PubMed:26300263).
CC {ECO:0000269|PubMed:26300263, ECO:0000269|PubMed:30842662}.
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:26300263}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q86WV6}; Multi-pass membrane protein
CC {ECO:0000255}.
CC -!- SIMILARITY: Belongs to the TMEM173 family. {ECO:0000305}.
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DR EMBL; DS469703; EDO35285.1; -; Genomic_DNA.
DR RefSeq; XP_001627385.1; XM_001627335.1.
DR PDB; 5CFL; X-ray; 1.84 A; A/B=193-377.
DR PDB; 5CFM; X-ray; 1.99 A; A/B=193-377.
DR PDB; 5CFN; X-ray; 2.95 A; A/B=193-377.
DR PDB; 5CFO; X-ray; 2.10 A; A/B=178-377.
DR PDB; 5CFP; X-ray; 2.07 A; A/B=178-377.
DR PDB; 5CFQ; X-ray; 2.10 A; A/B=193-377.
DR PDB; 5CFR; X-ray; 2.85 A; A/B=178-377.
DR PDBsum; 5CFL; -.
DR PDBsum; 5CFM; -.
DR PDBsum; 5CFN; -.
DR PDBsum; 5CFO; -.
DR PDBsum; 5CFP; -.
DR PDBsum; 5CFQ; -.
DR PDBsum; 5CFR; -.
DR AlphaFoldDB; A7SLZ2; -.
DR SMR; A7SLZ2; -.
DR STRING; 45351.EDO35285; -.
DR PRIDE; A7SLZ2; -.
DR EnsemblMetazoa; EDO35285; EDO35285; NEMVEDRAFT_v1g246111.
DR GeneID; 5506676; -.
DR KEGG; nve:5506676; -.
DR eggNOG; ENOG502R15M; Eukaryota.
DR HOGENOM; CLU_062449_0_0_1; -.
DR InParanoid; A7SLZ2; -.
DR OMA; FAMSQYG; -.
DR OrthoDB; 865174at2759; -.
DR Proteomes; UP000001593; Unassembled WGS sequence.
DR GO; GO:0005776; C:autophagosome; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0061507; F:2',3'-cyclic GMP-AMP binding; IDA:UniProtKB.
DR GO; GO:0035438; F:cyclic-di-GMP binding; IDA:UniProtKB.
DR GO; GO:0002218; P:activation of innate immune response; IEA:InterPro.
DR GO; GO:0000045; P:autophagosome assembly; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0016239; P:positive regulation of macroautophagy; IDA:UniProtKB.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:InterPro.
DR GO; GO:0061709; P:reticulophagy; IBA:GO_Central.
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; Endoplasmic reticulum; Membrane;
KW Nucleotide-binding; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..377
FT /note="Stimulator of interferon genes protein"
FT /id="PRO_0000434975"
FT TOPO_DOM 1..21
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 22..42
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 43..57
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 58..80
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 81..101
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 102..122
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 123..154
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 155..175
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 176..377
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT BINDING 206
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000269|PubMed:26300263,
FT ECO:0007744|PDB:5CFQ"
FT BINDING 206
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000269|PubMed:26300263,
FT ECO:0007744|PDB:5CFL, ECO:0007744|PDB:5CFP"
FT BINDING 272
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000269|PubMed:26300263,
FT ECO:0007744|PDB:5CFQ"
FT BINDING 272
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6,
FT ECO:0000269|PubMed:26300263, ECO:0007744|PDB:5CFL,
FT ECO:0007744|PDB:5CFP"
FT BINDING 278..279
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000269|PubMed:26300263,
FT ECO:0007744|PDB:5CFQ"
FT BINDING 278
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6,
FT ECO:0000269|PubMed:26300263, ECO:0007744|PDB:5CFL,
FT ECO:0007744|PDB:5CFP"
FT BINDING 300..303
FT /ligand="cyclic di-3',5'-guanylate"
FT /ligand_id="ChEBI:CHEBI:58805"
FT /evidence="ECO:0000250|UniProtKB:Q86WV6,
FT ECO:0000269|PubMed:26300263, ECO:0007744|PDB:5CFL,
FT ECO:0007744|PDB:5CFP"
FT BINDING 303
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0000269|PubMed:26300263,
FT ECO:0007744|PDB:5CFQ"
FT MUTAGEN 276
FT /note="F->K: Specifically reduces 3'-3' linked cGAMP
FT binding while retaining 2'-3' linked cGAMP recognition."
FT /evidence="ECO:0000269|PubMed:26300263"
FT HELIX 195..204
FT /evidence="ECO:0007829|PDB:5CFL"
FT HELIX 207..210
FT /evidence="ECO:0007829|PDB:5CFL"
FT TURN 211..213
FT /evidence="ECO:0007829|PDB:5CFL"
FT HELIX 214..218
FT /evidence="ECO:0007829|PDB:5CFL"
FT HELIX 222..226
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 228..239
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 259..264
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:5CFL"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 276..280
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 283..287
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 295..301
FT /evidence="ECO:0007829|PDB:5CFL"
FT HELIX 305..314
FT /evidence="ECO:0007829|PDB:5CFL"
FT TURN 316..318
FT /evidence="ECO:0007829|PDB:5CFL"
FT HELIX 321..340
FT /evidence="ECO:0007829|PDB:5CFL"
FT HELIX 343..345
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 348..354
FT /evidence="ECO:0007829|PDB:5CFL"
FT STRAND 356..358
FT /evidence="ECO:0007829|PDB:5CFR"
FT HELIX 360..369
FT /evidence="ECO:0007829|PDB:5CFL"
SQ SEQUENCE 377 AA; 43357 MW; D808033619A4B882 CRC64;
MRRAEENNGF GTIPKRRNQH TPFYASIGMI VVIIVAFTSY HITSYGDDRN RAMRQYSFTF
SLAYLAFLVG ELLRRCCLFA EEYRHIETRY NGSLKKAIQT TFSFGHNNVL FVASLLFFVV
FVASNDPNGS SSVIQGNSTA EPHTEMRQTS GWQGLWGQFI ISALLTPLVV HLLGLRELSK
VEESQLNEKE NKNVADGLAW SYYFGYLKFV LPELEKQIEK TSKFRSKEKF VKKMFILIPS
NCFWDDKIPG SDYDPQNRIT FEGNTEPLEK TRGGVFLRHY KHSVYEIKDG ENEPWFCIME
YATPLLTLYD MSVAQPGELS REERDAQVVV FLRKLQDILE GDRACQGKYE LVTFSPDRDL
ADVMLRKLKD SELEIGG
