STING_CRAGI
ID STING_CRAGI Reviewed; 415 AA.
AC P0DUE1;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Stimulator of interferon genes protein {ECO:0000305};
DE Short=TIR-STING {ECO:0000303|PubMed:32877915};
DE AltName: Full=Probable NAD(+) hydrolase {ECO:0000255|PROSITE-ProRule:PRU00204};
DE EC=3.2.2.6 {ECO:0000255|PROSITE-ProRule:PRU00204};
OS Crassostrea gigas (Pacific oyster) (Crassostrea angulata).
OC Eukaryota; Metazoa; Spiralia; Lophotrochozoa; Mollusca; Bivalvia;
OC Autobranchia; Pteriomorphia; Ostreida; Ostreoidea; Ostreidae; Crassostrea.
OX NCBI_TaxID=29159;
RN [1] {ECO:0007744|PDB:6WT6, ECO:0007744|PDB:6WT7}
RP X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 2-415, X-RAY CRYSTALLOGRAPHY
RP (2.90 ANGSTROMS) OF 2-415 IN COMPLEX WITH 2'3'-CGAMP, NUCLEOTIDE-BINDING,
RP SUBUNIT, AND DOMAIN.
RX PubMed=32877915; DOI=10.1038/s41586-020-2719-5;
RA Morehouse B.R., Govande A.A., Millman A., Keszei A.F.A., Lowey B., Ofir G.,
RA Shao S., Sorek R., Kranzusch P.J.;
RT "STING cyclic dinucleotide sensing originated in bacteria.";
RL Nature 586:429-433(2020).
CC -!- FUNCTION: Sensor of cytosolic DNA from bacteria and viruses that
CC promotes autophagy (By similarity). Binds c-di-AMP, 2'3'-cGAMP, 3'3'-
CC cGAMP and to a lesser extent c-di-GMP. Nucleotide binding has not been
CC seen to stimulate NAD(+) hydrolase activity (PubMed:32877915).
CC {ECO:0000250|UniProtKB:A7SLZ2, ECO:0000269|PubMed:32877915}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + NAD(+) = ADP-D-ribose + H(+) + nicotinamide;
CC Xref=Rhea:RHEA:16301, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:17154, ChEBI:CHEBI:57540, ChEBI:CHEBI:57967; EC=3.2.2.6;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:16302;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00204};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:32877915}.
CC -!- DOMAIN: Homodimerizes by swapping the N-terminal TIR and C-terminal
CC nucleotide-binding domains. Ligand binding induces lid closure and
CC repositions the TIR domain (PubMed:32877915). The TIR domain mediates
CC NAD(+) hydrolase (NADase) activity. Self-association of TIR domains is
CC required for NADase activity (By similarity). {ECO:0000255|PROSITE-
CC ProRule:PRU00204, ECO:0000269|PubMed:32877915}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the Toll-like
CC receptor family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the TMEM173 family.
CC {ECO:0000305}.
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DR PDB; 6WT6; X-ray; 2.41 A; A=2-415.
DR PDB; 6WT7; X-ray; 2.90 A; A=2-415.
DR PDBsum; 6WT6; -.
DR PDBsum; 6WT7; -.
DR AlphaFoldDB; P0DUE1; -.
DR SMR; P0DUE1; -.
DR Proteomes; UP000005408; Unplaced.
DR GO; GO:0050135; F:NAD(P)+ nucleosidase activity; IEA:UniProtKB-EC.
DR GO; GO:0061809; F:NAD+ nucleotidase, cyclic ADP-ribose generating; IEA:UniProtKB-EC.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0002218; P:activation of innate immune response; IEA:InterPro.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0032481; P:positive regulation of type I interferon production; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
DR Gene3D; 3.40.50.10140; -; 1.
DR Gene3D; 3.40.50.12100; -; 1.
DR InterPro; IPR029158; STING.
DR InterPro; IPR038623; STING_C_sf.
DR InterPro; IPR000157; TIR_dom.
DR InterPro; IPR035897; Toll_tir_struct_dom_sf.
DR PANTHER; PTHR34339; PTHR34339; 1.
DR Pfam; PF13676; TIR_2; 1.
DR Pfam; PF15009; TMEM173; 1.
DR SMART; SM00255; TIR; 1.
DR SUPFAM; SSF52200; SSF52200; 1.
DR PROSITE; PS50104; TIR; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autophagy; Hydrolase; Immunity; NAD; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..415
FT /note="Stimulator of interferon genes protein"
FT /id="PRO_0000451875"
FT DOMAIN 29..163
FT /note="TIR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204"
FT REGION 387..415
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 401..415
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 104
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00204,
FT ECO:0000305|PubMed:32877915"
FT BINDING 256
FT /ligand="2',3'-cGAMP"
FT /ligand_id="ChEBI:CHEBI:143093"
FT /evidence="ECO:0007744|PDB:6WT7"
FT CONFLICT 344
FT /note="K -> R (in Ref. 1)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="P -> S (in Ref. 1)"
FT /evidence="ECO:0000305"
FT STRAND 31..36
FT /evidence="ECO:0007829|PDB:6WT6"
FT TURN 39..42
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 43..56
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 60..62
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 63..66
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 74..82
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 84..91
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 93..97
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 100..102
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 104..108
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 113..119
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 120..124
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 130..132
FT /evidence="ECO:0007829|PDB:6WT6"
FT TURN 135..137
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 138..140
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 153..159
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 176..186
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 188..204
FT /evidence="ECO:0007829|PDB:6WT6"
FT TURN 205..207
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 211..221
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 237..243
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 246..250
FT /evidence="ECO:0007829|PDB:6WT7"
FT STRAND 253..258
FT /evidence="ECO:0007829|PDB:6WT7"
FT STRAND 260..266
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 272..279
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 281..283
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 284..291
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 293..295
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 299..319
FT /evidence="ECO:0007829|PDB:6WT6"
FT TURN 321..325
FT /evidence="ECO:0007829|PDB:6WT6"
FT STRAND 326..332
FT /evidence="ECO:0007829|PDB:6WT6"
FT HELIX 341..356
FT /evidence="ECO:0007829|PDB:6WT6"
SQ SEQUENCE 415 AA; 47031 MW; 03C59D725799BEBD CRC64;
MEKNGAHSFL SDTPVTSLTM SVPVLRHPHV YHAFISYCAD ADTSHARTIL DSVESRGFTC
CFAERDFLPG ECTSDVVVDA IHCSKNVILV ISPASLQSEW SKFEMLMAVD DSHQRNNVCL
VPVLLGGVKV DDLPPPLRPL TCIELMDDFR NTDDIIQAIS KPEDTWESLL PVGNLAHGFA
WGYYYGYLKI ILPDLDKTVR QWRRVNNAEG RMSEKLFLFF PQSCRCRDSI ADESSLIKHR
GHLPIITKDR AGIIERQYKN TIYSVTDDNG EDYFFAGEYI GVIHTMFEME QNATTGLQTR
EKYVQSMRFY LTLKRILDTD PECSKKCKIV FYKDVNNSSD AMPKLICNEI KNQLRKESSD
DTTVCMTPFN SPFPSISSPD FARCSLKSPS STNMVKSEPN IYREESGKTK SVERG
