Stimulator of interferon genes protein

Details

Name

Stimulator of interferon genes protein

Kind

protein

Synonyms

• Endoplasmic reticulum interferon stimulator
• ERIS
• hMITA
• hSTING
• Mediator of IRF3 activation
• MITA
• STING
• TMEM173
• Transmembrane protein 173

Gene Name

STING1

UniProtKB Entry

Q86WV6Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0053691|Stimulator of interferon genes protein
MPHSSLHPSIPCPRGHGAQKAALVLLSACLVTLWGLGEPPEHTLRYLVLHLASLQLGLLL
NGVCSLAEELRHIHSRYRGSYWRTVRACLGCPLRRGALLLLSIYFYYSLPNAVGPPFTWM
LALLGLSQALNILLGLKGLAPAEISAVCEKGNFNVAHGLAWSYYIGYLRLILPELQARIR
TYNQHYNNLLRGAVSQRLYILLPLDCGVPDNLSMADPNIRFLDKLPQQTGDHAGIKDRVY
SNSIYELLENGQRAGTCVLEYATPLQTLFAMSQYSQAGFSREDRLEQAKLFCRTLEDILA
DAPESQNNCRLIAYQEPADDSSFSLSQEVLRHLRQEEKEEVTVGSLKTSAVPSTSTMSQE
PELLISGMEKPLPLRTDFS

Number of residues

379

Molecular Weight

42192.08

Theoretical pI

Not Available

GO Classification

Functions

proton channel activity

Processes

cGAS/STING signaling pathway / cytoplasmic pattern recognition receptor signaling pathway / protein localization to endoplasmic reticulum

General Function

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:18724357, PubMed:18818105, PubMed:19433799, PubMed:19776740, PubMed:23027953, PubMed:23747010, PubMed:23910378, PubMed:27801882, PubMed:29973723, PubMed:30842659, PubMed:35045565, PubMed:35388221, PubMed:36808561, PubMed:37832545). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm (PubMed:26300263). Acts by binding cyclic dinucleotides: recognizes and binds cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, cyclic UMP-AMP (2',3'-cUAMP), and cyclic GMP-AMP (cGAMP), a messenger produced by CGAS in response to DNA virus in the cytosol (PubMed:21947006, PubMed:23258412, PubMed:23707065, PubMed:23722158, PubMed:23747010, PubMed:23910378, PubMed:26229117, PubMed:30842659, PubMed:35388221, PubMed:37379839). Upon binding to c-di-GMP, cUAMP or cGAMP, STING1 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:22394562, PubMed:25636800, PubMed:29973723, PubMed:30842653, PubMed:35045565, PubMed:35388221). 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:23747010, PubMed:23910378, 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 STING1-bound conformation and pays low energy costs in changing into the active conformation (PubMed:26150511). In addition to promote the production of type I interferons, plays a direct role in autophagy (PubMed:30568238, PubMed:30842662). Following cGAMP-binding, STING1 buds from the endoplasmic reticulum into COPII vesicles, which then form the endoplasmic reticulum-Golgi intermediate compartment (ERGIC) (PubMed:30842662). 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 (PubMed:30842662). Promotes autophagy by acting as a proton channel that directs proton efflux from the Golgi to facilitate MAP1LC3B/LC3B lipidation (PubMed:37535724). The autophagy- and interferon-inducing activities can be uncoupled and autophagy induction is independent of TBK1 phosphorylation (PubMed:30568238, PubMed:30842662). Autophagy is also triggered upon infection by bacteria: following c-di-GMP-binding, which is produced by live Gram-positive bacteria, promotes reticulophagy (By similarity). May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons (PubMed:18724357). May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II) (By similarity)

Specific Function

2',3'-cyclic gmp-amp binding

Pfam Domain Function

• TMEM173 (PF15009)

Signal Regions

Not Available

Transmembrane Regions

18-34 45-69 92-106 117-134

Cellular Location

Endoplasmic reticulum membrane

Gene sequence

>lcl|BSEQ0053692|Stimulator of interferon genes protein (STING1)
ATGCCCCACTCCAGCCTGCATCCATCCATCCCGTGTCCCAGGGGTCACGGGGCCCAGAAG
GCAGCCTTGGTTCTGCTGAGTGCCTGCCTGGTGACCCTTTGGGGGCTAGGAGAGCCACCA
GAGCACACTCTCCGGTACCTGGTGCTCCACCTAGCCTCCCTGCAGCTGGGACTGCTGTTA
AACGGGGTCTGCAGCCTGGCTGAGGAGCTGCGCCACATCCACTCCAGGTACCGGGGCAGC
TACTGGAGGACTGTGCGGGCCTGCCTGGGCTGCCCCCTCCGCCGTGGGGCCCTGTTGCTG
CTGTCCATCTATTTCTACTACTCCCTCCCAAATGCGGTCGGCCCGCCCTTCACTTGGATG
CTTGCCCTCCTGGGCCTCTCGCAGGCACTGAACATCCTCCTGGGCCTCAAGGGCCTGGCC
CCAGCTGAGATCTCTGCAGTGTGTGAAAAAGGGAATTTCAACGTGGCCCATGGGCTGGCA
TGGTCATATTACATCGGATATCTGCGGCTGATCCTGCCAGAGCTCCAGGCCCGGATTCGA
ACTTACAATCAGCATTACAACAACCTGCTACGGGGTGCAGTGAGCCAGCGGCTGTATATT
CTCCTCCCATTGGACTGTGGGGTGCCTGATAACCTGAGTATGGCTGACCCCAACATTCGC
TTCCTGGATAAACTGCCCCAGCAGACCGGTGACCATGCTGGCATCAAGGATCGGGTTTAC
AGCAACAGCATCTATGAGCTTCTGGAGAACGGGCAGCGGGCGGGCACCTGTGTCCTGGAG
TACGCCACCCCCTTGCAGACTTTGTTTGCCATGTCACAATACAGTCAAGCTGGCTTTAGC
CGGGAGGATAGGCTTGAGCAGGCCAAACTCTTCTGCCGGACACTTGAGGACATCCTGGCA
GATGCCCCTGAGTCTCAGAACAACTGCCGCCTCATTGCCTACCAGGAACCTGCAGATGAC
AGCAGCTTCTCGCTGTCCCAGGAGGTTCTCCGGCACCTGCGGCAGGAGGAAAAGGAAGAG
GTTACTGTGGGCAGCTTGAAGACCTCAGCGGTGCCCAGTACCTCCACGATGTCCCAAGAG
CCTGAGCTCCTCATCAGTGGAATGGAAAAGCCCCTCCCTCTCCGCACGGATTTCTCTTGA

Chromosome Location

5

Locus

5q31.2

External Identifiers

Resource	Link
UniProtKB ID	Q86WV6
UniProtKB Entry Name	STING_HUMAN
GeneCard ID	STING1
HGNC ID	HGNC:27962
PDB ID(s)	4EF4, 4EF5, 4EMT, 4EMU, 4F5D, 4F5E, 4F5W, 4F5Y, 4F9E, 4F9G, 4KSY, 4LOH, 4LOI, 4QXO, 4QXP, 4QXQ, 4QXR, 5BQX, 5JEJ, 6CFF, 6CY7, 6DNK, 6DXG, 6DXL, 6MX0, 6MX3, 6MXE, 6NT5, 6O8B, 6O8C, 6S26, 6S27, 6S86, 6UKM, 6UKU, 6UKV, 6UKW, 6UKX, 6UKY, 6UKZ, 6UL0, 6XF3, 6XF4, 6XNP, 6Y99, 6YDB, 6YDZ, 6YEA, 6YWA, 6YWB, 6Z0Z, 6Z15, 7A90, 7KVX, 7KVZ, 7KW1, 7MHC, 7OB3, 7Q3B, 7Q85, 7R4H, 7SHO, 7SHP, 7SII, 7SSM, 7T9U, 7T9V, 7X9P, 7X9Q, 8A2H, 8A2I, 8A2J, 8A2K, 8B2J, 8FLK, 8FLM, 8GJX, 8GSZ, 8GT6, 8IK3, 8P45, 8STH, 8STI, 8T5K, 8T5L
KEGG ID	hsa:340061
IUPHAR/Guide To Pharmacology ID	2902
NCBI Gene ID	340061

General References

Not Available

Associated Data

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
ADU-S100	investigational	yes	target	activator	Details