Molecular Target Synopsis
Overview
Domains and Structures
Drugs and Clinical Candidates
Druggability
Chemistry
Ligand Efficiency Plot
Pathways
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Interaction Network
Gene Expression
Gene Copy Number Variation
RNAi
Mutations
Germline Genetics

TMEM173 (Q86WV6) - Overview - Molecular Target Synopsis

Protein


TMEM173, Stimulator of interferon genes protein
UniProt Q86WV6

Also Known as STING_HUMAN, TMEM173, ERIS, MITA, STING

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). Innate immune response is triggered in response to non-CpG double-stranded DNA from viruses and bacteria delivered to the cytoplasm. Acts by recognizing and binding cyclic di-GMP (c-di-GMP), a second messenger produced by bacteria, and cyclic GMP-AMP (cGAMP), a messenger produced in response to DNA virus in the cytosol: upon binding of c-di-GMP or cGAMP, autoinhibition is alleviated and TMEM173/STING is able to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon and exert a potent anti-viral state. May be involved in translocon function, the translocon possibly being able to influence the induction of type I interferons. May be involved in transduction of apoptotic signals via its association with the major histocompatibility complex class II (MHC-II). Mediates death signaling via activation of the extracellular signal-regulated kinase (ERK) pathway. Essential for the induction of IFN-beta in response to human herpes simplex virus 1 (HHV-1) infection. Exhibits 2',3' phosphodiester linkage-specific ligand recognition. Can bind both 2'-3' linked cGAMP and 3'-3' linked cGAMP but is preferentially activated by 2'-3' linked cGAMP (PubMed:26300263)., (Microbial infection) Antiviral activity is antagonized by oncoproteins, such as papillomavirus (HPV) protein E7 and adenovirus early E1A protein (PubMed:26405230). Such oncoproteins prevent the ability to sense cytosolic DNA (PubMed:26405230). Associates with the MHC-II complex (By similarity). Homodimer; 'Lys-63'-linked ubiquitination at Lys-150 is required for homodimerization. Interacts with DDX58/RIG-I, MAVS and SSR2. Interacts with RNF5 and TRIM56. Interacts with TBK1; when homodimer, leading to subsequent production of IFN-beta. Interacts with IFIT1 and IFIT2. Interacts with TRIM29; this interaction induces TMEM173/STING ubiquitination and subsequent degradation (PubMed:29038422).

6O8C
14 RESIDUE FRAGMENT OF
STIMULATOR OF INTERFERON GENES PROTEIN
IN THE STRUCTURE OF
CRYSTAL STRUCTURE OF STING CTT IN COMPLEX WITH TBK1
RCSB/PDB
Inspect Structure
See all 3D Structures for TMEM173

Isoforms / Transcripts (Protein Coding)


Protein Length Ensembl Gene Ensembl Transcript Ensembl Protein Uniprot Isoform
379ENSG00000184584ENST00000330794ENSP00000331288Q86WV6-1
253ENSG00000184584ENST00000510817ENSP00000427455

Sub-cellular localization


UniProt: TMEM173 is active in the following subcellular-locations: cell membrane, cytoplasm, endoplasmic reticulum membrane, mitochondrion outer membrane, perinuclear region.
GO terms: TMEM173 is active in the following subcellular-locations: cytoplasmic vesicle membrane, endoplasmic reticulum membrane, Golgi apparatus, integral component of membrane, mitochondrial outer membrane, perinuclear region of cytoplasm, peroxisome, plasma membrane, secretory granule membrane.



UniProt
GO terms

Gene Copy Number Variation


In COSMIC - Cell Lines Project TMEM173 has gain in 1 cell-lines, loss in 1 cell-lines and no signal in 1001 cell-lines. (see details)

Gene Expression


In NCI60, the highest expressing cell lines are: SR, OVCAR_4, LOXIMVI

In Array Express (RNA-seq of 675 commonly used human cancer cell lines), the highest expressing cell lines are: THP-1, SR-786, SU-DHL-1

In Array Express (RNA-seq of long poly adenylated RNA and long non poly adenylated RNA from ENCODE cell lines), the highest expressing cell lines are: SK-N-SH, BJ, NHLF

(see details)

3D Structures


For TMEM173 there are:
29 structures (48 chains) solved
21 are solved in complex with at least one small molecule ligand



(see details)
Molecular Target 3D Synopsis