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Aliases for TMEM173 Gene

Aliases for TMEM173 Gene

  • Transmembrane Protein 173 2 3 4 5
  • Endoplasmic Reticulum Interferon Stimulator 3 4
  • HSTING 3 4
  • STING 3 4
  • HMITA 3 4
  • ERIS 3 4
  • MITA 3 4
  • N-Terminal Methionine-Proline-Tyrosine-Serine Plasma Membrane Tetraspanner 3
  • Mitochondrial Mediator Of IRF3 Activation 3
  • Endoplasmic Reticulum IFN Stimulator 3
  • Mediator Of IRF3 Activation 4
  • NET23 3
  • MPYS 3
  • SAVI 3

External Ids for TMEM173 Gene

Previous GeneCards Identifiers for TMEM173 Gene

  • GC05M138836
  • GC05M134001

Summaries for TMEM173 Gene

Entrez Gene Summary for TMEM173 Gene

  • This gene encodes a five transmembrane protein that functions as a major regulator of the innate immune response to viral and bacterial infections. The encoded protein is a pattern recognition receptor that detects cytosolic nucleic acids and transmits signals that activate type I interferon responses. The encoded protein has also been shown to play a role in apoptotic signaling by associating with type II major histocompatibility complex. Mutations in this gene are the cause of infantile-onset STING-associated vasculopathy. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2014]

GeneCards Summary for TMEM173 Gene

TMEM173 (Transmembrane Protein 173) is a Protein Coding gene. Diseases associated with TMEM173 include sting-associated vasculopathy, infantile-onset and wolfram syndrome 2. Among its related pathways are Immune System and Cytosolic sensors of pathogen-associated DNA. GO annotations related to this gene include protein homodimerization activity and protein kinase binding.

UniProtKB/Swiss-Prot for TMEM173 Gene

  • 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).

No data available for Tocris Summary , Gene Wiki entry , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TMEM173 Gene

Genomics for TMEM173 Gene

Regulatory Elements for TMEM173 Gene

Promoters for TMEM173 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters

ENSRs around TMEM173 on UCSC Golden Path with GeneCards custom track

Genomic Location for TMEM173 Gene

Chromosome:
5
Start:
139,475,528 bp from pter
End:
139,482,935 bp from pter
Size:
7,408 bases
Orientation:
Minus strand

Genomic View for TMEM173 Gene

Genes around TMEM173 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TMEM173 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TMEM173 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TMEM173 Gene

Proteins for TMEM173 Gene

  • Protein details for TMEM173 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q86WV6-STING_HUMAN
    Recommended name:
    Stimulator of interferon genes protein
    Protein Accession:
    Q86WV6
    Secondary Accessions:
    • A8K3P6
    • B6EB35
    • D6RBX0
    • D6RE01
    • D6RID9

    Protein attributes for TMEM173 Gene

    Size:
    379 amino acids
    Molecular mass:
    42193 Da
    Quaternary structure:
    • 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.

    Three dimensional structures from OCA and Proteopedia for TMEM173 Gene

neXtProt entry for TMEM173 Gene

Proteomics data for TMEM173 Gene at MOPED

Post-translational modifications for TMEM173 Gene

  • Phosphorylated on tyrosine residues upon MHC-II aggregation (By similarity). Phosphorylated on Ser-358 by TBK1, leading to activation and production of IFN-beta.
  • Ubiquitinated. Lys-63-linked ubiquitination mediated by TRIM56 at Lys-150 promotes homodimerization and recruitment of the antiviral kinase TBK1 and subsequent production of IFN-beta. Lys-48-linked polyubiquitination at Lys-150 occurring after viral infection is mediated by RNF5 and leads to proteasomal degradation.
  • Ubiquitination at Lys 150
  • Modification sites at PhosphoSitePlus

Other Protein References for TMEM173 Gene

ENSEMBL proteins:
REFSEQ proteins:

Antibody Products

  • R&D Systems Antibodies for TMEM173 (STING/TMEM173)
  • Cell Signaling Technology (CST) Antibodies for TMEM173 (TMEM173)

No data available for DME Specific Peptides for TMEM173 Gene

Domains & Families for TMEM173 Gene

Protein Domains for TMEM173 Gene

InterPro:
ProtoNet:

Suggested Antigen Peptide Sequences for TMEM173 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q86WV6

UniProtKB/Swiss-Prot:

STING_HUMAN :
  • The c-di-GMP-binding domain (CBD) forms a homodimer via hydrophobic interactions and binds both the cyclic diguanylate monophosphate (c-di-GMP) and the cyclic GMP-AMP (cGAMP) messengers. In absence of c-di-GMP or cGAMP, the protein is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT). Binding of c-di-GMP or cGAMP to the CBD releases the autoinhibition by displacing the CTT, leading to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon. The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660 and PubMed:22728659).
  • Belongs to the TMEM173 family.
Domain:
  • The c-di-GMP-binding domain (CBD) forms a homodimer via hydrophobic interactions and binds both the cyclic diguanylate monophosphate (c-di-GMP) and the cyclic GMP-AMP (cGAMP) messengers. In absence of c-di-GMP or cGAMP, the protein is autoinhibited by an intramolecular interaction between the CBD and the C-terminal tail (CTT). Binding of c-di-GMP or cGAMP to the CBD releases the autoinhibition by displacing the CTT, leading to activate both NF-kappa-B and IRF3 transcription pathways to induce expression of type I interferon. The N-terminal part of the CBD region was initially though to contain a fifth transmembrane region (TM5) but is part of the folded, soluble CBD (PubMed:22579474, PubMed:22705373, PubMed:22728658, PubMed:22728660 and PubMed:22728659).
Family:
  • Belongs to the TMEM173 family.
genes like me logo Genes that share domains with TMEM173: view

No data available for Gene Families for TMEM173 Gene

Function for TMEM173 Gene

Molecular function for TMEM173 Gene

UniProtKB/Swiss-Prot 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). 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).

Gene Ontology (GO) - Molecular Function for TMEM173 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0031625 ubiquitin protein ligase binding IEA --
GO:0042803 protein homodimerization activity IDA 19433799
genes like me logo Genes that share ontologies with TMEM173: view
genes like me logo Genes that share phenotypes with TMEM173: view

Human Phenotype Ontology for TMEM173 Gene

HPO Id HPO Name Alternative Ids Definition Synonyms

Animal Models for TMEM173 Gene

MGI Knock Outs for TMEM173:

Animal Model Products

CRISPR Products

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targets and HOMER Transcription for TMEM173 Gene

Localization for TMEM173 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TMEM173 Gene

Endoplasmic reticulum membrane; Multi-pass membrane protein. Mitochondrion outer membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein. Cytoplasm, perinuclear region. Cytoplasm. Note=In response to double-stranded DNA stimulation, relocalizes to perinuclear region, where the kinase TBK1 is recruited.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for TMEM173 Gene COMPARTMENTS Subcellular localization image for TMEM173 gene
Compartment Confidence
endoplasmic reticulum 5
mitochondrion 5
plasma membrane 4
peroxisome 3
cytosol 2
golgi apparatus 2

Gene Ontology (GO) - Cellular Components for TMEM173 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005777 peroxisome IEA --
GO:0048471 perinuclear region of cytoplasm IEA,ISS --
genes like me logo Genes that share ontologies with TMEM173: view

Pathways & Interactions for TMEM173 Gene

genes like me logo Genes that share pathways with TMEM173: view

Gene Ontology (GO) - Biological Process for TMEM173 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0002218 activation of innate immune response IMP 18818105
GO:0002230 positive regulation of defense response to virus by host IMP 18818105
GO:0006915 apoptotic process IEA --
GO:0032092 positive regulation of protein binding IDA 18818105
GO:0033160 positive regulation of protein import into nucleus, translocation IDA 18818105
genes like me logo Genes that share ontologies with TMEM173: view

No data available for SIGNOR curated interactions for TMEM173 Gene

Drugs & Compounds for TMEM173 Gene

No Compound Related Data Available

Transcripts for TMEM173 Gene

Unigene Clusters for TMEM173 Gene

Transmembrane protein 173:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for TMEM173 Gene

ExUns: 1a · 1b · 1c · 1d · 1e · 1f ^ 2a · 2b · 2c · 2d ^ 3a · 3b · 3c · 3d ^ 4a · 4b ^ 5a · 5b ^ 6a · 6b ^ 7a · 7b · 7c ^ 8a · 8b
SP1: - - - -
SP2: - - - -
SP3: - - - - - - -
SP4: - - - - - -
SP5: - - - - -
SP6: - - - - -
SP7: - -
SP8: - - -
SP9: - -
SP10: -
SP11:

Relevant External Links for TMEM173 Gene

GeneLoc Exon Structure for
TMEM173
ECgene alternative splicing isoforms for
TMEM173

Expression for TMEM173 Gene

mRNA expression in normal human tissues for TMEM173 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Protein differential expression in normal tissues from HIPED for TMEM173 Gene

This gene is overexpressed in Nasal epithelium (17.4), Monocytes (16.8), and Peripheral blood mononuclear cells (8.5).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MOPED, and MaxQB for TMEM173 Gene



SOURCE GeneReport for Unigene cluster for TMEM173 Gene Hs.379754

mRNA Expression by UniProt/SwissProt for TMEM173 Gene

Q86WV6-STING_HUMAN
Tissue specificity: Ubiquitously expressed. Expressed in skin endothelial cells, alveolar type 2 pneumocytes, bronchial epithelium and alveolar macrophages.
genes like me logo Genes that share expression patterns with TMEM173: view

Protein tissue co-expression partners for TMEM173 Gene

- Elite partner

Primer Products

In Situ Assay Products

No data available for mRNA differential expression in normal tissues for TMEM173 Gene

Orthologs for TMEM173 Gene

This gene was present in the common ancestor of chordates.

Orthologs for TMEM173 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TMEM173 35
  • 99.38 (n)
  • 99.21 (a)
TMEM173 36
  • 99 (a)
OneToOne
cow
(Bos Taurus)
Mammalia TMEM173 36
  • 79 (a)
OneToOne
TMEM173 35
  • 85.46 (n)
  • 79.79 (a)
dog
(Canis familiaris)
Mammalia TMEM173 35
  • 84.05 (n)
  • 77.27 (a)
TMEM173 36
  • 77 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Tmem173 16
Tmem173 36
  • 69 (a)
OneToOne
Tmem173 35
  • 76.92 (n)
  • 69.23 (a)
oppossum
(Monodelphis domestica)
Mammalia TMEM173 36
  • 62 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TMEM173 36
  • 40 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tmem173 35
  • 77.25 (n)
  • 69.05 (a)
chicken
(Gallus gallus)
Aves TMEM173 35
  • 56.33 (n)
  • 45.71 (a)
TMEM173 36
  • 43 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia TMEM173 36
  • 39 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tmem173 35
  • 51.46 (n)
  • 42.3 (a)
zebrafish
(Danio rerio)
Actinopterygii tmem173 36
  • 33 (a)
OneToOne
tmem173 35
  • 47.85 (n)
  • 39.93 (a)
Species with no ortholog for TMEM173:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • fruit fly (Drosophila melanogaster)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TMEM173 Gene

ENSEMBL:
Gene Tree for TMEM173 (if available)
TreeFam:
Gene Tree for TMEM173 (if available)

Paralogs for TMEM173 Gene

No data available for Paralogs for TMEM173 Gene

Variants for TMEM173 Gene

Sequence variations from dbSNP and Humsavar for TMEM173 Gene

SNP ID Clin Chr 05 pos Sequence Context AA Info Type
rs11554776 - 139,481,493(-) GCTGC(A/G)CCACA intron-variant, reference, missense
rs1131769 - 139,478,334(-) TGACC(A/G)TGCTG reference, missense
rs7380824 - 139,477,397(+) GTGTC(C/T)GGCAG intron-variant, downstream-variant-500B, reference, missense
VAR_071878 STING-associated vasculopathy, infantile-onset (SAVI)
VAR_071879 STING-associated vasculopathy, infantile-onset (SAVI)

Structural Variations from Database of Genomic Variants (DGV) for TMEM173 Gene

Variant ID Type Subtype PubMed ID
nsv519808 CNV Loss 19592680
nsv516200 CNV Loss 19592680

Variation tolerance for TMEM173 Gene

Residual Variation Intolerance Score: 81.6% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 12.88; 94.85% of all genes are more intolerant (likely to be disease-causing)

Relevant External Links for TMEM173 Gene

HapMap Linkage Disequilibrium report
TMEM173
Human Gene Mutation Database (HGMD)
TMEM173

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TMEM173 Gene

Disorders for TMEM173 Gene

MalaCards: The human disease database

(5) MalaCards diseases for TMEM173 Gene - From: OMIM, ClinVar, GeneTests, Orphanet, Swiss-Prot, DISEASES, and GeneCards

- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

STING_HUMAN
  • STING-associated vasculopathy, infantile-onset (SAVI) [MIM:615934]: An autoinflammatory disease characterized by early-onset systemic inflammation and cutaneous vasculopathy, resulting in severe skin lesions. Violaceous, scaling lesions of fingers, toes, nose, cheeks and ears progress to acral necrosis in most of the patients. Some patients have severe interstitial lung disease. {ECO:0000269 PubMed:25029335}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Relevant External Links for TMEM173

Genetic Association Database (GAD)
TMEM173
Human Genome Epidemiology (HuGE) Navigator
TMEM173
Atlas of Genetics and Cytogenetics in Oncology and Haematology:
TMEM173
genes like me logo Genes that share disorders with TMEM173: view

No data available for Genatlas for TMEM173 Gene

Publications for TMEM173 Gene

  1. Activated STING in a vascular and pulmonary syndrome. (PMID: 25029335) Liu Y. … Goldbach-Mansky R. (N. Engl. J. Med. 2014) 3 4 67
  2. Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. (PMID: 12477932) Strausberg R.L. … Marra M.A. (Proc. Natl. Acad. Sci. U.S.A. 2002) 2 3
  3. Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. (PMID: 25636800) Liu S. … Chen Z.J. (Science 2015) 3
  4. Molecular basis for the specific recognition of the metazoan cyclic GMP-AMP by the innate immune adaptor protein STING. (PMID: 26150511) Shi H. … Chen C. (Proc. Natl. Acad. Sci. U.S.A. 2015) 3
  5. UV Light Potentiates STING (Stimulator of Interferon Genes)-dependent Innate Immune Signaling through Deregulation of ULK1 (Unc51-like Kinase 1). (PMID: 25792739) Kemp M.G. … Sancar A. (J. Biol. Chem. 2015) 3

Products for TMEM173 Gene

Sources for TMEM173 Gene

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