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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q86WV6: Variant p.Val155Met

Stimulator of interferon genes protein
Gene: STING1
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Variant information Variant position: help 155 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help LP/P [Disclaimer] The variants are classified into three categories: LP/P, LB/B and US.
  • LP/P: likely pathogenic or pathogenic.
  • LB/B: likely benign or benign.
  • US: uncertain significance
Residue change: help From Valine (V) to Methionine (M) at position 155 (V155M, p.Val155Met). Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.
Physico-chemical properties: help Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help 1 The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page
Variant description: help In SAVI; constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 155 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 379 The length of the canonical sequence.
Location on the sequence: help GLKGLAPAEISAVCEKGNFN V AHGLAWSYYIGYLRLILPEL The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.
Residue conservation: help The multiple alignment of the region surrounding the variant against various orthologous sequences. 
Human                         GLKGLAPAEISA---VCEKGNFNVAHGLAWSYYIGYLRLILP-----EL

Mouse                         GLQSLTPAEVSA---VCEEKKLNVAHGLAWSYYIGYLRLIL

Rat                           DLQSLAPAEVSA---VCEEKNFNVAHGLAWSYYIGYLKLIL

Pig                           GLQHLAPAEVSA---ICEKRNFNVAHGLAWSYYIGYLRLIL

Bovine                        GLQGLAPAEVSA---ICEKRNFNVAHGLAWSYYIGYLRLIL

Chicken                       GLQKLSAVEVSE---LTESSKKNVAHGLAWSYYIGYLKVVL

Xenopus tropicalis            GIQGPTPATISE---ITEIKQLNVAHGLAWSYYVGYLQFVL

Zebrafish                     GVLGPAPVEISE---ICEAKKMNVAHGLAWSFYIGYLKFLL

Drosophila                    SFTDMDQSTLSYSHWIRDSHGLDYAAGMASNYFHGYLKLSL
Sequence annotation in neighborhood: help The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.
TypePositionsDescription
Chain 1 – 379 Stimulator of interferon genes protein
Topological domain 135 – 379 Cytoplasmic
Region 1 – 190 Mediates interaction with ZDHHC1 and ZDHHC11
Region 153 – 340 Cyclic dinucleotide-binding domain (CBD)
Binding site 162 – 162
Binding site 162 – 162
Binding site 167 – 167
Binding site 167 – 167
Binding site 167 – 167
Cross 150 – 150 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis 137 – 137 K -> R. Does not affect amount of ubiquitination.
Mutagenesis 150 – 150 K -> R. Abolishes ubiquitination, homodimerization and subsequent production of IFN-beta.
Mutagenesis 153 – 153 F -> A. Partially constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand.
Mutagenesis 158 – 158 G -> A. Constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand.
Mutagenesis 158 – 158 G -> E. Abolished homodimerization and activation.
Mutagenesis 158 – 158 G -> SV. Partially constitutively active mutant that promotes the production of type I interferon in absence of cGAMP ligand.
Mutagenesis 162 – 162 S -> A. Slight decrease in c-di-GMP-binding. Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway. Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug; when associated with I-266.
Mutagenesis 166 – 166 G -> S. Slight decrease in c-di-GMP-binding.



Literature citations
Cryo-EM structures of STING reveal its mechanism of activation by cyclic GMP-AMP.
Shang G.; Zhang C.; Chen Z.J.; Bai X.C.; Zhang X.;
Nature 567:389-393(2019)
Cited for: STRUCTURE BY ELECTRON MICROSCOPY (4.1 ANGSTROMS) OF 1-379; FUNCTION; SUBCELLULAR LOCATION; PHOSPHORYLATION; MUTAGENESIS OF ILE-10; ARG-14; GLU-68; GLU-69; PHE-153 AND GLY-158; CHARACTERIZATION OF VARIANT SAVI MET-155; Inherited STING-activating mutation underlies a familial inflammatory syndrome with lupus-like manifestations.
Jeremiah N.; Neven B.; Gentili M.; Callebaut I.; Maschalidi S.; Stolzenberg M.C.; Goudin N.; Fremond M.L.; Nitschke P.; Molina T.J.; Blanche S.; Picard C.; Rice G.I.; Crow Y.J.; Manel N.; Fischer A.; Bader-Meunier B.; Rieux-Laucat F.;
J. Clin. Invest. 124:5516-5520(2014)
Cited for: VARIANT SAVI MET-155; CHARACTERIZATION OF VARIANT SAVI MET-155; Activated STING in a vascular and pulmonary syndrome.
Liu Y.; Jesus A.A.; Marrero B.; Yang D.; Ramsey S.E.; Montealegre Sanchez G.A.; Tenbrock K.; Wittkowski H.; Jones O.Y.; Kuehn H.S.; Lee C.C.; DiMattia M.A.; Cowen E.W.; Gonzalez B.; Palmer I.; DiGiovanna J.J.; Biancotto A.; Kim H.; Tsai W.L.; Trier A.M.; Huang Y.; Stone D.L.; Hill S.; Kim H.J.; St Hilaire C.; Gurprasad S.; Plass N.; Chapelle D.; Horkayne-Szakaly I.; Foell D.; Barysenka A.; Candotti F.; Holland S.M.; Hughes J.D.; Mehmet H.; Issekutz A.C.; Raffeld M.; McElwee J.; Fontana J.R.; Minniti C.P.; Moir S.; Kastner D.L.; Gadina M.; Steven A.C.; Wingfield P.T.; Brooks S.R.; Rosenzweig S.D.; Fleisher T.A.; Deng Z.; Boehm M.; Paller A.S.; Goldbach-Mansky R.;
N. Engl. J. Med. 371:507-518(2014)
Cited for: VARIANTS SAVI LEU-147; SER-154 AND MET-155; TISSUE SPECIFICITY;
Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.