UniProtKB/Swiss-Prot Q86WV6: Variant p.Arg284Ser

Stimulator of interferon genes protein
Gene: STING1
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Variant information Variant position:

284 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant:

US 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:

From Arginine (R) to Serine (S) at position 284 (R284S, p.Arg284Ser). 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:

Change from large size and basic (R) to small size and polar (S) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score:

-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:

Found in a 9-month-old patient who died following a fever and severe neck abscess without indication of any severe bacterial infection; likely pathogenic; may affect splicing; constitutively active mutant that promotes the production of type I interferon in absence of cyclic dinucleotide ligand; localizes to the perinuclear region in absence of cyclic dinucleotide ligand. Any additional useful information about the variant.

Sequence information Variant position:

284 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length:

379 The length of the canonical sequence.
Location on the sequence:

PLQTLFAMSQYSQAGFSRED R LEQAKLFCRTLEDILADAPE 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:

The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         PLQTLFAMSQYSQAGFSREDRLEQAKL--FCRTLEDILADAPE

Mouse                         PLQTLFAMSQDAKAGFSREDRLEQAKL--FCRTLEEILEDV

Rat                           PLQTLFAMSQDGKAGFSREDRLEQAKL--FCRTLEEILADV

Pig                           PLQTLFAMSQDGRAGFSREDRLEQAKL--FCRTLEDILADA

Bovine                        PLQTLFAMSQDGRAGFSREDRLEQAKL--FCRTLEDILANA

Chicken                       PLQTLCAMSQDDCAAFSREQRLEQARL--FYRSLRDILGSS

Xenopus tropicalis            PLASLLKMTDIPSAAFSADDRLQQTKL--FYRTLKDILENA

Zebrafish                     PLLTLYQMSQESSAGFGERERKQQVLL--FYRTLSQILDNS

Drosophila                    PMISFFDATYSNLSGTWQMQELKREIWIKFYKHLKELITTW

Sequence annotation in neighborhood:

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.

Type	Positions	Description
Chain	1 – 379	Stimulator of interferon genes protein
Topological domain	135 – 379	Cytoplasmic
Region	153 – 340	Cyclic dinucleotide-binding domain (CBD)
Mutagenesis	264 – 264	P -> A. Strong decrease in c-di-GMP-binding.
Mutagenesis	266 – 266	Q -> I. Renders the enzyme sensitive to 5,6-dimethylxanthenone 4-acetic acid (DMXAA) drug, leading to activation of the STING1 pathway; when associated with A-162.
Mutagenesis	267 – 267	T -> A. Strong decrease in c-di-GMP-binding.
Mutagenesis	273 – 273	Q -> A. Abolished translocation from the endoplasmic reticulum in response to cGAMP-binding. Reduced phosphorylation by TBK1.
Mutagenesis	277 – 277	A -> Q. Abolished translocation from the endoplasmic reticulum in response to cGAMP-binding. Reduced phosphorylation by TBK1.
Helix	281 – 301

Literature citations
Pro-inflammation associated with a gain-of-function mutation (R284S) in the innate immune sensor STING.
Konno H.; Chinn I.K.; Hong D.; Orange J.S.; Lupski J.R.; Mendoza A.; Pedroza L.A.; Barber G.N.;
Cell Rep. 23:1112-1123(2018)
Cited for: VARIANT SER-284; CHARACTERIZATION OF VARIANT SER-284; SUBCELLULAR LOCATION;

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.