UniProtKB/SwissProt variant VAR

Variant information

Variant position:

285

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:

Disease [Disclaimer]

The variants are classified into three categories: Disease, Polymorphism and Unclassified.

Disease: Variants implicated in disease according to literature reports.
Polymorphism: Variants not reported to be implicated in disease.
Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:

From Arginine (R) to Glutamine (Q) at position 285 (R285Q, p.Arg285Gln).

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 medium size and polar (Q)

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

Involvement in disease:

Encephalopathy, acute, infection-induced, Herpes-specific, 7 (IIAE7) [MIM:616532]: A rare complication of human herpesvirus 1 (HHV-1) infection, occurring in only a small minority of HHV-1 infected individuals. It is characterized by hemorrhagic necrosis of parts of the temporal and frontal lobes. Onset is over several days and involves fever, headache, seizures, stupor, and often coma, frequently with a fatal outcome. {ECO:0000269|PubMed:26216125}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

The name and a short description of the disease associated with the variant. For more information about the disease, the user can refer to OMIM, following the link provided after the disease acronym.

Variant description:

In IIAE7; loss of viral infection-induced phosphorylation at S-386; loss of viral infection-induced homodimerization; loss of viral infection-induced transcription factor activity; unable to activate interferon transcription in response to viral infection.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs750526659 [ dbSNP | Ensembl ]

Sequence information

Variant position:

285

The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:

427

The length of the canonical sequence.

Location on the sequence:

LSCLGGGLALWRAGQWLWAQ R LGHCHTYWAVSEELLPNSGH

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                         LSCLGGGLALWRAGQWLWAQRLGHCHTYWAVSEELLPNSGH

Mouse                         LKGLGNGLALWQAGQCLWAQRLGHSHAFWALGEELLPDSGR

Pig                           LSCLGGGLALWRAGQWLWAQRLGHCHVYWAMGEELIPDSGH

Bovine                        LSCLGGGLALWRAGQWLCAQRLGHCHVYWAIGEELLPSCGH

Chicken                       LEVAGLRLEQ-RAGQ-LLATRLKKCKVFWALSQQL--EGGE

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 – 427	Interferon regulatory factor 3
Region	200 – 360	Interaction with HERC5
Disulfide bond	267 – 289
Alternative sequence	105 – 427	Missing. In isoform 5.
Alternative sequence	201 – 327	Missing. In isoform 2 and isoform 3.
Mutagenesis	285 – 285	R -> S. Abolished interaction with TMEM173/STING, MAVS or TICAM1.
Mutagenesis	288 – 288	H -> S. Decreased interaction with TICAM1.
Mutagenesis	290 – 290	H -> S. Decreased interaction with TICAM1.
Beta strand	280 – 285

Literature citations

Functional IRF3 deficiency in a patient with herpes simplex encephalitis.
Andersen L.L.; Moerk N.; Reinert L.S.; Kofod-Olsen E.; Narita R.; Joergensen S.E.; Skipper K.A.; Hoening K.; Gad H.H.; Oestergaard L.; Oerntoft T.F.; Hornung V.; Paludan S.R.; Mikkelsen J.G.; Fujita T.; Christiansen M.; Hartmann R.; Mogensen T.H.;
J. Exp. Med. 212:1371-1379(2015)
Cited for: INVOLVEMENT IN IIAE7; VARIANT IIAE7 GLN-285; CHARACTERIZATION OF VARIANT IIAE7 GLN-285;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q14653: Variant p.Arg285Gln