UniProtKB/SwissProt variant VAR

Variant information

Variant position:

298

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

Type of variant:

Unclassified

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 Glutamate (E) to Lysine (K) at position 298 (E298K, p.Glu298Lys).

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 medium size and acidic (E) to large size and basic (K)

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:

Unknown pathological significance.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs763636007 [ dbSNP | Ensembl ]

Sequence information

Variant position:

298

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

Protein sequence length:

545

The length of the canonical sequence.

Location on the sequence:

SVPAPLALPSDPQLHQKNED E CAVCRDGGELICCDGCPRAF

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                         SVPAPLALPSDPQLHQKNEDECAVCRDGGELICCDGCPRAF

Mouse                         GVPPLPSLPSEPQVNQKNEDECAVCHDGGELICCDGCPRAF

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 – 545	Autoimmune regulator
Zinc finger	296 – 343	PHD-type 1
Region	295 – 298	Interaction with histone H3 not methylated at 'Lys-4'
Alternative sequence	293 – 293	Q -> PVCMGVSCLCQ. In isoform 4.
Mutagenesis	295 – 295	N -> A. Abolishes interaction with histone H3.
Mutagenesis	297 – 297	D -> A. Strongly reduces interaction with unmethylated histone H3 and abolishes interaction with histone H3 trimethylated at 'Lys-4'. No effect on doted nuclear localization. Dominant-negatif effect on target gene transcription.
Mutagenesis	298 – 298	E -> A. Reduces interaction with histone H3.
Mutagenesis	302 – 302	C -> P. Reduces transcriptional activation.
Mutagenesis	303 – 303	R -> P. Alters protein folding and abolishes interaction with histone H3. No effect on doted nuclear localization. Dominant-negatif effect on target gene transcription.
Mutagenesis	304 – 304	D -> A. Strongly reduces interaction with histone H3.
Mutagenesis	307 – 307	E -> A. Reduces interaction with histone H3.
Mutagenesis	312 – 312	D -> A. Abolishes interaction with histone H3.
Mutagenesis	312 – 312	D -> N. No effect on doted nuclear localization. Dominant-negatif effect on target gene transcription.
Beta strand	298 – 303

Literature citations

Dominant mutations in the autoimmune regulator AIRE are associated with common organ-specific autoimmune diseases.
Oftedal B.E.; Hellesen A.; Erichsen M.M.; Bratland E.; Vardi A.; Perheentupa J.; Kemp E.H.; Fiskerstrand T.; Viken M.K.; Weetman A.P.; Fleishman S.J.; Banka S.; Newman W.G.; Sewell W.A.; Sozaeva L.S.; Zayats T.; Haugarvoll K.; Orlova E.M.; Haavik J.; Johansson S.; Knappskog P.M.; Loevaas K.; Wolff A.S.; Abramson J.; Husebye E.S.;
Immunity 42:1185-1196(2015)
Cited for: INVOLVEMENT IN APS1; FUNCTION; SUBCELLULAR LOCATION; VARIANTS APS1 PRO-28; CYS-90; MET-301; TYR-311 AND LEU-326; CHARACTERIZATION OF VARIANTS PRO-28; CYS-90; MET-301; TYR-311 AND LEU-326; MUTAGENESIS OF 28-LEU-LEU-29; LEU-97; ASP-297; ARG-303; ASP-312; CYS-446 AND ARG-471; VARIANTS LYS-298; TRP-299; TYR-302; GLN-303; TRP-303; SER-305; ARG-306; MET-309; GLN-316; TRP-316; PRO-319; GLN-328; TRP-328; ARG-332 AND ALA-484; CHARACTERIZATION OF VARIANTS LYS-298; TYR-302; SER-305 AND GLN-328;

UniProtKB/Swiss-Prot O43918: Variant p.Glu298Lys