UniProtKB/SwissProt variant VAR

Variant information

Variant position:

278

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

Type of variant:

LB/B

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 Serine (S) to Arginine (R) at position 278 (S278R, p.Ser278Arg).

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 small size and polar (S) to large size and basic (R)

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

Other resources:

Links to websites of interest for the variant.

Variant rs1800520 [ dbSNP | Ensembl ]

Sequence information

Variant position:

278

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:

AKGAQGAAPGGGEARLGQQG S VPAPLALPSDPQLHQKNEDE

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                         AKGAQGAAPGGGEARLGQQGSVPAPLALPSDPQLHQKNEDE

Mouse                         AKGAQVTIPGRDEQKVGQQCGVPPLPSLPSEPQVNQKNEDE

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
Domain	181 – 280	SAND
Region	234 – 290	Disordered
Alternative sequence	1 – 292	MATDAALRRLLRLHRTEIAVAVDSAFPLLHALADHDVVPEDKFQETLHLKEKEGCPQAFHALLSWLLTQDSTAILDFWRVLFKDYNLERYGRLQPILDSFPKDVDLSQPRKGRKPPAVPKALVPPPRLPTKRKASEEARAAAPAALTPRGTASPGSQLKAKPPKKPESSAEQQRLPLGNGIQTMSASVQRAVAMSSGDVPGARGAVEGILIQQVFESGGSKKCIQVGGEFYTPSKFEDSGSGKNKARSSSGPKPLVRAKGAQGAAPGGGEARLGQQGSVPAPLALPSDPQLH -> MWLVYSSGAPGTQQPARNRVFFPIGMAPGGVCWRPDGWGTGGQGRISGPGSMGAGQRLGSSGTQRCCWGSCFGKEVALRRVLHPS. In isoform 2, isoform 3 and isoform 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-negative effect on target gene transcription.
Mutagenesis	298 – 298	E -> A. Reduces interaction with histone H3.

Literature citations

Common mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy patients of different origins.
Scott H.S.; Heino M.; Peterson P.; Mittaz L.; Lalioti M.D.; Betterle C.; Cohen A.; Seri M.; Lerone M.; Romeo G.; Collin P.; Salo M.; Metcalfe R.; Weetman A.; Papasavvas M.-P.; Rossier C.; Nagamine K.; Kudoh J.; Shimizu N.; Krohn K.J.E.; Antonarakis S.E.;
Mol. Endocrinol. 12:1112-1119(1998)
Cited for: VARIANT ARG-278;

APECED mutations in the autoimmune regulator (AIRE) gene.
Heino M.; Peterson P.; Kudoh J.; Shimizu N.; Antonarakis S.E.; Scott H.S.; Krohn K.J.E.;
Hum. Mutat. 18:205-211(2001)
Cited for: VARIANTS APS1 LEU-15; MET-16; PRO-28; PR0-29; ARG-78; LEU-80; GLU-83; CYS-85; CYS-90; ARG-93; MET-301; TYR-311 AND GLN-326; VARIANT ARG-278;

A novel missense mutation of AIRE gene in a patient with autoimmune polyendocrinopathy, candidiasis and ectodermal dystrophy (APECED), accompanied with progressive muscular atrophy: case report and review of the literature in Japan.
Sato K.; Nakajima K.; Imamura H.; Deguchi T.; Horinouchi S.; Yamazaki K.; Yamada E.; Kanaji Y.; Takano K.;
Endocr. J. 49:625-633(2002)
Cited for: VARIANT APS1 CYS-15; VARIANT ARG-278;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot O43918: Variant p.Ser278Arg