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UniProtKB/Swiss-Prot O43918: Variant p.Ser278Arg

Autoimmune regulator
Gene: AIRE
Variant information

Variant position:  278
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Polymorphism
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 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.



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.

TypePositionsDescription
Chain 1 – 545 Autoimmune regulator
Domain 181 – 280 SAND
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-negatif 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;

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.