Sequence information
Variant position: 311 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:
LHQKNEDECAVCRDGGELIC
C DGCPRAFHLACLSPPLREIP
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 LHQKNEDECAVCRDGGELICC DGCPRAFHLACLSPPLREIP
Mouse VNQKNEDECAVCHDGGELICC DGCPRAFHLACLSPPLQEIP
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
304 – 312
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-negative 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-negative 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-negative effect on target gene transcription.
Literature citations
Mutations in the AIRE gene: effects on subcellular location and transactivation function of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy protein.
Bjeorses P.; Halonen M.; Palvimo J.J.; Kolmer M.; Aaltonen J.; Ellonen P.; Perheentupa J.; Ulmanen I.; Peltonen L.;
Am. J. Hum. Genet. 66:378-392(2000)
Cited for: SUBCELLULAR LOCATION; VARIANTS APS1 LEU-80; CYS-85; TYR-311 AND GLN-326;
The autoimmune regulator PHD finger binds to non-methylated histone H3K4 to activate gene expression.
Org T.; Chignola F.; Hetenyi C.; Gaetani M.; Rebane A.; Liiv I.; Maran U.; Mollica L.; Bottomley M.J.; Musco G.; Peterson P.;
EMBO Rep. 9:370-376(2008)
Cited for: INTERACTION WITH HISTONE H3 NON-METHYLATED OR MONO-METHYLATED AT LYS-4; FUNCTION; MUTAGENESIS OF ASP-297 AND ASP-312; CHARACTERIZATION OF VARIANTS APS1 MET-301 AND TYR-311;
NMR structure of the first PHD finger of autoimmune regulator protein (AIRE1). Insights into autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) disease.
Bottomley M.J.; Stier G.; Pennacchini D.; Legube G.; Simon B.; Akhtar A.; Sattler M.; Musco G.;
J. Biol. Chem. 280:11505-11512(2005)
Cited for: STRUCTURE BY NMR OF 293-354 IN COMPLEX WITH ZINC IONS; CHARACTERIZATION OF VARIANTS APS1 MET-301; TYR-311 AND GLN-326;
Structure and site-specific recognition of histone H3 by the PHD finger of human autoimmune regulator.
Chakravarty S.; Zeng L.; Zhou M.-M.;
Structure 17:670-679(2009)
Cited for: STRUCTURE BY NMR OF 294-347 IN COMPLEX WITH ZINC IONS AND UNMETHYLATED HISTONE H3 N-TERMINUS; CHARACTERIZATION OF VARIANTS APS1 MET-301; TYR-311; LEU-326 AND GLN-326;
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;
AIRE mutations and human leukocyte antigen genotypes as determinants of the autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy phenotype.
Halonen M.; Eskelin P.; Myhre A.-G.; Perheentupa J.; Husebye E.S.; Kaempe O.; Rorsman F.; Peltonen L.; Ulmanen I.; Partanen J.;
J. Clin. Endocrinol. Metab. 87:2568-2574(2002)
Cited for: VARIANTS APS1 VAL-21; CYS-85 AND TYR-311;
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;
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.