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UniProtKB/Swiss-Prot P25963: Variant p.Ser32Ile

NF-kappa-B inhibitor alpha
Gene: NFKBIA
Variant information

Variant position:  32
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 Serine (S) to Isoleucine (I) at position 32 (S32I, p.Ser32Ile).
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 medium size and hydrophobic (I)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -2
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:  Ectodermal dysplasia and immunodeficiency 2 (EDAID2) [MIM:612132]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. This form of ectodermal dysplasia is associated with decreased production of pro-inflammatory cytokines and certain interferons, rendering patients susceptible to infection. EDAID2 inheritance is autosomal dominant. {ECO:0000269|PubMed:14523047, ECO:0000269|PubMed:18412279}. Note=The disease is caused by mutations 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 EDAID2.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  32
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  317
The length of the canonical sequence.

Location on the sequence:   AMEGPRDGLKKERLLDDRHD  S GLDSMKDEEYEQMVKELQEI
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                         AMEGPRDGLKKERLL--DDRHDSGLDSMKDEEYEQMVKELQEI

Mouse                         AMEGPRDGLKKERLV--DDRHDSGLDSMKDEEYEQMVKELR

Rat                           AMEGPRDGLKKERLV--DDRHDSGLDSMKDEDYEQMVKELR

Pig                           AMEGPRDALKKERLL--DDRHDSGLDSMKDEEYEQMVKELR

Chicken                       GCEPPRKE-RQGGLLPPDDRHDSGLDSMKEEEYRQLVRELE

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 – 317 NF-kappa-B inhibitor alpha
Motif 30 – 36 Destruction motif
Modified residue 32 – 32 Phosphoserine; by IKKA and IKKE
Modified residue 36 – 36 Phosphoserine; by IKKA, IKKB, IKKE and TBK1
Modified residue 42 – 42 Phosphotyrosine; by Tyr-kinases
Cross 21 – 21 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO or ubiquitin); alternate
Cross 21 – 21 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 22 – 22 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis 21 – 21 K -> R. Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-22.
Mutagenesis 22 – 22 K -> R. Little change in Tax-stimulated transactivation. No sumoylation. Greatly reduced Tax- or cytokine-stimulated transactivation and decrease in ubiquitination and degradation; when associated with R-21.
Mutagenesis 31 – 31 D -> A. Loss of phosphorylation; when associated with A-35.
Mutagenesis 32 – 32 S -> A. Loss of phosphorylation, ubiquitination and degradation; when associated with A-36.
Mutagenesis 32 – 32 S -> T. Decrease in phosphorylation and degradation; when associated with T-36.
Mutagenesis 35 – 35 D -> A. Loss in phosphorylation; when associated with A-31.
Mutagenesis 35 – 35 D -> G. No change neither in phosphorylation, nor on degradation.
Mutagenesis 36 – 36 S -> A. Loss of phosphorylation, ubiquitination, and degradation; when associated with A-32.
Mutagenesis 36 – 36 S -> T. Decrease in phosphorylation and degradation; when associated with T-32.
Mutagenesis 38 – 38 K -> R. No change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-47.
Mutagenesis 42 – 42 Y -> F. No phosphorylation.
Mutagenesis 47 – 47 K -> R. Little change in Tax-stimulated transactivation. No change in Tax-stimulated transactivation; when associated with R-38.


Literature citations

A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency.
Courtois G.; Smahi A.; Reichenbach J.; Doffinger R.; Cancrini C.; Bonnet M.; Puel A.; Chable-Bessia C.; Yamaoka S.; Feinberg J.; Dupuis-Girod S.; Bodemer C.; Livadiotti S.; Novelli F.; Rossi P.; Fischer A.; Israel A.; Munnich A.; Le Deist F.; Casanova J.L.;
J. Clin. Invest. 112:1108-1115(2003)
Cited for: VARIANT EDAID2 ILE-32;

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.