UniProtKB/SwissProt variant VAR

Variant information

Variant position:

32

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

Type of variant:

LP/P [Disclaimer]

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 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

Variant description:

In EDAID2.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs28933100 [ dbSNP | Ensembl ]

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.

Type	Positions	Description
Chain	1 – 317	NF-kappa-B inhibitor alpha
Region	1 – 39	Disordered
Motif	30 – 36	Destruction motif
Compositional bias	11 – 39	Basic and acidic residues
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;

UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot P25963: Variant p.Ser32Ile