UniProtKB/SwissProt variant VAR

Variant information

Variant position:

57

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 Glutamate (E) to Lysine (K) at position 57 (E57K, p.Glu57Lys).

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 medium size and acidic (E) to large size and basic (K)

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

Involvement in disease:

Incontinentia pigmenti (IP) [MIM:308300]: A genodermatosis usually prenatally lethal in males. In affected females, it causes abnormalities of the skin, hair, eyes, nails, teeth, skeleton, heart, and central nervous system. The prominent skin signs occur in four classic cutaneous stages: perinatal inflammatory vesicles, verrucous patches, a distinctive pattern of hyperpigmentation and dermal scarring. {ECO:0000269|PubMed:10839543, ECO:0000269|PubMed:11590134, ECO:0000269|PubMed:15229184, ECO:0000269|PubMed:17728323, ECO:0000269|PubMed:19033441, ECO:0000269|PubMed:20434027, ECO:0000269|PubMed:24339369}. 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 IP; shows the same luciferase activity as the control.

Any additional useful information about the variant.

Other resources:

Links to websites of interest for the variant.

Variant rs148695964 [ dbSNP | Ensembl ]

Sequence information

Variant position:

57

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

Protein sequence length:

419

The length of the canonical sequence.

Location on the sequence:

AMLHLPSEQGAPETLQRCLE E NQELRDAIRQSNQILRERCE

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                         AMLHLPSEQGAPETLQRCLEENQELRDAIRQSNQILRERCE

Mouse                         AMLHLPSEQGTPETLQRCLEENQELRDAIRQSNQMLRERCE

Rat                           AMLHLPSEQGTPETLQRCLEENQELRDAIRQSNQMLRERCE

Pig                           TMLHLPSEQGAPETFQRCLEENQELRDAIRQSNQMLRERCE

Bovine                        AMLHVPSEQGTPETFQRCLEENQELRDAIRQSNQMLRERCE

Drosophila                    TVNCIPVSITASQQQHKSLDSGSSQQQSLATSFIMGEIQSD

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 – 419	NF-kappa-B essential modulator
Region	44 – 111	Interaction with CHUK/IKBKB
Coiled coil	49 – 356
Modified residue	43 – 43	Phosphoserine; by IKKB
Modified residue	68 – 68	Phosphoserine
Disulfide bond	54 – 54	Interchain
Mutagenesis	68 – 68	S -> A. Increases formation of homodimers.
Mutagenesis	68 – 68	S -> E. Abolishes interaction with IKBKB; abolishes TNF-alpha induced NF-kappa-B activity.
Helix	38 – 129

Literature citations

A recurrent deletion in the ubiquitously expressed NEMO (IKK-gamma) gene accounts for the vast majority of incontinentia pigmenti mutations.
Aradhya S.; Woffendin H.; Jakins T.; Bardaro T.; Esposito T.; Smahi A.; Shaw C.; Levy M.; Munnich A.; D'Urso M.; Lewis R.A.; Kenwrick S.; Nelson D.L.;
Hum. Mol. Genet. 10:2171-2179(2001)
Cited for: VARIANTS IP LYS-57 AND VAL-407;

Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-kappaB activation.
Fusco F.; Bardaro T.; Fimiani G.; Mercadante V.; Miano M.G.; Falco G.; Israeel A.; Courtois G.; D'Urso M.; Ursini M.V.;
Hum. Mol. Genet. 13:1763-1773(2004)
Cited for: VARIANTS IP LYS-57; LYS-90 DEL AND TRP-123; VARIANT ASN-113; CHARACTERIZATION OF VARIANTS IP LYS-57; LYS-90 DEL AND TRP-123; CHARACTERIZATION OF VARIANT ASN-113;

UniProtKB/Swiss-Prot Q9Y6K9: Variant p.Glu57Lys