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UniProtKB/Swiss-Prot Q9Y6K9: Variant p.His413Tyr

NF-kappa-B essential modulator
Chromosomal location: Xq28
Variant information

Variant position:  413
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 Histidine (H) to Tyrosine (Y) at position 413 (H413Y, p.His413Tyr).
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 polar (H) to large size and aromatic (Y)
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:  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.
Any additional useful information about the variant.

Sequence information

Variant position:  413
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:   PDFCCPKCQYQAPDMDTLQI  H VMECIE
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                         PDFCCPKCQYQAPDMDTLQIHVMECIE--

Mouse                         PDFCCPKCQYQAPDMDTLQIHVMECIE

Rat                           PDFCCPKCQYQAPDMDTLQIHVMECIE

Pig                           PNFCCPKCQYQAPDMDTLQIHVMECIE

Bovine                        PKFCCPKCQYQAPDIDTLQIHVMECIE

Drosophila                    TTLRCPICSKSFNALSVLQSHVNDCLD

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.

Chain 1 – 419 NF-kappa-B essential modulator
Zinc finger 389 – 419 CCHC NOA-type
Region 251 – 419 Required for interaction with TNFAIP3
Region 382 – 419 Interaction with CYLD
Cross 399 – 399 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Mutagenesis 399 – 399 K -> R. Abolishes BCL10-mediated but not RIPK2-mediated ubiquitination. Important decrease in the ubiquitination level; when associated with R-285. No change in the ubiquitination level; when associated with R-115 or R-224.
Mutagenesis 414 – 414 V -> S. Abolishes binding to polyubiquitin.
Mutagenesis 415 – 415 M -> S. Impairs binding to polyubiquitin.
Helix 407 – 416

Literature citations

Insight into IKBKG/NEMO locus: report of new mutations and complex genomic rearrangements leading to incontinentia pigmenti disease.
Conte M.I.; Pescatore A.; Paciolla M.; Esposito E.; Miano M.G.; Lioi M.B.; McAleer M.A.; Giardino G.; Pignata C.; Irvine A.D.; Scheuerle A.E.; Royer G.; Hadj-Rabia S.; Bodemer C.; Bonnefont J.P.; Munnich A.; Smahi A.; Steffann J.; Fusco F.; Ursini M.V.;
Hum. Mutat. 35:165-177(2014)
Cited for: VARIANTS IP PRO-170; GLN-173; PRO-314; PRO-322 AND TYR-413;

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.