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UniProtKB/Swiss-Prot Q9Y6K9: Variant p.Ala288Gly

NF-kappa-B essential modulator
Variant information

Variant position:  288
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 Alanine (A) to Glycine (G) at position 288 (A288G, p.Ala288Gly).
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 hydrophobic (A) to glycine (G)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  0
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 1 (EDAID1) [MIM:300291]: A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. Characterized by absence of sweat glands, sparse scalp hair, rare conical teeth and immunological abnormalities resulting in severe infectious diseases. {ECO:0000269|PubMed:11047757, ECO:0000269|PubMed:11224521, ECO:0000269|PubMed:11242109, ECO:0000269|PubMed:12045264, ECO:0000269|PubMed:14651848, ECO:0000269|PubMed:15100680, ECO:0000269|PubMed:16547522, ECO:0000269|PubMed:19185524, ECO:0000269|PubMed:21606507}. 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 EDAID1.
Any additional useful information about the variant.

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

Sequence information

Variant position:  288
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  419
The length of the canonical sequence.

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.






Drosophila                    -------------INELKARDIQKQ---EVIKGLQIQNDIY

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
Region 242 – 350 Ubiquitin-binding (UBD)
Region 246 – 365 Self-association
Region 251 – 419 Required for interaction with TNFAIP3
Coiled coil 49 – 356
Cross 277 – 277 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross 277 – 277 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 283 – 283 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 285 – 285 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 292 – 292 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 302 – 302 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Alternative sequence 257 – 304 Missing. In isoform 3.
Mutagenesis 277 – 277 K -> A. Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-309.
Mutagenesis 285 – 285 K -> R. Important decrease in the ubiquitination level; when associated with R-399.
Mutagenesis 296 – 296 E -> A. No effet on oligomerization,impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation.
Mutagenesis 300 – 300 V -> D. Greatly impairs tandem ubiquitin binding.
Mutagenesis 301 – 301 L -> A. Impairs tandem ubiquitin binding.
Mutagenesis 304 – 304 Q -> A. Complete loss of cleavage by HAV protease 3c.
Mutagenesis 304 – 304 Q -> A. Impairs tandem ubiquitin binding.
Mutagenesis 307 – 307 I -> N. Greatly impairs tandem ubiquitin binding.
Mutagenesis 308 – 308 Y -> A. Greatly impairs tandem ubiquitin binding.
Helix 271 – 295

Literature citations

X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappa B signaling.
Doeffinger R.; Smahi A.; Bessia C.; Geissmann F.; Feinberg J.; Durandy A.; Bodemer C.; Kenwrick S.J.; Dupuis-Girod S.; Blanche S.; Wood P.; Rabia S.H.; Headon D.J.; Overbeek P.A.; Le Deist F.; Holland S.M.; Belani K.; Kumararatne D.S.; Fischer A.; Shapiro R.; Conley M.E.; Reimund E.; Kalhoff H.; Abinun M.; Munnich A.; Israael A.; Courtois G.; Casanova J.-L.;
Nat. Genet. 27:277-285(2001)

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.