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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y6K9: Variant p.Glu315Ala

NF-kappa-B essential modulator
Gene: IKBKG
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Variant information Variant position: help 315 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Type of variant: help 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: help From Glutamate (E) to Alanine (A) at position 315 (E315A, p.Glu315Ala). 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: help Change from medium size and acidic (E) to small size and hydrophobic (A) The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -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

Variant description: help In IMD33; greatly impairs tandem ubiquitin binding. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin and linear tetra-ubiquitin, impairs TNF-induced NF-kappa-B activation. Any additional useful information about the variant.
Other resources: help Links to websites of interest for the variant.


Sequence information Variant position: help 315 The position of the amino-acid change on the UniProtKB canonical protein sequence.
Protein sequence length: help 419 The length of the canonical sequence.
Location on the sequence: help METVPVLKAQADIYKADFQA E RQAREKLAEKKELLQEQLEQ 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: help The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human                         METVPVLKAQADIYKADFQAERQAREKLAEKKELLQEQLEQ

Mouse                         METVPVLKAQADIYKADFQAERHAREKLVEKKEYLQEQLEQ

Rat                           METVPVLKAQADIYKADFQAERHAREKLVERKELLQEQLEQ

Pig                           METVPVLKAQADIYKADFQAERQAREQLAERKELLQEQLEQ

Bovine                        METVPVLKAQADIYKADFQAERQAREKLAEKKEFLQEQLEQ

Drosophila                    -EVIKGLQIQNDIYRRDFEMERADREKNAGEKDQYLMDLRS

Sequence annotation in neighborhood: help 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 – 419 NF-kappa-B essential modulator
Region 242 – 350 Ubiquitin-binding (UBAN)
Region 246 – 365 Self-association
Region 251 – 419 Required for interaction with TNFAIP3
Coiled coil 49 – 356
Cross 302 – 302 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 309 – 309 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO); alternate
Cross 309 – 309 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Cross 321 – 321 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 325 – 325 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)
Cross 326 – 326 Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin and interchain with MARCHF2)
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 302 – 302 K -> R. No effect on MARCH2F-mediated K48-linked ubiquitination.
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.
Mutagenesis 309 – 309 K -> A. Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277. No effect on MARCH2F-mediated K48-linked ubiquitination.
Mutagenesis 312 – 312 F -> A. Greatly impairs tandem ubiquitin binding,impairs oligomerization, impairs TNF-induced NF-kappa-B activation.
Mutagenesis 312 – 312 F -> W. MNo effet on oligomerization, preferentially binds tri-ubiquitin chains ('Lys-48' or 'Lys-63'-linked).
Mutagenesis 312 – 312 F -> Y. Impairs tandem ubiquitin binding.
Mutagenesis 313 – 313 Q -> A. Impairs tandem ubiquitin binding.
Mutagenesis 315 – 315 E -> Q. Greatly impairs tandem ubiquitin binding.
Mutagenesis 317 – 317 Q -> AW. Greatly impairs tandem ubiquitin binding.
Mutagenesis 321 – 321 K -> R. No effect on MARCH2F-mediated K48-linked ubiquitination.
Mutagenesis 323 – 323 A -> D. Greatly impairs tandem ubiquitin binding.
Mutagenesis 325 – 325 K -> R. No effect on MARCH2F-mediated K48-linked ubiquitination.
Mutagenesis 326 – 326 K -> R. Abolishes MARCH2F-mediated K48-linked ubiquitination and subsequent suppression of antiviral and antibacterial innate immune response.
Mutagenesis 329 – 329 L -> A. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-336.
Mutagenesis 329 – 329 L -> P. Abolished ubiquitin-binding.
Helix 297 – 341



Literature citations
DARPin-assisted crystallography of the CC2-LZ domain of NEMO reveals a coupling between dimerization and ubiquitin binding.
Grubisha O.; Kaminska M.; Duquerroy S.; Fontan E.; Cordier F.; Haouz A.; Raynal B.; Chiaravalli J.; Delepierre M.; Israel A.; Veron M.; Agou F.;
J. Mol. Biol. 395:89-104(2010)
Cited for: MUTAGENESIS OF GLU-296; PHE-312; GLU-315; ALA-323; LEU-329 AND LEU-336; CHARACTERIZATION OF VARIANTS IMD33 ALA-315 AND PRO-323; Structural basis for recognition of diubiquitins by NEMO.
Lo Y.C.; Lin S.C.; Rospigliosi C.C.; Conze D.B.; Wu C.J.; Ashwell J.D.; Eliezer D.; Wu H.;
Mol. Cell 33:602-615(2009)
Cited for: X-RAY CRYSTALLOGRAPHY (3.2 ANGSTROMS) OF 246-337; FUNCTION; UBIQUITIN-BINDING; MUTAGENESIS OF VAL-300; LEU-301; GLN-304; ILE-307; TYR-308; PHE-312; GLN-313 AND GLN-317; CHARACTERIZATION OF VARIANT EDAID1 ASN-311; CHARACTERIZATION OF VARIANT IMD33 ALA-315; CHARACTERIZATION OF VARIANTS GLN-319 AND IP PRO-323; X-linked susceptibility to mycobacteria is caused by mutations in NEMO impairing CD40-dependent IL-12 production.
Filipe-Santos O.; Bustamante J.; Haverkamp M.H.; Vinolo E.; Ku C.-L.; Puel A.; Frucht D.M.; Christel K.; von Bernuth H.; Jouanguy E.; Feinberg J.; Durandy A.; Senechal B.; Chapgier A.; Vogt G.; de Beaucoudrey L.; Fieschi C.; Picard C.; Garfa M.; Chemli J.; Bejaoui M.; Tsolia M.N.; Kutukculer N.; Plebani A.; Notarangelo L.; Bodemer C.; Geissmann F.; Israeel A.; Veron M.; Knackstedt M.; Barbouche R.; Abel L.; Magdorf K.; Gendrel D.; Agou F.; Holland S.M.; Casanova J.-L.;
J. Exp. Med. 203:1745-1759(2006)
Cited for: VARIANTS IMD33 ALA-315 AND GLN-319;
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.