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UniProtKB/Swiss-Prot variant pages

UniProtKB/Swiss-Prot Q9Y6K9: Variant p.Leu322Pro

NF-kappa-B essential modulator
Gene: IKBKG
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Variant information Variant position: help 322 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 Leucine (L) to Proline (P) at position 322 (L322P, p.Leu322Pro). 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 Similar physico-chemical property. Both residues are medium size and hydrophobic. The physico-chemical property of the reference and variant residues and the change implicated.
BLOSUM score: help -3 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 IP. Any additional useful information about the variant.


Sequence information Variant position: help 322 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 KAQADIYKADFQAERQAREK L AEKKELLQEQLEQLQREYSK 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                         KAQADIYKADFQAERQAREKLAEKKELLQEQLEQLQR----------EYSK

Mouse                         KAQADIYKADFQAERHAREKLVEKKEYLQEQLEQLQR----

Rat                           KAQADIYKADFQAERHAREKLVERKELLQEQLEQLQR----

Pig                           KAQADIYKADFQAERQAREQLAERKELLQEQLEQLQR----

Bovine                        KAQADIYKADFQAERQAREKLAEKKEFLQEQLEQLQR----

Drosophila                    QIQNDIYRRDFEMERADREKNAGEKDQYLMDLRSLQRRNQE
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
Region 322 – 343 Leucine-zipper
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 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.
Mutagenesis 336 – 336 L -> A. Impairs oligomerization, impairs binding of 'Lys-63'-linked ubiuitin, impairs TNF-induced NF-kappa-B activation; when associated with A-329.
Mutagenesis 342 – 342 K -> R. No effect on MARCH2F-mediated K48-linked ubiquitination.
Helix 297 – 341



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.