Sequence information
Variant position: 315 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:
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: The multiple alignment of the region surrounding the variant against various orthologous sequences.
Human METVPVLKAQADIYKADFQAE RQAREKLAEKKELLQEQLEQ
Mouse METVPVLKAQADIYKADFQAE RHAREKLVEKKEYLQEQLEQ
Rat METVPVLKAQADIYKADFQAE RHAREKLVERKELLQEQLEQ
Pig METVPVLKAQADIYKADFQAE RQAREQLAERKELLQEQLEQ
Bovine METVPVLKAQADIYKADFQAE RQAREKLAEKKEFLQEQLEQ
Drosophila -EVIKGLQIQNDIYRRDFEME RADREKNAGEKDQYLMDLRS
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
242 – 350
Ubiquitin-binding (UBD)
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)
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.
Mutagenesis
309 – 309
K -> A. Partial abolition of sumoylation. Abolishes sumoylation and IKK activation; when associated with A-277.
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
323 – 323
A -> D. Greatly impairs tandem ubiquitin binding.
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. Abolishes binding to polyubiquitin.
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; 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; 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.