Phospho-IKB alpha (S36) Recombinant Rabbit Monoclonal Antibody [JE56-65]

Function

On the basis of both functional and structural considerations, members of the IκB family of proteins can be divided into four groups. The first of these groups, IκB-α, includes the avian protein pp40 and the mammalian MAD-3, both of which inhibit binding of p50-p65 NFkB complex or Rel protein to their cognate binding sites but do not inhibit the binding of p50 homodimer to κB sites, suggesting that the IκB-α family binds to the p65 subunit of p50-p65 heterocomplex through ankyrin repeats. The second member of the IκB family is represented by a protein designated IκB-β. The third group of IκB proteins is represented by IκB-γ, which is identical in sequence with the C-terminal domain of the p110 precursor of NFkB p50 and is expressed predominantly in lymphoid cells. An additional IκB family member, IκB-ε, has several phosphorylated forms and is primarily found complexed with Rel A and/or c-Rel.

Background References

1. Liu Y et al. The natural compound magnolol inhibits invasion and exhibits potential in human breast cancer therapy. Sci Rep 3:3098 (2013).

2. Kiefel H et al. EMT-associated up-regulation of L1CAM provides insights into L1CAM-mediated integrin signalling and NF- B activation. Carcinogenesis 33:1919-29 (2012).

Sequence Similarity

Belongs to the NF-kappa-B inhibitor family.

Post-translational Modification

Phosphorylated; disables inhibition of NF-kappa-B DNA-binding activity. Phosphorylation at positions 32 and 36 is prerequisite to recognition by UBE2D3 leading to polyubiquitination and subsequent degradation.; Sumoylated; sumoylation requires the presence of the nuclear import signal. Sumoylation blocks ubiquitination and proteasome-mediated degradation of the protein thereby increasing the protein stability.; Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3. Ubiquitin chain elongation is then performed by CDC34 in cooperation with the SCF(FBXW11) E3 ligase complex, building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. The resulting polyubiquitination leads to protein degradation. Also ubiquitinated by SCF(BTRC) following stimulus-dependent phosphorylation at Ser-32 and Ser-36.; Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation.

Subcellular Location

Cytoplasm, Nucleus.

UNIPROT

SwissProt: Q9Z1E3 Mouse

SwissProt: Q63746 Rat

Synonyms