Recombinant Human IKB alpha protein

Specifications

Form

Liquid

Additional notes

ab113133 was purified by using conventional chromatography techniques.

General info

Function

Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed : 1493333, PubMed : 36651806, PubMed : 7479976). On cellular stimulation by immune and pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription (PubMed : 7479976, PubMed : 7628694, PubMed : 7796813, PubMed : 7878466).

Sequence similarities

Belongs to the NF-kappa-B inhibitor family.

Post-translational modifications

Phosphorylated at Ser-32 and Ser-36 by IKKA/CHUK and IKKB/IKBKB; disables inhibition of NF-kappa-B DNA-binding activity (PubMed:10329681, PubMed:10882136, PubMed:7628694, PubMed:7796813, PubMed:7878466, PubMed:8631829, PubMed:9701247). Phosphorylation at positions 32 and 36 is prerequisite to recognition by the SCF(FBXW11) and SCF(BTRC) complexes, leading to polyubiquitination and subsequent degradation (PubMed:10329681, PubMed:7628694, PubMed:8631829, PubMed:9701247). Phosphorylated at Ser-32 in response to FK506 treatment: phosphorylation is independent of IKKA/CHUK and IKKB/IKBKB and promotes NFKBIA degradation, followed by NF-kappa-B activation (PubMed:10574930). Phosphorylated at Tyr-42: its effect is however unclear (PubMed:8797825, PubMed:8940099). According to a report, phosphorylation at Tyr-42 activates NF-kappa-B without triggering proteolytic degradation of NFKBIA (PubMed:8797825). According to another publication, phosphorylation at Tyr-42 inhibits NF-kappa-B activity by preventing phosphorylation at Ser-32 and Ser-36 and subsequent ubiquitination and degradation (PubMed:8940099).. Polyubiquitinated at Lys-21 and/or Lys-22 following phosphorylation at Ser-32 and Ser-36 (PubMed:10329681, PubMed:20347421, PubMed:7479976, PubMed:8631829, PubMed:9701247). Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3 (PubMed:10329681, PubMed:20347421, PubMed:7479976). 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 (PubMed:10437795, PubMed:20347421). The resulting polyubiquitination leads to protein degradation (PubMed:20347421, PubMed:7479976, PubMed:7628694). Also ubiquitinated by the SCF(BTRC) complex following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (PubMed:10644755). Deubiquitinated by USP38, leading to NF-kappa-B inhibition (PubMed:36651806).. 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.. Hydroxylated by HIF1AN.. (Microbial infection) Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation.

Subcellular localisation

Nucleus