Nfkbia
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:10097128, PubMed:9990853). 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:10097128, PubMed:7878466, PubMed:9990853).
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:10097128, PubMed:7878466, PubMed:9859996, PubMed:9990853). 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:10097128, PubMed:9859996).
Polyubiquitinated at Lys-21 and/or Lys-22 following phosphorylation at Ser-32 and Ser-36 (PubMed:9990853). Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3 (By similarity). 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 (By similarity). The resulting polyubiquitination leads to protein degradation (By similarity). Also ubiquitinated by the SCF(BTRC) complex following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (By similarity). Deubiquitinated by USP38, leading to NF-kappa-B inhibition (By similarity).
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.
Sequence Similarities
Belongs to the NF-kappa-B inhibitor family.
Tissue Specificity
Highly expressed in lymph node, thymus followed by liver, brain, muscle, kidney, gastrointestinal and reproductive tract.
Cellular localization
- Cytoplasm
- Nucleus
- Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export.
Alternative names
Ikba, Nfkbia, NF-kappa-B inhibitor alpha, I-kappa-B-alpha, IkB-alpha, IkappaBalpha