NF-kappa B inhibitor alpha; IKB-alpha; MHC enhancer-binding protein MAD3; NF-kappa-B inhibitor alpha; I-kappa-B-alpha; IkappaBalpha; IkB-alpha; NFKBIA; IKBA (MAD3, NFKBI)
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Function
- IKB-alpha specifically binds to NF-kappa B p65 inhibiting transcriptional activity of NF-kappa B by retaining it in the cytoplasm
- binding to NF-kappa B is inhibited by H2O2, TNF, LPS, IL-1 & dsRNA, with all such in vitro inhibitions reversed by thiols
- various stimuli, typically those associated with stress or pathogens, rapidly inactivate IKB-alpha, liberating NF-kappa B to translocate to the nucleus & initiate transcription of genes important for the defense of the organism[2]
- activation of NF-kappa B correlates with phosphorylation of IKB-alpha on Ser-32 & Ser-36 which is required for ubiquitination & subsequent proteolysis of IKB-alpha
- phosphorylation of IKB-alpha does not itself dissociate complexes of NF-kappa B/IKB-alpha[2]
- inhibits activity of dimeric NF-kappa-B/REL complexes by trapping REL dimers in the cytoplasm through masking of their nuclear localization signals
- on cellular stimulation by immune & proinflammatory responses, becomes phosphorylated promoting ubiquitination & degradation, enabling the dimeric RELA to translocate to the nucleus & activate transcription
- interacts with RELA; the interaction requires the nuclear import signal
- interacts with NKIRAS1 & NKIRAS2
- part of a 70-90 kD complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, IKBKAP & MAP3K14
- interacts with HBV protein X
- interacts with RWDD3; interaction enhances sumoylation
- phosphorylated; disables inhibition of NF-kappa-B DNA-binding activity
- ubiquitinated; subsequent to stimulus-dependent Ser phosphorylation
- sumoylated; sumoylation requires the presence of the nuclear import signal
Structure
- belongs to the NF-kappa-B inhibitor family
- contains 5 ANK repeats
Compartment
- cytoplasm. nucleus
- shuttles between the nucleus & the cytoplasm by a nuclear localization signal (NLS) & a CRM1-dependent nuclear export (putative)
Expression
induced in adherent monocytes
Pathology
- defects in NFKBIA are a cause of autosomal dominant anhidrotic ectodermal dysplasia with immunodeficiency
More general terms
References
- ↑ Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Oct 4;254(5028):11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1925549
Ruben SM, Dillon PJ, Schreck R, Henkel T, Chen CH, Maher M, Baeuerle PA, Rosen CA. Isolation of a rel-related human cDNA that potentially encodes the 65-kD subunit of NF-kappa B. Science. 1991 Mar 22;251(5000):1490-3. Erratum in: Science. 1991 Oct 4;254(5028):11. PMID: https://www.ncbi.nlm.nih.gov/pubmed/2006423 - ↑ 2.0 2.1 2.2 Nigg EA, Baeuerle PA, Luhrmann R. Nuclear import-export: in search of signals and mechanisms. Cell. 1991 Jul 12;66(1):15-22. Review. No abstract available. PMID: https://www.ncbi.nlm.nih.gov/pubmed/1712670
- ↑ Brown K, Gerstberger S, Carlson L, Franzoso G, Siebenlist U. Control of I kappa B-alpha proteolysis by site-specific, signal-induced phosphorylation. Science. 1995 Mar 10;267(5203):1485-8. PMID: https://www.ncbi.nlm.nih.gov/pubmed/7878466
- ↑ UniProt http://www.uniprot.org/uniprot/P25963.html
- ↑ NFKBIAbase; Note: NFKBIA mutation db http://bioinf.uta.fi/NFKBIAbase/
- ↑ SeattleSNPs http://pga.gs.washington.edu/data/nfkbia/