Disease:Defects in NFKBIA are the cause of ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant (ADEDAID) [MIM:612132]. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. ADEDAID is an ectodermal dysplasia associated with decreased production of pro-inflammatory cytokines and certain interferons , rendering patients susceptible to infection. ,Function:Inhibits the 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 and proinflammatory responses , becomes phosphorylated promoting ubiquitination and degradation , enabling the dimeric RELA to tranlocate to the nucleus and activate transcription. ,induction:Induced in adherent monocytes. ,online information:NFKBIA mutation db ,PTM:Phosphorylated; disables inhibition of NF-kappa-B DNA-binding activity. ,PTM:Sumoylated; sumoylation requires the presence of the nuclear import signal. ,PTM:Ubiquitinated; subsequent to stimulus-dependent phosphorylation on serines. ,similarity:Belongs to the NF-kappa-B inhibitor family. ,similarity:Contains 5 ANK repeats. ,subcellular location:Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export. ,subunit:Interacts with RELA; the interaction requires the nuclear import signal. Interacts with NKIRAS1 and NKIRAS2. Part of a 70-90 kDa complex at least consisting of CHUK , IKBKB , NFKBIA , RELA , IKBKAP and MAP3K14. Interacts with HBV protein X. Interacts with RWDD3; the interaction enhances sumoylation. ,
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