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NFKBIA

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 translocate to the nucleus and activate transcription.

Involvement in disease

Ectodermal dysplasia and immunodeficiency 2

EDAID2

A form of ectoderma dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. This form of ectodermal dysplasia is associated with decreased production of pro-inflammatory cytokines and certain interferons, rendering patients susceptible to infection. EDAID2 inheritance is autosomal dominant.

None

The disease is caused by variants affecting the gene represented in this entry.

Post-translational modifications

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.

Sequence similarities

Belongs to the NF-kappa-B inhibitor family.

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

  • NF-kappa-B inhibitor alpha
  • I-kappa-B-alpha
  • Major histocompatibility complex enhancer-binding protein MAD3
  • IkB-alpha
  • IkappaBalpha
  • MAD3
  • NFKBI
  • IKBA
  • NFKBIA

Target type

Proteins

Primary research area

Immunology & Infectious Disease

Molecular weight

35609Da