Phospho-NFKBIA (Ser32/36)

This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have been found in ectodermal dysplasia anhidrotic with T-cell immunodeficiency autosomal dominant disease. [provided by RefSeq, Aug 2011]

NFKB Inhibitor Alpha

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 pro-inflammatory responses, becomes phosphorylated promoting ubiquitination and degradation, enabling the dimeric RELA to translocate to the nucleus and activate transcription.

Apoptotic processManual Assertion Based On ExperimentTAS:ProtInc
Cellular response to cold1 PublicationNAS:BHF-UCL
Cytoplasmic sequestering of NF-kappaBManual Assertion Based On ExperimentIMP:BHF-UCL
Cytoplasmic sequestering of transcription factorManual Assertion Based On ExperimentIDA:UniProtKB
I-kappaB kinase/NF-kappaB signalingManual Assertion Based On ExperimentIDA:CAFA
Lipopolysaccharide-mediated signaling pathwayIEA:Ensembl
Negative regulation of DNA binding1 PublicationNAS:UniProtKB
Negative regulation of lipid storageManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of macrophage derived foam cell differentiationManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of myeloid cell differentiationIEA:Ensembl
Negative regulation of NF-kappaB transcription factor activityManual Assertion Based On ExperimentIDA:MGI
Negative regulation of Notch signaling pathwayIEA:Ensembl
Nucleotide-binding oligomerization domain containing 1 signaling pathwayIEA:Ensembl
Nucleotide-binding oligomerization domain containing 2 signaling pathwayIEA:Ensembl
Positive regulation of cellular protein metabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of cholesterol effluxManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of inflammatory responseManual Assertion Based On ExperimentIDA:CAFA
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:UniProtKB
Protein import into nucleusIEA:Ensembl
Regulation of cell population proliferationIEA:Ensembl
Regulation of NIK/NF-kappaB signaling1 PublicationNAS:UniProtKB
Response to exogenous dsRNAIEA:Ensembl
Response to muramyl dipeptideIEA:Ensembl
Response to muscle stretchIEA:Ensembl
Toll-like receptor 4 signaling pathwayIEA:Ensembl
Tumor necrosis factor-mediated signaling pathwayManual Assertion Based On ExperimentIDA:CAFA

Cytoplasm
Nucleus
Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export.

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.

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.