NFKBIA

Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkB alpha, NFKBIA, or IKBA), is a member of the NF-kappa-B inhibitor family that function to inhibit the NF-kB transcription factor. NFKBIA inhibits NF-kB by masking the nuclear localization signals (NLS) of NF-kB proteins and keeping them sequestered in an inactive state in the cytoplasm. In addition, NFKBIA blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NF-kB's proper functioning. Signal-induced degradation of I kappa B alpha exposes the nuclear localization signal of NF-kappa B, thus allowing it to translocate into the nucleus and activate transcription from responsive genes. An autoregulatory loop is established when NF-kappa B induces expression of the I kappa B alpha gene and newly synthesized I kappa B alpha accumulates in the nucleus where it negatively regulates NF-kappa B-dependent transcription. As part of this post-induction repression, the nuclear export signal on I kappa B alpha mediates transport of NF-kappa B-I kappa B alpha complexes from the nucleus to the cytoplasm. Deletion of NFKBIA has an effect that is similar to the effect of EGFR amplification in the pathogenesis of glioblastoma and is associated with comparatively short survival. Polymorphisms in NFKBIA may be important in pre-disposition to and outcome after treatment, of multiple myeloma (MM). The NFKBIA gene product, IkappaBalpha, binds to NF-kappaB preventing its activation and is important in mediating resistance to apoptosis in B-cell lymphoproliferative diseases.

NFKBIA Related Areas

Signal Transduction>>NFkB pathway>>IkB alpha/NFKBIA

Cancer>>NFkB pathway>>IkB alpha/NFKBIA

NFKBIA Alternative Names

IkB alpha, NFKBIA, IKBA, MAD-3, NFKBI [Homo sapiens]

IkB alpha, Nfkbia, AI462015, Nfkbi [Mus musculus]

Summaries for NFKBIA

Entrez Gene summary for NFKBIA:

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

OMIM - description for NFKBIA:

NFKB1 or NFKB2 is bound to REL , RELA , or RELB to form the NFKB complex. The NFKB complex is inhibited by I-kappa-B proteins (NFKBIA or NFKBIB), which inactivate NF-kappa-B by trapping it in the cytoplasm. Phosphorylation of serine residues on the I-kappa-B proteins by kinases (IKBKA or IKBKB) marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kappa-B complex. Activated NFKB complex translocates into the nucleus and binds DNA at kappa-B-binding motifs such as 5-prime GGGRNNYYCC 3-prime or 5-prime HGGARNYYCC 3-prime (where H is A, C, or T; R is an A or G purine; and Y is a C or T pyrimidine).

Wikipedia summary for NFKBIA:

IκBα (nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha;NFKBIA) is one member of a family of cellular proteins that function to inhibit the NF-κB transcription factor. NFKBIA inhibits NF-κB by masking the nuclear localization signals (NLS) of NF-κB proteins and keeping them sequestered in an inactive state in the cytoplasm. In addition, NFKBIA blocks the ability of NF-κB transcription factors to bind to DNA, which is required for NFKBIA's proper functioning.

Human NFKBIA Protein General Information

 

• Protein names: NF-kappa-B inhibitor alpha,Short name=NFKBIA
• Sequence length: 317 AA.
• Domain: ANK repeat Repeat
• Sequence similarities: Belongs to the NF-kappa-B inhibitor family. Contains 5 ANK repeats.
• Post-translational modification: 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.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 polyubiquitinatin leads to protein degredation. 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 interefers with NFKBIA degradation and impairs subsequenbt NF-kappa-B activation.
• Subunit structure: 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. Interacts (when phosphorylated at the 2 serine residues in the destruction motif D-S-G-X(2,3,4)-S) with BTRC. Associates with the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC; the association is mediated via interaction with BTRC. Part of a SCF(BTRC)-like complex lacking CUL1, which is associated with RELA; RELA interacts directly with NFKBIA. Interacts with PRMT2. Interacts with PRKACA in platlets; this interaction is disrupted by thrombin and collagen.
• Subcellular location: Cytoplasm. Nucleus. Note: Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export
• Involvement in 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.
• Induction: Induced in adherent monocytes.

General information above from UniProt

Function for NFKBIA Protein

UniProtKB:

NFKBIA 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, NFKBIA becomes phosphorylated promoting ubiquitination and degradation, NFKBIA enables the dimeric RELA to tranlocate to the nucleus and activate transcription.

Genatlas:

• NFKBIA is a transcription factor of kappa light chain gene enhancer in B cells (NF-kappa B) inhibitor alpha, sequestering NFKB in the cytoplasm, inhibiting NFKB activation after modification by UBL1

Phenotype Information for NFKBIA

• Gene/Locus: NFKBIA, IKBA
• Phenotype: Ectodermal dysplasia, anhidrotic, with T-cell immunodeficiency

Phenotype Information for NFKBIA from OMIM (Online Mendelian Inheritance in Man)