Description: Homo sapiens nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (NFKBIA), mRNA. RefSeq Summary (NM_020529): 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]. Transcript (Including UTRs) Position: hg19 chr14:35,870,716-35,873,960 Size: 3,245 Total Exon Count: 6 Strand: - Coding Region Position: hg19 chr14:35,871,219-35,873,850 Size: 2,632 Coding Exon Count: 6
ID:IKBA_HUMAN DESCRIPTION: RecName: Full=NF-kappa-B inhibitor alpha; AltName: Full=I-kappa-B-alpha; Short=IkB-alpha; Short=IkappaBalpha; AltName: Full=Major histocompatibility complex enhancer-binding protein MAD3; 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. 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. 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 platelets; this interaction is disrupted by thrombin and collagen. Interacts with HIF1AN. INTERACTION: Self; NbExp=2; IntAct=EBI-307386, EBI-307386; O15111:CHUK; NbExp=6; IntAct=EBI-307386, EBI-81249; Q60680-2:Chuk (xeno); NbExp=2; IntAct=EBI-307386, EBI-646264; Q8N668:COMMD1; NbExp=3; IntAct=EBI-307386, EBI-1550112; O14920:IKBKB; NbExp=9; IntAct=EBI-307386, EBI-81266; Q9Y6K9:IKBKG; NbExp=2; IntAct=EBI-307386, EBI-81279; P19838:NFKB1; NbExp=2; IntAct=EBI-307386, EBI-300010; Q04206:RELA; NbExp=12; IntAct=EBI-307386, EBI-73886; SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export (By similarity). INDUCTION: Induced in adherent monocytes. PTM: 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. PTM: Sumoylated; sumoylation requires the presence of the nuclear import signal. PTM: 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. PTM: Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation. 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. SIMILARITY: Belongs to the NF-kappa-B inhibitor family. SIMILARITY: Contains 5 ANK repeats. WEB RESOURCE: Name=NFKBIAbase; Note=NFKBIA mutation db; URL="http://bioinf.uta.fi/NFKBIAbase/"; WEB RESOURCE: Name=SeattleSNPs; URL="http://pga.gs.washington.edu/data/nfkbia/";
Arthritis, Rheumatoid|Rheumatoid Arthritis|Anti-TNF Response Potter C et al. 2010, Association between anti-tumour necrosis factor treatment response and genetic variants within the TLR and NF{kappa}B signalling pathways., Annals of the rheumatic diseases 69(7) : 1315-20 2010.
[PubMed 20448286]
Several SNPs mapping to the TLR and NFkappaB signalling systems demonstrated association with anti-TNF response as a whole and, in particular, with response to etanercept. Validation of these findings in an independent cohort is now warranted.
autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency Courtois G 2003, A hypermorphic IkappaBalpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency., The Journal of clinical investigation. 2003 Oct;112(7):1108-15.
[PubMed 14523047]
colorectal cancer Gao, J. et al. 2007, Association of NFKBIA polymorphism with colorectal cancer risk and prognosis in Swedish and Chinese populations, Scand J Gastroenterol 2007 42(3) 345-50.
[PubMed 17354114]
Chinese individuals >or=50 years of age carrying the AG genotype of NFKBIA may be at an increased risk of developing CRC, and the GG genotype of NFKBIA may be considered as a prognostic factor for Swedish CRC patients.
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P25963
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
