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MGP002090

UniProt Annotations

Entry Information
Gene Namenuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha
Protein EntryIKBA_HUMAN
UniProt IDP25963
SpeciesHuman
Comments
Comment typeDescription
DiseaseEctodermal dysplasia, anhidrotic, with T-cell immunodeficiency autosomal dominant (ADEDAID) [MIM:612132]: 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. {ECO:0000269|PubMed:14523047, ECO:0000269|PubMed:18412279}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionInhibits 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. {ECO:0000269|PubMed:7479976}.
InductionInduced in adherent monocytes.
InteractionSelf; NbExp=2; IntAct=EBI-307386, EBI-307386; O15111:CHUK; NbExp=14; 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=12; IntAct=EBI-307386, EBI-81266; Q9Y6K9:IKBKG; NbExp=5; IntAct=EBI-307386, EBI-81279; P19838:NFKB1; NbExp=2; IntAct=EBI-307386, EBI-300010; Q04206:RELA; NbExp=14; IntAct=EBI-307386, EBI-73886; P23396:RPS3; NbExp=6; IntAct=EBI-307386, EBI-351193; P0CG48:UBC; NbExp=3; IntAct=EBI-307386, EBI-3390054; Q9J0X9:UL54 (xeno); NbExp=3; IntAct=EBI-307386, EBI-7967856;
PtmDeubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation.
PtmMonoubiquitinated 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. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136, ECO:0000269|PubMed:20347421, ECO:0000269|PubMed:20504922, ECO:0000269|PubMed:7479976}.
PtmPhosphorylated; 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. {ECO:0000269|PubMed:10329681, ECO:0000269|PubMed:10882136, ECO:0000269|PubMed:20504922}.
PtmSumoylated; sumoylation requires the presence of the nuclear import signal. Sumoylation blocks ubiquitination and proteasome- mediated degradation of the protein thereby increasing the protein stability. {ECO:0000269|PubMed:11124955, ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:20504922}.
SimilarityBelongs to the NF-kappa-B inhibitor family. {ECO:0000305}.
SimilarityContains 5 ANK repeats. {ECO:0000255|PROSITE- ProRule:PRU00023}.
Subcellular LocationCytoplasm. Nucleus. Note=Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export. {ECO:0000250}.
SubunitInteracts 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 isoform 1 and isoform 2 of 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. Interacts with MEFV. {ECO:0000269|PubMed:10454581, ECO:0000269|PubMed:10657303, ECO:0000269|PubMed:1493333, ECO:0000269|PubMed:16648481, ECO:0000269|PubMed:17003112, ECO:0000269|PubMed:17956732, ECO:0000269|PubMed:18577712, ECO:0000269|PubMed:20356841, ECO:0000269|PubMed:23469069}.
Web ResourceName=NFKBIAbase; Note=NFKBIA mutation db; URL="http://structure.bmc.lu.se/idbase/NFKBIAbase/";
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/nfkbia/";
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