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Details on Person UniProt:P25963 NFKBIA
| Class:Id | ReferenceGeneProduct:57208 |
|---|---|
| _chainChangeLog | chain:1-317 added on Sat February 7 2015 |
| _displayName | UniProt:P25963 NFKBIA |
| _timestamp | 2025-02-21 19:07:49 |
| chain | chain:1-317 |
| checksum | 088B313226786395 |
| comment | FUNCTION Inhibits the activity of dimeric NF-kappa-B/REL complexes by trapping REL (RELA/p65 and NFKB1/p50) dimers in the cytoplasm by masking their nuclear localization signals (PubMed:1493333, PubMed:36651806, PubMed:7479976). 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 (PubMed:7479976, PubMed:7628694, PubMed:7796813, PubMed:7878466).SUBUNIT Interacts with RELA; the interaction requires the nuclear import signal (PubMed:1493333). Part of a 70-90 kDa complex at least consisting of CHUK, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14 (PubMed:9751059). Interacts with NKIRAS1 and NKIRAS2 (PubMed:10657303). Interacts with isoform 1 and isoform 2 of RWDD3; the interaction enhances sumoylation (PubMed:17956732, PubMed:23469069). Interacts with PRMT2 (PubMed:16648481). Interacts with PRKACA in platelets; this interaction is disrupted by thrombin and collagen (PubMed:20356841). Interacts with MEFV (PubMed:18577712). Interacts with DDRGK1; positively regulates NFKBIA phosphorylation and degradation (PubMed:23675531). Interacts with HNRNPA2B1; the interaction may be mediated by the RRM2 domain of HNRNPA2B1, and HNRNPA2B1 may interact simultaneously with FAM76B and either NFKBIA or NFKBIE to form a complex (PubMed:37643469).SUBUNIT (Microbial infection) Interacts with HBV protein X.INTERACTION Shuttles between the nucleus and the cytoplasm by a nuclear localization signal (NLS) and a CRM1-dependent nuclear export.INDUCTION Induced in adherent monocytes.PTM Phosphorylated at Ser-32 and Ser-36 by IKKA/CHUK and IKKB/IKBKB; disables inhibition of NF-kappa-B DNA-binding activity (PubMed:10329681, PubMed:10882136, PubMed:7628694, PubMed:7796813, PubMed:7878466, PubMed:8631829, PubMed:9701247). Phosphorylation at positions 32 and 36 is prerequisite to recognition by the SCF(FBXW11) and SCF(BTRC) complexes, leading to polyubiquitination and subsequent degradation (PubMed:10329681, PubMed:7628694, PubMed:8631829, PubMed:9701247). Phosphorylated at Ser-32 in response to FK506 treatment: phosphorylation is independent of IKKA/CHUK and IKKB/IKBKB and promotes NFKBIA degradation, followed by NF-kappa-B activation (PubMed:10574930). Phosphorylated at Tyr-42: its effect is however unclear (PubMed:8797825, PubMed:8940099). According to a report, phosphorylation at Tyr-42 activates NF-kappa-B without triggering proteolytic degradation of NFKBIA (PubMed:8797825). According to another publication, phosphorylation at Tyr-42 inhibits NF-kappa-B activity by preventing phosphorylation at Ser-32 and Ser-36 and subsequent ubiquitination and degradation (PubMed:8940099).PTM Polyubiquitinated at Lys-21 and/or Lys-22 following phosphorylation at Ser-32 and Ser-36 (PubMed:10329681, PubMed:20347421, PubMed:7479976, PubMed:8631829, PubMed:9701247). Monoubiquitinated at Lys-21 and/or Lys-22 by UBE2D3 (PubMed:10329681, PubMed:20347421, PubMed:7479976). 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 (PubMed:10437795, PubMed:20347421). The resulting polyubiquitination leads to protein degradation (PubMed:20347421, PubMed:7479976, PubMed:7628694). Also ubiquitinated by the SCF(BTRC) complex following stimulus-dependent phosphorylation at Ser-32 and Ser-36 (PubMed:10644755). Deubiquitinated by USP38, leading to NF-kappa-B inhibition (PubMed:36651806).PTM 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.PTM Hydroxylated by HIF1AN.PTM (Microbial infection) Deubiquitinated by porcine reproductive and respiratory syndrome virus Nsp2 protein, which thereby interferes with NFKBIA degradation and impairs subsequent NF-kappa-B activation.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the NF-kappa-B inhibitor family.ONLINE INFORMATION NFKBIA mutation db |
| description | recommendedName: NF-kappa-B inhibitor alpha alternativeName: I-kappa-B-alpha shortName: IkB-alpha shortName: IkappaBalpha alternativeName: Major histocompatibility complex enhancer-binding protein MAD3 |
| geneName | NFKBIA IKBA MAD3 NFKBI |
| identifier | P25963 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure ANK repeat Cytoplasm Disease variant Ectodermal dysplasia Host-virus interaction Hydroxylation Isopeptide bond Nucleus Phosphoprotein Proteomics identification Reference proteome Repeat Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 |
| name | NFKBIA |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990180] ENSEMBL:ENSG00000100906 NFKBIA [Homo sapiens] |
| secondaryIdentifier | IKBA_HUMAN B2R8L6 |
| sequenceLength | 317 |
| species | [Species:48887] Homo sapiens |
| (referenceEntity) | [EntityWithAccessionedSequence:168151] NFKBIA [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:177677] p-S32,S36-NFKBIA [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:1168581] Ub-K21,22-p-S32,S36-NFKBIA [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:4656929] NFKBIA [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:4656935] monoSUMO1-K21-NFKBIA [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:5228805] NFKBIA M37K [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:5228846] NFKBIA S32I [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:6782960] PolyUb-NFKBIA [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9630119] NFKBIA F2_M37del [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:177659] O-phospho-L-serine at 32 [ModifiedResidue:203803] O-phospho-L-serine at 32 [ModifiedResidue:203804] O-phospho-L-serine at 36 [GroupModifiedResidue:1168566] ubiquitinylated lysine (K48polyUb [cytosol]) at 21 [GroupModifiedResidue:1168569] ubiquitinylated lysine (K48polyUb [cytosol]) at 22 [GroupModifiedResidue:4656996] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 21 [FragmentDeletionModification:5228817] Deletion of residues 1 to 36 [ReplacedResidue:5228849] L-methionine 37 replaced with L-lysine [ReplacedResidue:5228852] L-serine 32 replaced with L-isoleucine [GroupModifiedResidue:5607638] ubiquitinylated lysine (K48polyUb [cytosol]) at 21 |
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No pathways have been reviewed or authored by UniProt:P25963 NFKBIA (57208)
