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Details on Person UniProt:O14920 IKBKB
| Class:Id | ReferenceGeneProduct:57216 |
|---|---|
| _chainChangeLog | chain:1-756 added on Fri February 6 2015 |
| _displayName | UniProt:O14920 IKBKB |
| _timestamp | 2026-02-20 23:06:34 |
| chain | chain:1-756 |
| checksum | F9CADF671AE9E14E |
| comment | FUNCTION Serine kinase that plays an essential role in the NF-kappa-B signaling pathway which is activated by multiple stimuli such as inflammatory cytokines, bacterial or viral products, DNA damages or other cellular stresses (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:30337470, PubMed:9346484). Acts as a part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation (PubMed:9346484). Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In turn, free NF-kappa-B is translocated into the nucleus and activates the transcription of hundreds of genes involved in immune response, growth control, or protection against apoptosis (PubMed:20434986, PubMed:20797629, PubMed:21138416, PubMed:9346484). In addition to the NF-kappa-B inhibitors, phosphorylates several other components of the signaling pathway including NEMO/IKBKG, NF-kappa-B subunits RELA and NFKB1, as well as IKK-related kinases TBK1 and IKBKE (PubMed:11297557, PubMed:14673179, PubMed:20410276, PubMed:21138416). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs (PubMed:11297557, PubMed:20410276, PubMed:21138416). Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NAA10, NCOA3, BCL10 and IRS1 (PubMed:17213322, PubMed:19716809). Phosphorylates RIPK1 at 'Ser-25' which represses its kinase activity and consequently prevents TNF-mediated RIPK1-dependent cell death (By similarity). Phosphorylates the C-terminus of IRF5, stimulating IRF5 homodimerization and translocation into the nucleus (PubMed:25326418). Following bacterial lipopolysaccharide (LPS)-induced TLR4 endocytosis, phosphorylates STAT1 at 'Thr-749' which restricts interferon signaling and anti-inflammatory responses and promotes innate inflammatory responses (PubMed:38621137). IKBKB-mediated phosphorylation of STAT1 at 'Thr-749' promotes binding of STAT1 to the ARID5A promoter, resulting in transcriptional activation of ARID5A and subsequent ARID5A-mediated stabilization of IL6 (PubMed:32209697). It also promotes binding of STAT1 to the IL12B promoter and activation of IL12B transcription (PubMed:32209697).CATALYTIC ACTIVITY L-seryl-[I-kappa-B protein] + ATP = O-phospho-L-seryl-[I-kappa-B protein] + ADP + H(+)CATALYTIC ACTIVITY L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H(+)CATALYTIC ACTIVITY L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H(+)SUBUNIT Component of the I-kappa-B-kinase (IKK) core complex consisting of CHUK, IKBKB and IKBKG; probably four alpha/CHUK-beta/IKBKB dimers are associated with four gamma/IKBKG subunits (PubMed:32935379). The IKK core complex seems to associate with regulatory or adapter proteins to form a IKK-signalosome holo-complex (PubMed:12612076). The IKK complex associates with TERF2IP/RAP1, leading to promote IKK-mediated phosphorylation of RELA/p65 (By similarity). Part of a complex composed of NCOA2, NCOA3, CHUK/IKKA, IKBKB, IKBKG and CREBBP (PubMed:11971985). Part of a 70-90 kDa complex at least consisting of CHUK/IKKA, IKBKB, NFKBIA, RELA, ELP1 and MAP3K14 (PubMed:9751059). Found in a membrane raft complex, at least composed of BCL10, CARD11, DPP4 and IKBKB (PubMed:17287217). Interacts with SQSTM1 through PRKCZ or PRKCI (PubMed:10356400). Forms an NGF-induced complex with IKBKB, PRKCI and TRAF6 (By similarity). May interact with MAVS/IPS1 (PubMed:16177806). Interacts with NALP2 (PubMed:15456791). Interacts with TICAM1 (PubMed:14739303). Interacts with FAF1; the interaction disrupts the IKK complex formation (PubMed:17684021). Interacts with ATM (PubMed:16497931). Part of a ternary complex consisting of TANK, IKBKB and IKBKG (PubMed:12133833). Interacts with NIBP; the interaction is direct (PubMed:15951441). Interacts with ARRB1 and ARRB2 (PubMed:15173580). Interacts with TRIM21 (PubMed:19675099). Interacts with NLRC5; prevents IKBKB phosphorylation and kinase activity (PubMed:20434986). Interacts with PDPK1 (PubMed:16207722). Interacts with EIF2AK2/PKR (PubMed:10848580). The phosphorylated form interacts with PPM1A and PPM1B (PubMed:18930133). Interacts with ZNF268 isoform 2; the interaction is further increased in a TNF-dependent manner (PubMed:23091055). Interacts with IKBKE (PubMed:23453969). Interacts with AKAP13 (PubMed:23090968). Interacts with IFIT5; the interaction synergizes the recruitment of IKK to MAP3K7 and enhances IKK phosphorylation (PubMed:26334375). Interacts with LRRC14; disrupts IKBKB-IKBKG interaction preventing I-kappa-B-kinase (IKK) core complex formation and leading to a decrease of IKBKB phosphorylation and NF-kappaB activation (PubMed:27426725). Interacts with SASH1 (PubMed:23776175). Interacts with ARFIP2 (PubMed:26296658). Interacts with FKBP5 (PubMed:26101251, PubMed:31434731). Interacts with kinase TBK1; the complex interacts with STAT1, leading to phosphorylation of STAT1 on 'Thr-749' by IKBKB (PubMed:32209697).SUBUNIT (Microbial infection) Interacts with Yersinia YopJ.SUBUNIT (Microbial infection) Interacts with vaccinia virus protein B14.INTERACTION Colocalized with DPP4 in membrane rafts.ALTERNATIVE PRODUCTS Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.DOMAIN The kinase domain is located in the N-terminal region. The leucine zipper is important to allow homo- and hetero-dimerization. At the C-terminal region is located the region responsible for the interaction with NEMO/IKBKG.PTM Upon cytokine stimulation, phosphorylated on Ser-177 and Ser-181 by MEKK1 and/or MAP3K14/NIK as well as TBK1 and PRKCZ; which enhances activity (PubMed:10022904, PubMed:16207722). Phosphorylated by MAP3K7/TAK1 in response to NOD1 and NOD2 signaling, promoting activation and phosphorylation of NF-kappa-B inhibitors, leading to NF-kappa-B activation (PubMed:11460167). Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response (PubMed:10195894). Phosphorylated by the IKK-related kinases TBK1 and IKBKE, which is associated with reduced CHUK/IKKA and IKBKB activity and NF-kappa-B-dependent gene transcription (PubMed:10783893). Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B (PubMed:18930133).PTM (Microbial infection) Acetylation of Thr-180 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway.PTM Ubiquitinated. Monoubiquitination involves TRIM21 that leads to inhibition of Tax-induced NF-kappa-B signaling. According to PubMed:19675099, 'Ser-163' does not serve as a monoubiquitination site. According to PubMed:16267042, ubiquitination on 'Ser-163' modulates phosphorylation on C-terminal serine residues.PTM (Microbial infection) Monoubiquitination by TRIM21 is disrupted by Yersinia YopJ.PTM Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappa-B.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily. |
| description | recommendedName: Inhibitor of nuclear factor kappa-B kinase subunit beta shortName: I-kappa-B-kinase beta shortName: IKK-B shortName: IKK-beta shortName: IkBKB ecNumber evidence="58"2.7.11.10 alternativeName: fullName evidence="64"I-kappa-B kinase 2 shortName evidence="64"IKK-2 shortName evidence="64"IKK2 alternativeName: Nuclear factor NF-kappa-B inhibitor kinase beta shortName: NFKBIKB alternativeName: Serine/threonine protein kinase IKBKB ecNumber evidence="47 55 57"2.7.11.1 |
| geneName | IKBKB IKKB |
| identifier | O14920 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing ATP-binding Cytoplasm Direct protein sequencing Disease variant Host-virus interaction Hydroxylation Isopeptide bond Kinase Membrane Nucleotide-binding Nucleus Phosphoprotein Proteomics identification Reference proteome S-nitrosylation SCID Serine/threonine-protein kinase Transferase Ubl conjugation |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9841277] Weiser, Joel [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9939033] Weiser, Joel, 2025-02-21 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | IKBKB |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:8990767] ENSEMBL:ENSG00000104365 IKBKB [Homo sapiens] |
| secondaryIdentifier | IKKB_HUMAN B4DZ30 B4E0U4 O75327 |
| sequenceLength | 756 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8972439] UniProt:O14920-1 IKBKB [Homo sapiens] [ReferenceIsoform:8972440] UniProt:O14920-2 IKBKB [Homo sapiens] [ReferenceIsoform:8972441] UniProt:O14920-3 IKBKB [Homo sapiens] [ReferenceIsoform:8972442] UniProt:O14920-4 IKBKB [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:168114] IKBKB [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:177657] p-IKBKB [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:202506] p-S177,S181-IKBKB [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:1168584] IKBKB [plasma membrane] [Homo sapiens] [EntityWithAccessionedSequence:9628518] IKBKB Q432Pfs*62 [cytosol] [Homo sapiens] |
| (referenceSequence) | [ModifiedResidue:177665] phosphorylated residue at unknown position [ModifiedResidue:193953] O-phospho-L-serine at 181 [ModifiedResidue:193958] O-phospho-L-serine at 177 [FragmentReplacedModification:9628517] Replacement of residues 432 to 493 |
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No pathways have been reviewed or authored by UniProt:O14920 IKBKB (57216)
