IKBKB
entrez
3551
canonical
uniprot
O14920
canonical
ensembl
ENSG00000104365
resolver
ensp
ENSP00000428186
resolver
ensp
ENSP00000428922
resolver
ensp
ENSP00000430684
resolver
ensp
ENSP00000430868
resolver
ensp
ENSP00000540252
resolver
ensp
ENSP00000652607
resolver
ensp
ENSP00000784963
resolver
enst
ENST00000520655
resolver
enst
ENST00000520835
resolver
enst
ENST00000521661
resolver
genesymbol
IKBKB
resolver
genesymbol_syn
IKKB
resolver
hgnc
HGNC:5960
resolver
uniprot
A0A499FJS7
resolver
uniprot
B4DZ30
resolver
uniprot
B4E0U4
resolver
uniprot
G3V105
resolver
uniprot
O75327
resolver
uniprot_entry
A0A499FJS7_HUMAN
resolver
uniprot_entry
G3V105_HUMAN
resolver
uniprot_entry
IKKB_HUMAN
resolver
uniprot_sec
B4DZ30
resolver
uniprot_sec
B4E0U4
resolver
uniprot_sec
O75327
resolver
amino_acid_sequence
MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSPRNRERWCLEIQIMRRLTHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRKYLNQFENCCGLREGAILTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEQRLIHKIIDLGYAKELDQGSLCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCFKALDDILNLKLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLALIPDKPATQCISDGKLNEGHTLDMDLVFLFDNSKITYETQISPRPQPESVSCILQEPKRNLAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKMKNSMASMSQQLKAKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMALQTDIVDLQRSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQSFEKKVRVIYTQLSKTVVCKQKALELLPKVEEVVSLMNEDEKTVVRLQEKRQKELWNLLKIACSKVRGPVSGSPDSMNASRLSQPGQLMSQPSTASNSLPEPAKKSEELVAEAHNLCTLLENAIQDTVREQDQSFTALDWSWLQTEEEEHSCLEQAS
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 15B (IMD15B) [MIM:615592]: An autosomal recessive primary immunodeficiency disorder characterized by onset in infancy of life-threatening bacterial, fungal, and viral infections and failure to thrive. Laboratory studies show hypo- or agammaglobulinemia with relatively normal numbers of B and T-cells, and impaired differentiation and activation of immune cells. {ECO:0000269|PubMed:24369075}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Immunodeficiency 15A (IMD15A) [MIM:618204]: An autosomal dominant primary immunodeficiency disorder characterized by lymphopenia, inflammation and immune activation of both CD4+ and CD8+ T cells. Patients suffer from recurrent respiratory tract infections, oral candidiasis, and otitis media. {ECO:0000269|PubMed:30337470}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
ec_number
2.7.11.10
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:O88351, ECO:0000269|PubMed:11297557, ECO:0000269|PubMed:14673179, ECO:0000269|PubMed:15084260, ECO:0000269|PubMed:17213322, ECO:0000269|PubMed:19716809, ECO:0000269|PubMed:20410276, ECO:0000269|PubMed:20434986, ECO:0000269|PubMed:20797629, ECO:0000269|PubMed:21138416, ECO:0000269|PubMed:25326418, ECO:0000269|PubMed:30337470, ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:38621137, ECO:0000269|PubMed:9346484}.
uniprot
proteins
mass_dalton
86564
uniprot
proteins
mutagenesis
MUTAGEN 44; /note="K->A: Loss of kinase activity and no effect on binding to NIK. Does not phosphorylate STAT1 at 'Thr-749'."; /evidence="ECO:0000269|PubMed:32209697, ECO:0000269|PubMed:9346484, ECO:0000269|PubMed:9346485"; MUTAGEN 163; /note="K->R: Monoubiquitinated; when associated with E-177 and E-181."; /evidence="ECO:0000269|PubMed:19675099"; MUTAGEN 166; /note="D->A: Loss of protein kinase activity."; /evidence="ECO:0000269|PubMed:25326418"; MUTAGEN 171; /note="K->E: Increased activation of NF-kappa-B signaling."; /evidence="ECO:0000269|PubMed:30337470"; MUTAGEN 177..181; /note="SLCTS->ALCTA: COmplete loss of TBK1-mediated phosphorylation."; /evidence="ECO:0000269|PubMed:10783893"; MUTAGEN 177; /note="S->A: Decrease of activity."; /evidence="ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:9346484"; MUTAGEN 177; /note="S->E: Full activation. Interaction with TRIM21 is enhanced; when associated with E-181. Monoubiquitinated; when associated with R-163 and E-181. Strongly promoted NF-kappa-B gene expression; when associated with E-181."; /evidence="ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:9346484"; MUTAGEN 181; /note="S->A: Decrease of activity."; /evidence="ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:9346484"; MUTAGEN 181; /note="S->E: Full activation. Interaction with TRIM21 is enhanced; when associated with E-177. Monoubiquitinated; when associated with R-163 and E-177. Strongly promoted NF-kappa-B gene expression; when associated with E-177."; /evidence="ECO:0000269|PubMed:19675099, ECO:0000269|PubMed:9346484"; MUTAGEN 191; /note="P->A: Loss of hypoxic inducibility."; /evidence="ECO:0000269|PubMed:17114296"; MUTAGEN 272..756; /note="Missing: Loss of activation of NF-kappa-B signaling."; /evidence="ECO:0000269|PubMed:30337470
uniprot
proteins
post_translational_modification
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). {ECO:0000269|PubMed:10022904, ECO:0000269|PubMed:10195894, ECO:0000269|PubMed:10783893, ECO:0000269|PubMed:11460167, ECO:0000269|PubMed:16207722, ECO:0000269|PubMed:18930133}.; PTM: (Microbial infection) Acetylation of Thr-180 by Yersinia YopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway. {ECO:0000269|PubMed:16728640, ECO:0000269|PubMed:17116858}.; 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. {ECO:0000269|PubMed:16267042, ECO:0000269|PubMed:19675099}.; PTM: (Microbial infection) Monoubiquitination by TRIM21 is disrupted by Yersinia YopJ. {ECO:0000269|PubMed:19675099}.; PTM: Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappa-B. {ECO:0000269|PubMed:17114296}.
uniprot
proteins
protein_family
I-kappa-B kinase subfamily
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
Ser/Thr protein kinase family
uniprot
proteins
pubmed
10022904
uniprot
proteins
pubmed
10195894
uniprot
proteins
pubmed
10356400
uniprot
proteins
pubmed
10712233
uniprot
proteins
pubmed
10783893
uniprot
proteins
pubmed
10848580
uniprot
proteins
pubmed
11297557
uniprot
proteins
pubmed
11460167
uniprot
proteins
pubmed
11971985
uniprot
proteins
pubmed
12133833
uniprot
proteins
pubmed
12612076
uniprot
proteins
pubmed
14673179
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14739303
uniprot
proteins
pubmed
15084260
uniprot
proteins
pubmed
15173580
uniprot
proteins
pubmed
15184672
uniprot
proteins
pubmed
15456791
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15951441
uniprot
proteins
pubmed
16177806
uniprot
proteins
pubmed
16207722
uniprot
proteins
pubmed
16267042
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
16497931
uniprot
proteins
pubmed
16728640
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17114296
uniprot
proteins
pubmed
17116858
uniprot
proteins
pubmed
17213322
uniprot
proteins
pubmed
17287217
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17684021
uniprot
proteins
pubmed
18462684
uniprot
proteins
pubmed
18626576
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18930133
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19675099
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19716809
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
20410276
uniprot
proteins
pubmed
20434986
uniprot
proteins
pubmed
20797629
uniprot
proteins
pubmed
21138416
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
23090968
uniprot
proteins
pubmed
23091055
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23453969
uniprot
proteins
pubmed
23776175
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24369075
uniprot
proteins
pubmed
25326418
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26101251
uniprot
proteins
pubmed
26296658
uniprot
proteins
pubmed
26334375
uniprot
proteins
pubmed
27426725
uniprot
proteins
pubmed
29748387
uniprot
proteins
pubmed
30337470
uniprot
proteins
pubmed
31434731
uniprot
proteins
pubmed
32209697
uniprot
proteins
pubmed
32935379
uniprot
proteins
pubmed
38621137
uniprot
proteins
pubmed
9346484
uniprot
proteins
pubmed
9346485
uniprot
proteins
pubmed
9751059
uniprot
proteins
pubmed
9763654
uniprot
proteins
pubmed
9813230
uniprot
proteins
pubmed
9819420
uniprot
proteins
sequence_length
756
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:20797629}. Nucleus {ECO:0000269|PubMed:20797629}. Membrane raft {ECO:0000269|PubMed:17287217}. Note=Colocalized with DPP4 in membrane rafts. {ECO:0000269|PubMed:17287217}.
uniprot
proteins