IKBKB (inhibitor of nuclear factor kappa B kinase subunit beta)

Gene

• Entrez ID: 3551
• Gene name: Inhibitor of nuclear factor kappa B kinase subunit beta
• Gene symbol: IKBKB
• Synonyms: IKK-beta, IKK2, IKKB, IMD15, IMD15A, IMD15B, NFKBIKB
• Chromosome: 8
• Chromosome location: 8p11.21
• Summary: The protein encoded by this gene phosphorylates the inhibitor in the inhibitor/NF-kappa-B complex, causing dissociation of the inhibitor and activation of NF-kappa-B. The encoded protein itself is found in a complex of proteins. Several transcript variants, some protein-coding and some not, have been found for this gene. [provided by RefSeq, Sep 2011]

SNPs

SNP ID	Visualize variation	Clinical significance	Consequence
rs200296680	C>T	Pathogenic	Stop gained, non coding transcript variant, 5 prime UTR variant, coding sequence variant
rs886041036	->G	Pathogenic	Frameshift variant, non coding transcript variant, coding sequence variant
rs1563340753	G>A	Pathogenic	Coding sequence variant, intron variant, missense variant, 5 prime UTR variant, non coding transcript variant

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT003828	hsa-miR-199a-5p	Reporter assay, Western blot, GFP reporter assay, Luciferase reporter assay, qRT-PCR	18408758
MIRT004030	hsa-miR-218-5p	Luciferase reporter assay, qRT-PCR, Western blot	20933503
MIRT006884	hsa-miR-200c-3p	Luciferase reporter assay, Western blot	22569286
MIRT006884	hsa-miR-200c-3p	Luciferase reporter assay	24755559
MIRT018148	hsa-miR-335-5p	Microarray	18185580
MIRT043610	hsa-miR-151a-3p	CLASH	23622248
MIRT054428	hsa-miR-503-5p	Immunohistochemistry, In situ hybridization, Luciferase reporter assay, qRT-PCR, Western blot	24550137
MIRT438803	hsa-miR-451a	Luciferase reporter assay	23740840
MIRT733211	hsa-miR-148a-3p	Luciferase reporter assay, Microarray, Next Generation Sequencing (NGS), qRT-PCR, Western blot	25630970
MIRT733756	hsa-miR-200b-3p	Luciferase reporter assay, qRT-PCR, Western blot	26433127
MIRT735342	hsa-miR-497-5p	Luciferase reporter assay, qRT-PCR, Western blot	26175947

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0002223	Process	Stimulatory C-type lectin receptor signaling pathway	TAS
GO:0002479	Process	Antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent	TAS
GO:0002756	Process	MyD88-independent toll-like receptor signaling pathway	TAS
GO:0004672	Function	Protein kinase activity	IDA	20434986
GO:0004674	Function	Protein serine/threonine kinase activity	EXP	18692471, 23613522
GO:0004674	Function	Protein serine/threonine kinase activity	IBA	21873635
GO:0004674	Function	Protein serine/threonine kinase activity	IDA	15084260, 25326418, 25636800
GO:0004674	Function	Protein serine/threonine kinase activity	TAS
GO:0005515	Function	Protein binding	IPI	9520446, 9751060, 10521409, 10733566, 11297557, 11971985, 12482991, 12486103, 12842894, 14743216, 15084260, 15389287, 15601829, 15749833, 16126728, 16129692, 16286467, 16319058, 16365431, 16938294, 17568778, 17693255, 17939994, 18198944, 18266467, 18462684, 18930133, 19196987, 19345
GO:0005524	Function	ATP binding	IEA
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IBA	21873635
GO:0005829	Component	Cytosol	IDA
GO:0005829	Component	Cytosol	TAS
GO:0006468	Process	Protein phosphorylation	IDA	15084260, 20434986
GO:0006468	Process	Protein phosphorylation	NAS	9346484
GO:0006954	Process	Inflammatory response	TAS	18626576
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	IMP	15383541, 25816133
GO:0007249	Process	I-kappaB kinase/NF-kappaB signaling	TAS	18626576
GO:0007252	Process	I-kappaB phosphorylation	IEA
GO:0008384	Function	IkappaB kinase activity	IBA	21873635
GO:0008384	Function	IkappaB kinase activity	TAS	18626576
GO:0008385	Component	IkappaB kinase complex	IBA	21873635
GO:0008385	Component	IkappaB kinase complex	TAS	18626576
GO:0009615	Process	Response to virus	TAS	18626576
GO:0009898	Component	Cytoplasmic side of plasma membrane	ISS
GO:0010803	Process	Regulation of tumor necrosis factor-mediated signaling pathway	TAS
GO:0016032	Process	Viral process	IEA
GO:0018105	Process	Peptidyl-serine phosphorylation	IBA	21873635
GO:0018105	Process	Peptidyl-serine phosphorylation	IDA	21399639, 25326418
GO:0019901	Function	Protein kinase binding	IPI	12492477
GO:0030866	Process	Cortical actin cytoskeleton organization	IMP	25816133
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IBA	21873635
GO:0033209	Process	Tumor necrosis factor-mediated signaling pathway	IMP	15084260, 25816133
GO:0035509	Process	Negative regulation of myosin-light-chain-phosphatase activity	IMP	25816133
GO:0035631	Component	CD40 receptor complex	ISS
GO:0035666	Process	TRIF-dependent toll-like receptor signaling pathway	TAS
GO:0038095	Process	Fc-epsilon receptor signaling pathway	TAS
GO:0042325	Process	Regulation of phosphorylation	IDA	26212789
GO:0042802	Function	Identical protein binding	IPI	16319058, 21423167, 23776406
GO:0042803	Function	Protein homodimerization activity	IDA	23091055
GO:0043066	Process	Negative regulation of apoptotic process	TAS
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	IMP	30337470
GO:0043123	Process	Positive regulation of I-kappaB kinase/NF-kappaB signaling	TAS
GO:0045087	Process	Innate immune response	TAS	18626576
GO:0045121	Component	Membrane raft	IEA
GO:0045893	Process	Positive regulation of transcription, DNA-templated	NAS	9346484, 9346485, 9813230
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IBA	21873635
GO:0045944	Process	Positive regulation of transcription by RNA polymerase II	IDA	23091055, 23453807
GO:0046982	Function	Protein heterodimerization activity	IDA	23091055
GO:0050852	Process	T cell receptor signaling pathway	TAS
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IBA	21873635
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	IDA	15790681
GO:0051092	Process	Positive regulation of NF-kappaB transcription factor activity	TAS	18626576
GO:0051403	Process	Stress-activated MAPK cascade	TAS
GO:0070498	Process	Interleukin-1-mediated signaling pathway	IMP	25816133
GO:0070498	Process	Interleukin-1-mediated signaling pathway	TAS
GO:0071356	Process	Cellular response to tumor necrosis factor	IDA	23091055
GO:0072659	Process	Protein localization to plasma membrane	IMP	25816133
GO:0097110	Function	Scaffold protein binding	IDA	23776175
GO:0106310	Function	Protein serine kinase activity	IEA
GO:0106311	Function	Protein threonine kinase activity	IEA
GO:1903140	Process	Regulation of establishment of endothelial barrier	IMP	25816133
GO:1903347	Process	Negative regulation of bicellular tight junction assembly	IMP	25816133
GO:1990459	Function	Transferrin receptor binding	IPI	23016877

Other IDs

• MIM: 603258
• HGNC: 5960
• e!Ensembl: ENSG00000104365

Protein

• UniProt ID: O14920
• Protein name: Inhibitor of nuclear factor kappa-B kinase subunit beta (I-kappa-B-kinase beta) (IKK-B) (IKK-beta) (IkBKB) (EC 2.7.11.10) (I-kappa-B kinase 2) (IKK2) (Nuclear factor NF-kappa-B inhibitor kinase beta) (NFKBIKB) (Serine/threonine protein kinase IKBKB) (EC 2.7.11.1)
• Protein 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:30337470). Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation. Phosphorylates inhibitors of NF-kappa-B on 2 critical serine residues. These modifications allow polyubiquitination of the inhibitors and subsequent degradation by the proteasome. 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. 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:20410276). IKK-related kinase phosphorylations may prevent the overproduction of inflammatory mediators since they exert a negative regulation on canonical IKKs. Phosphorylates FOXO3, mediating the TNF-dependent inactivation of this pro-apoptotic transcription factor (PubMed:15084260). Also phosphorylates other substrates including NCOA3, BCL10 and IRS1 (PubMed:17213322). Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation (PubMed:11297557). 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).
• PDB: 3BRT, 3BRV, 4E3C, 4KIK
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF00069	Pkinase	15 → 297	Protein kinase domain	Domain
  PF18397	IKBKB_SDD	389 → 663	IQBAL scaffold dimerization domain	Domain
  PF12179	IKKbetaNEMObind	706 → 742	I-kappa-kinase-beta NEMO binding domain	Domain

• Sequence:

  MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSPRNRERWCL
  EIQIMRRLTHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRKYLNQFENCCGLREG
  AILTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEQRLIHKIIDLGYAKELDQGSLCT
  SFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSE
  VDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCF
  KALDDILNLKLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLA
  LIPDKPATQCISDGKLNEGHTLDMDLVFLFDNSKITYETQISPRPQPESVSCILQEPKRN
  LAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKMKNSMASMSQQLK
  AKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMAL
  QTDIVDLQRSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQS
  FEKKVRVIYTQLSKTVVCKQKALELLPKVEEVVSLMNEDEKTVVRLQEKRQKELWNLLKI
  ACSKVRGPVSGSPDSMNASRLSQPGQLMSQPSTASNSLPEPAKKSEELVAEAHNLCTLLE
  NAIQDTVREQDQSFTALDWSWLQTEEEEHSCLEQAS

• Sequence length: 756