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Protein

Inhibitor of nuclear factor kappa-B kinase subunit beta

Gene

IKBKB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Acts as part of the canonical IKK complex in the conventional pathway of NF-kappa-B activation and 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. 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. Also phosphorylates other substrates including NCOA3, BCL10 and IRS1. Within the nucleus, acts as an adapter protein for NFKBIA degradation in UV-induced NF-kappa-B activation.8 Publications

Catalytic activityi

ATP + [I-kappa-B protein] = ADP + [I-kappa-B phosphoprotein].

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei44ATPPROSITE-ProRule annotation1
Active sitei145Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi21 – 29ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • IkappaB kinase activity Source: UniProtKB
  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB
  • scaffold protein binding Source: MGI

GO - Biological processi

  • cellular response to tumor necrosis factor Source: UniProtKB
  • cortical actin cytoskeleton organization Source: UniProtKB
  • establishment of protein localization to plasma membrane Source: UniProtKB
  • Fc-epsilon receptor signaling pathway Source: Reactome
  • I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • inflammatory response Source: UniProtKB
  • innate immune response Source: UniProtKB
  • interleukin-1-mediated signaling pathway Source: UniProtKB
  • negative regulation of apoptotic process Source: Reactome
  • negative regulation of bicellular tight junction assembly Source: UniProtKB
  • negative regulation of myosin-light-chain-phosphatase activity Source: UniProtKB
  • nucleotide-binding oligomerization domain containing signaling pathway Source: Reactome
  • positive regulation of I-kappaB kinase/NF-kappaB signaling Source: Reactome
  • positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of establishment of endothelial barrier Source: UniProtKB
  • regulation of phosphorylation Source: ParkinsonsUK-UCL
  • regulation of tumor necrosis factor-mediated signaling pathway Source: Reactome
  • response to virus Source: UniProtKB
  • serine phosphorylation of STAT protein Source: UniProtKB
  • stimulatory C-type lectin receptor signaling pathway Source: Reactome
  • stress-activated MAPK cascade Source: Reactome
  • T cell receptor signaling pathway Source: Reactome
  • TRIF-dependent toll-like receptor signaling pathway Source: Reactome
  • tumor necrosis factor-mediated signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02571-MONOMER.
BRENDAi2.7.11.10. 2681.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1236974. ER-Phagosome pathway.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-202424. Downstream TCR signaling.
R-HSA-209543. p75NTR recruits signalling complexes.
R-HSA-209560. NF-kB is activated and signals survival.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
SABIO-RKO14920.
SignaLinkiO14920.
SIGNORiO14920.

Names & Taxonomyi

Protein namesi
Recommended name:
Inhibitor of nuclear factor kappa-B kinase subunit beta (EC:2.7.11.10)
Short name:
I-kappa-B-kinase beta
Short name:
IKK-B
Short name:
IKK-beta
Short name:
IkBKB
Alternative name(s):
I-kappa-B kinase 2
Short name:
IKK2
Nuclear factor NF-kappa-B inhibitor kinase beta
Short name:
NFKBIKB
Gene namesi
Name:IKBKB
Synonyms:IKKB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:5960. IKBKB.

Subcellular locationi

GO - Cellular componenti

  • CD40 receptor complex Source: BHF-UCL
  • cytoplasm Source: HPA
  • cytoplasmic side of plasma membrane Source: BHF-UCL
  • cytosol Source: Reactome
  • IkappaB kinase complex Source: UniProtKB
  • membrane raft Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Immunodeficiency 15 (IMD15)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:615592

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi44K → A: Loss of kinase activity and no effect on binding to NIK. 2 Publications1
Mutagenesisi163K → R: Monoubiquitinated; when associated with E-177 and E-181. 1 Publication1
Mutagenesisi177 – 181SLCTS → ALCTA: COmplete loss of TBK1-mediated phosphorylation. 1 Publication5
Mutagenesisi177S → A: Decrease of activity. 2 Publications1
Mutagenesisi177S → 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. 2 Publications1
Mutagenesisi181S → A: Decrease of activity. 2 Publications1
Mutagenesisi181S → 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. 2 Publications1
Mutagenesisi191P → A: Loss of hypoxic inducibility. 1 Publication1

Keywords - Diseasei

SCID

Organism-specific databases

DisGeNETi3551.
MalaCardsiIKBKB.
MIMi615592. phenotype.
OpenTargetsiENSG00000104365.
Orphaneti397787. Severe combined immunodeficiency due to IKK2 deficiency.
PharmGKBiPA29776.

Chemistry databases

ChEMBLiCHEMBL1991.
DrugBankiDB06151. Acetylcysteine.
DB00945. Acetylsalicylic acid.
DB01169. Arsenic trioxide.
DB00995. Auranofin.
DB00244. Mesalazine.
DB00795. Sulfasalazine.
GuidetoPHARMACOLOGYi2039.

Polymorphism and mutation databases

BioMutaiIKBKB.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000860131 – 756Inhibitor of nuclear factor kappa-B kinase subunit betaAdd BLAST756

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki163Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
Modified residuei177Phosphoserine; by TBK1 and PKC/PRKCZ3 Publications1
Modified residuei179S-nitrosocysteine1 Publication1
Modified residuei180O-acetylthreonine; by Yersinia yopJ1 Publication1
Modified residuei181Phosphoserine; by TBK1, PKC/PRKCZ and PDPK14 Publications1
Modified residuei191Hydroxyproline1 Publication1
Modified residuei670Phosphoserine; by autocatalysis1 Publication1
Modified residuei672PhosphoserineCombined sources1 Publication1
Modified residuei675PhosphoserineCombined sources1
Modified residuei675Phosphoserine; by autocatalysis1 Publication1
Modified residuei682Phosphoserine; by autocatalysis1 Publication1
Modified residuei689Phosphoserine; by autocatalysis1 Publication1
Modified residuei692Phosphoserine; by autocatalysis1 Publication1
Modified residuei695Phosphoserine; by autocatalysis1 Publication1
Modified residuei697Phosphoserine; by autocatalysis1 Publication1
Modified residuei705Phosphoserine; by autocatalysis1 Publication1
Modified residuei733Phosphoserine; by autocatalysis1 Publication1
Modified residuei740Phosphoserine; by autocatalysis1 Publication1
Modified residuei750Phosphoserine; by autocatalysis1 Publication1

Post-translational modificationi

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. Once activated, autophosphorylates on the C-terminal serine cluster; which decreases activity and prevents prolonged activation of the inflammatory response. 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. Dephosphorylated at Ser-177 and Ser-181 by PPM1A and PPM1B.4 Publications
(Microbial infection) Acetylation of Thr-180 by Yersinia yopJ prevents phosphorylation and activation, thus blocking the I-kappa-B pathway.2 Publications
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.2 Publications
(Microbial infection) Monoubiquitination by TRIM21 is disrupted by Yersinia yopJ.1 Publication
Hydroxylated by PHD1/EGLN2, loss of hydroxylation under hypoxic conditions results in activation of NF-kappa-B.1 Publication

Keywords - PTMi

Acetylation, Hydroxylation, Isopeptide bond, Phosphoprotein, S-nitrosylation, Ubl conjugation

Proteomic databases

EPDiO14920.
MaxQBiO14920.
PaxDbiO14920.
PeptideAtlasiO14920.
PRIDEiO14920.

PTM databases

iPTMnetiO14920.
PhosphoSitePlusiO14920.

Expressioni

Tissue specificityi

Highly expressed in heart, placenta, skeletal muscle, kidney, pancreas, spleen, thymus, prostate, testis and peripheral blood.

Gene expression databases

BgeeiENSG00000104365.
CleanExiHS_IKBKB.
ExpressionAtlasiO14920. baseline and differential.
GenevisibleiO14920. HS.

Organism-specific databases

HPAiCAB004447.
HPA001249.

Interactioni

Subunit structurei

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. 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, IKBKAP 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-alpha-dependent manner (PubMed:23091055). Interacts with IKBKE (PubMed:23453969). Interacts with NAA10, leading to NAA10 degradation (PubMed:19716809). Interacts with FOXO3 (PubMed:15084260). Interacts with AKAP13 (PubMed:23090968).By similarity22 Publications
(Microbial infection) Interacts with Yersinia yopJ.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CDC37Q165434EBI-81266,EBI-295634
CHUKO1511115EBI-81266,EBI-81249
CREBBPQ927932EBI-81266,EBI-81215
HSP90AB1P082382EBI-81266,EBI-352572
IKBKGQ9Y6K928EBI-81266,EBI-81279
KEAP1Q141456EBI-81266,EBI-751001
MAP3K14Q995583EBI-81266,EBI-358011
NCOA3Q9Y6Q93EBI-81266,EBI-81196
NFKB1P198383EBI-81266,EBI-300010
NFKBIAP2596320EBI-81266,EBI-307386
PPP2CAP677753EBI-81266,EBI-712311
RELAQ042062EBI-81266,EBI-73886
RPS3P233964EBI-81266,EBI-351193
STAP2Q9UGK37EBI-81266,EBI-1553984
taxP034093EBI-81266,EBI-5236464From a different organism.
TSC1Q925743EBI-81266,EBI-1047085
VACWR196P247723EBI-81266,EBI-4291651From a different organism.
Zc3h12aQ5D1E74EBI-81266,EBI-5326026From a different organism.

GO - Molecular functioni

  • protein heterodimerization activity Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • scaffold protein binding Source: MGI

Protein-protein interaction databases

BioGridi109767. 136 interactors.
DIPiDIP-27527N.
IntActiO14920. 65 interactors.
MINTiMINT-107608.
STRINGi9606.ENSP00000430684.

Chemistry databases

BindingDBiO14920.

Structurei

Secondary structure

1756
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi15 – 22Combined sources8
Beta strandi29 – 34Combined sources6
Turni35 – 37Combined sources3
Beta strandi40 – 44Combined sources5
Helixi52 – 67Combined sources16
Turni81 – 83Combined sources3
Helixi84 – 86Combined sources3
Beta strandi87 – 91Combined sources5
Beta strandi94 – 97Combined sources4
Helixi104 – 109Combined sources6
Helixi111 – 113Combined sources3
Helixi119 – 138Combined sources20
Helixi148 – 150Combined sources3
Beta strandi151 – 155Combined sources5
Beta strandi157 – 164Combined sources8
Helixi182 – 185Combined sources4
Turni186 – 188Combined sources3
Helixi191 – 195Combined sources5
Helixi202 – 217Combined sources16
Helixi228 – 235Combined sources8
Beta strandi244 – 247Combined sources4
Beta strandi253 – 258Combined sources6
Helixi267 – 280Combined sources14
Turni285 – 289Combined sources5
Turni292 – 294Combined sources3
Turni296 – 298Combined sources3
Helixi299 – 307Combined sources9
Beta strandi310 – 316Combined sources7
Turni317 – 320Combined sources4
Beta strandi321 – 327Combined sources7
Helixi333 – 344Combined sources12
Helixi348 – 350Combined sources3
Beta strandi353 – 355Combined sources3
Helixi367 – 370Combined sources4
Turni382 – 385Combined sources4
Beta strandi386 – 389Combined sources4
Helixi408 – 415Combined sources8
Helixi423 – 499Combined sources77
Turni500 – 504Combined sources5
Helixi509 – 520Combined sources12
Helixi527 – 548Combined sources22
Helixi559 – 575Combined sources17
Helixi579 – 581Combined sources3
Helixi588 – 661Combined sources74
Helixi706 – 729Combined sources24
Helixi734 – 736Combined sources3
Helixi740 – 742Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BRTX-ray2.25A/C701-730[»]
3BRVX-ray2.20A/C701-745[»]
4E3CX-ray3.98A/B/C/D/E/F11-669[»]
4KIKX-ray2.83A/B2-664[»]
ProteinModelPortaliO14920.
SMRiO14920.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO14920.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini15 – 300Protein kinasePROSITE-ProRule annotationAdd BLAST286

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni458 – 479Leucine-zipperAdd BLAST22
Regioni737 – 742NEMO-binding6

Domaini

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.1 Publication

Sequence similaritiesi

Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. I-kappa-B kinase subfamily.PROSITE-ProRule annotation
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
GeneTreeiENSGT00820000127009.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiO14920.
KOiK07209.
OMAiEVKFSSC.
OrthoDBiEOG091G02VC.
PhylomeDBiO14920.
TreeFamiTF324269.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
IPR000626. Ubiquitin_dom.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O14920-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSWSPSLTTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL
60 70 80 90 100
SPRNRERWCL EIQIMRRLTH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ
110 120 130 140 150
GGDLRKYLNQ FENCCGLREG AILTLLSDIA SALRYLHENR IIHRDLKPEN
160 170 180 190 200
IVLQQGEQRL IHKIIDLGYA KELDQGSLCT SFVGTLQYLA PELLEQQKYT
210 220 230 240 250
VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE VDIVVSEDLN
260 270 280 290 300
GTVKFSSSLP YPNNLNSVLA ERLEKWLQLM LMWHPRQRGT DPTYGPNGCF
310 320 330 340 350
KALDDILNLK LVHILNMVTG TIHTYPVTED ESLQSLKARI QQDTGIPEED
360 370 380 390 400
QELLQEAGLA LIPDKPATQC ISDGKLNEGH TLDMDLVFLF DNSKITYETQ
410 420 430 440 450
ISPRPQPESV SCILQEPKRN LAFFQLRKVW GQVWHSIQTL KEDCNRLQQG
460 470 480 490 500
QRAAMMNLLR NNSCLSKMKN SMASMSQQLK AKLDFFKTSI QIDLEKYSEQ
510 520 530 540 550
TEFGITSDKL LLAWREMEQA VELCGRENEV KLLVERMMAL QTDIVDLQRS
560 570 580 590 600
PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTEGDSQEM VRLLLQAIQS
610 620 630 640 650
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMNEDE KTVVRLQEKR
660 670 680 690 700
QKELWNLLKI ACSKVRGPVS GSPDSMNASR LSQPGQLMSQ PSTASNSLPE
710 720 730 740 750
PAKKSEELVA EAHNLCTLLE NAIQDTVREQ DQSFTALDWS WLQTEEEEHS

CLEQAS
Length:756
Mass (Da):86,564
Last modified:January 1, 1998 - v1
Checksum:iF9CADF671AE9E14E
GO
Isoform 2 (identifier: O14920-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-34: MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHN → MFSGGCHSPGFGRPSPAFPAPGSPPPAPRPCR

Show »
Length:754
Mass (Da):85,945
Checksum:i9C31F5C1DC92661E
GO
Isoform 3 (identifier: O14920-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     231-256: WHSKVRQKSEVDIVVSEDLNGTVKFS → CVRMWPGTVAHSCNPSTLGGRGRWIS
     257-756: Missing.

Show »
Length:256
Mass (Da):29,236
Checksum:i8B4762DD49F4065A
GO
Isoform 4 (identifier: O14920-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-66: MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSPRNRERWCLEIQIMR → MSSDGTI

Note: No experimental confirmation available.
Show »
Length:697
Mass (Da):79,509
Checksum:i21B61110941FE1D9
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti259L → S in BAG63942 (PubMed:14702039).Curated1
Sequence conflicti259L → S in BAH14789 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035626360A → S in breast cancer samples; infiltrating ductal carcinoma; somatic mutation. 2 Publications1
Natural variantiVAR_040567369Q → R.1 PublicationCorresponds to variant rs56411242dbSNPEnsembl.1
Natural variantiVAR_040568526R → Q.1 PublicationCorresponds to variant rs2272736dbSNPEnsembl.1
Natural variantiVAR_021124554R → W.1 PublicationCorresponds to variant rs17875749dbSNPEnsembl.1
Natural variantiVAR_040569710A → T.1 PublicationCorresponds to variant rs34309584dbSNPEnsembl.1
Natural variantiVAR_040570734F → L.1 PublicationCorresponds to variant rs56301637dbSNPEnsembl.1
Natural variantiVAR_051628736A → T.Corresponds to variant rs17611716dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0434081 – 66MSWSP…IQIMR → MSSDGTI in isoform 4. 1 PublicationAdd BLAST66
Alternative sequenceiVSP_0418251 – 34MSWSP…IRWHN → MFSGGCHSPGFGRPSPAFPA PGSPPPAPRPCR in isoform 2. 1 PublicationAdd BLAST34
Alternative sequenceiVSP_041826231 – 256WHSKV…TVKFS → CVRMWPGTVAHSCNPSTLGG RGRWIS in isoform 3. 1 PublicationAdd BLAST26
Alternative sequenceiVSP_041827257 – 756Missing in isoform 3. 1 PublicationAdd BLAST500

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF029684 mRNA. Translation: AAC51860.1.
AF080158 mRNA. Translation: AAD08997.1.
AF031416 mRNA. Translation: AAC64675.1.
AK302723 mRNA. Translation: BAG63942.1.
AK303528 mRNA. Translation: BAG64556.1.
AK316418 mRNA. Translation: BAH14789.1.
AY663108 Genomic DNA. Translation: AAT65965.1.
AC083973 Genomic DNA. No translation available.
BC006231 mRNA. Translation: AAH06231.1.
CCDSiCCDS55228.1. [O14920-2]
CCDS56535.1. [O14920-4]
CCDS6128.1. [O14920-1]
RefSeqiNP_001177649.1. NM_001190720.2. [O14920-2]
NP_001229707.1. NM_001242778.1. [O14920-4]
NP_001547.1. NM_001556.2. [O14920-1]
UniGeneiHs.597664.

Genome annotation databases

EnsembliENST00000416505; ENSP00000404920; ENSG00000104365. [O14920-4]
ENST00000519735; ENSP00000430483; ENSG00000104365. [O14920-3]
ENST00000520810; ENSP00000430684; ENSG00000104365. [O14920-1]
ENST00000520835; ENSP00000430868; ENSG00000104365. [O14920-2]
GeneIDi3551.
KEGGihsa:3551.
UCSCiuc003xow.3. human. [O14920-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF029684 mRNA. Translation: AAC51860.1.
AF080158 mRNA. Translation: AAD08997.1.
AF031416 mRNA. Translation: AAC64675.1.
AK302723 mRNA. Translation: BAG63942.1.
AK303528 mRNA. Translation: BAG64556.1.
AK316418 mRNA. Translation: BAH14789.1.
AY663108 Genomic DNA. Translation: AAT65965.1.
AC083973 Genomic DNA. No translation available.
BC006231 mRNA. Translation: AAH06231.1.
CCDSiCCDS55228.1. [O14920-2]
CCDS56535.1. [O14920-4]
CCDS6128.1. [O14920-1]
RefSeqiNP_001177649.1. NM_001190720.2. [O14920-2]
NP_001229707.1. NM_001242778.1. [O14920-4]
NP_001547.1. NM_001556.2. [O14920-1]
UniGeneiHs.597664.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BRTX-ray2.25A/C701-730[»]
3BRVX-ray2.20A/C701-745[»]
4E3CX-ray3.98A/B/C/D/E/F11-669[»]
4KIKX-ray2.83A/B2-664[»]
ProteinModelPortaliO14920.
SMRiO14920.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109767. 136 interactors.
DIPiDIP-27527N.
IntActiO14920. 65 interactors.
MINTiMINT-107608.
STRINGi9606.ENSP00000430684.

Chemistry databases

BindingDBiO14920.
ChEMBLiCHEMBL1991.
DrugBankiDB06151. Acetylcysteine.
DB00945. Acetylsalicylic acid.
DB01169. Arsenic trioxide.
DB00995. Auranofin.
DB00244. Mesalazine.
DB00795. Sulfasalazine.
GuidetoPHARMACOLOGYi2039.

PTM databases

iPTMnetiO14920.
PhosphoSitePlusiO14920.

Polymorphism and mutation databases

BioMutaiIKBKB.

Proteomic databases

EPDiO14920.
MaxQBiO14920.
PaxDbiO14920.
PeptideAtlasiO14920.
PRIDEiO14920.

Protocols and materials databases

DNASUi3551.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000416505; ENSP00000404920; ENSG00000104365. [O14920-4]
ENST00000519735; ENSP00000430483; ENSG00000104365. [O14920-3]
ENST00000520810; ENSP00000430684; ENSG00000104365. [O14920-1]
ENST00000520835; ENSP00000430868; ENSG00000104365. [O14920-2]
GeneIDi3551.
KEGGihsa:3551.
UCSCiuc003xow.3. human. [O14920-1]

Organism-specific databases

CTDi3551.
DisGeNETi3551.
GeneCardsiIKBKB.
HGNCiHGNC:5960. IKBKB.
HPAiCAB004447.
HPA001249.
MalaCardsiIKBKB.
MIMi603258. gene.
615592. phenotype.
neXtProtiNX_O14920.
OpenTargetsiENSG00000104365.
Orphaneti397787. Severe combined immunodeficiency due to IKK2 deficiency.
PharmGKBiPA29776.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4250. Eukaryota.
ENOG410XRMU. LUCA.
GeneTreeiENSGT00820000127009.
HOGENOMiHOG000038048.
HOVERGENiHBG018241.
InParanoidiO14920.
KOiK07209.
OMAiEVKFSSC.
OrthoDBiEOG091G02VC.
PhylomeDBiO14920.
TreeFamiTF324269.

Enzyme and pathway databases

BioCyciZFISH:HS02571-MONOMER.
BRENDAi2.7.11.10. 2681.
ReactomeiR-HSA-1169091. Activation of NF-kappaB in B cells.
R-HSA-1236974. ER-Phagosome pathway.
R-HSA-168638. NOD1/2 Signaling Pathway.
R-HSA-1810476. RIP-mediated NFkB activation via ZBP1.
R-HSA-202424. Downstream TCR signaling.
R-HSA-209543. p75NTR recruits signalling complexes.
R-HSA-209560. NF-kB is activated and signals survival.
R-HSA-2871837. FCERI mediated NF-kB activation.
R-HSA-445989. TAK1 activates NFkB by phosphorylation and activation of IKKs complex.
R-HSA-446652. Interleukin-1 signaling.
R-HSA-5357905. Regulation of TNFR1 signaling.
R-HSA-5357956. TNFR1-induced NFkappaB signaling pathway.
R-HSA-5603027. IKBKG deficiency causes anhidrotic ectodermal dysplasia with immunodeficiency (EDA-ID) (via TLR).
R-HSA-5603029. IkBA variant leads to EDA-ID.
R-HSA-5607764. CLEC7A (Dectin-1) signaling.
R-HSA-5684264. MAP3K8 (TPL2)-dependent MAPK1/3 activation.
R-HSA-933542. TRAF6 mediated NF-kB activation.
R-HSA-933543. NF-kB activation through FADD/RIP-1 pathway mediated by caspase-8 and -10.
R-HSA-937039. IRAK1 recruits IKK complex.
R-HSA-937041. IKK complex recruitment mediated by RIP1.
R-HSA-975144. IRAK1 recruits IKK complex upon TLR7/8 or 9 stimulation.
SABIO-RKO14920.
SignaLinkiO14920.
SIGNORiO14920.

Miscellaneous databases

ChiTaRSiIKBKB. human.
EvolutionaryTraceiO14920.
GeneWikiiIKK2.
GenomeRNAii3551.
PROiO14920.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104365.
CleanExiHS_IKBKB.
ExpressionAtlasiO14920. baseline and differential.
GenevisibleiO14920. HS.

Family and domain databases

InterProiIPR022007. IKKbetaNEMObind.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
IPR000626. Ubiquitin_dom.
[Graphical view]
PfamiPF12179. IKKbetaNEMObind. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM01239. IKKbetaNEMObind. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiIKKB_HUMAN
AccessioniPrimary (citable) accession number: O14920
Secondary accession number(s): B4DZ30, B4E0U4, O75327
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: January 1, 1998
Last modified: November 30, 2016
This is version 189 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.