dbPAF Protein Information


Tag Content
dbPAF ID dbPAF-0000789
Uniprot Accession O14920; IKKB_HUMAN; B4DZ30; B4E0U4; O75327;
Genbank Protein ID NP_001177649.1; NP_001229707.1; NP_001547.1;
Genbank Nucleotide ID NM_001190720.2; NM_001242778.1; NM_001556.2;
Protein Name Inhibitor of nuclear factor kappa-B kinase subunit beta
Protein Synonyms/Alias
Gene Name IKBKB
Gene Synonyms/Alias IKKB;
Organism Homo sapiens(Human)
NCBI Taxa ID 9606
Functional Description
(View all)
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.
Phosphorylation Sites
dbPAF PTMs: 62 (View all)
PositionPeptidesSourceReferences ( PMIDs )
2------MSWSPSLTTcurated25627689
4----MSWSPSLTTQTPhosphoSitePlus;curated22135298; 25627689; 22199227
6--MSWSPSLTTQTCGPhosphoSitePlus22135298
23EMKERLGTGGFGNVIPhosphoSitePlus22135298
169HKIIDLGYAKELDQGPhosphoSitePlus22135298
177AKELDQGSLCTSFVGdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;curated10022904; 10195894; 10783893; 16381945; 23193290; 10779355;
180LDQGSLCTSFVGTLQPhosphoSitePlus;curated22135298; 25849741
181DQGSLCTSFVGTLQYdbPTM 3.0;Phospho.ELM 9.0;HPRD 9;PhosphoSitePlus;curated10022904; 10195894; 10783893; 16207722; 16381945; 23193290;
188SFVGTLQYLAPELLEdbPTM 3.0;PhosphoSitePlus;curated12645577; 12707358; 20450893; 16381945; 23193290; 22135298;
199ELLEQQKYTVTVDYWdbPTM 3.0;PhosphoSitePlus;curated12645577; 12707358; 20450893; 16381945; 23193290; 22135298;
239HSKVRQKSEVDIVVSPhosphoSitePlus22135298
246SEVDIVVSEDLNGTVPhosphoSitePlus;curated22135298; 25849741
256LNGTVKFSSSLPYPNPhosphoSitePlus22135298
257NGTVKFSSSLPYPNNPhosphoSitePlus22135298
258GTVKFSSSLPYPNNLPhosphoSitePlus22135298
261KFSSSLPYPNNLNSVPhosphoSitePlus22135298
267PYPNNLNSVLAERLEPhosphoSitePlus22135298
324MVTGTIHTYPVTEDEPhosphoSitePlus22135298
325VTGTIHTYPVTEDESPhosphoSitePlus22135298
332YPVTEDESLQSLKARPhosphoSitePlus22135298
Sequence
(Fasta)
MSWSPSLTTQ TCGAWEMKER LGTGGFGNVI RWHNQETGEQ IAIKQCRQEL SPRNRERWCL 60
EIQIMRRLTH PNVVAARDVP EGMQNLAPND LPLLAMEYCQ GGDLRKYLNQ FENCCGLREG 120
AILTLLSDIA SALRYLHENR IIHRDLKPEN IVLQQGEQRL IHKIIDLGYA KELDQGSLCT 180
SFVGTLQYLA PELLEQQKYT VTVDYWSFGT LAFECITGFR PFLPNWQPVQ WHSKVRQKSE 240
VDIVVSEDLN GTVKFSSSLP YPNNLNSVLA ERLEKWLQLM LMWHPRQRGT DPTYGPNGCF 300
KALDDILNLK LVHILNMVTG TIHTYPVTED ESLQSLKARI QQDTGIPEED QELLQEAGLA 360
LIPDKPATQC ISDGKLNEGH TLDMDLVFLF DNSKITYETQ ISPRPQPESV SCILQEPKRN 420
LAFFQLRKVW GQVWHSIQTL KEDCNRLQQG QRAAMMNLLR NNSCLSKMKN SMASMSQQLK 480
AKLDFFKTSI QIDLEKYSEQ TEFGITSDKL LLAWREMEQA VELCGRENEV KLLVERMMAL 540
QTDIVDLQRS PMGRKQGGTL DDLEEQAREL YRRLREKPRD QRTEGDSQEM VRLLLQAIQS 600
FEKKVRVIYT QLSKTVVCKQ KALELLPKVE EVVSLMNEDE KTVVRLQEKR QKELWNLLKI 660
ACSKVRGPVS GSPDSMNASR LSQPGQLMSQ PSTASNSLPE PAKKSEELVA EAHNLCTLLE 720
NAIQDTVREQ DQSFTALDWS WLQTEEEEHS CLEQAS 757
Keyword

KW-0002--3D-structure
KW-0007--Acetylation
KW-0025--Alternative splicing
KW-0067--ATP-binding
KW-0181--Complete proteome
KW-0963--Cytoplasm
KW-0903--Direct protein sequencing
KW-0379--Hydroxylation
KW-1017--Isopeptide bond
KW-0418--Kinase
KW-0472--Membrane
KW-0547--Nucleotide-binding
KW-0539--Nucleus
KW-0597--Phosphoprotein
KW-0621--Polymorphism
KW-1185--Reference proteome
KW-0702--S-nitrosylation
KW-0705--SCID
KW-0723--Serine/threonine-protein kinase
KW-0808--Transferase
KW-0832--Ubl conjugation

Interpro

IPR022007--IKKbetaNEMObind
IPR011009--Kinase-like_dom
IPR000719--Prot_kinase_dom
IPR008271--Ser/Thr_kinase_AS
IPR029071--Ubiquitin-rel_dom
IPR000626--Ubiquitin_dom

PROSITE

PS50011--PROTEIN_KINASE_DOM
PS00108--PROTEIN_KINASE_ST

Pfam

PF12179--IKKbetaNEMObind
PF00069--Pkinase

Gene Ontology

GO:0035631--C:CD40 receptor complex
GO:0005737--C:cytoplasm
GO:0009898--C:cytoplasmic side of plasma membrane
GO:0005829--C:cytosol
GO:0008385--C:IkappaB kinase complex
GO:0045121--C:membrane raft
GO:0005634--C:nucleus
GO:0005524--F:ATP binding
GO:0008384--F:IkappaB kinase activity
GO:0046982--F:protein heterodimerization activity
GO:0042803--F:protein homodimerization activity
GO:0004672--F:protein kinase activity
GO:0019901--F:protein kinase binding
GO:0004674--F:protein serine/threonine kinase activity
GO:0097110--F:scaffold protein binding
GO:0001782--P:B cell homeostasis
GO:0007166--P:cell surface receptor signaling pathway
GO:0071356--P:cellular response to tumor necrosis factor
GO:0030866--P:cortical actin cytoskeleton organization
GO:0090002--P:establishment of protein localization to plasma membrane
GO:0038095--P:Fc-epsilon receptor signaling pathway
GO:0007249--P:I-kappaB kinase/NF-kappaB signaling
GO:0007252--P:I-kappaB phosphorylation
GO:0006954--P:inflammatory response
GO:0045087--P:innate immune response
GO:0070498--P:interleukin-1-mediated signaling pathway
GO:0002755--P:MyD88-dependent toll-like receptor signaling pathway
GO:0002756--P:MyD88-independent toll-like receptor signaling pathway
GO:0043066--P:negative regulation of apoptotic process
GO:1903347--P:negative regulation of bicellular tight junction assembly
GO:0035509--P:negative regulation of myosin-light-chain-phosphatase activity
GO:0031175--P:neuron projection development
GO:0048011--P:neurotrophin TRK receptor signaling pathway
GO:0035872--P:nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
GO:0070423--P:nucleotide-binding oligomerization domain containing signaling pathway
GO:2001259--P:positive regulation of cation channel activity
GO:0008284--P:positive regulation of cell proliferation
GO:0043123--P:positive regulation of I-kappaB kinase/NF-kappaB signaling
GO:1901216--P:positive regulation of neuron death
GO:0051092--P:positive regulation of NF-kappaB transcription factor activity
GO:0010765--P:positive regulation of sodium ion transport
GO:0045944--P:positive regulation of transcription from RNA polymerase II promoter
GO:0045893--P:positive regulation of transcription, DNA-templated
GO:0032481--P:positive regulation of type I interferon production
GO:0006468--P:protein phosphorylation
GO:1903140--P:regulation of establishment of endothelial barrier
GO:0042325--P:regulation of phosphorylation
GO:0010803--P:regulation of tumor necrosis factor-mediated signaling pathway
GO:0042493--P:response to drug
GO:0070542--P:response to fatty acid
GO:0009636--P:response to toxic substance
GO:0009615--P:response to virus
GO:0042501--P:serine phosphorylation of STAT protein
GO:0003009--P:skeletal muscle contraction
GO:0002223--P:stimulatory C-type lectin receptor signaling pathway
GO:0051403--P:stress-activated MAPK cascade
GO:0050852--P:T cell receptor signaling pathway
GO:0034166--P:toll-like receptor 10 signaling pathway
GO:0034134--P:toll-like receptor 2 signaling pathway
GO:0034138--P:toll-like receptor 3 signaling pathway
GO:0034142--P:toll-like receptor 4 signaling pathway
GO:0034146--P:toll-like receptor 5 signaling pathway
GO:0034162--P:toll-like receptor 9 signaling pathway
GO:0002224--P:toll-like receptor signaling pathway
GO:0038123--P:toll-like receptor TLR1:TLR2 signaling pathway
GO:0038124--P:toll-like receptor TLR6:TLR2 signaling pathway
GO:0035666--P:TRIF-dependent toll-like receptor signaling pathway
GO:0033209--P:tumor necrosis factor-mediated signaling pathway