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Names & Taxonomy

Uniprot ID:: O14920
Entry Name:: IKKB_HUMAN
Status:: reviewed
Protein Names:: 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)
Gene Names:: IKBKB IKKB
Gene Names Primary:: IKBKB
Organism:: Homo sapiens (Human)

Structure

Length:: 756
Sequence:: MSWSPSLTTQTCGAWEMKERLGTGGFGNVIRWHNQETGEQIAIKQCRQELSPRNRERWCLEIQIMRRLTHPNVVAARDVPEGMQNLAPNDLPLLAMEYCQGGDLRKYLNQFENCCGLREGAILTLLSDIASALRYLHENRIIHRDLKPENIVLQQGEQRLIHKIIDLGYAKELDQGSLCTSFVGTLQYLAPELLEQQKYTVTVDYWSFGTLAFECITGFRPFLPNWQPVQWHSKVRQKSEVDIVVSEDLNGTVKFSSSLPYPNNLNSVLAERLEKWLQLMLMWHPRQRGTDPTYGPNGCFKALDDILNLKLVHILNMVTGTIHTYPVTEDESLQSLKARIQQDTGIPEEDQELLQEAGLALIPDKPATQCISDGKLNEGHTLDMDLVFLFDNSKITYETQISPRPQPESVSCILQEPKRNLAFFQLRKVWGQVWHSIQTLKEDCNRLQQGQRAAMMNLLRNNSCLSKMKNSMASMSQQLKAKLDFFKTSIQIDLEKYSEQTEFGITSDKLLLAWREMEQAVELCGRENEVKLLVERMMALQTDIVDLQRSPMGRKQGGTLDDLEEQARELYRRLREKPRDQRTEGDSQEMVRLLLQAIQSFEKKVRVIYTQLSKTVVCKQKALELLPKVEEVVSLMNEDEKTVVRLQEKRQKELWNLLKIACSKVRGPVSGSPDSMNASRLSQPGQLMSQPSTASNSLPEPAKKSEELVAEAHNLCTLLENAIQDTVREQDQSFTALDWSWLQTEEEEHSCLEQAS
Proteomes:: UP000005640

Subcellular location

Subcellular Location:: Cytoplasm

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. 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.
Catalytic Activity:: ATP + = ADP + .
Active Site:: ACT_SITE 145 145 Proton acceptor.
Cross Reference Drug Bank:: DB06151 DB00945 DB01169 DB00995 DB00244 DB00795
Gene Ontology Go:: CD40 receptor complex
cytoplasm
cytoplasmic side of plasma membrane
cytosol
IkappaB kinase complex
membrane raft
nucleus
ATP binding
identical protein binding
IkappaB kinase activity
protein heterodimerization activity
protein homodimerization activity
protein kinase activity
protein kinase binding
protein serine/threonine kinase activity
scaffold protein binding
cell surface receptor signaling pathway
cellular response to tumor necrosis factor
cortical actin cytoskeleton organization
establishment of protein localization to plasma membrane
Fc-epsilon receptor signaling pathway
I-kappaB kinase/NF-kappaB signaling
I-kappaB phosphorylation
inflammatory response
innate immune response
interleukin-1-mediated signaling pathway
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of bicellular tight junction assembly
negative regulation of myosin-light-chain-phosphatase activity
neuron projection development
neurotrophin TRK receptor signaling pathway
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
nucleotide-binding oligomerization domain containing signaling pathway
positive regulation of cell proliferation
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of neuron death
positive regulation of neuron projection development
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription, DNA-templated
positive regulation of type I interferon production
protein phosphorylation
regulation of establishment of endothelial barrier
regulation of phosphorylation
regulation of tumor necrosis factor-mediated signaling pathway
response to drug
response to fatty acid
response to lipopolysaccharide
response to toxic substance
response to virus
serine phosphorylation of STAT protein
skeletal muscle contraction
stimulatory C-type lectin receptor signaling pathway
stress-activated MAPK cascade
T cell receptor signaling pathway
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
tumor necrosis factor-mediated signaling pathway
Gene Ontology Biological Process:: cell surface receptor signaling pathway
cellular response to tumor necrosis factor
cortical actin cytoskeleton organization
establishment of protein localization to plasma membrane
Fc-epsilon receptor signaling pathway
I-kappaB kinase/NF-kappaB signaling
I-kappaB phosphorylation
inflammatory response
innate immune response
interleukin-1-mediated signaling pathway
MyD88-dependent toll-like receptor signaling pathway
MyD88-independent toll-like receptor signaling pathway
negative regulation of apoptotic process
negative regulation of bicellular tight junction assembly
negative regulation of myosin-light-chain-phosphatase activity
neuron projection development
neurotrophin TRK receptor signaling pathway
nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway
nucleotide-binding oligomerization domain containing signaling pathway
positive regulation of cell proliferation
positive regulation of I-kappaB kinase/NF-kappaB signaling
positive regulation of neuron death
positive regulation of neuron projection development
positive regulation of NF-kappaB transcription factor activity
positive regulation of transcription, DNA-templated
positive regulation of transcription from RNA polymerase II promoter
positive regulation of type I interferon production
protein phosphorylation
regulation of establishment of endothelial barrier
regulation of phosphorylation
regulation of tumor necrosis factor-mediated signaling pathway
response to drug
response to fatty acid
response to lipopolysaccharide
response to toxic substance
response to virus
serine phosphorylation of STAT protein
skeletal muscle contraction
stimulatory C-type lectin receptor signaling pathway
stress-activated MAPK cascade
T cell receptor signaling pathway
toll-like receptor 10 signaling pathway
toll-like receptor 2 signaling pathway
toll-like receptor 3 signaling pathway
toll-like receptor 4 signaling pathway
toll-like receptor 5 signaling pathway
toll-like receptor 9 signaling pathway
toll-like receptor signaling pathway
toll-like receptor TLR1:TLR2 signaling pathway
toll-like receptor TLR6:TLR2 signaling pathway
TRIF-dependent toll-like receptor signaling pathway
tumor necrosis factor-mediated signaling pathway
Gene Ontology Molecular Function:: ATP binding
identical protein binding
IkappaB kinase activity
protein heterodimerization activity
protein homodimerization activity
protein kinase activity
protein kinase binding
protein serine/threonine kinase activity
scaffold protein binding
Gene Ontology Cellular Component:: CD40 receptor complex
cytoplasm
cytoplasmic side of plasma membrane
cytosol
IkappaB kinase complex
membrane raft
nucleus
Keywords:: 3D-structure
ATP-binding
Acetylation
Alternative splicing
Complete proteome
Cytoplasm
Direct protein sequencing
Hydroxylation
Isopeptide bond
Kinase
Membrane
Nucleotide-binding
Nucleus
Phosphoprotein
Polymorphism
Reference proteome
S-nitrosylation
SCID
Serine/threonine-protein kinase
Transferase
Ubl conjugation
Interacts With:: Q16543; O15111; Q92793; P08238; Q9Y6K9; Q14145; Q99558; Q9Y6Q9; P25963; P67775; Q04206; P23396; Q9UGK3; P03409; Q92574; P24772; Q5D1E7

Names & Taxonomy

Structure

Subcellular location

Function

Publication