CPLM-001352

Genbank Nucleotide ID

Inhibitor of nuclear factor kappa-B kinase subunit beta

Protein Synonyms/Alias

I-kappa-B-kinase beta; IKK-B; IKK-beta; IkBKB; I-kappa-B kinase 2; IKK2; Nuclear factor NF-kappa-B inhibitor kinase beta; NFKBIKB

Mus musculus (Mouse)

Position	Peptide	Type	References
498	QIDLEKYKEQTEFGI	ubiquitination	[1]
555	QRSPMGRKQGGTLDD	ubiquitination	[1]

[1] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]

Functional Description

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. 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 (By similarity).

DOMAIN 15 300 Protein kinase.
NP_BIND 21 29 ATP (By similarity).
REGION 458 479 Leucine-zipper.
REGION 737 742 NEMO-binding.
ACT_SITE 145 145 Proton acceptor (By similarity).
BINDING 44 44 ATP (By similarity).
MOD_RES 177 177 Phosphoserine; by TBK1 and PKC/PRKCZ (By
MOD_RES 181 181 Phosphoserine; by TBK1, PKC/PRKCZ and
MOD_RES 670 670 Phosphoserine; by autocatalysis (By
MOD_RES 672 672 Phosphoserine; by autocatalysis (By
MOD_RES 675 675 Phosphoserine; by autocatalysis (By
MOD_RES 682 682 Phosphoserine; by autocatalysis (By
MOD_RES 689 689 Phosphoserine; by autocatalysis (By
MOD_RES 692 692 Phosphoserine; by autocatalysis (By
MOD_RES 697 697 Phosphoserine; by autocatalysis (By
MOD_RES 705 705 Phosphoserine; by autocatalysis (By
MOD_RES 733 733 Phosphoserine; by autocatalysis (By
MOD_RES 740 740 Phosphoserine; by autocatalysis (By

ATP-binding; Complete proteome; Cytoplasm; Kinase; Membrane; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Transferase; Ubl conjugation.

UniProt (SWISSPROT/TrEMBL); GenBank; EMBL

GO:0035631; C:CD40 receptor complex; IDA:BHF-UCL.
GO:0005737; C:cytoplasm; TAS:MGI.
GO:0009898; C:internal side of plasma membrane; IDA:BHF-UCL.
GO:0045121; C:membrane raft; IEA:UniProtKB-SubCell.
GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO:0008384; F:IkappaB kinase activity; IDA:MGI.
GO:0004702; F:receptor signaling protein serine/threonine kinase activity; TAS:MGI.
GO:0001782; P:B cell homeostasis; IMP:MGI.
GO:2001259; P:positive regulation of cation channel activity; IGI:MGI.
GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISO:MGI.
GO:0010765; P:positive regulation of sodium ion transport; IGI:MGI.

IPR022007; IKKbetaNEMObind.
IPR011009; Kinase-like_dom.
IPR000719; Prot_kinase_cat_dom.
IPR008271; Ser/Thr_kinase_AS.

PF12179; IKKbetaNEMObind
PF00069; Pkinase

PS00107; PROTEIN_KINASE_ATP
PS50011; PROTEIN_KINASE_DOM
PS00108; PROTEIN_KINASE_ST