Letunic et al. (2017) Nucleic Acids Res doi: 10.1093/nar/gkx922
Letunic et al. (2020) Nucleic Acids Res doi: 10.1093/nar/gkaa937

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IKKbetaNEMObind I-kappa-kinase-beta NEMO binding domain

SMART accession number:	SM01239
Description:	This domain family is found in eukaryotes, and is approximately 40 amino acids in length. The family is found in association with S_TKc. These proteins are involved in inflammatory reactions. They cause release of NF-kappa-B into the nucleus of inflammatory cells and upregulation of transcription of proinflammatory cytokines. They perform this function by phosphorylating I-kappa-B proteins which are targeted for degradation to release NF-kappa-B. This kinase (I-kappa-kinase-beta) is found in association with IKK-alpha and NEMO (NF-kappa-B essential modulator). This domain is the binding site of IKK-beta for NEMO.
Interpro abstract (IPR022007):	This domain family is found in eukaryotes, and is approximately 40 amino acids in length. The family is found in association with . These proteins are involved in inflammatory reactions. They cause release of NF-kappa-B into the nucleus of inflammatory cells and upregulation of transcription of proinflammatory cytokines. They perform this function by phosphorylating I-kappa-B proteins which are targeted for degradation to release NF-kappa-B. This kinase (I-kappa-kinase-beta) is found in association with IKK-alpha and NEMO (NF-kappa-B essential modulator). This domain is the binding site of IKK-beta for NEMO.
GO function:	IkappaB kinase activity (GO:0008384)
Family alignment:	View or CHROMA formatHMM/Web logoCLUSTALW formatMSF formatFASTA formatPIR format

There are 606 IKKbetaNEMObind domains in 603 proteins in SMART's nrdb database.

Click on the following links for more information.

• Evolution (species in which this domain is found)

• Taxonomic distribution of proteins containing IKKbetaNEMObind domain.

  This tree includes only several representative species. The complete taxonomic breakdown of all proteins with IKKbetaNEMObind domain is also avaliable.

  Click on the protein counts, or double click on taxonomic names to display all proteins containing IKKbetaNEMObind domain in the selected taxonomic class.

• Cellular role (predicted cellular role)

• Cellular role: signalling
  

• Literature (relevant references for this domain)

• Primary literature is listed below; Automatically-derived, secondary literature is also avaliable.

  • Rushe M et al.
  • Structure of a NEMO/IKK-associating domain reveals architecture of theinteraction site.
  • Structure. 2008; 16: 798-808
  • Display abstract

  • The phosphorylation of IkappaB by the IKK complex targets it for degradation and releases NF-kappaB for translocation into the nucleus to initiate theinflammatory response, cell proliferation, or cell differentiation. The IKKcomplex is composed of the catalytic IKKalpha/beta kinases and a regulatoryprotein, NF-kappaB essential modulator (NEMO; IKKgamma). NEMO associates with theunphosphorylated IKK kinase C termini and activates the IKK complex's catalyticactivity. However, detailed structural information about the NEMO/IKK interactionis lacking. In this study, we have identified the minimal requirements for NEMOand IKK kinase association using a variety of biophysical techniques and havesolved two crystal structures of the minimal NEMO/IKK kinase associating domains.We demonstrate that the NEMO core domain is a dimer that binds two IKK fragments and identify energetic hot spots that can be exploited to inhibit IKK complexformation with a therapeutic agent.

• Structure (3D structures containing this domain)

• 3D Structures of IKKbetaNEMObind domains in PDB

  PDB code	Main view	Title
  3brt		NEMO/IKK association domain structure
  3brv		NEMO/IKKb association domain structure

• Links (links to other resources describing this domain)

• INTERPRO	IPR022007
  PFAM	IKKbetaNEMObind

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