BioPAX pathway converted from "NF-kappa-B inhibitor binds NF-kappa-B complex" in the Reactome database. NF-kappa-B inhibitor binds NF-kappa-B complex NF-kappa-B inhibitor binds NF-kappa-B complex This event has been computationally inferred from an event that has been demonstrated in another species.<p>The inference is based on the homology mapping from PANTHER. Briefly, reactions for which all involved PhysicalEntities (in input, output and catalyst) have a mapped orthologue/paralogue (for complexes at least 75% of components must have a mapping) are inferred to the other species. High level events are also inferred for these events to allow for easier navigation.<p><a href='/electronic_inference_compara.html' target = 'NEW'>More details and caveats of the event inference in Reactome.</a> For details on PANTHER see also: <a href='http://www.pantherdb.org/about.jsp' target='NEW'>http://www.pantherdb.org/about.jsp</a> Reactome DB_ID: 9942477 1 cytosol GO 0005829 NFKB1(1-433), NFKB2(1-454):RELA [cytosol] NFKB1(1-433), NFKB2(1-454):RELA Reactome DB_ID: 9942471 1 UniProt:Q7TQN4 Rela Reactome http://www.reactome.org Rattus norvegicus NCBI Taxonomy 10116 UniProt Q7TQN4 Chain Coordinates 1 EQUAL 551 EQUAL Reactome DB_ID: 9942475 1 UniProt:Q5U2Z4 Nfkb2 UniProt Q5U2Z4 1 EQUAL 454 EQUAL Reactome Database ID Release 82 9942477 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9942477 Reactome R-RNO-168155 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-168155.1 Converted from EntitySet in Reactome Reactome DB_ID: 9942487 1 NFkB inhibitor [cytosol] Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntity Nfkbia [cytosol] Nfkbib [cytosol] UniProt Q63746 UniProt Q9JIA3 Reactome DB_ID: 9942489 1 NFkB inhibitor:NFkB complex [cytosol] NFkB inhibitor:NFkB complex Reactome DB_ID: 9942477 1 Converted from EntitySet in Reactome Reactome DB_ID: 9942487 1 Reactome Database ID Release 82 9942489 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=9942489 Reactome R-RNO-168130 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-168130.1 Reactome Database ID Release 82 10030260 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=10030260 Reactome R-RNO-9630923 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-RNO-9630923.1 NF-kappa-B is sequestered in the cytosol of unstimulated cells through the interactions with a class of inhibitor proteins, called NF-kappa-B inhibitors (IkBs, NFKBIA or NFKBIB). IkBs proteins such as NFKBIA, NFKBIB or NFKBIE are characterized by the presence of six to seven ankyrin repeat motifs, which mediate interaction with the Rel homology domain (RHD). RHD mediates DNA binding, dimerization and nuclear localization (Jacobs MD & Harrison SC 1998; Manavalan B et al. 2010). NF-kappa-B inhibitors (IkBs) mask the nuclear localization signal (NLS) of the NF-kappa-B p65 subunit (ReLA, p65) preventing the nuclear translocation of NF-kappa-B (Jacobs MD & Harrison SC 1998; Cervantes CF et al. 2011). A key event in NF-kappa-B activation involves phosphorylation of IkB (at sites equivalent to Ser32 and Ser36 of NFKBIA (IkB-alpha) or Ser19 and Ser22 of NFKBIB (IkB-beta) by the IκB kinase (IKK) complex. The phosphorylated NFKBIA is recognized by the E3 ligase complex leading to K48-linked ubiquitination, and targeted for ubiquitin-mediated proteasomal degradation, releasing the NF-kappa-B dimer p50/p65 (RelA:NFKB1) into the nucleus to turn on target genes (Karin M & Ben-Neriah Y 2000, Kanarek N & Ben-Neriah Y 2012; Hoffmann A et al. 2006). Crystal structures of NF-kappa-B inhibitors:NF-kappaB complexes revealed that an NF-kappa-B dimer binds to one IkB molecule (Jacobs MD & Harrison SC 1998; Ghosh G et 2012). 22435548 Pubmed 2012 Regulation of NF-κB by ubiquitination and degradation of the IκBs Kanarek, Naama Ben-Neriah, Yinon Immunol. Rev. 246:77-94 9865693 Pubmed 1998 Structure of an IkappaBalpha/NF-kappaB complex Jacobs, M D Harrison, S C Cell 95:749-58 17072323 Pubmed 2006 Transcriptional regulation via the NF-kappaB signaling module Hoffmann, A Natoli, G Ghosh, G Oncogene 25:6706-16 10837071 Pubmed 2000 Phosphorylation meets ubiquitination: the control of NF-[kappa]B activity Karin, M Ben-Neriah, Y Annu. Rev. Immunol. 18:621-63 22435546 Pubmed 2012 NF-κB regulation: lessons from structures Ghosh, Gourisankar Wang, Vivien Ya-Fan Huang, De-Bin Fusco, Amanda Immunol. Rev. 246:36-58 15145317 Pubmed 2004 The two NF-kappaB activation pathways and their role in innate and adaptive immunity Bonizzi, G Karin, M Trends Immunol 25:280-8 21203422 Pubmed 2010 Structure-function relationship of cytoplasmic and nuclear IκB proteins: an in silico analysis Manavalan, Balachandran Basith, Shaherin Choi, Yong-Min Lee, Gwang Choi, Sangdun PLoS ONE 5:e15782 21094161 Pubmed 2011 The RelA nuclear localization signal folds upon binding to IκBα Cervantes, Carla F Bergqvist, Simon Kjaergaard, Magnus Kroon, Gerard Sue, Shih-Che Dyson, H Jane Komives, Elizabeth A J. Mol. Biol. 405:754-64 inferred by electronic annotation IEA GO IEA