BioPAX pathway converted from "beta-TRCP ubiquitinates IkB-alpha in p-S32,33-IkB-alpha:NF-kB complex" in the Reactome database.LEFT-TO-RIGHT6.3.2.19beta-TRCP ubiquitinates IkB-alpha in p-S32,33-IkB-alpha:NF-kB complexThis 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>p-S32,36-IkB-alpha:NF-kB complexReactome DB_ID: 9728125cytosolGENE ONTOLOGYGO:0005829Q9Z1E3phospho-Nfkbiap-S32,S36-NFKBIAReactome DB_ID: 9720093UniProt:Q9Z1E3NfkbiaMus musculusNCBI Taxonomy10090UniProtQ9Z1E332EQUALO-phospho-L-serineMODMOD:0004636EQUAL1EQUAL317EQUALReactome Database ID Release 759720093Database 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=9720093ReactomeR-MMU-1776771Reactome 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-MMU-177677.1Reactomehttp://www.reactome.org1NFKB1(1-433):RELAReactome DB_ID: 9724393Nfkb1NFKB1(1-433)P25799Reactome DB_ID: 9720069UniProt:P25799Nfkb1UniProtP257991EQUAL433EQUALReactome Database ID Release 759720069Database 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=9720069ReactomeR-MMU-1681681Reactome 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-MMU-168168.11RelaRELAQ04207Reactome DB_ID: 9720065UniProt:Q04207RelaUniProtQ042071EQUAL551EQUALReactome Database ID Release 759720065Database 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=9720065ReactomeR-MMU-1681721Reactome 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-MMU-168172.11Reactome Database ID Release 759724393Database 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=9724393ReactomeR-MMU-1940431Reactome 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-MMU-194043.11Reactome Database ID Release 759728125Database 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=9728125ReactomeR-MMU-56076711Reactome 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-MMU-5607671.1Converted from EntitySet in ReactomeUBE2D2,UBE2D1,(CDC34)Reactome DB_ID: 9783551Ube2d2UBE2D2P62838Reactome DB_ID: 9720377UniProt:P62838Ube2d2UniProtP628381EQUAL147EQUALReactome Database ID Release 759720377Database 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=9720377ReactomeR-MMU-9346281Reactome 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-MMU-934628.1Ube2d1UBE2D1P61080Reactome DB_ID: 9707948UniProt:P61080Ube2d1UniProtP610801EQUAL147EQUALReactome Database ID Release 759707948Database 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=9707948ReactomeR-MMU-1742361Reactome 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-MMU-174236.1Cdc34CDC34Q8CFI2Reactome DB_ID: 9752032UniProt:Q8CFI2Cdc34UniProtQ8CFI21EQUAL236EQUALReactome Database ID Release 759752032Database 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=9752032ReactomeR-MMU-9476211Reactome 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-MMU-947621.1Reactome Database ID Release 759783551Database 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=9783551ReactomeR-MMU-56076691Reactome 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-MMU-5607669.1Converted from EntitySet in ReactomeK48-UbK48-ubiquitinReactome DB_ID: 9746900Rps27aUb-48-RPS27A(1-76)P62983Reactome DB_ID: 9746859UniProt:P62983 Rps27aRps27aUba80Ubcep1SUBUNIT Ribosomal protein S27a is part of the 40S ribosomal subunit.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eS31 family.UniProtP6298348EQUALubiquitinylated lysineMODMOD:011481EQUAL76EQUALReactome Database ID Release 759746859Database 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=9746859ReactomeR-MMU-9392021Reactome 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-MMU-939202.1Uba52Ub-48-UBA52(1-76)P62984Reactome DB_ID: 9746862UniProt:P62984 Uba52Uba52Ubcep2SUBUNIT Ribosomal protein L40 is part of the 60S ribosomal subunit. Interacts with UBQLN1 (via UBA domain).MISCELLANEOUS Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.SIMILARITY In the N-terminal section; belongs to the ubiquitin family.SIMILARITY In the C-terminal section; belongs to the eukaryotic ribosomal protein eL40 family.UniProtP6298448EQUAL1EQUAL76EQUALReactome Database ID Release 759746862Database 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=9746862ReactomeR-MMU-9392501Reactome 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-MMU-939250.1UbcUb-48-UBB(1-76)P0CG50Reactome DB_ID: 9746865UniProt:P0CG50 UbcUbcMISCELLANEOUS Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.SIMILARITY Belongs to the ubiquitin family.UniProtP0CG5048EQUAL1EQUAL76EQUALReactome Database ID Release 759746865Database 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=9746865ReactomeR-MMU-9392491Reactome 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-MMU-939249.1UbbUb-48-UBC(1-76)P0CG49Reactome DB_ID: 9746874UniProt:P0CG49 UbbUbbSUBUNIT Interacts with SKP1-KMD2A and SKP1-KMD2B complexes.MISCELLANEOUS Ubiquitin is encoded by 4 different genes. Uba52 and Rps27a genes code for a single copy of ubiquitin fused to the ribosomal proteins L40 and S27a, respectively. UBB and UBC genes code for a polyubiquitin precursor with exact head to tail repeats, the number of repeats differ between species and strains.MISCELLANEOUS For the sake of clarity sequence features are annotated only for the first chain, and are not repeated for each of the following chains.SIMILARITY Belongs to the ubiquitin family.UniProtP0CG4948EQUAL1EQUAL76EQUALReactome Database ID Release 759746874Database 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=9746874ReactomeR-MMU-9392191Reactome 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-MMU-939219.1Reactome Database ID Release 759746900Database 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=9746900ReactomeR-MMU-9127221Reactome 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-MMU-912722.14CUL1:FBXW11:SKP1Reactome DB_ID: 9754338Skp1SKP1Q9WTX5Reactome DB_ID: 9721342UniProt:Q9WTX5 Skp1Skp1Skp1aFUNCTION Essential component of the SCF (SKP1-CUL1-F-box protein) ubiquitin ligase complex, which mediates the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. In the SCF complex, serves as an adapter that links the F-box protein to CUL1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5, CEP68 and probably NFKB2. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO11) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2 (By similarity).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with KDM2B, forming heterodimers (By similarity). The KDM2B-SKP1 heterodimeric complex interacts with the PCGF1-BCORL heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (By similarity). Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit. Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXw2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44. Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC. This complex binds phosphorylated NFKBIA. Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7. Component of the SCF(FBXW15) complex containing FBXW15 (PubMed:23319590). Interacts with CEP68 (By similarity). Interacts with FBXW15 (PubMed:23319590). Interacts with NOTCH2 (By similarity). The SKP1-KDM2A and SKP1-KDM2B complexes interact with UBB (By similarity).PTM Undergoes autophagy-mediated degradation in the liver in a time-dependent manner.SIMILARITY Belongs to the SKP1 family.UniProtQ9WTX52EQUAL163EQUALReactome Database ID Release 759721342Database 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=9721342ReactomeR-MMU-1741501Reactome 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-MMU-174150.11Cul1CUL1Q9WTX6Reactome DB_ID: 9721344UniProt:Q9WTX6 Cul1Cul1FUNCTION Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins. In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68. SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of cyclin E, NOTCH1 released notch intracellular domain (NICD), and probably PSEN1. SCF(FBXW2) directs ubiquitination of GCM1. SCF(FBXO32) directs ubiquitination of MYOD1. SCF(FBXO7) directs ubiquitination of BIRC2 and DLGAP5. SCF(FBXO33) directs ubiquitination of YBX1. SCF(FBXO1) directs ubiquitination of BCL6 and DTL but does not seem to direct ubiquitination of TP53. SCF(BTRC) mediates the ubiquitination of NFKBIA at 'Lys-21' and 'Lys-22'; the degradation frees the associated NFKB1-RELA dimer to translocate into the nucleus and to activate transcription. SCF(CCNF) directs ubiquitination of CCP110. SCF(FBXL3) and SCF(FBXL21) direct ubiquitination of CRY1 and CRY2. SCF(FBXO9) directs ubiquitination of TTI1 and TELO2. SCF(FBXO10) directs ubiquitination of BCL2.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Component of multiple SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complexes formed of CUL1, SKP1, RBX1 and a variable F-box domain-containing protein as substrate-specific subunit (PubMed:10097128, PubMed:12140560, PubMed:16880526, PubMed:23452855, PubMed:23452856). Component of the SCF(FBXW11) complex containing FBXW11. Component of the SCF(SKP2) complex containing SKP2, in which it interacts directly with SKP1, SKP2 and RBX1. Component of the SCF(FBXW2) complex containing FBXW2. Component of the SCF(FBXO32) complex containing FBXO32. Component of the probable SCF(FBXO7) complex containing FBXO7. Component of the SCF(FBXO10) complex containing FBXO10. Component of the SCF(FBXO11) complex containing FBXO11. Component of the SCF(FBXO25) complex containing FBXO25. Component of the SCF(FBXO33) complex containing FBXO33. Component of the probable SCF(FBXO4) complex containing FBXO4. Component of the SCF(FBXO44) complex, composed of SKP1, CUL1 and FBXO44 (By similarity). Component of the SCF(BTRC) complex, composed of SKP1, CUL1 and BTRC (PubMed:10097128, PubMed:11735228). This complex binds phosphorylated NFKBIA (PubMed:10097128). Part of a SCF complex consisting of CUL1, RBX1, SKP1 and FBXO2. Component of a SCF(SKP2)-like complex containing CUL1, SKP1, TRIM21 and SKP2. Component of the SCF(FBXO17) complex, composed of SKP1, CUL1 and FBXO17. Component of the SCF(FBXO27) complex, composed of SKP1, CUL1 and FBXO27. Component of the SCF(CCNF) complex consisting of CUL1, RBX1, SKP1 and CCNF. Component of the SCF(FBXL3) complex composed of CUL1, SKP1, RBX1 and FBXL3. Component of the SCF(FBXL21) complex composed of CUL1, SKP1, RBX1 and FBXL21. Component of the SCF(FBXO9) composed of CUL1, SKP1, RBX1 and FBXO9. Component of the SCF(FBXW7) composed of CUL1, SKP1, RBX1 and FBXW7. Interacts with CHEK2; mediates CHEK2 ubiquitination and regulates its function. Part of a complex with TIP120A/CAND1 and RBX1. The unneddylated form interacts with TIP120A/CAND1 and the interaction mediates the exchange of the F-box substrate-specific subunit. Can self-associate (By similarity). Interacts with FBXW8 (PubMed:16880526). Interacts with RNF7 (By similarity). Interacts with CUL7; the interaction seems to be mediated by FBXW8 (PubMed:16880526). Interacts with TRIM21 (By similarity). Interacts with COPS2 (PubMed:11967155). Interacts with DCUN1D1 and UBE2M. Interacts with DCUN1D3. Interacts with DCUN1D4 (By similarity). Identified in a complex with RBX1 and GLMN (By similarity). Interacts with CEP68 as part of the SCF(FBXW11) complex; the interaction is probably mediated by FBXW11 and the complex also contains CDK5RAP2 and PCNT. Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1. Interacts with COPS9. Interacts with UBXN1 (By similarity). Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (PubMed:23319590). Interacts with NOTCH2 (By similarity).SUBUNIT (Microbial infection) Interacts with murine cytomegalovirus M48.TISSUE SPECIFICITY Embryo fibroblasts and embryo preadipocytes.PTM Neddylated; which enhances the ubiquitination activity of SCF. Deneddylated via its interaction with the COP9 signalosome (CSN) complex.PTM (Microbial infection) Deneddylated by murine cytomegalovirus M48 leading to a S-phase-like environment that is required for efficient replication of the viral genome.SIMILARITY Belongs to the cullin family.UniProtQ9WTX61EQUAL776EQUALReactome Database ID Release 759721344Database 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=9721344ReactomeR-MMU-1742301Reactome 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-MMU-174230.11Fbw1bFbxw11Btrcp2Fbxw1bReactome DB_ID: 5610356UniProt:Q5SRY7 Fbxw11Fbxw11Btrcp2Fbw1bFbxw1bFUNCTION Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Probably recognizes and binds to phosphorylated target proteins. SCF(FBXW11) mediates the ubiquitination of phosphorylated CTNNB1 and participates in Wnt signaling. SCF(FBXW11) mediates the ubiquitination of phosphorylated NFKBIA, which degradation frees the associated NFKB1 to translocate into the nucleus and to activate transcription. SCF(FBXW11) mediates the ubiquitination of IFNAR1. SCF(FBXW11) mediates the ubiquitination of CEP68; this is required for centriole separation during mitosis (By similarity). Involved in the oxidative stress-induced a ubiquitin-mediated decrease in RCAN1. Mediates the degradation of CDC25A induced by ionizing radiation in cells progressing through S phase and thus may function in the intra-S-phase checkpoint. Has an essential role in the control of the clock-dependent transcription via degradation of phosphorylated PER1 and phosphorylated PER2. SCF(FBXW11) mediates the ubiquitination of CYTH1, and probably CYTH2 (By similarity).SUBUNIT Self-associates. Component of the SCF(FBXW11) complex formed of CUL1, SKP1, RBX1 and a FBXW11 dimer. Interacts with BTRC, BST2, PER1, RCAN1 and USP47. Interacts with phosphorylated ubiquitination substrates CTNNB1, NFKBIA, IFNAR1, PER1 and PER2; the interaction requires the phosphorylation of the two serine residues in the substrates' destruction motif D-S-G-X(2,3,4)-S. Interacts with TRIM21. Interacts with PER3. Interacts with phosphorylated ubiquitination substrate CEP68 (By similarity). Interacts with INAVA (By similarity). Interacts with REST (By similarity).INDUCTION Expression is negatively regulated by Wnt/beta-catenin pathway.DOMAIN The N-terminal D domain mediates homodimerization.UniProtQ5SRY71EQUAL542EQUALReactome Database ID Release 755610356Database 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=5610356ReactomeR-MMU-56103561Reactome 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-MMU-5610356.11Reactome Database ID Release 759754338Database 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=9754338ReactomeR-MMU-11685921Reactome 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-MMU-1168592.1K48PolyUb-K21,22-p-S32,36-IkBA:NF-kB complexReactome DB_ID: 97835361Q9Z1E3phospho-NfkbiaK48PolyUb-K21,22-p-S32,S36-IkBAReactome DB_ID: 978353421EQUAL22EQUAL1EQUAL317EQUALReactome Database ID Release 759783534Database 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=9783534ReactomeR-MMU-56076591Reactome 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-MMU-5607659.11Reactome Database ID Release 759783536Database 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=9783536ReactomeR-MMU-56076971Reactome 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-MMU-5607697.1ACTIVATIONGENE ONTOLOGYGO:0004842gene ontology term for cellular functionMIMI:0355Same Catalyst ActivityReactome Database ID Release 759783552Database 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=9783552Reactome Database ID Release 759783554Database 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=9783554ReactomeR-MMU-56077281Reactome 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-MMU-5607728.1Two major signaling steps are required for the removal of IkappaB (IkB) alpha an inhibitor of NF-kB: activation of the IkB kinase (IKK) and degradation of the phosphorylated IkB alpha. IKK activation and IkB degradation involve different ubiquitination modes; the former is mediated by K63-ubiquitination and the later by K48-ubiquitination. Mutational analysis of IkB alpha has indicated that K21 and K22 are the primary sites for addition of multiubiquitination chains while K38 and K47 are the secondary sites. In a transesterification reaction the ubiquitin is transferred from the ubiquitin-activating enzyme (E1) to an E2 ubiquitin-conjugating enzyme, which may, in turn, transfer the ubiquitin to an E3 ubiquitin protein ligase. UBE2D2 (UBC4) or UBE2D1 (UBCH5) or CDC34 (UBC3) acts as the E2 and SCF (SKP1-CUL1-F-box)-beta-TRCP complex acts as the E3 ubiquitin ligase (Strack et al. 2000, Wu et al. 2010). beta-TRCP (beta-transducin repeats-containing protein) is the substrate recognition subunit for the SCF-beta-TRCP E3 ubiquitin ligase. beta-TRCP binds specifically to phosphorylated IkB alpha and recruits it to the SCF complex, allowing the associated E2, such as UBC4 and or UBCH5 to ubiquitinate Ikappa B alpha (Baldi et al. 1996, Rodriguez et al. 1996, Scherer et al. 1995, Alkalay et al. 1995).10918611Pubmed2000SCF(beta-TRCP) and phosphorylation dependent ubiquitinationof I kappa B alpha catalyzed by Ubc3 and Ubc4Strack, PCaligiuri, MPelletier, MBoisclair, MTheodoras, ABeer-Romero, PGlass, SParsons, TCopeland, R AAuger, K RBenfield, PBrizuela, LRolfe, MOncogene 19:3529-367479848Pubmed1995Stimulation-dependent I kappa B alpha phosphorylation marks the NF-kappa B inhibitor for degradation via the ubiquitin-proteasome pathwayAlkalay, IYaron, AHatzubai, AOrian, ACiechanover, ABen-Neriah, YProc Natl Acad Sci U S A 92:10599-60320347421Pubmed2010Priming and extending: a UbcH5/Cdc34 E2 handoff mechanism for polyubiquitination on a SCF substrateWu, KKovacev, JPan, ZQMol Cell 37:784-967479976Pubmed1995Signal-induced degradation of I kappa B alpha requires site-specific ubiquitinationScherer, DCBrockman, JAChen, ZManiatis, TBallard, DWProc Natl Acad Sci U S A 92:11259-6314514672Pubmed2003Signal-induced ubiquitination of I kappaB Kinase-betaCarter, Robert SPennington, Kevin NUngurait, Bradley JArrate, PiaBallard, Dean WJ. Biol. Chem. 278:48903-69990853Pubmed1999Signal-induced ubiquitination of IkappaBalpha by the F-box protein Slimb/beta-TrCPSpencer, EJiang, JChen, ZJGenes Dev 13:284-948649784Pubmed1996Identification of lysine residues required for signal-induced ubiquitination and degradation of I kappa B-alpha in vivoRodriguez, M SWright, JThompson, JThomas, DBaleux, FVirelizier, J LHay, R TArenzana-Seisdedos, FOncogene 12:2425-358550590Pubmed1996Critical role for lysines 21 and 22 in signal-induced, ubiquitin-mediated proteolysis of I kappa B-alphaBaldi, LBrown, KFranzoso, GSiebenlist, UJ. Biol. Chem. 271:376-9inferred from electronic annotationEVIDENCE CODEECO:0000203