BioPAX pathway converted from "SCF-FBXL18 ubiquitinates FBXL7" in the Reactome database.SCF-FBXL18 ubiquitinates FBXL7

SCF-FBXL18 ubiquitinates FBXL7

FBXL18, a substrate recognition subunit of the SCF E3 ubiquitin ligase complex can bind to the FQ motif of FBXL7. The E3 ubiquitin ligase complex SCF-FBXL18 (SKP1:CUL1:RBX1:FBXL18) polyubiquitinates FBXL7 on lysine residue K109, targeting it for proteasome-mediated degradation (Liu et al. 2015).

Authored: Orlic-Milacic, Marija, 2016-01-26Reviewed: Grant, Rhys, 2016-05-13Reviewed: Lindon, Catherine, 2016-05-13Edited: Orlic-Milacic, Marija, 2016-01-26

Converted from EntitySet in Reactome

Reactome DB_ID: 113595

cytosolGO0005829

Ub [cytosol]Converted from EntitySet in Reactome. Each synonym is a name of a PhysicalEntity, and each XREF points to one PhysicalEntityUBC(609-684) [cytosol]UBB(77-152) [cytosol]UBB(1-76) [cytosol]UBC(305-380) [cytosol]UBC(1-76) [cytosol]UBA52(1-76) [cytosol]RPS27A(1-76) [cytosol]UBC(533-608) [cytosol]UBB(153-228) [cytosol]UBC(457-532) [cytosol]UBC(77-152) [cytosol]UBC(229-304) [cytosol]UBC(381-456) [cytosol]UBC(153-228) [cytosol]

Reactomehttp://www.reactome.orgHomo sapiens

NCBI Taxonomy9606UniProtP0CG48UniProtP0CG47UniProtP62987UniProtP62979

Reactome DB_ID: 8854032

UniProt:Q9UJT9 FBXL7

FBXL7

FBL6KIAA0840FBL7FBXL7FUNCTION Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex (PubMed:25778398). During mitosis, it mediates the ubiquitination and subsequent proteasomal degradation of AURKA, causing mitotic arrest (By similarity). It also regulates mitochondrial function by mediating the ubiquitination and proteasomal degradation of the apoptosis inhibitor BIRC5 (PubMed:25778398, PubMed:28218735).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Part of the SCF (SKP1-CUL1-F-box) E3 ubiquitin-protein ligase complex SCF(FBXL7) composed of CUL1, SKP1, RBX1 and FBXL7 (By similarity). Interacts with AURKA; interaction takes place during mitosis but not in interphase (By similarity). Interacts with BIRC5; this interaction allows BIRC5 to be polyubiquitinated by the SCF(FBXL7) E3 ubiquitin-protein ligase complex (PubMed:28218735).SIMILARITY Belongs to the FBXL7 family.

UniProtQ9UJT9

Chain Coordinates

EQUAL

491

EQUAL

Reactome DB_ID: 8854053

ubiquitinylated lysine (polyubiquitin chain [cytosol]) at 109

109

EQUAL

ubiquitinylated lysine [MOD:01148]

EQUAL

491

EQUAL

PHYSIOL-LEFT-TO-RIGHT

ACTIVATION

Reactome DB_ID: 8854059

SKP1:CUL1:RBX1:FBXL18 [cytosol]

SKP1:CUL1:RBX1:FBXL18

SCF-FBXL18

Reactome DB_ID: 174230

UniProt:Q13616 CUL1

CUL1

CUL1FUNCTION 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 (PubMed:27565346). 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 (PubMed:25704143, PubMed:25503564). 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 CCNE1, 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:10230406, PubMed:15145941, PubMed:15531760, PubMed:16714087, PubMed:16797541, PubMed:17098746, PubMed:18203720, PubMed:20596027, PubMed:22405651, PubMed:22113614, PubMed:23263282, PubMed:23431138, PubMed:25503564, PubMed:11961546, PubMed:22748924). 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 (PubMed:22405651). 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. Interacts with FBXW8. Interacts with RNF7. Interacts with CUL7; the interaction seems to be mediated by FBXW8. Interacts with TRIM21. Interacts with COPS2. Interacts with DCUN1D1 and UBE2M (PubMed:21940857). Interacts with DCUN1D3 (PubMed:25349211). Interacts with DCUN1D4 (PubMed:28581483). Identified in a complex with RBX1 and GLMN (PubMed:22405651, PubMed:22748924). 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 (PubMed:25503564). Interacts (when neddylated) with ARIH1; leading to activate the E3 ligase activity of ARIH1 (PubMed:24076655, PubMed:27565346). Interacts with COPS9 isoform 2 (PubMed:23776465). Interacts with UBXN1 (PubMed:28152074). Interacts with KAT7, probably as part of an SCF complex; the interaction mediates KAT7 ubiquitination (By similarity). Interacts with NOTCH2 (PubMed:29149593).SUBUNIT (Microbial infection) Interacts with Epstein-Barr virus BPLF1.SUBUNIT (Microbial infection) Interacts with Human adenovirus early E1A protein; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBXW7) complex.SUBUNIT (Microbial infection) Interacts with vaccinia virus protein C9L.TISSUE SPECIFICITY Expressed in lung fibroblasts.PTM Neddylated; which enhances the ubiquitination activity of SCF and prevents binding of the inhibitor CAND1. Deneddylated via its interaction with the COP9 signalosome (CSN) complex (PubMed:10597293, PubMed:10713156, PubMed:15537541, PubMed:18805092).PTM (Microbial infection) Deneddylated by Epstein-Barr virus BPLF1 leading to a S-phase-like environment that is required for efficient replication of the viral genome (PubMed:20190741).SIMILARITY Belongs to the cullin family.

UniProtQ13616

EQUAL

776

EQUAL

Reactome DB_ID: 174150

UniProt:P63208 SKP1

SKP1

TCEB1LOCP2EMC19SKP1ASKP1FUNCTION 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 (PubMed:25704143). 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. SCF(FBXO10) directs ubiquitination of BCL2.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Interacts with KDM2B, forming heterodimers (PubMed:27568929). The KDM2B-SKP1 heterodimeric complex interacts with the PCGF1-BCORL heterodimeric complex to form a homotetrameric polycomb repression complex 1 (PRC1.1) (PubMed:27568929). 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 (PubMed:28727686). Interacts with CEP68 (PubMed:25503564). Interacts with NOTCH2 (PubMed:29149593). Interacts with FBXW15 (By similarity). The SKP1-KDM2A and SKP1-KDM2B complexes interact with UBB (PubMed:30033217).SUBUNIT (Microbial infection) Interacts with vaccinia virus protein C9L.PTM Undergoes autophagy-mediated degradation in the liver in a time-dependent manner.SIMILARITY Belongs to the SKP1 family.

UniProtP63208

EQUAL

163

EQUAL

Reactome DB_ID: 180582

UniProt:P62877 RBX1

RBX1

RNF75ROC1RBX1FUNCTION E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair (PubMed:10230407, PubMed:10579999, PubMed:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:11961546, PubMed:22748924). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (PubMed:27565346). The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM.PATHWAY Protein modification; protein ubiquitination.SUBUNIT Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2 (PubMed:11961546). Part of a SCF-like complex consisting of CUL7, RBX1, SKP1 and FBXW8. Part of CBC(VHL) complexes with elongin BC complex (ELOB and ELOC), CUL2 or CUL5 and VHL. Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II. Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1. Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), elongin A/ELOA or SOCS1 or WSB1 and CUL5. Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7. Interacts with CDC34 (PubMed:22748924). Interacts with GLMN. GLMN competes for the binding site of the E2 ubiquitin-conjugating enzyme CDC34 and disrupts CDC34 binding (PubMed:22748924). Interacts with COPS6. Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1. Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B. Interacts with UBE2M. Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3. Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF. Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34. Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein. Part of the BCR(ENC1) complex containing ENC1. Part of the BCR(GAN) complex containing GAN. Part of the BCR(KLHL41) complex containing KLHL41. Part of the BCR(KEAP1) complex containing KEAP1. Interacts with DCUN1D3. Interacts with SESN1 and SESN2 (PubMed:23274085). Interacts with NOTCH2 (PubMed:29149593). Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (PubMed:23455478).SUBUNIT (Microbial infection) Interacts with human adenovirus 5 protein E1A; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex.TISSUE SPECIFICITY Widely expressed.DOMAIN The RING-type zinc finger domain is essential for ubiquitin ligase activity (PubMed:10230407). It coordinates an additional third zinc ion (PubMed:11961546, PubMed:22748924).SIMILARITY Belongs to the RING-box family.

UniProtP62877

EQUAL

108

EQUAL

Reactome DB_ID: 8854063

UniProt:Q96ME1 FBXL18

FBXL18

FBXL18FBL18FUNCTION Substrate-recognition component of the SCF (SKP1-CUL1-F-box protein)-type E3 ubiquitin ligase complex.SUBUNIT Directly interacts with SKP1 and CUL1.

UniProtQ96ME1

EQUAL

805

EQUAL

Reactome Database ID Release 738854059Database 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=8854059ReactomeR-HSA-8854059

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-HSA-8854059.1GO0061630

GO molecular function

Reactome Database ID Release 738854055Database 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=8854055Reactome Database ID Release 738854051Database 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=8854051ReactomeR-HSA-8854051

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-HSA-8854051.325654763Pubmed2015F-box protein Fbxl18 mediates polyubiquitylation and proteasomal degradation of the pro-apoptotic SCF subunit Fbxl7Liu, YLear, TZhao, YZhao, JZou, CChen, B BMallampalli, R KCell Death Dis 6:e1630GO0031146

GO biological process