RBX1

UniProt ID: P62877
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

RBX1 (ROC1, RNF75) is a 108-residue RING-H2 protein that forms the catalytic subunit of most human cullin-RING ubiquitin ligases (CRLs). Its N-terminal strand pairs with the C-terminal domain of a cullin through an intermolecular beta-sheet, while its cross-braced RING domain, which coordinates two structural zinc ions (a third is seen in SCF structures), binds a modifier-charged E2 enzyme and holds it in the closed, transfer-competent conformation. RBX1 forms no thioester of its own: ubiquitin passes directly from the E2 (CDC34/UBE2R, UBE2D) to a lysine on a substrate that a variable receptor module has recruited at the far end of the cullin, roughly 100 A away. The same RING also acts in the NEDD8 pathway, where RBX1 binds UBE2M/UBC12~NEDD8 - assisted by DCN-type co-E3s (DCUN1D1-5) - and rotates to neddylate the conserved cullin lysine, the modification that activates the ligase and blocks CAND1 binding; the paralogue RBX2/RNF7 performs the equivalent reaction with UBE2F for CUL5. RBX1 is therefore shared by CRL1/SCF (with SKP1 and about 70 F-box proteins), CRL2 (elongin BC with VHL-box receptors), CRL3 (BTB proteins such as KEAP1, SPOP, KLHL and KCTD family members), CRL4A/B (DDB1 with DCAFs) and the CUL7-FBXW8 and hexameric CUL9 assemblies, and substrate choice resides in these receptors rather than in RBX1 itself. Its outputs are correspondingly broad: mainly K48-linked chains that commit substrates to the proteasome (p27/CDKN1B via SCF(SKP2) at the G1/S transition, IkappaB-alpha, beta-catenin and DEPTOR via SCF(beta-TrCP), c-Myc and NOTCH via SCF(FBXW7), CDT1 and p21 via CRL4(CDT2), NRF2 via CUL3-KEAP1, HIF-alpha via CRL2(VHL), RNA polymerase II subunits via CRL3(ARMC5) and CRL4(CSA)), but also monoubiquitination (SEC31, PCNA) and K63- or K27-linked signals. RBX1 acts in both nucleus and cytosol, with its effective location set by the assembled ligase, and it is essential: mouse Rbx1 disruption causes p27 accumulation, hypoproliferation and early embryonic lethality that deleting p27 only partly delays.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000082 G1/S transition of mitotic cell cycle
NAS
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga...
ACCEPT
Summary: Through SCF(SKP2), which degrades Thr187-phosphorylated p27/CDKN1B, and through CRL1/CRL4 turnover of CDT1, p21 and E2F1, RBX1 is required for the G1/S transition; mouse Rbx1 disruption accumulates p27 and causes early embryonic lethality with hypoproliferation.
Reason: Core process: RBX1 performs the ubiquitin-transfer step of the p27 degradation switch, and the genetic evidence shows the requirement is not redundant with RBX2.
Supporting Evidence:
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0000109 nucleotide-excision repair complex
IPI
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
MODIFY
Summary: IPI row from the CRL4(DDB2)/CRL4(CSA) architecture study; the RBX1-containing entity characterised there is the DDB1-DDB2-CUL4A/B-RBX1 ubiquitin ligase, which acts in nucleotide-excision repair.
Reason: The complex RBX1 belongs to is the Cul4A-RING ligase (GO:0031464, annotated from the same paper), not the NER incision machinery that 'nucleotide-excision repair complex' denotes; CRL4(DDB2) delivers ubiquitin to chromatin at the lesion and is regulated by the CSN, but it is not a subcomplex of the repair machinery itself.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0000122 negative regulation of transcription by RNA polymerase II
NAS
PMID:28591624
Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligas...
MARK AS OVER ANNOTATED
Summary: Author statement from the CRL2(VHL) crystal-structure paper.
Reason: Over-annotation: the paper establishes complex architecture, not a role for RBX1 in repressing Pol II transcription. The CRL2 complex membership from the same reference is the supportable claim.
Supporting Evidence:
PMID:28591624
Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0000165 MAPK cascade
TAS
Reactome:R-HSA-5673001
MARK AS OVER ANNOTATED
Summary: Reactome places RBX1-containing ligases in the RAF/MAP kinase cascade pathway.
Reason: Over-annotation: RBX1 does not transduce the cascade; it ubiquitinates substrates whose turnover impinges on it. The direct events are already annotated as ubiquitination and CRL-dependent proteolysis.
Supporting Evidence:
Reactome:R-HSA-5673001
The RAS-RAF-MEK-ERK pathway regulates processes such as proliferation, differentiation, survival, senescence and cell motility in response to growth factors, hormones and cytokines, among others.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0000209 protein polyubiquitination
IDA
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi...
ACCEPT
Summary: BTB-CUL3-ROC1 ligases assembled in vitro build polyubiquitin chains on receptor-bound substrates such as MEI-1/katanin.
Reason: Core process: polyubiquitination is the characteristic output of RBX1-containing CRLs, and RBX1 performs the transfer step.
Supporting Evidence:
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0004842 ubiquitin-protein transferase activity
IDA
PMID:15983046
Ubiquitination of Keap1, a BTB-Kelch substrate adaptor prote...
ACCEPT
Summary: RBX1 supplies the RING activity that transfers ubiquitin from a charged E2 onto CRL-recruited substrates; the annotation is the parent of the more precise ubiquitin protein ligase activity (GO:0061630) also annotated here.
Reason: Correct, if one step broader than GO:0061630: RBX1 does not form a ubiquitin thioester itself but activates the E2~ubiquitin conjugate for direct transfer, which is what ubiquitin-protein transferase activity denotes. The contributes_to qualifier on the IDA rows is appropriate for a subunit that is catalytic only within an assembled cullin-RING complex.
Supporting Evidence:
PMID:15983046
Keap1 is a BTB-Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0004842 ubiquitin-protein transferase activity
IDA
PMID:20389280
The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti...
ACCEPT
Summary: RBX1 supplies the RING activity that transfers ubiquitin from a charged E2 onto CRL-recruited substrates; the annotation is the parent of the more precise ubiquitin protein ligase activity (GO:0061630) also annotated here.
Reason: Correct, if one step broader than GO:0061630: RBX1 does not form a ubiquitin thioester itself but activates the E2~ubiquitin conjugate for direct transfer, which is what ubiquitin-protein transferase activity denotes. The contributes_to qualifier on the IDA rows is appropriate for a subunit that is catalytic only within an assembled cullin-RING complex.
Supporting Evidence:
PMID:20389280
The KLHL20-Cul3-ROC1 E3 ligase complex promotes DAPK polyubiquitination, thereby inducing the proteasomal degradation of DAPK.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0004842 ubiquitin-protein transferase activity
IEA
GO_REF:0000117
ACCEPT
Summary: RBX1 supplies the RING activity that transfers ubiquitin from a charged E2 onto CRL-recruited substrates; the annotation is the parent of the more precise ubiquitin protein ligase activity (GO:0061630) also annotated here.
Reason: Correct, if one step broader than GO:0061630: RBX1 does not form a ubiquitin thioester itself but activates the E2~ubiquitin conjugate for direct transfer, which is what ubiquitin-protein transferase activity denotes. The contributes_to qualifier on the IDA rows is appropriate for a subunit that is catalytic only within an assembled cullin-RING complex.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0004842 ubiquitin-protein transferase activity
TAS
Reactome:R-HSA-69598
ACCEPT
Summary: RBX1 supplies the RING activity that transfers ubiquitin from a charged E2 onto CRL-recruited substrates; the annotation is the parent of the more precise ubiquitin protein ligase activity (GO:0061630) also annotated here.
Reason: Correct, if one step broader than GO:0061630: RBX1 does not form a ubiquitin thioester itself but activates the E2~ubiquitin conjugate for direct transfer, which is what ubiquitin-protein transferase activity denotes. The contributes_to qualifier on the IDA rows is appropriate for a subunit that is catalytic only within an assembled cullin-RING complex.
Supporting Evidence:
Reactome:R-HSA-69598
<p>Exposure of various human cell lines to ultraviolet (UV) light leads to rapid appearance of polyubiquitinated CDC25A (PolyUb-CDC25A) (Mailand et al. 2000).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:12504026
CAND1 binds to unneddylated CUL1 and regulates the formation...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:12504026
We found the majority of CUL1 is in a complex with CAND1 and ROC1 independent of SKP1 and F box protein SKP2.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:12609982
TIP120A associates with cullins and modulates ubiquitin liga...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:12609982
TIP120A formed a complex with CUL1 and Rbx1, but interfered with the binding of Skp1 and F-box proteins to CUL1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:12609982
TIP120A associates with cullins and modulates ubiquitin liga...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL4B.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:12609982
TIP120A formed a complex with CUL1 and Rbx1, but interfered with the binding of Skp1 and F-box proteins to CUL1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:15601820
VHL-box and SOCS-box domains determine binding specificity f...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL2.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:15601820
VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:17183367
COMMD1 promotes the ubiquitination of NF-kappaB subunits thr...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL2.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:17183367
COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:17543862
A Cul3-based E3 ligase removes Aurora B from mitotic chromos...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL3.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:17543862
Moreover, Aurora B is ubiquitylated in a Cul3-dependent manner in vivo, and by reconstituted Cul3/KLHL9/KLHL13 ligase in vitro.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:18239684
Phosphorylation of Skp2 regulated by CDK2 and Cdc14B protect...
REMOVE
Summary: IPI row pairing RBX1 with SKP2 in a study of how CDK2/Cdc14B phosphorylation protects SKP2 from APC(Cdh1).
Reason: SKP2 joins the SCF through SKP1 and the CUL1 N-terminus, not through RBX1, and this paper characterises SKP2 stability rather than an RBX1 activity. The supportable statements (SCF complex membership, SCF-dependent proteolysis) are annotated from other references. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:18239684
The activity of SCF(Skp2) is regulated by the APC(Cdh1), which targets Skp2 for degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:18805092
Structural insights into NEDD8 activation of cullin-RING lig...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:18805092
Second, in a model of Rbx1 bound to a ubiquitin E2, a predicted ~60Γ… gap between an E2’s Cys and the substrate binding site raises the question of how ubiquitin is transferred to targets.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:18805092
Structural insights into NEDD8 activation of cullin-RING lig...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL5.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:18805092
Second, in a model of Rbx1 bound to a ubiquitin E2, a predicted ~60Γ… gap between an E2’s Cys and the substrate binding site raises the question of how ubiquitin is transferred to targets.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:18826954
SCCRO (DCUN1D1) is an essential component of the E3 complex ...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D1), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:18826954
In contrast to findings in cellular systems where no binding is seen, we show that SCCRO and CAND1 can bind to the neddylated Cul1-ROC1 complex in assays using purified recombinant proteins.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:19250909
E2-RING expansion of the NEDD8 cascade confers specificity t...
MODIFY
Summary: IPI row recording the interaction of RBX1 with the NEDD8-conjugating E2 UBE2M/UBC12.
Reason: The informative function is engagement of the charged E2: RBX1 binds UBE2M~NEDD8 and rotates its RING to position the E2 next to the cullin acceptor lysine. Ubiquitin conjugating enzyme binding (GO:0031624) captures this; the catalytic consequence is annotated as NEDD8 transferase/ligase activity.
Supporting Evidence:
PMID:19250909
The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2).
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:19327355
Requirement for microtubule integrity in the SOCS1-mediated ...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL2.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:19327355
SOCS1 facilitates Gag ubiquitination and the co-expression of a dominant-negative ubiquitin significantly inhibits the association of Gag with microtubules.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:19549727
Analysis of the human E2 ubiquitin conjugating enzyme protei...
REMOVE
Summary: Generic protein-binding row recording RBX1 with UBE2M, from a systematic yeast two-hybrid map of E2/E3-RING pairs.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:19549727
Analysis of the human E2 ubiquitin conjugating enzyme protein interaction network.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:20399188
Structural insights into the COP9 signalosome and its common...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:20399188
Structural insights into the COP9 signalosome and its common architecture with the 26S proteasome lid and eIF3.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:21765416
A RING E3-substrate complex poised for ubiquitin-like protei...
MODIFY
Summary: IPI row recording the interaction of RBX1 with the NEDD8-conjugating E2 UBE2M/UBC12.
Reason: The informative function is engagement of the charged E2: RBX1 binds UBE2M~NEDD8 and rotates its RING to position the E2 next to the cullin acceptor lysine. Ubiquitin conjugating enzyme binding (GO:0031624) captures this; the catalytic consequence is annotated as NEDD8 transferase/ligase activity.
Supporting Evidence:
PMID:21765416
The NEDD8-modified CUL1 assembles with SKP1–F-box protein–substrate, RBX1 binds a ubiquitin-charged E2 such as UBCH5 or CDC34, and ubiquitin is ligated to a substrate15,16.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:21765416
A RING E3-substrate complex poised for ubiquitin-like protei...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:21765416
The NEDD8-modified CUL1 assembles with SKP1–F-box protein–substrate, RBX1 binds a ubiquitin-charged E2 such as UBCH5 or CDC34, and ubiquitin is ligated to a substrate15,16.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:22660580
F-box protein FBXL19-mediated ubiquitination and degradation...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:22660580
Three enzyme complexes (E1, E2 and E3) are involved in linking ubiquitin chains onto target proteins25.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:23238014
CRL4B catalyzes H2AK119 monoubiquitination and coordinates w...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL4B.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:23238014
CRL4B catalyzes H2AK119 monoubiquitination and coordinates with PRC2 to promote tumorigenesis.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:23274085
Sestrins activate Nrf2 by promoting p62-dependent autophagic...
REMOVE
Summary: IPI row recording RBX1 (Rbx1) among the proteins that sestrin-1/2 associate with, alongside KEAP1 and p62.
Reason: The mechanism established here is p62-dependent autophagic degradation of KEAP1, with the sestrins as the adaptors; the RBX1 contact is incidental and 'protein binding' states nothing about RBX1 function. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:23274085
We now show that Sesn1 and Sesn2 interact with the Nrf2 suppressor Keap1, the autophagy substrate p62, and the ubiquitin ligase Rbx1 and that the antioxidant function of Sesns is mediated through activation of Nrf2 in a manner reliant on p62-dependent autophagic degradation of Keap1.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 supplies catalytic E2 recruitment but ordinarily does **not** select protein substrates by itself.
GO:0005515 protein binding
IPI
PMID:23401859
DCNL1 functions as a substrate sensor and activator of culli...
MODIFY
Summary: Co-purification of RBX1 with the CRL2/ECV components VHL, CUL2: DCNL1 senses substrate engagement by VHL and triggers CUL2 neddylation.
Reason: The interaction recorded is membership of the elongin BC-CUL2-VHL (ECV/CRL2) ligase, which is informative, whereas 'protein binding' is not; HIF1A/EPAS1 appear as the substrates recruited by VHL, not as RBX1-binding partners.
Supporting Evidence:
PMID:23401859
Substrate engagement by F-box proteins promotes NEDD8 modification of cullins, which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:23401859
DCNL1 functions as a substrate sensor and activator of culli...
MODIFY
Summary: Co-purification of RBX1 with the CRL2/ECV components VHL, CUL2, ELOB, HIF1A: DCNL1 senses substrate engagement by VHL and triggers CUL2 neddylation.
Reason: The interaction recorded is membership of the elongin BC-CUL2-VHL (ECV/CRL2) ligase, which is informative, whereas 'protein binding' is not; HIF1A/EPAS1 appear as the substrates recruited by VHL, not as RBX1-binding partners.
Supporting Evidence:
PMID:23401859
Substrate engagement by F-box proteins promotes NEDD8 modification of cullins, which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:23401859
DCNL1 functions as a substrate sensor and activator of culli...
MODIFY
Summary: Co-purification of RBX1 with the CRL2/ECV components VHL, CUL2, HIF1A: DCNL1 senses substrate engagement by VHL and triggers CUL2 neddylation.
Reason: The interaction recorded is membership of the elongin BC-CUL2-VHL (ECV/CRL2) ligase, which is informative, whereas 'protein binding' is not; HIF1A/EPAS1 appear as the substrates recruited by VHL, not as RBX1-binding partners.
Supporting Evidence:
PMID:23401859
Substrate engagement by F-box proteins promotes NEDD8 modification of cullins, which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:23401859
DCNL1 functions as a substrate sensor and activator of culli...
MODIFY
Summary: Co-purification of RBX1 with the CRL2/ECV components VHL, CUL2, EPAS1: DCNL1 senses substrate engagement by VHL and triggers CUL2 neddylation.
Reason: The interaction recorded is membership of the elongin BC-CUL2-VHL (ECV/CRL2) ligase, which is informative, whereas 'protein binding' is not; HIF1A/EPAS1 appear as the substrates recruited by VHL, not as RBX1-binding partners.
Supporting Evidence:
PMID:23401859
Substrate engagement by F-box proteins promotes NEDD8 modification of cullins, which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:23401859
DCNL1 functions as a substrate sensor and activator of culli...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL2.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:23401859
Substrate engagement by F-box proteins promotes NEDD8 modification of cullins, which is necessary for the activation of cullin-RING E3 ubiquitin ligases (CRLs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:24192928
Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylatio...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D1), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:24192928
Our previous work showed that SCCRO promotes nuclear translocation of Cullin-ROC1, which is required for neddylation in vivo.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:24192928
Oncogenic function of SCCRO5/DCUN1D5 requires its Neddylatio...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D5), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:24192928
Our previous work showed that SCCRO promotes nuclear translocation of Cullin-ROC1, which is required for neddylation in vivo.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:24793696
CUL9 mediates the functions of the 3M complex and ubiquityla...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL9.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:24793696
Together, these results indicate that ROC1 mediates CUL7-CUL9 heterodimerization.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:24949976
Structure of a RING E3 trapped in action reveals ligation me...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:24949976
Nonetheless, RING E3 mechanisms matching a specific UBL and acceptor lysine remain elusive, including for RBX1, which mediates NEDD8 ligation to cullins and >10% of all ubiquitination.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:25619834
KLHL39 suppresses colon cancer metastasis by blocking KLHL20...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL3.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:25619834
Instead, KLHL39 blocks KLHL20-mediated ubiquitination of PML and DAPK by disrupting the binding of these substrates to KLHL20 as well as the binding of KLHL20 to Cul3.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ...
MODIFY
Summary: RBX1 co-purifies with the BTB adaptors KBTBD6 in the CUL3-KBTBD6/KBTBD7 ligase that degrades TIAM1.
Reason: The evidence supports membership of a Cul3-RING ligase complex (GO:0031463, also annotated from this paper), which is informative; bare protein binding is not, and the BTB proteins bind CUL3 rather than RBX1.
Supporting Evidence:
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ...
MODIFY
Summary: RBX1 co-purifies with the BTB adaptors KBTBD7 in the CUL3-KBTBD6/KBTBD7 ligase that degrades TIAM1.
Reason: The evidence supports membership of a Cul3-RING ligase complex (GO:0031463, also annotated from this paper), which is informative; bare protein binding is not, and the BTB proteins bind CUL3 rather than RBX1.
Supporting Evidence:
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:26496610
A human interactome in three quantitative dimensions organiz...
REMOVE
Summary: Generic protein-binding row recording RBX1 with CUL4B, from a quantitative proteome-wide interactome survey.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:26496610
A human interactome in three quantitative dimensions organized by stoichiometries and abundances.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:26906416
Characterization of the mammalian family of DCN-type NEDD8 E...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D2), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:26906416
Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:26906416
Characterization of the mammalian family of DCN-type NEDD8 E...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D3), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:26906416
Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:26906416
Characterization of the mammalian family of DCN-type NEDD8 E...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D4), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:26906416
Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:26906416
Characterization of the mammalian family of DCN-type NEDD8 E...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D1), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:26906416
Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:26906416
Characterization of the mammalian family of DCN-type NEDD8 E...
MODIFY
Summary: RBX1 binds the DCN-type (DCUN1D/SCCRO) neddylation co-E3 proteins (DCUN1D5), which deliver UBE2M~NEDD8 to the cullin-RBX1 module.
Reason: These interactions define a bipartite NEDD8 E3 in which the DCNL protein positions UBE2M~NEDD8 and RBX1 provides the RING that catalyses transfer to the cullin; NEDD8 ligase activity (GO:0061663) is the informative function behind the interaction, whereas bare protein binding is not.
Proposed replacements: NEDD8 ligase activity
Supporting Evidence:
PMID:26906416
Cullin-RING ligases (CRL) are ubiquitin E3 enzymes that bind substrates through variable substrate receptor proteins and are activated by attachment of the ubiquitin-like protein NEDD8 to the cullin subunit.
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0005515 protein binding
IPI
PMID:29149593
NOTCH2 Hajdu-Cheney Mutations Escape SCF(FBW7)-Dependent Pro...
MODIFY
Summary: RBX1 was found with SKP1, CUL1 and FBXW7 in the SCF(FBW7) complex that degrades NOTCH2; Hajdu-Cheney mutations let NOTCH2 escape it.
Reason: The informative statement is that RBX1 is part of the SCF(FBW7) ligase (GO:0019005); NOTCH2 is the substrate, recruited by FBXW7 rather than by RBX1.
Proposed replacements: SCF ubiquitin ligase complex
Supporting Evidence:
PMID:29149593
Furthermore, Skp1 and Rbx1, additional components of the SCF complex, also interacted with NOTCH2 in cells (Figures S1D and S1E).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005515 protein binding
IPI
PMID:29294217
RBX1-mediated ubiquitination of SESN2 promotes cell death up...
MODIFY
Summary: RBX1 was identified as an interacting partner and E3 ligase for sestrin-2, mediating its K48-linked ubiquitination after prolonged mitochondrial damage.
Reason: The paper supports an informative molecular function rather than bare binding: RBX1 acts as the ubiquitin ligase for SESN2, so ubiquitin protein ligase activity (GO:0061630) is the term the evidence justifies. As always for RBX1 the substrate is presented by a cullin receptor module, so the specificity should not be read as intrinsic to RBX1.
Supporting Evidence:
PMID:29294217
RBX1-mediated ubiquitination of SESN2 promotes cell death upon prolonged mitochondrial damage in SH-SY5Y neuroblastoma cells.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 supplies catalytic E2 recruitment but ordinarily does **not** select protein substrates by itself.
GO:0005515 protein binding
IPI
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL4B.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Generic protein-binding row recording RBX1 with KRTAP12-2, from the HuRI binary interactome map.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:32296183
A reference map of the human binary protein interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Generic protein-binding row recording RBX1 with UBE2M, from the HuRI binary interactome map.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:32296183
A reference map of the human binary protein interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Generic protein-binding row recording RBX1 with CUL2, from the HuRI binary interactome map.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:32296183
A reference map of the human binary protein interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Generic protein-binding row recording RBX1 with GLMN, from the HuRI binary interactome map.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:32296183
A reference map of the human binary protein interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:32296183
A reference map of the human binary protein interactome.
REMOVE
Summary: Generic protein-binding row recording RBX1 with PBX4, from the HuRI binary interactome map.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:32296183
A reference map of the human binary protein interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:32726803
Papain-like protease regulates SARS-CoV-2 viral spread and i...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:32726803
CUL1–RBX1, SKP1–β-TRCP2, UBE2M, UBE2D3, NEDD8, UB, APPBP1–UBA3 and UBA1 were purified as previously described47.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:33692209
KDM2B Overexpression Facilitates Lytic De Novo KSHV Infectio...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL1.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:33692209
CUL1 acts as the scaffold protein in the SCF complex recruiting ROC1, which is the E3 ubiquitin ligase component of SCF ( 22 ).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Generic protein-binding row recording RBX1 with SKP2, from the BioPlex proteome-scale affinity-purification network.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Generic protein-binding row recording RBX1 with CUL1, from the BioPlex proteome-scale affinity-purification network.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Generic protein-binding row recording RBX1 with CUL2, from the BioPlex proteome-scale affinity-purification network.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Generic protein-binding row recording RBX1 with CUL4B, from the BioPlex proteome-scale affinity-purification network.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling...
REMOVE
Summary: Generic protein-binding row recording RBX1 with GLMN, from the BioPlex proteome-scale affinity-purification network.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:33961781
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:34591642
A protein network map of head and neck cancer reveals PIK3CA...
REMOVE
Summary: Generic protein-binding row recording RBX1 with CUL3, from a head-and-neck-cancer protein network map.
Reason: The source is a systematic, proteome-scale interaction screen and 'protein binding' conveys no functional information about RBX1. Its informative binding activities - cullin family protein binding (GO:0097602) and engagement of ubiquitin-charged E2s - are annotated from focused studies. Per repository policy for bare GO:0005515 rows, this records that the generic term is uninformative, not that the reported interaction is false.
Supporting Evidence:
PMID:34591642
A protein network map of head and neck cancer reveals PIK3CA mutant drug sensitivity.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005515 protein binding
IPI
PMID:37788672
Cryo-EM structure of the KLHL22 E3 ligase bound to an oligom...
MODIFY
Summary: IPI row recording the interaction of RBX1 with CUL3.
Reason: RBX1's binding to cullin C-terminal domains is exactly what cullin family protein binding (GO:0097602) denotes, and that term is already supported by IDA and by PAINT inference; the generic protein-binding row should be replaced by it rather than removed, because the specific function is established.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:37788672
CULLIN3KLHL22-RBX1 ligase mediated the polyubiquitination of GDH1 in vitro.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0005634 nucleus
IBA
GO_REF:0000033
ACCEPT
Summary: RBX1 is present in the nucleus, where CRL1/CRL2/CRL3/CRL4 ligases act on nuclear substrates (p27, cyclin E, CDT1, NRF2, RNA Pol II subunits); ROC1 binding also promotes nuclear accumulation of CUL1.
Reason: Well-supported nuclear pool: direct immunofluorescence/fractionation, curator inference from nuclear CRL substrates, the UniProt subcellular location, and a PAINT inference placed at the RING-box family node whose descendants (yeast Hrt1/Apc11, fly and mouse Rbx1, human RBX1) all act on nuclear substrates.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000129805 Β· PANTHER:PTN000129805 SUPPORTS TRANSFER
RING-box family node spanning RBX1, RBX2/RNF7 and APC11; the descendant experimental evidence includes human RBX1 itself, mouse Rbx1, fly Roc1a/Roc1b and yeast Hrt1/Rbx1 and Apc11, so the function is inherited rather than lineage-specific.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005634 nucleus
IC
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for effic...
ACCEPT
Summary: RBX1 is present in the nucleus, where CRL1/CRL2/CRL3/CRL4 ligases act on nuclear substrates (p27, cyclin E, CDT1, NRF2, RNA Pol II subunits); ROC1 binding also promotes nuclear accumulation of CUL1.
Reason: Well-supported nuclear pool: direct immunofluorescence/fractionation, curator inference from nuclear CRL substrates, the UniProt subcellular location, and a PAINT inference placed at the RING-box family node whose descendants (yeast Hrt1/Apc11, fly and mouse Rbx1, human RBX1) all act on nuclear substrates.
Supporting Evidence:
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005634 nucleus
IC
PMID:20870715
HIV-1 Vpr loads uracil DNA glycosylase-2 onto DCAF1, a subst...
ACCEPT
Summary: RBX1 is present in the nucleus, where CRL1/CRL2/CRL3/CRL4 ligases act on nuclear substrates (p27, cyclin E, CDT1, NRF2, RNA Pol II subunits); ROC1 binding also promotes nuclear accumulation of CUL1.
Reason: Well-supported nuclear pool: direct immunofluorescence/fractionation, curator inference from nuclear CRL substrates, the UniProt subcellular location, and a PAINT inference placed at the RING-box family node whose descendants (yeast Hrt1/Apc11, fly and mouse Rbx1, human RBX1) all act on nuclear substrates.
Supporting Evidence:
PMID:20870715
To date, three of the four HIV-1 accessory proteins, including Vpr, have been found to interact with cullin-RING finger E3 ubiquitin ligases (CRLs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005634 nucleus
IC
PMID:27626656
Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 t...
ACCEPT
Summary: RBX1 is present in the nucleus, where CRL1/CRL2/CRL3/CRL4 ligases act on nuclear substrates (p27, cyclin E, CDT1, NRF2, RNA Pol II subunits); ROC1 binding also promotes nuclear accumulation of CUL1.
Reason: Well-supported nuclear pool: direct immunofluorescence/fractionation, curator inference from nuclear CRL substrates, the UniProt subcellular location, and a PAINT inference placed at the RING-box family node whose descendants (yeast Hrt1/Apc11, fly and mouse Rbx1, human RBX1) all act on nuclear substrates.
Supporting Evidence:
PMID:27626656
These findings suggest that HBx may assemble an HBx-DDB1-CUL4-ROC1 E3 ligase complex (referred to as CRL4HBx hereafter) to target host proteins that antagonize HBV replication for ubiquitylation and degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005634 nucleus
IDA
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for effic...
ACCEPT
Summary: RBX1 is present in the nucleus, where CRL1/CRL2/CRL3/CRL4 ligases act on nuclear substrates (p27, cyclin E, CDT1, NRF2, RNA Pol II subunits); ROC1 binding also promotes nuclear accumulation of CUL1.
Reason: Well-supported nuclear pool: direct immunofluorescence/fractionation, curator inference from nuclear CRL substrates, the UniProt subcellular location, and a PAINT inference placed at the RING-box family node whose descendants (yeast Hrt1/Apc11, fly and mouse Rbx1, human RBX1) all act on nuclear substrates.
Supporting Evidence:
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005634 nucleus
IEA
GO_REF:0000044
ACCEPT
Summary: RBX1 is present in the nucleus, where CRL1/CRL2/CRL3/CRL4 ligases act on nuclear substrates (p27, cyclin E, CDT1, NRF2, RNA Pol II subunits); ROC1 binding also promotes nuclear accumulation of CUL1.
Reason: Well-supported nuclear pool: direct immunofluorescence/fractionation, curator inference from nuclear CRL substrates, the UniProt subcellular location, and a PAINT inference placed at the RING-box family node whose descendants (yeast Hrt1/Apc11, fly and mouse Rbx1, human RBX1) all act on nuclear substrates.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005634 nucleus
NAS
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: RBX1 is present in the nucleus, where CRL1/CRL2/CRL3/CRL4 ligases act on nuclear substrates (p27, cyclin E, CDT1, NRF2, RNA Pol II subunits); ROC1 binding also promotes nuclear accumulation of CUL1.
Reason: Well-supported nuclear pool: direct immunofluorescence/fractionation, curator inference from nuclear CRL substrates, the UniProt subcellular location, and a PAINT inference placed at the RING-box family node whose descendants (yeast Hrt1/Apc11, fly and mouse Rbx1, human RBX1) all act on nuclear substrates.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
IDA
GO_REF:0000052
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-1234169
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-1234169
The VHL component of the VHL:ElonginB:ElonginC:CUL2:RBX1 binds HIF-alpha that have hydroxylated proline residues (Cockman et al. 2000, Ohh et al. 2000, Tanimoto et al. 2000, Jaakkola et al. 2001, Ivan et al. 2001, Yu et al. 2001, Bonicalzi et al. 2001).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-1234172
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-1234172
VHL is an E3 ubiquitin ligase that conjugates ubiquitin to hydroxylated HIF-alpha (Iwai et al. 1999, Kamura et al. 2000, Ohh et al. 2000, Groulx and Lee 2002, Maynard et al. 2003).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-1234175
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-1234175
When hypoxic cells return to normoxia, HIF-alpha is ubiquitinated in the nucleus and exported to the cytosol (Groulx and Lee 2002).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-2220967
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-2220967
As binding of WD40 repeats of FBXW7 requires conserved phosphodegron in the PEST domain of NICD1, especially phosphorylation of threonine residue T2511 and serine residue S2513, FBXW7 cannot bind NICD1 PEST domain mutants which lack the conserved phosphodegron due to truncation of the PEST domain,
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-2220978
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-2220978
FBXW7 (FBW7) mutations are found in ~20% of T-cell acute lymphoblastic leukemia samples.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5635854
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5635854
SPOP:CUL3:RBX1-mediated ubiquitination of the transcriptionally active GLI proteins attenuates Hh-dependent signaling by promoting their degradation by the proteasome (Zhang et al, 2009; Chen et al, 2009; Humke et al, 2010; Tukachinsky et al, 2010; Wen et al, 2010).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5635855
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5635855
Full-length GLI proteins are labile transcription factors that are rapidly degraded after ubiquitination by the SPOP:CUL3:RBX1 E3 ligase (Ohlmeyer et al, 1998; Humke et al, 2010; Tukachinsky et al, 2010; Chen et al, 2009; Zhang et al, 2009; Wen et al, 2010).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5635856
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5635856
The transcriptional activity of full-length activated Ci/GLI proteins is restricted by their rapid ubiquitin-mediated degradation after initiation of Hh signaling (Ohlmeyer et al, 1998; Humke et al, 2010; Tukachinsky et al, 2010; Wen et al, 2010).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5652005
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5652005
The complex of RAD18, an E3 ubiquitin ligase, and UBE2B (RAD6), an E2 ubiquitin-conjugating enzyme, binds the replication complex consisting of PCNA, DNA polymerase complex delta (POLD) or DNA polymerase complex epsilon (POLE), RPA and RFC on damaged dsDNA.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5652009
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5652009
The complex of RAD18, an E3 ubiquitin ligase, and UBE2B (RAD6), an E2 ubiquitin conjugating enzyme, monoubiquitinates PCNA associated with damaged DNA on lysine residue K164, using the ubiquitin residue K63 to create the covalent bond (Hoege et al. 2002).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5689317
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5689317
Once an open bubble structure is generated in damaged dsDNA through a DNA helicase activity of the TFIIH complex, the RPA heterotrimer composed of RPA1, RPA2 and RPA3, coats the undamaged single strand DNA (ssDNA) (de Laat et al. 1998), thereby protecting it from incision and enabling the correct
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5689861
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5689861
XPA binds the DNA damage site through interaction with the TFIIH complex subunit GTF2H5 (TTDA) (Ziani et al. 2014), and also interacts with the DDB2 subunit of the UV-DDB complex (Wakasugi et al. 2001, Wakasugi et al. 2009, Takedachi et al. 2010).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690213
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5690213
The DNA repair synthesis complex, consisting of PCNA, RFC, RPA and polymerase delta (POLD) or epsilon (POLE) complexes, or DNA translesion synthesis polymerase kappa (POLK) (Ogi et al. 2010), is formed at the nucleotide excision repair (NER) site following the incision of the damaged DNA strand 5'
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690988
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5690988
In global genome nucleotide excision repair (GG-NER), as well as transcription-coupled nucleotide excision repair (TC-NER), the cleavage of the damaged DNA strand 3' to the site of damage is carried out by a DNA endonuclease XPG (ERCC5).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690990
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5690990
In global genome nucleotide excision repair (GG-NER), just like in transcription-coupled nucleotide excision repair (TC-NER), the cleavage of the damaged strand of DNA 5' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690991
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5690991
ERCC1:ERCC4 (ERCC1:XPF) DNA endonuclease complex binds 5' to the DNA damage at global genome nucleotide excision repair (GG-NER) sites to form the incision complex.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5690996
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5690996
Two DNA helicases XPB (ERCC3) and XPD (ERCC2), which are part of the TFIIH complex, unwind the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5691000
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5691000
Transcription factor II H (TFIIH) complex is recruited to DNA damage sites after the damage is recognized by the XPC:RAD23:CETN2 complex and the UV-DDB complex (DDB1:DDB2) (Volker et al. 2001, Araujo and Wood 1999).<p>TFIIH consists of ten subunits organized into a ring-like structure (Schultz et
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5691006
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5691006
XPC, in complex with RAD23B or RAD23A and CETN2, employs a two-stage process to recognize a distorted DNA helix.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5696655
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5696655
PARP1 and/or PARP2 homo- or heterodimers recruited to global genomic nucleotide excision repair (GG-NER) site poly(ADP)ribosylate (PARylate) DDB2 and also progressively autoPARylate.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5696664
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5696664
PARP1 (or PARP2) is recruited to global genomic nucleotide excision repair (GG-NER) site through interaction with DDB2 and, probably, distorted single strand DNA (Pines et al. 2012, Robu et al. 2013).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-5696670
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-5696670
A chromatin remodeling enzyme CHD1L (ALC1) is recruited to DNA damage sites through interaction with PARylated PARP1 (or possibly PARP2) (Ahel et al. 2009) or PARylated DDB2 (Pines et al. 2012).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6781833
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6781833
Cockayne syndrome protein A (ERCC8, also known as CSA) is recruited to a stalled RNA polymerase II complex (RNA Pol II) at a site of DNA damage in an ERCC6 (CSB) dependent manner (Kamiuchi et al. 2002; van der Weegen et al. 2020).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6781867
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6781867
The ubiquitin ligase complex ERCC8:DDB1:CUL4:RBX1 may ubiquitinate ERCC6 (CSB) (Groisman et al. 2006) at the later steps of TC-NER and may also be required in the ubiquitination of the RNA Pol II subunit POLR2A in response to damage (Bregman et al. 1996, Lee et al. 2002).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782004
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782004
In addition to ERCC6 (CSB) and the ERCC8 (CSA) ubiquitin ligase complex, several other proteins and protein complexes are loaded onto stalled RNA polymerase II (RNA Pol II) at DNA damage sites to form a pre-incision complex that operates in the transcription-coupled nucleotide excision repair
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782069
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782069
UVSSA stabilizes ERCC6 (CSB) during transcription-coupled nucleotide excision repair (TC-NER) by targeting ubiquitin protease USP7 to ubiquitinated ERCC6, thus preventing proteasome-mediated degradation of ERCC6.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782131
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782131
The DNA helicase XPD (ERCC2), which is part of the TFIIH complex, unwinds the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782138
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782138
It has been suggested that, similar to the UvrD helicase involved in TC-NER in E.coli, the DNA helicase activity of TFIIH complex may facilitate damage-stalled RNA polymerase II (RNA Pol II) backtracking (Epshtein et al. 2014).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782141
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782141
ERCC1:ERCC4 (ERCC1:XPF) DNA endonuclease complex binds to the pre-incision complex at the transcription-coupled nucleotide excision repair (TC-NER) site to form the incision complex.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782204
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782204
In transcription-coupled nucleotide excision repair (TC-NER), just like in global genome nucleotide excision repair (GG-NER), the cleavage of the damaged strand of DNA 5' to the site of damage occurs at the junction of single-stranded DNA and double-stranded DNA that is formed when the DNA duplex
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782208
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782208
In transcription-coupled nucleotide excision repair (TC-NER), as well as in global genome nucleotide excision repair (GG-NER), the DNA synthesis complex (NER post-incision complex) consisting of PCNA, RPA, RFC and polymerase delta (POLD) or epsilon (POLE) complexes performs DNA repair synthesis
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782211
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782211
The DNA repair synthesis complex, consisting of PCNA, RFC, RPA and polymerase delta (POLD) or epsilon (POLE) complexes, or polymerase kappa (POLK), is formed at the transcription coupled nucleotide excision repair (TC-NER) site, as well as the global genome nucleotide excision repair (GG-NER) site,
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782224
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782224
In transcription-coupled nucleotide excision repair (TC-NER), as well as in global genome nucleotide excision repair (GG-NER), the cleavage of the damaged DNA strand 3' to the site of damage is carried out by a DNA endonuclease XPG (ERCC5).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782227
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782227
The nucleotide excision repair (NER) is completed when the newly synthesized fragment is ligated to the incised DNA strand, thus sealing the single stranded nick (SSB).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782234
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782234
After DNA repair synthesis is completed at transcription-coupled nucleotide excision repair (TC-NER) sites, transcription resumes.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6782943
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6782943
The role of UV-DDB-mediated ubiquitination in global genome nucleotide excision repair (GG-NER) has not been fully elucidated.<p>In the absence of DNA damage, the ubiquitin ligase activity of UV-DDB complex is inhibited by association with the COP9 signalosome (CSN complex), which dissociates from
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6790454
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6790454
XPC undergoes SUMOylation following UV irradiation on several consensus SUMOylation sites (van Cuijk et al. 2015).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-6790487
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-6790487
SUMOylated XPC is recognized by the SUMO-targeted ubiquitin ligase RNF111 (Arcadia) that, together with the E2 ubiquitin conjugating complex of UBE2N (UBC13) and UBE2V2 (MMS2), generates K63-linked polyubiquitin chains on XPC (Poulsen et al. 2013) to efficiently release XPC from UV lesions (van
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-68946
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-68946
ORC1 is ubiquitinated by the SKP2-containing ubiquitin ligase complex and targeted for proteasome-mediated degradation, which may play an important role in the maintenace of ploidy.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-69598
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-69598
<p>Exposure of various human cell lines to ultraviolet (UV) light leads to rapid appearance of polyubiquitinated CDC25A (PolyUb-CDC25A) (Mailand et al. 2000).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8939688
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-8939688
The E3 ubiquitin ligase complex SCF binds RUNX2 through direct interaction between SKP2 subunit of the SCF complex and RUNX2 (Thacker et al. 2016).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8939706
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-8939706
The SCF(SKP2) E3 ubiquitin ligase complex polyubiquitinates RUNX2 on unknown lysine residues, targeting it for proteasome-mediated degradation.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8952638
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-8952638
UBE2M transfers NEDD8 to lysine 705 of CUL4A and lysine 859 of CUL4B (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8952639
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-8952639
UBE2M is the E2 for CRL complexes containing cullin 1, 2, 3 and 4 (Huang et al, 2009; Monda et al, 2013).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8955245
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-8955245
CRL complexes consist of a cullin protein (CUL1, 2, 3, 4A, 4B, 5, 7 and 9 in humans) and a RING box protein (RBX1 or 2) in addition to one or more substrate binding proteins that confer substrate specificity to the complex (reviewed in Petroski and Deshaies, 2005; Lipkowitz and Weismann, 2011).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8955285
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-8955285
COMMD1 is a member of a family of 10 copper metabolism MURR1 domain-containing proteins that have pleiotropic roles in copper metabolism, NF kappa beta-mediated transcription, the hypoxic response and electrolyte transport (Burstein et al, 2005; reviewed in Maine and Burstein, 2007).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-8956045
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-8956045
The COP9 signalosome (also known as CSN) is a highly conserved multi-subunit enzymatic complex that plays a role as the sole CRL ubiquitin ligase deneddylase.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9684118
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9684118
The DNA helicase XPB (ERCC3), which is part of the TFIIH complex, unwinds the distorted DNA duplex around the lesion to form an open bubble structure that exposes the damaged site.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9708517
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9708517
The leucine-rich repeat family of F-box proteins (FBXLs) function as adapter for the SKP1-CUL1-F-box protein (SCF) E3 ubiquitin ligase.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9708525
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9708525
The leucine-rich repeat family of F-box proteins (FBXLs) function as adapter for the SKP1-CUL1-F-box protein (SCF) E3 ubiquitin ligase.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9725023
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9725023
ZC3HC1, also known as NIPA (nuclear interacting partner of anaplastic lymphoma kinase), was identified as a protein partner of NPM-ALK fusion in two hybrid and co-imuunoprecipitation studies (Ouyang et al, 2003).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9725030
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9725030
NPM-ALK-mediated activation of the MAP kinase signaling pathway leads to phosphorylation and activation of MAPK1 (ERK2) (Illert et al, 2012).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9762091
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9762091
GSK3-dependent phosphorylation of NFE2L2 promotes its subsequent ubiquitination by a BTRC:CUL1 E3 ligase complex (Salazar et al, 2006; Rada et al, 2011; Rada et al, 2012; Rojo et al, 2012; reviewed in Baird and Yamamoto, 2020; Yamamoto et al, 2018).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9762093
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9762093
In response to GSK3B-dependent phosphorylation at, minimally, serine residues 344 and 347, the CUL1:BTRC complex binds to NFE2L2 through the Neh6 domain (Salazar et al, 2006; Rada et al, 2011; Rada et al, 2012; Rojo et al, 2012; reviewed in Baird and Yamamoto, 2020; Yamamoto et al, 2018).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-HSA-9762096
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-HSA-9762096
After BTRC:CUL1-mediated ubiquitination, NFE2L2 is degraded by the proteasome (Rada et al, 2011; Rada et al, 2012; reviewed in Baird and Yamamoto, 2020; Yamamoto et al, 2018).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-2064853
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-NUL-2064853
The E3 ubiquitin ligase FBXW7, a homologue of C. elegans sel-10, binds to Notch1 intracellular domain NICD1.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-2064883
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-NUL-2064883
A recombinant mouse NICD1 was shown to be ubiquitinated upon binding to recombinant human FBXW7 (Oberg et al. 2001), which is followed by NICD1 degradation (Fyer et al. 2004).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005654 nucleoplasm
TAS
Reactome:R-NUL-9604628
ACCEPT
Summary: Nucleoplasmic localisation of RBX1-containing ligases, as assigned to the individual Reactome reactions in which the RBX1-cullin catalytic module ubiquitinates nuclear substrates, and as seen by immunofluorescence.
Reason: Consistent with the nuclear CRL substrates (HIF-alpha, GLI2/3, beta-catenin, PCNA, RNA Pol II, NER factors) and with the UniProt nuclear localisation; these are pathway compartment assignments rather than RBX1-specific imaging, but they are not in conflict with the direct evidence.
Supporting Evidence:
Reactome:R-NUL-9604628
The human E3 ubiquitin ligase FBXW7, a component of the SCF ubiquitin ligase complex, binds to and ubiquitinates phosphorylated mouse NICD4 (Notch4 intracellular domain fragment), targeting it for proteasome-mediated degradation (Wu et al. 2001).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005737 cytoplasm
IC
PMID:27708159
Insulin resistance and diabetes caused by genetic or diet-in...
ACCEPT
Summary: RBX1 also functions in the cytoplasm, where CRLs degrade signalling proteins (IkappaB-alpha, DEPTOR, IRS1, p85alpha, RhoA/RhoB) and where cullin neddylation is initiated.
Reason: Direct evidence plus the UniProt cytoplasmic location; a cytoplasmic pool is expected for a subunit shared by ligases with cytoplasmic receptors.
Supporting Evidence:
PMID:27708159
Kbtbd2 encodes a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005737 cytoplasm
IC
PMID:36394357
XAF1 prevents hyperproduction of type I interferon upon vira...
ACCEPT
Summary: RBX1 also functions in the cytoplasm, where CRLs degrade signalling proteins (IkappaB-alpha, DEPTOR, IRS1, p85alpha, RhoA/RhoB) and where cullin neddylation is initiated.
Reason: Direct evidence plus the UniProt cytoplasmic location; a cytoplasmic pool is expected for a subunit shared by ligases with cytoplasmic receptors.
Supporting Evidence:
PMID:36394357
Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005737 cytoplasm
IDA
PMID:27708159
Insulin resistance and diabetes caused by genetic or diet-in...
ACCEPT
Summary: RBX1 also functions in the cytoplasm, where CRLs degrade signalling proteins (IkappaB-alpha, DEPTOR, IRS1, p85alpha, RhoA/RhoB) and where cullin neddylation is initiated.
Reason: Direct evidence plus the UniProt cytoplasmic location; a cytoplasmic pool is expected for a subunit shared by ligases with cytoplasmic receptors.
Supporting Evidence:
PMID:27708159
Kbtbd2 encodes a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005737 cytoplasm
IDA
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase dur...
ACCEPT
Summary: RBX1 also functions in the cytoplasm, where CRLs degrade signalling proteins (IkappaB-alpha, DEPTOR, IRS1, p85alpha, RhoA/RhoB) and where cullin neddylation is initiated.
Reason: Direct evidence plus the UniProt cytoplasmic location; a cytoplasmic pool is expected for a subunit shared by ligases with cytoplasmic receptors.
Supporting Evidence:
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005737 cytoplasm
IEA
GO_REF:0000044
ACCEPT
Summary: RBX1 also functions in the cytoplasm, where CRLs degrade signalling proteins (IkappaB-alpha, DEPTOR, IRS1, p85alpha, RhoA/RhoB) and where cullin neddylation is initiated.
Reason: Direct evidence plus the UniProt cytoplasmic location; a cytoplasmic pool is expected for a subunit shared by ligases with cytoplasmic receptors.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005794 Golgi apparatus
IDA
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase dur...
KEEP AS NON CORE
Summary: Golgi-apparatus signal for RBX1 reported alongside the CRL4-DCAF12 study of MOV10 turnover.
Reason: Retained but non-core: no Golgi-specific function of RBX1 is established, and a shared CRL subunit is expected to appear wherever a receptor concentrates it. The observation is kept as a context-specific localisation rather than a site of the core ligase activity.
Supporting Evidence:
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005813 centrosome
NAS
PMID:20596027
SCF(Cyclin F) controls centrosome homeostasis and mitotic fi...
KEEP AS NON CORE
Summary: Author statement placing the SCF(cyclin F) ligase, which contains RBX1, on centrioles in G2 where it degrades CP110.
Reason: Genuine but receptor-specific: cyclin F, not RBX1, targets the complex to centrosomes. Kept as a non-core localisation of the shared catalytic module.
Supporting Evidence:
PMID:20596027
SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation.
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0005829 cytosol
IEA
GO_REF:0000107
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
ISS
GO_REF:0000024
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1170539
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1170539
PRLR is regulated by ubiquitination of the activated receptor, leading to lysosomal degradation (Djiane et al. 1981, 1982, Lu et al. 2002).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234159
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1234159
Destruction of ubiquitinated HIF-alpha can occur in both the cytosol and nucleus (Berra et al. 2001).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234163
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1234163
VHL is an E3 ubiquitin ligase that conjugates ubiquitin to hydroxylated HIF-alpha (Iwai et al. 1999, Kamura et al. 2000, Ohh et al. 2000, Groulx and Lee 2002, Maynard et al. 2003).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234173
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1234173
Proline hydroxylases PHD2 (EGLN1) and PHD3 (EGLN3) located in the cytosol (Metzen et al. 2003) hydroxylate HIF3A at proline-492 (Hirsila et al. 2003, Maynard et al. 2003).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234175
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1234175
When hypoxic cells return to normoxia, HIF-alpha is ubiquitinated in the nucleus and exported to the cytosol (Groulx and Lee 2002).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234177
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1234177
Proline hydroxylases PHD2 (EGLN1) and PHD3 (EGLN3) located in the cytosol (Metzen et al. 2003) hydroxylate HIF1A at proline-402 and proline-564 (Bruick and McKnight 2001, Jaakkola et al. 2001, Ivan et al. 2001, Ivan et al. 2002, Berra et al. 2003, Hirsila et al. 2003, Appelhoff et al. 2004,
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1234183
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1234183
VHL within the VHL:ElonginB:ElonginC:CUL2:RBX1 Complex binds HIF-alpha subunits that have hydroxylated proline residues (Cockman et al. 2000, Ohh et al. 2000, Tanimoto et al. 2000, Jaakkola et al. 2001, Ivan et al. 2001, Yu et al. 2001).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1370500
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1370500
Phosphorylation of PRLR on Ser-349 by an unidentified kinase enables recruitment of the SCF beta-TrCP ubiquitin ligase complex, which catalyzes ubiquitination of the receptor (Li et al. 2004).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1504190
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1504190
CUL3:KLHL12:RBX1 polyubiquitinates Dishevelled, targeting it for degradation by the proteasome (Angers et al, 2006).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1504193
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1504193
Ubiquitinated Dishevelled is degraded by the proteasome.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-1504213
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-1504213
In response to WNT signaling, DVL is recruited to the CUL3:KLHL12:RBX1 ubiquitin ligase complex and is subsequently polyubiquitinated and degraded.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-180540
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-180540
APOBEC3G is multi-ubiquitinated by the Vif-Cul5-SCF complex.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-180555
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-180555
The interaction between Vif and the E3 ubiquitin ligase complex (Cullin5, Elongin B and Elongin C, and Rbx1) takes place through direct binding of the SOCS box motif in the viral protein Vif to the host protein Elongin C.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-180603
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-180603
Following multi-ubiquitination by the Vif-Cul5-SCF complex, APOBEC3G is degraded by the 26S proteasome.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-209063
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-209063
SCF (Beta-TrCP) ubiquitinates phosphorylated I kappa B alpha.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-209125
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-209125
Human beta-TrCP forms part of the SCF E3 ubiquitin ligase complex which binds to phosphorylated residues Ser32 and Ser 36 at the IKK target motif in IKBA complex with P65:P50 heterodimer.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2130279
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-2130279
B-TrCP associates with phosphorylated beta-catenin through the B-TrCP WD40 repeat region.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2130282
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-2130282
Ubiquitinated beta-catenin is degraded by the proteasome.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-2130286
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-2130286
Beta-catenin is ubiquitinated by the SCF-B-TrCP1 complex.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5610742
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-5610742
GLI1 protein is degraded by the proteasome in the absence of Hh signal.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5610746
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-5610746
Hyperphosphorylated GLI3 binds directly with beta-TrCP though at least three independent domains and is polyubiquitinated at lysines 773, 778, 784 and 800 (Tempe et al, 2006).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-5658424
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-5658424
NF1 levels are controlled by proteasomal degradation in response to stimulation by some growth factors (Cichowski et al, 2003).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8853496
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8853496
FBXL7, a component of the SCF E3 ubiquitin ligase complex, associates with aurora kinase A (AURKA) during mitosis (Coon et al. 2012).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854041
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8854041
The SCF-FBXL7 E3 ubiquitin ligase complex, composed of SKP1, CUL1, RBX1 and FBXL7, ubiquitinates aurora kinase A (AURKA), targeting it for degradation (Coon et al. 2012).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854044
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8854044
Upon ubiquitination by the SCF-FBXL7 E3 ubiquitin ligase complex, aurora kinase A (AURKA) is degraded by the proteasome (Coon et al. 2012).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854051
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8854051
FBXL18, a substrate recognition subunit of the SCF E3 ubiquitin ligase complex can bind to the FQ motif of FBXL7.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8854052
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8854052
FBXL7 associates with SKP1, CUL1 and RBX1 to form the SCF E3 ubiquitin ligase complex (Coon et al. 2011).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8932327
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8932327
Under the basal resting conditions, cytosolic Nuclear factor erythroid 2-related NFE2L2 (NRF2) is maintained at low basal levels by constitutive proteasomal degradation.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952618
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8952618
UBE2M transfers NEDD8 to lysine 720 of CUL1 in the CRL E3 ubiquitin ligase complex (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952620
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8952620
UBE2M is the E2 for CRL complexes containing cullin 1, 2, 3 and 4 (Huang et al, 2009; Monda et al, 2013).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952625
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8952625
UBE2M is the E2 ubiquitin ligase for CRL complexes containing cullin 1, 2, 3 and 4 (Huang et al, 2009; Monda et al, 2013).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952626
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8952626
UBE2M transfers NEDD8 to lysine 689 of CUL2 in the E3 ligase complex (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952630
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8952630
UBE2M is the E2 for CRL complexes containing cullin 1, 2, 3 and 4 (Huang et al, 2009; Monda et al, 2013).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8952631
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8952631
UBE2M transfers NEDD8 to lysine 712 of CUL3 in the E3 ligase complex (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8955241
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8955241
CRL complexes consist of a cullin protein (CUL1, 2, 3, 4A, 4B, 5, 7 and 9 in humans) and a RING box protein (RBX1 or 2) in addition to one or more substrate binding proteins that confer substrate specificity to the complex (reviewed in Petroski and Deshaies, 2005; Lipkowitz and Weismann, 2011).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8955289
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8955289
COMMD1 is a member of a family of 10 copper metabolism MURR1 domain-containing proteins that have pleiotropic roles in copper metabolism, NF kappa beta-mediated transcription, the hypoxic response and electrolyte transport (Burstein et al, 2005; reviewed in Maine and Burstein, 2007).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956025
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956025
UBE2M transfers NEDD8 to lysine 1881 of CUL9 (Skaar et al, 2007; Li et al, 2014).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956026
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956026
One defined target of CUL9 ubiquitin ligase is BIRC5 (also known as Survivin), which has roles in cellular proliferation, inhibition of apoptosis and maintenance of genome stability (Zhao et al, 2000; Watanabe, 2010).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956031
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956031
CUL9 (also known as PARC for p53-associated PARkin-like cytoplasmic protein) is an atypical cullin that has been shown to form a ubiquitin ligase complex with RBX1, although other components of the putative CRL9 complex have not yet been identified (Skaar et al, 2007; Li et al, 2014).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956040
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956040
The COP9 signalosome (also known as CSN) is a highly conserved multi-subunit enzymatic complex that plays a role as the sole CRL ubiquitin ligase deneddylase.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956050
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956050
CUL7, CCDC8 and OBSL1 are part of a 3M complex that has roles in maintenace of genome stability and microtubule dynamics (Li et al, 2014; Yan et al, 2014).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956099
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956099
The best characterized CRL2 substrate binding F-box protein is the von Hippel- Lindau (VHL) tumor suppressor, which targets the alpha subunit of hypoxia inducible factor (HIFalpha) for ubiquitination and degradation through VCP/p97 and the 26 S proteasome (Sufan and Ohh, 2006; Heir et al, 2013;
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956103
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956103
The best characterized CRL2 substrate binding F-box protein is the von Hippel- Lindau (VHL) tumor suppressor, which targets the alpha subunit of hypoxia inducible factor (HIFalpha) for ubiquitination and degradation through VCP/p97 and the 26 S proteasome (Sufan and Ohh, 2006; Heir et al, 2013;
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956106
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956106
VHL is the substrate binding protein of a CUL2-based E3 ubiquitin ligase complex that conjugates ubiquitin to hydroxylated HIF-alpha (Iwai et al. 1999, Kamura et al. 2000, Ohh et al. 2000, Groulx and Lee 2002, Maynard et al. 2003).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-8956200
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-8956200
DCUN1D3 binds to CRL1 ligase complexes to antagonize their neddylation and activation.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9712274
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9712274
KEAP1:CUL3:RBX1-mediated degradation of NFE2L2 is relieved in the presence of oxidative or electrophilic stress, allowing NFE2L2 to translocate to the nucleus to support expression of target genes.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9755303
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9755303
Destruction of ubiquitinated HIF-alpha can occur in both the cytosol and nucleus (Berra et al. 2001).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9755505
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9755505
The KEAP1:CUL3:RBX1 E3-ubiquitin ligase complex is a negative regulator of Nuclear factor erythroid 2-related (NFE2L2).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9755507
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9755507
VCP (also known as p97) is a hexameric ATPase with known roles in extracting ubiquinated substrates from multimeric E3 ligase complexes to promote their degradation by the 26S proteasome (Richly et al, 2005; Meyer et al, 2000; Rape et al, 2001; Tao et al, 2017; reviewed in van den Boom and Meyer,
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9758090
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9758090
The complex of VCP/p97 with cofactors UFD1, NPLOC4 and UBXN7 extract ubiquitinated NFE2L2 from the KEAP1-CUL3 ubiquitin ligase complex prior to its 26S proteasome-mediated degradation (Tao et al, 2017; Di Gregorio et al, 2021; reviewed in van den Boom and Meyer, 2020).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9759169
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9759169
SQSTM1 binds to the KEAP1 subunit of the CRL3 ubiquitin ligase complex through the KEAP1 interacting region (KIR) located at residues 339-358 (Jain et al, 2010).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9759172
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9759172
SQSTM1 is an adaptor protein that mediates aggregation of target proteins for selective autophagy (reviewed in Lamark et al, 2017).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9766645
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9766645
KEAP1 is ubiquitinated by the CUL3:RBX1 complex in an SQSTM1-dependent manner (Zhang et al, 2005).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9766656
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9766656
KEAP1 is a substrate for SQSTM1-mediated autophagy (Zhang et al, 2005; Jain et al, 2010; Fan et al, 2010; Taguchi et al, 2012).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9766677
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9766677
SQSTM1 targets ubiquitinated cargo such as KEAP1 for degradation through the selective autophagy pathway.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9766687
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9766687
SESN1 and SESN2 are proteins with roles in oxidative stress response.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-983140
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-983140
Interaction of E3 with both substrate and E2-Ub, brings them into proximity so that ubiquitin is transferred from E2 to the substrate.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-983147
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-983147
K48 polyubiquitinated substrate dissociates from E3 to become a substrate for a multicatalytic complex called the 26S proteasome.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-983156
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-983156
Monoubiquitinated substrate acquires additional ubiquitin modifications in the form of multiple single attachments or a ubiquitin chain.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-983157
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-983157
Ubiquitin E3 ligases confer specificity to ubiquitination by recognizing target substrates and mediating transfer of ubiquitin from an E2 ubiquitin-conjugating enzyme to substrate (Raymond et al. 2009).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9833107
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9833107
hRSV nonstructural protein 1C (NS1) binds to the elongin C (ELOC) and cullin-5 (CUL5) components of the Cul5-SCF complex to direct the ubiquitination and proteasome-dependent degradation of STAT2 (Elliott et al, 2007).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9833155
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9833155
Human signal transducer and activator of transcription 2 (STAT2) is subject to ubiquitination by, among other E3 ubiquitin ligases, a complex consisting of human respiratory syncytial virus (hRSV) protein NS1 with elongin C (ELOC) and cullin-5 (CUL5).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929350
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9929350
Ξ²-TrCP-SCF complex catalyses PD-L1(CD274) polyubiquitination in the presence of GSK3Ξ².
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929352
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9929352
PD-L1 (CD274) is targeted for 26S proteasomal degradation through phosphorylation by GSK3B and the subsequent ubiquitination by the beta-TrCP-SCF E3 ubiquitin ligase complex (Li et al., 2016).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929353
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9929353
COP9 signalosome 5 (CSN5) poses deubiquitination activity and is known to regulate the SCF (Skp1- cullinF-box)-containing complexes.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929357
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9929357
Ξ²-TrCP (BTRC) is the substrate recognizing subunit of the E3 ubiquitin ligase complex SCF (Skip-Cullin-F-box).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929484
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9929484
The SPOP:CUL3:RBX1 E3 ubiquitin ligase complex regulates the ubiquitination and degradation of PD-L1(CD274) protein.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929486
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9929486
PD-L1 (CD274) polyubiquitinated by the SPOP:CUL3:RBX1 E3 ubiquitin ligase complex gets degraded by the 26S proteasome complex (Zhang et al., 2018, Dong et al, 2022).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9929490
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9929490
SPOP:CUL3:RBX1 E3-ubiquitin ligase complex polyubiquitinates PD-L1 and induces its proteasomal degradation (Zhang et al., 2018, Dong et al., 2022).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9954721
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9954721
The CRL-KLHDC10 E3 ubiquitin ligase complex (NEDD8-K699-CUL2:ELOB:ELOC:RBX1:KLHDC10) polymerizes ubiquitin monomers with K48 linkages onto exposed lysine residues of an alanine-tailed nascent peptide that has been extracted from a 60S ribosomal subunit (Thrun et al. 2021).
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0005829 cytosol
TAS
Reactome:R-HSA-9954723
ACCEPT
Summary: Cytosolic pool of the RBX1-cullin catalytic module, as assigned to Reactome reactions such as cytosolic VHL-EloBC-CUL2-RBX1 ubiquitination of hydroxyprolyl-HIF-alpha and SCF(beta-TrCP)-mediated degradation events.
Reason: Cytosol is a legitimate site of RBX1 activity and is consistent with the UniProt cytoplasmic annotation and with ortholog-based transfer from mouse Rbx1.
Supporting Evidence:
Reactome:R-HSA-9954723
The CRL2-KLHDC10 ubiquitin E3 ligase complex (NEDD8-K699-CUL2:ELOB:ELOC:RBX1:KLHDC10) binds C-terminal alanine residues that have been polymerized ("CAT-tailed") by NEMF onto a nascent peptide from a 60S ribosomal subunit that has been dissociated from a stalled 80S ribosome (Thrun et al. 2021,
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 is reported in both the **nucleus and cytoplasm**, consistent with degradation of substrates in both compartments.
GO:0006283 transcription-coupled nucleotide-excision repair
IDA
PMID:34526721
Structural basis of human transcription-DNA repair coupling.
KEEP AS NON CORE
Summary: In the CSA/ERCC8-CUL4-DDB1-RBX1 complex, RBX1 ubiquitinates RPB1/POLR2A at Lys1268 at DNA damage-stalled Pol II, a checkpoint step of transcription-coupled repair.
Reason: A real, structurally defined contribution, but specific to the ERCC8 receptor; kept as non-core for a RING shared by all CRLs.
Supporting Evidence:
PMID:34526721
RBX1 and the E2 enzyme–donor ubiquitin complex were modelled as described in the Methods.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0006289 nucleotide-excision repair
NAS
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
KEEP AS NON CORE
Summary: Author statement from the CRL4(DDB2) architecture study: the DDB2-CUL4-RBX1 ligase creates a ubiquitination zone around UV lesions and is required for nucleotide-excision repair.
Reason: Receptor-specific (DDB2) role of the shared catalytic subunit; retained as non-core, with the precise molecular event (ubiquitination at the lesion) annotated separately.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0006355 regulation of DNA-templated transcription
NAS
PMID:36372232
Identification of an E3 ligase that targets the catalytic su...
MARK AS OVER ANNOTATED
Summary: SCF(FBXL14) containing RBX1 degrades the Pol I catalytic subunit RPA194 under transcription stress.
Reason: Over-annotation for the shared RING: the direct process is ubiquitination leading to proteasomal degradation of a polymerase subunit; 'regulation of DNA-templated transcription' is a distal consequence.
Supporting Evidence:
PMID:36372232
RBX1 is a RING protein that recruits a ubiquitin-charged E2 to the E3 ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0006511 ubiquitin-dependent protein catabolic process
IBA
GO_REF:0000033
ACCEPT
Summary: Ubiquitin-dependent protein catabolism is the general destination of RBX1-catalysed ubiquitination, via K48 chains read by the proteasome.
Reason: Core process. The IBA at the RING-box family node is consistent with the experimental rows and with the conserved role of yeast Hrt1/Roc1 in Sic1 and Cln2 turnover.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000129805 Β· PANTHER:PTN000129805 SUPPORTS TRANSFER
RING-box family node spanning RBX1, RBX2/RNF7 and APC11; the descendant experimental evidence includes human RBX1 itself, mouse Rbx1, fly Roc1a/Roc1b and yeast Hrt1/Rbx1 and Apc11, so the function is inherited rather than lineage-specific.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
GO:0006511 ubiquitin-dependent protein catabolic process
IDA
PMID:17636018
ASB4 is a hydroxylation substrate of FIH and promotes vascul...
ACCEPT
Summary: Ubiquitin-dependent protein catabolism is the general destination of RBX1-catalysed ubiquitination, via K48 chains read by the proteasome.
Reason: Core process. The IBA at the RING-box family node is consistent with the experimental rows and with the conserved role of yeast Hrt1/Roc1 in Sic1 and Cln2 turnover.
Supporting Evidence:
PMID:17636018
Like other SOCS box-containing proteins, ASB4 is the substrate recognition molecule of an elongin B/elongin C/cullin/Roc ubiquitin ligase complex that mediates the ubiquitination and degradation of substrate protein(s).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0006511 ubiquitin-dependent protein catabolic process
IDA
PMID:18498745
The CUL7 E3 ubiquitin ligase targets insulin receptor substr...
ACCEPT
Summary: Ubiquitin-dependent protein catabolism is the general destination of RBX1-catalysed ubiquitination, via K48 chains read by the proteasome.
Reason: Core process. The IBA at the RING-box family node is consistent with the experimental rows and with the conserved role of yeast Hrt1/Roc1 in Sic1 and Cln2 turnover.
Supporting Evidence:
PMID:18498745
Recent genetic studies have documented a pivotal growth-regulatory role played by the Cullin 7 (CUL7) E3 ubiquitin ligase complex containing the Fbw8-substrate-targeting subunit, Skp1, and the ROC1 RING finger protein.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0006513 protein monoubiquitination
IDA
PMID:22358839
Ubiquitin-dependent regulation of COPII coat size and functi...
ACCEPT
Summary: RBX1-containing CRLs also perform monoubiquitination, e.g. CUL3-KLHL12-RBX1 monoubiquitinates the COPII subunit SEC31 and CRL4(CDT2) monoubiquitinates PCNA.
Reason: Core process with a non-degradative output; the same RING chemistry produces mono- or polyubiquitin depending on the E2 and the assembly.
Supporting Evidence:
PMID:22358839
For in vitro ubiquitination reactions, Cul3/Rbx1 purified from Sf9 cells was conjugated to NEDD8 using recombinant APPBP1-UBA3, Ubc12, and NEDD8.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0006513 protein monoubiquitination
IEA
GO_REF:0000117
ACCEPT
Summary: RBX1-containing CRLs also perform monoubiquitination, e.g. CUL3-KLHL12-RBX1 monoubiquitinates the COPII subunit SEC31 and CRL4(CDT2) monoubiquitinates PCNA.
Reason: Core process with a non-degradative output; the same RING chemistry produces mono- or polyubiquitin depending on the E2 and the assembly.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
GO:0006879 intracellular iron ion homeostasis
NAS
PMID:19762597
An E3 ligase possessing an iron-responsive hemerythrin domai...
KEEP AS NON CORE
Summary: SCF(FBXL5) containing RBX1 degrades IRP2 when iron and oxygen are plentiful; FBXL5's hemerythrin domain is the sensor.
Reason: Genuine but FBXL5-specific output; kept as non-core.
Supporting Evidence:
PMID:19762597
Degradation of FBXL5 would then preclude the assembly of the SCF complex allowing IRP2 to accumulate and bind IREs.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0006974 DNA damage response
EXP
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
KEEP AS NON CORE
Summary: CRL4(DDB2), CRL4(CSA) and SCF(FBXO31)/SCF(FBXO46) ligases containing RBX1 act in the DNA-damage response, degrading MDM2 and FBXO31 and ubiquitinating chromatin and stalled Pol II.
Reason: Genuine participation through several damage-specific receptors, but 'DNA damage response' is a receptor- and context-defined output of the shared RING rather than its core function.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0006974 DNA damage response
IDA
PMID:26124108
F-box protein FBXO31 directs degradation of MDM2 to facilita...
KEEP AS NON CORE
Summary: CRL4(DDB2), CRL4(CSA) and SCF(FBXO31)/SCF(FBXO46) ligases containing RBX1 act in the DNA-damage response, degrading MDM2 and FBXO31 and ubiquitinating chromatin and stalled Pol II.
Reason: Genuine participation through several damage-specific receptors, but 'DNA damage response' is a receptor- and context-defined output of the shared RING rather than its core function.
Supporting Evidence:
PMID:26124108
Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 stability.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0006974 DNA damage response
IDA
PMID:30171069
The SCF(FBXO46) ubiquitin ligase complex mediates degradatio...
KEEP AS NON CORE
Summary: CRL4(DDB2), CRL4(CSA) and SCF(FBXO31)/SCF(FBXO46) ligases containing RBX1 act in the DNA-damage response, degrading MDM2 and FBXO31 and ubiquitinating chromatin and stalled Pol II.
Reason: Genuine participation through several damage-specific receptors, but 'DNA damage response' is a receptor- and context-defined output of the shared RING rather than its core function.
Supporting Evidence:
PMID:30171069
The SCF(FBXO46) ubiquitin ligase complex mediates degradation of the tumor suppressor FBXO31 and thereby prevents premature cellular senescence.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0006974 DNA damage response
ISS
GO_REF:0000114
KEEP AS NON CORE
Summary: CRL4(DDB2), CRL4(CSA) and SCF(FBXO31)/SCF(FBXO46) ligases containing RBX1 act in the DNA-damage response, degrading MDM2 and FBXO31 and ubiquitinating chromatin and stalled Pol II.
Reason: Genuine participation through several damage-specific receptors, but 'DNA damage response' is a receptor- and context-defined output of the shared RING rather than its core function.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0007283 spermatogenesis
IDA
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase dur...
KEEP AS NON CORE
Summary: CRL4-DCAF12 containing RBX1 degrades the RNA helicase MOV10 during spermatogenesis, and Dcaf17-null mice are infertile.
Reason: Receptor-specific developmental output; kept as non-core.
Supporting Evidence:
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0007283 spermatogenesis
NAS
PMID:29907856
Deletion of DDB1- and CUL4- associated factor-17 (Dcaf17) ge...
KEEP AS NON CORE
Summary: CRL4-DCAF12 containing RBX1 degrades the RNA helicase MOV10 during spermatogenesis, and Dcaf17-null mice are infertile.
Reason: Receptor-specific developmental output; kept as non-core.
Supporting Evidence:
PMID:29907856
CUL4 proteins interact with the E2 enzyme via the RING finger protein Hrt1/ROC1/Rbx1 at their C terminus.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0007346 regulation of mitotic cell cycle
NAS
PMID:36395886
The SCF-FBXW7 E3 ubiquitin ligase triggers degradation of hi...
MARK AS OVER ANNOTATED
Summary: NAS row from the SCF(FBXW7)-WDR5 study of mitotic slippage.
Reason: Over-annotation at the pathway level: RBX1's contribution is the ubiquitin transfer in SCF(FBXW7); the cell-cycle terms it does support (G1/S transition, SCF-dependent proteolysis) are annotated directly.
Supporting Evidence:
PMID:36395886
SKP1-CUL1-F-Box-FBXW7 mediates ubiquitination of WDR5 and targets it for proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0008270 zinc ion binding
IEA
GO_REF:0000002
ACCEPT
Summary: The RING-H2 domain of RBX1 coordinates two zinc ions in a cross-brace arrangement, plus a third zinc ion seen in SCF structures.
Reason: Structural zinc binding is intrinsic to the RING-H2 fold and required for ligase activity; the InterPro-derived IEA is correct.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0008283 cell population proliferation
NAS
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
MARK AS OVER ANNOTATED
Summary: NAS row from a CRL4(DCAF4) study in colitis-associated cancer.
Reason: Over-annotation: proliferation phenotypes follow from the loss of many CRL substrates at once and do not describe a process RBX1 performs.
Supporting Evidence:
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0010506 regulation of autophagy
NAS
PMID:31267705
Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase ...
KEEP AS NON CORE
Summary: CRL4-DCAF12 degrades MAGE-A3/6, which is required for starvation-induced autophagy; CRL inactivation also stabilises DEPTOR.
Reason: Receptor- and context-specific; kept as non-core.
Supporting Evidence:
PMID:31267705
Regulation of MAGE-A3/6 by the CRL4-DCAF12 ubiquitin ligase and nutrient availability.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0010564 regulation of cell cycle process
NAS
PMID:31424118
E2F1 proteolysis via SCF-cyclin F underlies synthetic lethal...
MARK AS OVER ANNOTATED
Summary: NAS rows from reviews and studies of SCF-dependent cell-cycle proteolysis (cyclin F-E2F1, SCF genome stability, ubiquitination in metastasis).
Reason: Over-annotation: 'regulation of cell cycle process' adds nothing beyond the SCF-dependent catabolic and G1/S annotations, and the cited sources are review-level statements about SCF ligases generally.
Supporting Evidence:
PMID:31424118
Cyclin F, through the F‐box domain, forms a functional Skp1‐Cul1‐F‐Box (SCF) complex acting as an E3 ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0010564 regulation of cell cycle process
NAS
PMID:34445249
The SCF Complex Is Essential to Maintain Genome and Chromoso...
MARK AS OVER ANNOTATED
Summary: NAS rows from reviews and studies of SCF-dependent cell-cycle proteolysis (cyclin F-E2F1, SCF genome stability, ubiquitination in metastasis).
Reason: Over-annotation: 'regulation of cell cycle process' adds nothing beyond the SCF-dependent catabolic and G1/S annotations, and the cited sources are review-level statements about SCF ligases generally.
Supporting Evidence:
PMID:34445249
The SKP1, CUL1, F-box protein (SCF) complex encompasses a group of 69 SCF E3 ubiquitin ligase complexes that primarily modify protein substrates with poly-ubiquitin chains to target them for proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0010564 regulation of cell cycle process
NAS
PMID:35414786
The role of ubiquitination and deubiquitination in tumor inv...
MARK AS OVER ANNOTATED
Summary: NAS rows from reviews and studies of SCF-dependent cell-cycle proteolysis (cyclin F-E2F1, SCF genome stability, ubiquitination in metastasis).
Reason: Over-annotation: 'regulation of cell cycle process' adds nothing beyond the SCF-dependent catabolic and G1/S annotations, and the cited sources are review-level statements about SCF ligases generally.
Supporting Evidence:
PMID:35414786
Ubiquitination is catalyzed by a three-enzyme cascade composed of the E1 Ub-activating enzyme, the E2 Ub-conjugating enzyme, and the E3 Ub ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0010824 regulation of centrosome duplication
NAS
PMID:29348145
FBXL13 directs the proteolysis of CEP192 to regulate centros...
KEEP AS NON CORE
Summary: SCF(FBXL13) containing RBX1 degrades CEP192, and SCF(cyclin F) degrades CP110, restraining centrosome duplication.
Reason: Receptor-specific output; kept as non-core.
Supporting Evidence:
PMID:29348145
Here, we report that FBXL13, a binding determinant of SCF (SKP1-CUL1-F-box)-family E3 ubiquitin ligases, is enriched at centrosomes and interacts with the centrosomal proteins Centrin-2, Centrin-3, CEP152 and CEP192.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0014033 neural crest cell differentiation
NAS
PMID:30190310
Dimerization quality control ensures neuronal development an...
KEEP AS NON CORE
Summary: SCF(FBXL17) containing RBX1 clears aberrant BTB dimers (dimerisation quality control), which is required for neural-crest and neuronal development; CUL3(KBTBD8) likewise drives neural-crest specification.
Reason: Developmental output of specific receptors; non-core for the shared RING.
Supporting Evidence:
PMID:30190310
We conclude that metazoan organisms actively monitor BTB dimerization, and we predict that distinct E3 ligases similarly control complex formation by other recurrent domains.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0016485 protein processing
TAS
PMID:16705181
Multisite protein kinase A and glycogen synthase kinase 3bet...
MARK AS OVER ANNOTATED
Summary: TAS row from the Gli3 study: SCF(beta-TrCP)-mediated ubiquitination is required for proteolytic processing of Gli3 into its repressor form.
Reason: Over-annotation: RBX1 performs the ubiquitination, while the limited proteolysis that generates the Gli3 repressor is carried out by the proteasome. Protein ubiquitination and CRL-dependent catabolism already capture RBX1's role.
Supporting Evidence:
PMID:16705181
Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0016567 protein ubiquitination
IBA
GO_REF:0000033
ACCEPT
Summary: Protein ubiquitination is the process RBX1 executes: as the RING subunit it delivers ubiquitin from a charged E2 to substrates recruited by any cullin-RING receptor.
Reason: Core process, supported by IDA in multiple reconstituted CRLs, by the PAINT inference at the RING-box node, and by the UniProt pathway assignment (protein modification; protein ubiquitination).
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000129805 Β· PANTHER:PTN000129805 SUPPORTS TRANSFER
RING-box family node spanning RBX1, RBX2/RNF7 and APC11; the descendant experimental evidence includes human RBX1 itself, mouse Rbx1, fly Roc1a/Roc1b and yeast Hrt1/Rbx1 and Apc11, so the function is inherited rather than lineage-specific.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0016567 protein ubiquitination
IDA
PMID:15103331
Phosphorylation-dependent degradation of c-Myc is mediated b...
ACCEPT
Summary: Protein ubiquitination is the process RBX1 executes: as the RING subunit it delivers ubiquitin from a charged E2 to substrates recruited by any cullin-RING receptor.
Reason: Core process, supported by IDA in multiple reconstituted CRLs, by the PAINT inference at the RING-box node, and by the UniProt pathway assignment (protein modification; protein ubiquitination).
Supporting Evidence:
PMID:15103331
The SCF complex consists of four components: the invariable subunits Skp1, Cul1 (also known as Cdc53) and Rbx1 (Roc1, Hrt1) and a variable F-box protein that serves as a receptor for target proteins and thereby determines target specificity ( Elledge and Harper, 1998 ;
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0016567 protein ubiquitination
IDA
PMID:17543862
A Cul3-based E3 ligase removes Aurora B from mitotic chromos...
ACCEPT
Summary: Protein ubiquitination is the process RBX1 executes: as the RING subunit it delivers ubiquitin from a charged E2 to substrates recruited by any cullin-RING receptor.
Reason: Core process, supported by IDA in multiple reconstituted CRLs, by the PAINT inference at the RING-box node, and by the UniProt pathway assignment (protein modification; protein ubiquitination).
Supporting Evidence:
PMID:17543862
Moreover, Aurora B is ubiquitylated in a Cul3-dependent manner in vivo, and by reconstituted Cul3/KLHL9/KLHL13 ligase in vitro.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0016567 protein ubiquitination
IDA
PMID:20389280
The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti...
ACCEPT
Summary: Protein ubiquitination is the process RBX1 executes: as the RING subunit it delivers ubiquitin from a charged E2 to substrates recruited by any cullin-RING receptor.
Reason: Core process, supported by IDA in multiple reconstituted CRLs, by the PAINT inference at the RING-box node, and by the UniProt pathway assignment (protein modification; protein ubiquitination).
Supporting Evidence:
PMID:20389280
The KLHL20-Cul3-ROC1 E3 ligase complex promotes DAPK polyubiquitination, thereby inducing the proteasomal degradation of DAPK.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0016567 protein ubiquitination
IDA
PMID:34526721
Structural basis of human transcription-DNA repair coupling.
ACCEPT
Summary: Protein ubiquitination is the process RBX1 executes: as the RING subunit it delivers ubiquitin from a charged E2 to substrates recruited by any cullin-RING receptor.
Reason: Core process, supported by IDA in multiple reconstituted CRLs, by the PAINT inference at the RING-box node, and by the UniProt pathway assignment (protein modification; protein ubiquitination).
Supporting Evidence:
PMID:34526721
RBX1 and the E2 enzyme–donor ubiquitin complex were modelled as described in the Methods.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0016567 protein ubiquitination
IEA
GO_REF:0000120
ACCEPT
Summary: Protein ubiquitination is the process RBX1 executes: as the RING subunit it delivers ubiquitin from a charged E2 to substrates recruited by any cullin-RING receptor.
Reason: Core process, supported by IDA in multiple reconstituted CRLs, by the PAINT inference at the RING-box node, and by the UniProt pathway assignment (protein modification; protein ubiquitination).
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0016567 protein ubiquitination
IPI
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
ACCEPT
Summary: Protein ubiquitination is the process RBX1 executes: as the RING subunit it delivers ubiquitin from a charged E2 to substrates recruited by any cullin-RING receptor.
Reason: Core process, supported by IDA in multiple reconstituted CRLs, by the PAINT inference at the RING-box node, and by the UniProt pathway assignment (protein modification; protein ubiquitination).
Supporting Evidence:
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:11956208
The novel human DNA helicase hFBH1 is an F-box protein.
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:11956208
The hFBH1 enzyme interacted with human SKP1 and formed an SCF (SKP1/Cullin/F-box) complex together with human Cullin and ROC1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:15103331
Phosphorylation-dependent degradation of c-Myc is mediated b...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:15103331
The SCF complex consists of four components: the invariable subunits Skp1, Cul1 (also known as Cdc53) and Rbx1 (Roc1, Hrt1) and a variable F-box protein that serves as a receptor for target proteins and thereby determines target specificity ( Elledge and Harper, 1998 ;
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:16705181
Multisite protein kinase A and glycogen synthase kinase 3bet...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:16705181
Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:21572392
SCFFBXL¹⁡ regulates BMP signalling by directing the degradat...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:21572392
Here, we report that F-box and LRR domain-containing protein 15 (FBXL15), an F-box protein of the FBXL family, forms an Skp1-Cullin1-F-box protein-Roc1 (SCF) FBXL15 ubiquitin ligase complex and targets Smurf1 for ubiquitination and proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:23263282
SCFFbxo9 and CK2 direct the cellular response to growth fact...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:23263282
SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IDA
PMID:25585578
FBH1 influences DNA replication fork stability and homologou...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:25585578
Here we report that the central player in HR, RAD51, is ubiquitylated by the SCF(FBH1) complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IEA
GO_REF:0000120
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IPI
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IPI
PMID:17098746
FBXO11 promotes the Neddylation of p53 and inhibits its tran...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:17098746
It is unclear how the modular SCF complex, which comprises three constant subunits, Skp1, Cullin1, Roc1, and a variable substrate-binding F-box protein could distinguish between Nedd8 and ubiquitin conjugation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IPI
PMID:19762597
An E3 ligase possessing an iron-responsive hemerythrin domai...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:19762597
Degradation of FBXL5 would then preclude the assembly of the SCF complex allowing IRP2 to accumulate and bind IREs.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IPI
PMID:21572392
SCFFBXL¹⁡ regulates BMP signalling by directing the degradat...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:21572392
Here, we report that F-box and LRR domain-containing protein 15 (FBXL15), an F-box protein of the FBXL family, forms an Skp1-Cullin1-F-box protein-Roc1 (SCF) FBXL15 ubiquitin ligase complex and targets Smurf1 for ubiquitination and proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
IPI
PMID:33692209
KDM2B Overexpression Facilitates Lytic De Novo KSHV Infectio...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:33692209
CUL1 acts as the scaffold protein in the SCF complex recruiting ROC1, which is the E3 ubiquitin ligase component of SCF ( 22 ).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
ISS
GO_REF:0000024
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
NAS
PMID:15520277
Systematic analysis and nomenclature of mammalian F-box prot...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:15520277
CUL1 interacts with RBX1 through its C terminus and with SKP1 through its N terminus.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
NAS
PMID:20498703
Lamin A rod domain mutants target heterochromatin protein 1a...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:20498703
On the other hand, moderate induction of the HECW2 ligase and RNF123 RING finger protein was observed with G232E and R386K-expressing cells respectively (but not both).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
NAS
PMID:20596027
SCF(Cyclin F) controls centrosome homeostasis and mitotic fi...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:20596027
SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
NAS
PMID:26171402
The Human IL-22 Receptor Is Regulated through the Action of ...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:26171402
Skp-1, Rbx1, and Cul-1 were from Abnova (Taipei, Taiwan), and TnT Coupled Reticulocyte was from Promega (Madison, WI).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
NAS
PMID:34445249
The SCF Complex Is Essential to Maintain Genome and Chromoso...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:34445249
The SKP1, CUL1, F-box protein (SCF) complex encompasses a group of 69 SCF E3 ubiquitin ligase complexes that primarily modify protein substrates with poly-ubiquitin chains to target them for proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019005 SCF ubiquitin ligase complex
NAS
PMID:35982156
Structure of CRL7(FBXW8) reveals coupling with CUL1-RBX1/ROC...
ACCEPT
Summary: RBX1 is an invariant subunit of SCF (SKP1-CUL1-F-box-RBX1) ligases; with CUL1 it forms the catalytic core that all ~70 F-box receptors plug into.
Reason: Core complex membership, established structurally (the CUL1-RBX1-SKP1-SKP2 crystal structure) and in every SCF reconstitution cited here.
Supporting Evidence:
PMID:35982156
Several observations are consistent with CUL7 recruiting TP53 for neddylated CUL1–RBX1-mediated ubiquitination.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0019788 NEDD8 transferase activity
TAS
Reactome:R-HSA-8952618
ACCEPT
Summary: RBX1 is the RING E3 of the cullin neddylation reaction, binding UBE2M~NEDD8 and transferring NEDD8 to the conserved lysine of CUL1-CUL4.
Reason: Core function, supported by structure (the trapped RBX1-UBC12~NEDD8-CUL1-DCN1 intermediate) and by UniProt's EC 2.3.2.32 assignment; RBX2/RNF7-UBE2F provides the parallel activity for CUL5.
Supporting Evidence:
Reactome:R-HSA-8952618
UBE2M transfers NEDD8 to lysine 720 of CUL1 in the CRL E3 ubiquitin ligase complex (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0019788 NEDD8 transferase activity
TAS
Reactome:R-HSA-8952626
ACCEPT
Summary: RBX1 is the RING E3 of the cullin neddylation reaction, binding UBE2M~NEDD8 and transferring NEDD8 to the conserved lysine of CUL1-CUL4.
Reason: Core function, supported by structure (the trapped RBX1-UBC12~NEDD8-CUL1-DCN1 intermediate) and by UniProt's EC 2.3.2.32 assignment; RBX2/RNF7-UBE2F provides the parallel activity for CUL5.
Supporting Evidence:
Reactome:R-HSA-8952626
UBE2M transfers NEDD8 to lysine 689 of CUL2 in the E3 ligase complex (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0019788 NEDD8 transferase activity
TAS
Reactome:R-HSA-8952631
ACCEPT
Summary: RBX1 is the RING E3 of the cullin neddylation reaction, binding UBE2M~NEDD8 and transferring NEDD8 to the conserved lysine of CUL1-CUL4.
Reason: Core function, supported by structure (the trapped RBX1-UBC12~NEDD8-CUL1-DCN1 intermediate) and by UniProt's EC 2.3.2.32 assignment; RBX2/RNF7-UBE2F provides the parallel activity for CUL5.
Supporting Evidence:
Reactome:R-HSA-8952631
UBE2M transfers NEDD8 to lysine 712 of CUL3 in the E3 ligase complex (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0019788 NEDD8 transferase activity
TAS
Reactome:R-HSA-8952638
ACCEPT
Summary: RBX1 is the RING E3 of the cullin neddylation reaction, binding UBE2M~NEDD8 and transferring NEDD8 to the conserved lysine of CUL1-CUL4.
Reason: Core function, supported by structure (the trapped RBX1-UBC12~NEDD8-CUL1-DCN1 intermediate) and by UniProt's EC 2.3.2.32 assignment; RBX2/RNF7-UBE2F provides the parallel activity for CUL5.
Supporting Evidence:
Reactome:R-HSA-8952638
UBE2M transfers NEDD8 to lysine 705 of CUL4A and lysine 859 of CUL4B (Hori et al, 1999; Duda et al, 2008).
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0030174 regulation of DNA-templated DNA replication initiation
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
KEEP AS NON CORE
Summary: CRL4(CDT2) and SCF(SKP2) ligases containing RBX1 destroy CDT1 in S phase and after DNA damage, restraining re-licensing of replication origins.
Reason: Real but receptor-defined; RBX1's direct role is the ubiquitination. Kept as non-core.
Supporting Evidence:
PMID:16861906
Our studies suggest that L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0030510 regulation of BMP signaling pathway
NAS
PMID:21572392
SCFFBXL¹⁡ regulates BMP signalling by directing the degradat...
KEEP AS NON CORE
Summary: SCF(FBXL15) containing RBX1 degrades the HECT ligase SMURF1, positively regulating BMP signalling.
Reason: Receptor-specific pathway output; non-core.
Supporting Evidence:
PMID:21572392
Here, we report that F-box and LRR domain-containing protein 15 (FBXL15), an F-box protein of the FBXL family, forms an Skp1-Cullin1-F-box protein-Roc1 (SCF) FBXL15 ubiquitin ligase complex and targets Smurf1 for ubiquitination and proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin part...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:15103331
Phosphorylation-dependent degradation of c-Myc is mediated b...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:15103331
The SCF complex consists of four components: the invariable subunits Skp1, Cul1 (also known as Cdc53) and Rbx1 (Roc1, Hrt1) and a variable F-box protein that serves as a receptor for target proteins and thereby determines target specificity ( Elledge and Harper, 1998 ;
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:19762597
An E3 ligase possessing an iron-responsive hemerythrin domai...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:19762597
Degradation of FBXL5 would then preclude the assembly of the SCF complex allowing IRP2 to accumulate and bind IREs.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:22017875
mTOR drives its own activation via SCF(Ξ²TrCP)-dependent degr...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:22017875
To purify SCFΞ²-TRCP complex, 293T cells were transfected with vectors encoding GST-Ξ²-TRCP1, Myc-Cul-1, Myc-Skp1, and HA-Rbx1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:22017876
DEPTOR, an mTOR inhibitor, is a physiological substrate of S...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:22017876
Here we report that DEPTOR is a physiological substrate of SCF(Ξ²TrCP) E3 ligase for targeted degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:24936062
F-box only protein 31 (FBXO31) negatively regulates p38 mito...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:24936062
Here we report that the accumulation of F-box only protein 31 (FBXO31), a component of Skp1 Β· Cul1 Β· F-box protein E3 ligase, negatively regulated p38 activation in cancer cells upon genotoxic stresses.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:26124108
F-box protein FBXO31 directs degradation of MDM2 to facilita...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:26124108
Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 stability.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:30171069
The SCF(FBXO46) ubiquitin ligase complex mediates degradatio...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:30171069
The SCF(FBXO46) ubiquitin ligase complex mediates degradation of the tumor suppressor FBXO31 and thereby prevents premature cellular senescence.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IDA
PMID:36608670
A central role for regulated protein stability in the contro...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:36608670
The pulse reaction was quenched for 5 minutes on ice with 50 mM EDTA, and *ubiquitin was chased from UBE2D2 to SCF substrates.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
IEA
GO_REF:0000120
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
ISS
GO_REF:0000024
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:15520277
Systematic analysis and nomenclature of mammalian F-box prot...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:15520277
CUL1 interacts with RBX1 through its C terminus and with SKP1 through its N terminus.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:20498703
Lamin A rod domain mutants target heterochromatin protein 1a...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:20498703
On the other hand, moderate induction of the HECW2 ligase and RNF123 RING finger protein was observed with G232E and R386K-expressing cells respectively (but not both).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:20596027
SCF(Cyclin F) controls centrosome homeostasis and mitotic fi...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:20596027
SCF(Cyclin F) controls centrosome homeostasis and mitotic fidelity through CP110 degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:21572392
SCFFBXL¹⁡ regulates BMP signalling by directing the degradat...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:21572392
Here, we report that F-box and LRR domain-containing protein 15 (FBXL15), an F-box protein of the FBXL family, forms an Skp1-Cullin1-F-box protein-Roc1 (SCF) FBXL15 ubiquitin ligase complex and targets Smurf1 for ubiquitination and proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:26171402
The Human IL-22 Receptor Is Regulated through the Action of ...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:26171402
Skp-1, Rbx1, and Cul-1 were from Abnova (Taipei, Taiwan), and TnT Coupled Reticulocyte was from Promega (Madison, WI).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:33234069
The FBXL family of F-box proteins: variations on a theme.
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:33234069
Rbx1 engages an E2 enzyme conjugated to activated ubiquitin, thus enabling the direct transfer of ubiquitin to the substrate (figure 1).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:34445249
The SCF Complex Is Essential to Maintain Genome and Chromoso...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:34445249
The SKP1, CUL1, F-box protein (SCF) complex encompasses a group of 69 SCF E3 ubiquitin ligase complexes that primarily modify protein substrates with poly-ubiquitin chains to target them for proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
NAS
PMID:35982156
Structure of CRL7(FBXW8) reveals coupling with CUL1-RBX1/ROC...
ACCEPT
Summary: SCF-dependent proteasomal degradation: RBX1 provides the ligase activity for SCF(SKP2) (p27/CDKN1B), SCF(beta-TrCP) (IkappaB-alpha, beta-catenin, DEPTOR), SCF(FBXW7) (c-Myc, NOTCH), SCF(cyclin F), SCF(FBXL3/FBXL5) and many other F-box receptors.
Reason: Core process for the shared catalytic module: the F-box protein selects the substrate, but RBX1 performs the ubiquitin transfer that commits it to the proteasome.
Supporting Evidence:
PMID:35982156
Several observations are consistent with CUL7 recruiting TP53 for neddylated CUL1–RBX1-mediated ubiquitination.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031297 replication fork processing
NAS
PMID:30018425
The replication initiation determinant protein (RepID) modul...
KEEP AS NON CORE
Summary: CRL4(DCAF14) and CRL4(RepID/PHIP) ligases containing RBX1 act at stalled replication forks to protect nascent DNA.
Reason: Receptor-specific genome-maintenance output; non-core.
Supporting Evidence:
PMID:30018425
In the absence of RepID, cells rely on the alternative ubiquitin ligase, SKP2-containing SCF, to progress through the cell cycle.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031297 replication fork processing
NAS
PMID:33503431
DCAF14 promotes stalled fork stability to maintain genome in...
KEEP AS NON CORE
Summary: CRL4(DCAF14) and CRL4(RepID/PHIP) ligases containing RBX1 act at stalled replication forks to protect nascent DNA.
Reason: Receptor-specific genome-maintenance output; non-core.
Supporting Evidence:
PMID:33503431
CRL4s utilize DDB1- and CUL4-associated factors (DCAFs) as substrate receptors to recruit substrates for ubiquitination.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0031461 cullin-RING ubiquitin ligase complex
IBA
GO_REF:0000033
ACCEPT
Summary: RBX1 is the RING subunit of cullin-RING ubiquitin ligase complexes generally - the parent statement covering its membership in CRL1 through CRL4, CRL5, CRL7 and CRL9.
Reason: Core complex membership; the PAINT inference at the RING-box family node and the direct evidence (including Glomulin binding to the RBX1 RING within CRLs) agree.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000129805 Β· PANTHER:PTN000129805 SUPPORTS TRANSFER
RING-box family node spanning RBX1, RBX2/RNF7 and APC11; the descendant experimental evidence includes human RBX1 itself, mouse Rbx1, fly Roc1a/Roc1b and yeast Hrt1/Rbx1 and Apc11, so the function is inherited rather than lineage-specific.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0031461 cullin-RING ubiquitin ligase complex
IDA
PMID:22405651
The glomuvenous malformation protein Glomulin binds Rbx1 and...
ACCEPT
Summary: RBX1 is the RING subunit of cullin-RING ubiquitin ligase complexes generally - the parent statement covering its membership in CRL1 through CRL4, CRL5, CRL7 and CRL9.
Reason: Core complex membership; the PAINT inference at the RING-box family node and the direct evidence (including Glomulin binding to the RBX1 RING within CRLs) agree.
Supporting Evidence:
PMID:22405651
The glomuvenous malformation protein Glomulin binds Rbx1 and regulates cullin RING ligase-mediated turnover of Fbw7.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0031462 Cul2-RING ubiquitin ligase complex
IDA
PMID:17636018
ASB4 is a hydroxylation substrate of FIH and promotes vascul...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:17636018
Like other SOCS box-containing proteins, ASB4 is the substrate recognition molecule of an elongin B/elongin C/cullin/Roc ubiquitin ligase complex that mediates the ubiquitination and degradation of substrate protein(s).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
IDA
PMID:35978186
Post-translational control of beige fat biogenesis by PRDM16...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:35978186
The CUL2–APPBP2 E3 ligase complex catalyses polyubiquitination of PRDM16.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
IDA
PMID:37844242
Molecular basis for C-degron recognition by CRL2(APPBP2) ubi...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:37844242
Cryo-EM samples were generated by mixing two complexes, APPBP2-EB-EC-Peptide and NEDD8-CUL2Δ·RBX1, in a 1:1 ratio.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
IPI
PMID:15601820
VHL-box and SOCS-box domains determine binding specificity f...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:15601820
VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
IPI
PMID:21822215
The tumour antigen PRAME is a subunit of a Cul2 ubiquitin li...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:21822215
The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
IPI
PMID:28591624
Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligas...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:28591624
Crystal Structure of the Cul2-Rbx1-EloBC-VHL Ubiquitin Ligase Complex.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
NAS
PMID:22649776
The Role of Elongin BC-Containing Ubiquitin Ligases.
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:22649776
The S phase kinase-associated protein 1 (Skp1)–Cullin 1 (Cul1)–F box protein (SCF) family is a member of the RING finger-containing ubiquitin ligase family (Lipkowitz and Weissman, 2011).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
NAS
PMID:29779948
The Eukaryotic Proteome Is Shaped by E3Β Ubiquitin Ligases Ta...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:29779948
We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complex adaptors that regulate C-terminal degrons, including six CRL2 and two CRL4 complexes, and computationally implicate multiple non-CRLs in end recognition.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
NAS
PMID:33398168
Molecular basis for arginine C-terminal degron recognition b...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:33398168
Recently, a few classes of C-terminal degrons (C-degrons) that are recognized by dedicated cullin-RING ligases (CRLs) have been identified.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031462 Cul2-RING ubiquitin ligase complex
NAS
PMID:34743205
CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptos...
ACCEPT
Summary: RBX1 is the RING subunit of CRL2 complexes (CUL2-ELOB/ELOC plus a VHL-box receptor such as VHL, LRR1, FEM1A/B/C, PRAME, APPBP2 or KLHDC3).
Reason: Core complex membership: VHL-box receptors select CUL2-RBX1 while SOCS-box receptors select CUL5-RBX2, and the CRL2(VHL) and CRL2(APPBP2) structures contain RBX1 directly.
Supporting Evidence:
PMID:34743205
CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14(ARF) degradation.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:15983046
Ubiquitination of Keap1, a BTB-Kelch substrate adaptor prote...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:15983046
Keap1 is a BTB-Kelch protein that functions as a substrate adaptor protein for a Cul3-dependent E3 ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:17543862
A Cul3-based E3 ligase removes Aurora B from mitotic chromos...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:17543862
Moreover, Aurora B is ubiquitylated in a Cul3-dependent manner in vivo, and by reconstituted Cul3/KLHL9/KLHL13 ligase in vitro.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:19782033
Cullin mediates degradation of RhoA through evolutionarily c...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:19782033
BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:20389280
The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:20389280
The KLHL20-Cul3-ROC1 E3 ligase complex promotes DAPK polyubiquitination, thereby inducing the proteasomal degradation of DAPK.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:22358839
Ubiquitin-dependent regulation of COPII coat size and functi...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:22358839
For in vitro ubiquitination reactions, Cul3/Rbx1 purified from Sf9 cells was conjugated to NEDD8 using recombinant APPBP1-UBA3, Ubc12, and NEDD8.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:35687106
ARMC5 is part of an RPB1-specific ubiquitin ligase implicate...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:35687106
ARMC5-CUL3-RBX1 as an RPB1-specific E3 based on in vivo and in vitro ubiquitination.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:38225631
ARMC5 controls the degradation of most Pol II subunits, and ...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:38225631
ARMC5-CUL3-RBX1 was a novel dominant E3 controlling the degradation of all 12 Pol II subunits under physiological conditions.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:39504960
Redundant pathways for removal of defective RNA polymerase I...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:39504960
Tellingly, CUL3 E3 ligase relies on BTB domain-containing proteins as adaptors to recognize substrates for ubiquitylation75, suggesting that ARMC5 might connect CUL3 to RNAPII.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IDA
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form parallel mechanisms to control early stages of RNA Pol II transcription.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IPI
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor N...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IPI
PMID:22542517
KBTBD13 interacts with Cullin 3 to form a functional ubiquit...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:22542517
Taken together, our data demonstrate that KBTBD13–Cul3–Rbx1 is a muscle specific ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IPI
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IPI
PMID:26399832
Cell-fate determination by ubiquitin-dependent regulation of...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:26399832
CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IPI
PMID:37788672
Cryo-EM structure of the KLHL22 E3 ligase bound to an oligom...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:37788672
CULLIN3KLHL22-RBX1 ligase mediated the polyubiquitination of GDH1 in vitro.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
IPI
PMID:38332366
Dynamic molecular architecture and substrate recruitment of ...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:38332366
KBTBD2 assembles with Cullin3 (Cul3) and Rbx1 into the Cullin3-RING E3 ubiquitin ligase (CRL3KBTBD2).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
NAS
PMID:22632832
Adaptor protein self-assembly drives the control of a cullin...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:22632832
Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
NAS
PMID:29249570
Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mam...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:29249570
Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
NAS
PMID:31898230
CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases.
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:31898230
In most of Cullin-RING ubiquitin ligase (CRL) complexes, separate linker and adaptor proteins build the substrate recognition module.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031463 Cul3-RING ubiquitin ligase complex
NAS
PMID:37628845
The Role of PIK3R1 in Metabolic Function and Insulin Sensiti...
ACCEPT
Summary: RBX1 is the RING subunit of BTB-CUL3-RBX1 (BCR/CRL3) ligases formed with BTB-domain receptors such as KEAP1, SPOP, KLHL9/13, KLHL20, KLHL22, KCTD10, KBTBD6/7 and ARMC5.
Reason: Core complex membership, reconstituted repeatedly in vitro (Cul3-RBX1 with KEAP1, KLHL12, KLHL20, KLHL22, KBTBD13) and resolved in CRL3 cryo-EM structures.
Supporting Evidence:
PMID:37628845
KBTBD2 interacts with CUL3 and the iSH2 domain of p85Ξ± and leads to the degradation of p85Ξ± [69].
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
EXP
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IDA
PMID:12732143
The ubiquitin ligase activity in the DDB2 and CSA complexes ...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:12732143
Both complexes contain cullin 4A and Roc1 and display ubiquitin ligase activity.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IDA
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IDA
PMID:17085480
DTL/CDT2 is essential for both CDT1 regulation and the early...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:17085480
We show that DTL associates with the CUL4-DDB1 E3 ubiquitin ligase and is required for CDT1 down-regulation in unperturbed cells and following DNA damage.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IDA
PMID:18794347
PCNA-dependent regulation of p21 ubiquitylation and degradat...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:18794347
Cdt2 functions as the substrate recruiting factor for p21 to the rest of the CRL4 ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IDA
PMID:20129063
CRL4(Cdt2) E3 ubiquitin ligase monoubiquitinates PCNA to pro...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:20129063
CRL4Cdt2 consists of Cul4A or Cul4B, DDB1 (damage-specific DNA binding protein 1), the RING-finger protein ROC1 and the DCAF (DDB1 and Cul4-associated factor) and substrate recognition factor/WD40 protein Cdt2.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IDA
PMID:20223979
Identification of a primary target of thalidomide teratogeni...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:20223979
CRBN forms an E3 ubiquitin ligase complex with damaged DNA binding protein 1 (DDB1) and Cul4A that is important for limb outgrowth and expression of the fibroblast growth factor Fgf8 in zebrafish and chicks.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IDA
PMID:27113764
The antiobesity factor WDTC1 suppresses adipogenesis via the...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:27113764
Here, we demonstrate that WDTC1 is a component of a DDB1-CUL4-ROC1 (CRL4) E3 ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IEA
GO_REF:0000117
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IPI
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IPI
PMID:31693891
Aryl Sulfonamides Degrade RBM39 and RBM23 by Recruitment to ...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:31693891
Ubiquitination AssaysRecombinant human Cul4a-Rbx1(Ξ”1–14), DCAF15-DDB1-DDA1, and RBM39 (full-length) were combined with E1 enzyme (UBA1, Boston Biochem), E2 enzyme (UbcH5a and UbcH5b, Boston Biochem), and ubiquitin (Boston Biochem).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
IPI
PMID:34595758
The CRL4(DCAF1) cullin-RING ubiquitin ligase is activated fo...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:34595758
This architecture renders the RING domain of RBX1 inaccessible for the E2 ubiquitin‐conjugating enzyme.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:16861906
Our studies suggest that L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
NAS
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:16949367
Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta propeller Ddb1 adaptor protein, but few substrate receptors have been identified.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
NAS
PMID:25108355
Structure of the human Cereblon-DDB1-lenalidomide complex re...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:25108355
The Cul4-Rbx1-DDB1-Cereblon E3 ubiquitin ligase complex is the target of thalidomide, lenalidomide and pomalidomide, therapeutically important drugs for multiple myeloma and other B-cell malignancies.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
NAS
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates ...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
NAS
PMID:28212551
NRIP/DCAF6 stabilizes the androgen receptor protein by displ...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:28212551
More importantly, our previous in vitro study indicated that DDB2 enhances the ubiquitination and proteasomal degradation of the AR, mediated by the DDB2-DDB1-Cul4 complex [23].
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
NAS
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:29691401
The cullin-RING ubiquitin ligases (CRLs) comprise the largest families of ubiquitin E3 ligases23.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
NAS
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4A-DDB1-DCAF ligases, including the DDB2 and CSA (ERCC8) complexes, DET1-COP1, CRL4(CDT2), CRL4(CRBN) and CRL4(DCAF15).
Reason: Core complex membership; CUL4A-DDB1-RBX1 is the catalytic core in every CRL4 reconstitution and structure cited here.
Supporting Evidence:
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
IDA
PMID:18794347
PCNA-dependent regulation of p21 ubiquitylation and degradat...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:18794347
Cdt2 functions as the substrate recruiting factor for p21 to the rest of the CRL4 ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
IPI
PMID:27113764
The antiobesity factor WDTC1 suppresses adipogenesis via the...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:27113764
Here, we demonstrate that WDTC1 is a component of a DDB1-CUL4-ROC1 (CRL4) E3 ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:16861906
Our studies suggest that L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:16949367
A family of diverse Cul4-Ddb1-interacting proteins includes ...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:16949367
Cul4 E3 ubiquitin ligases contain the cullin 4 scaffold and the triple beta propeller Ddb1 adaptor protein, but few substrate receptors have been identified.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:25108355
Structure of the human Cereblon-DDB1-lenalidomide complex re...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:25108355
The Cul4-Rbx1-DDB1-Cereblon E3 ubiquitin ligase complex is the target of thalidomide, lenalidomide and pomalidomide, therapeutically important drugs for multiple myeloma and other B-cell malignancies.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates ...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:29691401
The cullin-RING ubiquitin ligases (CRLs) comprise the largest families of ubiquitin E3 ligases23.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:30945288
Inflammation-dependent overexpression of c-Myc enhances CRL4(DCAF4) E3 ligase activity and promotes ubiquitination of ST7 in colitis-associated cancer.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:31452512
Systematic identification of cancer cell vulnerabilities to ...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:31452512
CRL4 complexes enable cells to mark proteins for proteosomal degradation, helping regulate intracellular protein homeostasis.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:33898171
OTUD1 Activates Caspase-Independent and Caspase-Dependent Ap...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:33898171
The ubiquitination reaction is carried out by a three‐step enzymatic catalysis process involving ubiquitin‐activating enzymes (E1), ubiquitin‐conjugating enzymes (E2) and ubiquitin ligases (E3).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
NAS
PMID:34595758
The CRL4(DCAF1) cullin-RING ubiquitin ligase is activated fo...
ACCEPT
Summary: RBX1 is equally the RING subunit of the CUL4B-DDB1-DCAF ligases, which act largely on chromatin.
Reason: Core complex membership; CUL4A and CUL4B share DDB1, RBX1 and the DCAF receptor repertoire.
Supporting Evidence:
PMID:34595758
This architecture renders the RING domain of RBX1 inaccessible for the E2 ubiquitin‐conjugating enzyme.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031466 Cul5-RING ubiquitin ligase complex
IDA
PMID:17636018
ASB4 is a hydroxylation substrate of FIH and promotes vascul...
KEEP AS NON CORE
Summary: IDA row placing RBX1 in a CUL5-based elongin BC ligase (the ASB4 ECS complex); UniProt likewise records a CRL5 containing CUL5, ELOB, ELOC, ELOA and RBX1.
Reason: Kept but non-core: CUL5 preferentially pairs with the paralogue RBX2/RNF7 (SOCS-box receptors select CUL5-RBX2), so RBX1-CUL5 assemblies are the exception rather than the shared rule. The evidence is experimental and is not contradicted, so it is retained rather than removed.
Supporting Evidence:
PMID:17636018
Like other SOCS box-containing proteins, ASB4 is the substrate recognition molecule of an elongin B/elongin C/cullin/Roc ubiquitin ligase complex that mediates the ubiquitination and degradation of substrate protein(s).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0031467 Cul7-RING ubiquitin ligase complex
IDA
PMID:18498745
The CUL7 E3 ubiquitin ligase targets insulin receptor substr...
ACCEPT
Summary: RBX1 is a core subunit of the CUL7-SKP1-FBXW8 ligase, which targets IRS1 for degradation.
Reason: Correct complex membership. Note that in CRL7(FBXW8) the RBX1 RING is held in a non-productive orientation, so ubiquitination is carried out by a neddylated CUL1-RBX1 module recruited through SKP1-FBXW8 - RBX1 is present in both halves of that arrangement.
Supporting Evidence:
PMID:18498745
Recent genetic studies have documented a pivotal growth-regulatory role played by the Cullin 7 (CUL7) E3 ubiquitin ligase complex containing the Fbw8-substrate-targeting subunit, Skp1, and the ROC1 RING finger protein.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0031625 ubiquitin protein ligase binding
IDA
PMID:17636018
ASB4 is a hydroxylation substrate of FIH and promotes vascul...
MODIFY
Summary: IDA rows recording RBX1 engagement with components of the cullin-RING assemblies it works in (the elongin BC-cullin-ROC module and CUL3-KLHL22).
Reason: The partners here are cullin scaffolds and BTB adaptors rather than ubiquitin ligases in their own right, so cullin family protein binding (GO:0097602) states the same interaction more accurately. RBX1 does engage a genuine partner ligase - the RBR E3 ARIH1 on neddylated CRLs - but that is not what these rows record.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:17636018
Like other SOCS box-containing proteins, ASB4 is the substrate recognition molecule of an elongin B/elongin C/cullin/Roc ubiquitin ligase complex that mediates the ubiquitination and degradation of substrate protein(s).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0031625 ubiquitin protein ligase binding
IDA
PMID:29769719
KLHL22 activates amino-acid-dependent mTORC1 signalling to p...
MODIFY
Summary: IDA rows recording RBX1 engagement with components of the cullin-RING assemblies it works in (the elongin BC-cullin-ROC module and CUL3-KLHL22).
Reason: The partners here are cullin scaffolds and BTB adaptors rather than ubiquitin ligases in their own right, so cullin family protein binding (GO:0097602) states the same interaction more accurately. RBX1 does engage a genuine partner ligase - the RBR E3 ARIH1 on neddylated CRLs - but that is not what these rows record.
Proposed replacements: cullin family protein binding
Supporting Evidence:
PMID:29769719
Here we find that in response to amino acids, the CUL3-KLHL22 E3 ubiquitin ligase promotes K48-linked polyubiquitination and degradation of DEPDC5, an essential subunit of GATOR1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0032006 regulation of TOR signaling
NAS
PMID:23263282
SCFFbxo9 and CK2 direct the cellular response to growth fact...
KEEP AS NON CORE
Summary: SCF(FBXO9) containing RBX1 degrades TEL2/TTI1 within mTORC1 after growth-factor withdrawal.
Reason: Receptor-specific regulation of TOR signalling; kept as non-core.
Supporting Evidence:
PMID:23263282
SCFFbxo9 and CK2 direct the cellular response to growth factor withdrawal via Tel2/Tti1 degradation and promote survival in multiple myeloma.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
IPI
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
MODIFY
Summary: IPI row from the CUL4A-DDB1-DET1-COP1-ROC1 study, where the assembled ligase ubiquitinates c-Jun and promotes its proteasomal destruction.
Reason: As for the other positive-regulation-of-catabolism rows, RBX1 executes rather than regulates the degradative step; GO:0043161 is the accurate term.
Supporting Evidence:
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0032480 negative regulation of type I interferon production
IDA
PMID:36394357
XAF1 prevents hyperproduction of type I interferon upon vira...
KEEP AS NON CORE
Summary: The BTB-CUL3-RBX1 ligase with the KLHL22 adaptor, controlled by the XAF1-XIAP axis, limits IRF7 accumulation and thereby type I interferon production.
Reason: Genuine receptor-specific output; non-core for a RING shared by all CRL3 ligases.
Supporting Evidence:
PMID:36394357
Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0032814 regulation of natural killer cell activation
NAS
PMID:31452512
Systematic identification of cancer cell vulnerabilities to ...
KEEP AS NON CORE
Summary: Loss of the CRL4 substrate receptor DCAF15 sensitises leukaemia cells to natural killer cells.
Reason: Receptor-specific immunomodulatory output; kept as non-core for RBX1.
Supporting Evidence:
PMID:31452512
CRL4 complexes enable cells to mark proteins for proteosomal degradation, helping regulate intracellular protein homeostasis.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0034450 ubiquitin-ubiquitin ligase activity
IDA
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin part...
ACCEPT
Summary: ROC1 immunocomplexes catalyse isopeptide ligation into polyubiquitin chains in an E1- and E2-dependent manner, i.e. RBX1-containing CRLs elongate chains on already-conjugated ubiquitin.
Reason: Chain elongation by the RBX1 RING is genuine and distinguishable from chain initiation (which for many CRL substrates is primed by ARIH1); the term is narrow but accurate for this activity.
Supporting Evidence:
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0034599 cellular response to oxidative stress
IDA
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor N...
KEEP AS NON CORE
Summary: Under basal conditions the KEAP1-CUL3-RBX1 ligase ubiquitinates NRF2, keeping the antioxidant response low; oxidative or electrophilic stress modifies KEAP1 and relieves this.
Reason: Genuine involvement, but the redox sensor is KEAP1 and the pathway is one of many CRL3 outputs; kept as non-core for the shared RING.
Supporting Evidence:
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0034599 cellular response to oxidative stress
IDA
PMID:39880951
C-terminal amides mark proteins for degradation via SCF-FBXO...
KEEP AS NON CORE
Summary: Under basal conditions the KEAP1-CUL3-RBX1 ligase ubiquitinates NRF2, keeping the antioxidant response low; oxidative or electrophilic stress modifies KEAP1 and relieves this.
Reason: Genuine involvement, but the redox sensor is KEAP1 and the pathway is one of many CRL3 outputs; kept as non-core for the shared RING.
Supporting Evidence:
PMID:39880951
FBXO31 is a substrate receptor for the SKP1-CUL1-F-box protein (SCF) ubiquitin ligase SCF-FBXO31, which ubiquitylates CTAPs for subsequent proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0034644 cellular response to UV
EXP
PMID:22118460
The molecular basis of CRL4DDB2/CSA ubiquitin ligase archite...
KEEP AS NON CORE
Summary: The CRL4(DDB2) ligase containing RBX1 is activated on UV-damaged DNA when the COP9 signalosome is displaced, and UV-induced histone H3/H4 ubiquitination has been attributed to it.
Reason: Real but DDB2-dependent; kept as a non-core, context-specific process for the shared RING.
Supporting Evidence:
PMID:22118460
The DDB1-CUL4-RBX1 (CRL4) ubiquitin ligase family regulates a diverse set of cellular pathways through dedicated substrate receptors (DCAFs).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0034644 cellular response to UV
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: The CRL4(DDB2) ligase containing RBX1 is activated on UV-damaged DNA when the COP9 signalosome is displaced, and UV-induced histone H3/H4 ubiquitination has been attributed to it.
Reason: Real but DDB2-dependent; kept as a non-core, context-specific process for the shared RING.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0034644 cellular response to UV
ISS
GO_REF:0000114
KEEP AS NON CORE
Summary: The CRL4(DDB2) ligase containing RBX1 is activated on UV-damaged DNA when the COP9 signalosome is displaced, and UV-induced histone H3/H4 ubiquitination has been attributed to it.
Reason: Real but DDB2-dependent; kept as a non-core, context-specific process for the shared RING.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0040029 epigenetic regulation of gene expression
NAS
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
MARK AS OVER ANNOTATED
Summary: NAS rows citing CRL4 ligases that act on chromatin regulators (DNMT1, DNMT3A, SUV39H1, PHGDH).
Reason: Over-annotation for RBX1: degrading a chromatin modifier is ubiquitination with an epigenetic consequence, not participation in epigenetic regulation by the ligase subunit itself.
Supporting Evidence:
PMID:30111536
Mechanistically, CRL4-DCAF13 targets SUV39H1 for polyubiquitination and proteasomal degradation and therefore facilitates H3K9me3 removal and zygotic gene expression.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0040029 epigenetic regulation of gene expression
NAS
PMID:34429321
Systematic Profiling of DNMT3A Variants Reveals Protein Inst...
MARK AS OVER ANNOTATED
Summary: NAS rows citing CRL4 ligases that act on chromatin regulators (DNMT1, DNMT3A, SUV39H1, PHGDH).
Reason: Over-annotation for RBX1: degrading a chromatin modifier is ubiquitination with an epigenetic consequence, not participation in epigenetic regulation by the ligase subunit itself.
Supporting Evidence:
PMID:34429321
Systematic Profiling of DNMT3A Variants Reveals Protein Instability Mediated by the DCAF8 E3 Ubiquitin Ligase Adaptor.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0040029 epigenetic regulation of gene expression
NAS
PMID:34720086
Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate d...
MARK AS OVER ANNOTATED
Summary: NAS rows citing CRL4 ligases that act on chromatin regulators (DNMT1, DNMT3A, SUV39H1, PHGDH).
Reason: Over-annotation for RBX1: degrading a chromatin modifier is ubiquitination with an epigenetic consequence, not participation in epigenetic regulation by the ligase subunit itself.
Supporting Evidence:
PMID:34720086
Cul4A-DDB1-mediated monoubiquitination of phosphoglycerate dehydrogenase promotes colorectal cancer metastasis via increased S-adenosylmethionine.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0042110 T cell activation
IDA
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase dur...
KEEP AS NON CORE
Summary: The same CRL4-DCAF12 ligase controls MOV10 during T-cell activation, and Dcaf12 loss alters CD4+ and NKT populations.
Reason: Context-specific immunological output of one DCAF; non-core.
Supporting Evidence:
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0042127 regulation of cell population proliferation
NAS
PMID:33869224
Hippo-Independent Regulation of Yki/Yap/Taz: A Non-canonical...
MARK AS OVER ANNOTATED
Summary: NAS row from a review of Hippo-independent YAP/TAZ regulation.
Reason: Over-annotation of a downstream phenotype; the supportable claims are ubiquitination and proteasomal degradation of the relevant substrates.
Supporting Evidence:
PMID:33869224
Zhao et al., 2010), which is a substrate recognition subunit of a family of modular E3 ubiquitin ligases containing SKP1-Cul1-F-box protein (SCF) complexes (Jiang and Struhl, 1998;
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0042752 regulation of circadian rhythm
NAS
PMID:17463251
SCFFbxl3 controls the oscillation of the circadian clock by ...
KEEP AS NON CORE
Summary: SCF(FBXL3) and SCF(FBXL21) ligases containing RBX1 degrade the cryptochromes CRY1/CRY2, setting circadian period.
Reason: A well-established F-box-specific output; non-core for the shared catalytic subunit.
Supporting Evidence:
PMID:17463251
We found that both Cry1 and Cry2 proteins are ubiquitinated and degraded via the SCF(Fbxl3) ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0042752 regulation of circadian rhythm
NAS
PMID:23452855
Competing E3 ubiquitin ligases govern circadian periodicity ...
KEEP AS NON CORE
Summary: SCF(FBXL3) and SCF(FBXL21) ligases containing RBX1 degrade the cryptochromes CRY1/CRY2, setting circadian period.
Reason: A well-established F-box-specific output; non-core for the shared catalytic subunit.
Supporting Evidence:
PMID:23452855
In Vitro Ubiquitination AssaysCRY1 containing SCF complex were purified from Sf9 cells (Invitrogen) using M2 FLAG agarose.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0042770 signal transduction in response to DNA damage
IDA
PMID:24936062
F-box only protein 31 (FBXO31) negatively regulates p38 mito...
KEEP AS NON CORE
Summary: SCF(FBXO31) containing RBX1 mediates K48-linked ubiquitination and degradation of MKK6 after genotoxic stress, damping p38 signalling.
Reason: The molecular event RBX1 performs is the ubiquitination; participation in damage signalling is a downstream, receptor-specific consequence. Kept as non-core.
Supporting Evidence:
PMID:24936062
Here we report that the accumulation of F-box only protein 31 (FBXO31), a component of Skp1 Β· Cul1 Β· F-box protein E3 ligase, negatively regulated p38 activation in cancer cells upon genotoxic stresses.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0042981 regulation of apoptotic process
NAS
PMID:25654763
F-box protein Fbxl18 mediates polyubiquitylation and proteas...
MARK AS OVER ANNOTATED
Summary: NAS rows from studies of SCF(FBXL18)/FBXL7 and OTUD1-CRL4(DCAF10)-MCL1 in apoptosis.
Reason: Over-annotation: degradation of pro- and anti-apoptotic substrates by different receptors cannot be summed into a role for RBX1 in regulating apoptosis.
Supporting Evidence:
PMID:25654763
Neddylation-deficient Cul1-Rbx1 largely decreased the polyubiquitylation of Fbxl7, in support that Fbxl7 polyubiquitylation is dependent on a fully functional SCFFbxl18 complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0042981 regulation of apoptotic process
NAS
PMID:33898171
OTUD1 Activates Caspase-Independent and Caspase-Dependent Ap...
MARK AS OVER ANNOTATED
Summary: NAS rows from studies of SCF(FBXL18)/FBXL7 and OTUD1-CRL4(DCAF10)-MCL1 in apoptosis.
Reason: Over-annotation: degradation of pro- and anti-apoptotic substrates by different receptors cannot be summed into a role for RBX1 in regulating apoptosis.
Supporting Evidence:
PMID:33898171
The ubiquitination reaction is carried out by a three‐step enzymatic catalysis process involving ubiquitin‐activating enzymes (E1), ubiquitin‐conjugating enzymes (E2) and ubiquitin ligases (E3).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0043123 positive regulation of canonical NF-kappaB signal transduction
IDA
PMID:10644755
Homodimer of two F-box proteins betaTrCP1 or betaTrCP2 binds...
KEEP AS NON CORE
Summary: SCF(beta-TrCP) ligases containing RBX1 ubiquitinate phosphorylated IkappaB-alpha, releasing NF-kappaB; ROC1 immunocomplexes ubiquitinate phospho-IkappaB-alpha in vitro.
Reason: A classic, well-supported SCF output, but positive regulation of NF-kappaB signalling is a pathway-level consequence of one receptor; kept as non-core.
Supporting Evidence:
PMID:10644755
These results indicate that not only betaTrCP1 but also betaTrCP2 participates in the ubiquitination-dependent destruction of IkappaBalpha by forming SCF(betaTrCP1-betaTrCP1) and SCF(betaTrCP2-betaTrCP2) ubiquitin-ligase complexes.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0043124 negative regulation of canonical NF-kappaB signal transduction
IDA
PMID:33010352
The E3 ubiquitin ligase SCF(Fbxo7) mediates proteasomal degr...
KEEP AS NON CORE
Summary: SCF(FBXO7) containing RBX1 degrades UXT isoform 2, dampening NF-kappaB signalling.
Reason: Opposite-sign output of a different F-box receptor, which is exactly why such pathway terms are non-core for the shared RING; the annotation itself is defensible.
Supporting Evidence:
PMID:33010352
Fbxo7 is an F-box protein that interacts with SKP1, Cullin1 and RBX1 proteins to form an SCF(Fbxo7) E3 ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IC
PMID:36646384
E3 ligase adaptor FBXO7 contributes to ubiquitination and pr...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:36646384
For example, the SCF–FBXO7 interaction mediates the ubiquitination and degradation of PINK1 (21).
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin part...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor N...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:19782033
Cullin mediates degradation of RhoA through evolutionarily c...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:19782033
BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:20389280
The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquiti...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:20389280
The KLHL20-Cul3-ROC1 E3 ligase complex promotes DAPK polyubiquitination, thereby inducing the proteasomal degradation of DAPK.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:23453970
Impaired KLHL3-mediated ubiquitination of WNK4 causes human ...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:23453970
Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:29249570
Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mam...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:29249570
Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:29681526
A Designed Peptide Targets Two Types of Modifications of p53...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:29681526
We found that Morn3, a cancer-testis antigen, recruits different PTM enzymes, such as sirtuin deacetylase and ubiquitin ligase, to confer composite modifications on p53.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:29769719
KLHL22 activates amino-acid-dependent mTORC1 signalling to p...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:29769719
Here we find that in response to amino acids, the CUL3-KLHL22 E3 ubiquitin ligase promotes K48-linked polyubiquitination and degradation of DEPDC5, an essential subunit of GATOR1.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:29779948
The Eukaryotic Proteome Is Shaped by E3Β Ubiquitin Ligases Ta...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:29779948
We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complex adaptors that regulate C-terminal degrons, including six CRL2 and two CRL4 complexes, and computationally implicate multiple non-CRLs in end recognition.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:34480022
Endotoxin stabilizes protein arginine methyltransferase 4 (P...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:34480022
Among E3 ubiquitin ligases, a family of SCF (Skp1-Cullin1-Fbox) E3 proteins have been linked to bacterial infection, antiviral immunity, and host defense [29–36].
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:35687106
ARMC5 is part of an RPB1-specific ubiquitin ligase implicate...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:35687106
ARMC5-CUL3-RBX1 as an RPB1-specific E3 based on in vivo and in vitro ubiquitination.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:37788672
Cryo-EM structure of the KLHL22 E3 ligase bound to an oligom...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:37788672
CULLIN3KLHL22-RBX1 ligase mediated the polyubiquitination of GDH1 in vitro.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:38225631
ARMC5 controls the degradation of most Pol II subunits, and ...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:38225631
ARMC5-CUL3-RBX1 was a novel dominant E3 controlling the degradation of all 12 Pol II subunits under physiological conditions.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:39504960
Redundant pathways for removal of defective RNA polymerase I...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:39504960
Tellingly, CUL3 E3 ligase relies on BTB domain-containing proteins as adaptors to recognize substrates for ubiquitylation75, suggesting that ARMC5 might connect CUL3 to RNAPII.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form parallel mechanisms to control early stages of RNA Pol II transcription.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
IDA
PMID:39880951
C-terminal amides mark proteins for degradation via SCF-FBXO...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:39880951
FBXO31 is a substrate receptor for the SKP1-CUL1-F-box protein (SCF) ubiquitin ligase SCF-FBXO31, which ubiquitylates CTAPs for subsequent proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
ISS
GO_REF:0000024
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:22542517
KBTBD13 interacts with Cullin 3 to form a functional ubiquit...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:22542517
Taken together, our data demonstrate that KBTBD13–Cul3–Rbx1 is a muscle specific ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:22632832
Adaptor protein self-assembly drives the control of a cullin...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:22632832
Adaptor protein self-assembly drives the control of a cullin-RING ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:26399832
Cell-fate determination by ubiquitin-dependent regulation of...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:26399832
CUL3(KBTBD8) monoubiquitylates NOLC1 and its paralogue TCOF1, the mutation of which underlies the neurocristopathy Treacher Collins syndrome.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:29249570
Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mam...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:29249570
Cullin 3-Based Ubiquitin Ligases as Master Regulators of Mammalian Cell Differentiation.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:31273098
A glycine-specific N-degron pathway mediates the quality con...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:31273098
In addition to uncovering extended specificities of UBR E3 ligases, we characterized two related Cullin-RING E3 ligase complexes, Cul2ZYG11B and Cul2ZER1, that act redundantly to target N-terminal glycine.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:31898230
CRL3s: The BTB-CUL3-RING E3 Ubiquitin Ligases.
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:31898230
In most of Cullin-RING ubiquitin ligase (CRL) complexes, separate linker and adaptor proteins build the substrate recognition module.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
NAS
PMID:37628845
The Role of PIK3R1 in Metabolic Function and Insulin Sensiti...
ACCEPT
Summary: Proteasome-mediated ubiquitin-dependent catabolism of CRL substrates across all cullin families (NRF2, RhoA/RhoB, WNK4, DAPK, TIAM1, p14ARF, RNA Pol II subunits, DEPTOR and others).
Reason: Core process; RBX1 catalyses the K48-linked ubiquitination that targets these substrates for degradation.
Supporting Evidence:
PMID:37628845
KBTBD2 interacts with CUL3 and the iSH2 domain of p85Ξ± and leads to the degradation of p85Ξ± [69].
file:human/RBX1/RBX1-uniprot.txt
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
GO:0043687 post-translational protein modification
TAS
Reactome:R-HSA-597592
MARK AS OVER ANNOTATED
Summary: Reactome's top-level 'post-translational protein modification' assignment for RBX1.
Reason: Correct but uninformatively broad; protein ubiquitination (GO:0016567) and protein neddylation (GO:0045116) are the modifications RBX1 actually catalyses.
Supporting Evidence:
Reactome:R-HSA-597592
After translation, many newly formed proteins undergo further covalent modifications that alter their functional properties.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0044314 protein K27-linked ubiquitination
IDA
PMID:40307251
F-box protein FBXO32 ubiquitinates and stabilizes D-type cyc...
ACCEPT
Summary: K27-linked ubiquitination by an SCF(FBXO32) ligase, in which the modification stabilises rather than destroys D-type cyclins.
Reason: Accepted as another linkage type produced by the shared RING; RBX1 performs the transfer, while the unusual (stabilising) outcome is a property of the receptor and substrate.
Supporting Evidence:
PMID:40307251
F-box protein FBXO32 ubiquitinates and stabilizes D-type cyclins to drive cancer progression.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0045116 protein neddylation
IDA
PMID:19250909
E2-RING expansion of the NEDD8 cascade confers specificity t...
ACCEPT
Summary: Protein neddylation: RBX1 with UBE2M transfers NEDD8 onto the conserved lysine of CUL1-CUL4, the modification that activates their ligases.
Reason: Core process, distinct from the ubiquitination role and supported by the RBX1-UBC12~NEDD8-CUL1-DCN1 structure and the UniProt neddylation pathway assignment.
Supporting Evidence:
PMID:19250909
The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2).
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0045116 protein neddylation
IEA
GO_REF:0000041
ACCEPT
Summary: Protein neddylation: RBX1 with UBE2M transfers NEDD8 onto the conserved lysine of CUL1-CUL4, the modification that activates their ligases.
Reason: Core process, distinct from the ubiquitination role and supported by the RBX1-UBC12~NEDD8-CUL1-DCN1 structure and the UniProt neddylation pathway assignment.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0045724 positive regulation of cilium assembly
IDA
PMID:29358211
The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrie...
KEEP AS NON CORE
Summary: Author-supported role of CUL3-RBX1 ligases in ciliogenesis, alongside the KCTD10-dependent control of RhoB.
Reason: Kept as a non-core, receptor-specific output; RBX1's molecular contribution is the ubiquitin transfer.
Supporting Evidence:
PMID:29358211
The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0045732 positive regulation of protein catabolic process
IDA
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for effic...
MODIFY
Summary: IDA rows in which an RBX1-containing ligase (CUL1-ROC1 toward IkappaB-alpha, SCF(SKP2)/CRL4(CDT2) toward CDT1, CRL4(HBx) toward SMC5/6) promotes degradation of a substrate.
Reason: RBX1 does not regulate catabolism from outside; it catalyses the ubiquitination that commits the substrate to the proteasome. Proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) states the participation directly, and is already annotated from other references.
Supporting Evidence:
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0045732 positive regulation of protein catabolic process
IDA
PMID:16482215
Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target hum...
MODIFY
Summary: IDA rows in which an RBX1-containing ligase (CUL1-ROC1 toward IkappaB-alpha, SCF(SKP2)/CRL4(CDT2) toward CDT1, CRL4(HBx) toward SMC5/6) promotes degradation of a substrate.
Reason: RBX1 does not regulate catabolism from outside; it catalyses the ubiquitination that commits the substrate to the proteasome. Proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) states the participation directly, and is already annotated from other references.
Supporting Evidence:
PMID:16482215
This suggests that SCF-Skp2 is a major degradation pathway in this cell line.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0045732 positive regulation of protein catabolic process
IDA
PMID:27626656
Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 t...
MODIFY
Summary: IDA rows in which an RBX1-containing ligase (CUL1-ROC1 toward IkappaB-alpha, SCF(SKP2)/CRL4(CDT2) toward CDT1, CRL4(HBx) toward SMC5/6) promotes degradation of a substrate.
Reason: RBX1 does not regulate catabolism from outside; it catalyses the ubiquitination that commits the substrate to the proteasome. Proteasome-mediated ubiquitin-dependent protein catabolic process (GO:0043161) states the participation directly, and is already annotated from other references.
Supporting Evidence:
PMID:27626656
These findings suggest that HBx may assemble an HBx-DDB1-CUL4-ROC1 E3 ligase complex (referred to as CRL4HBx hereafter) to target host proteins that antagonize HBV replication for ubiquitylation and degradation.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0045879 negative regulation of smoothened signaling pathway
TAS
PMID:16705181
Multisite protein kinase A and glycogen synthase kinase 3bet...
KEEP AS NON CORE
Summary: SCF(beta-TrCP) containing RBX1 ubiquitinates phosphorylated GLI3 (and GLI1/GLI2 via CUL3-SPOP), promoting the processing/degradation that represses Hedgehog signalling.
Reason: Real pathway output through beta-TrCP and SPOP; kept as non-core.
Supporting Evidence:
PMID:16705181
Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0045995 regulation of embryonic development
NAS
PMID:30111536
DCAF13 promotes pluripotency by negatively regulating SUV39H...
KEEP AS NON CORE
Summary: CRL4-DCAF13 containing RBX1 degrades SUV39H1 during early embryonic development.
Reason: Receptor-specific developmental role; kept as non-core.
Supporting Evidence:
PMID:30111536
Mechanistically, CRL4-DCAF13 targets SUV39H1 for polyubiquitination and proteasomal degradation and therefore facilitates H3K9me3 removal and zygotic gene expression.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0046627 negative regulation of insulin receptor signaling pathway
IDA
PMID:18498745
The CUL7 E3 ubiquitin ligase targets insulin receptor substr...
KEEP AS NON CORE
Summary: The CUL7-SKP1-FBXW8-RBX1 ligase degrades IRS1, attenuating insulin/IGF1 signalling.
Reason: Genuine but receptor-specific (FBXW8); kept as non-core.
Supporting Evidence:
PMID:18498745
Recent genetic studies have documented a pivotal growth-regulatory role played by the Cullin 7 (CUL7) E3 ubiquitin ligase complex containing the Fbw8-substrate-targeting subunit, Skp1, and the ROC1 RING finger protein.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0050727 regulation of inflammatory response
NAS
PMID:23542741
A combinatorial F box protein directed pathway controls TRAF...
KEEP AS NON CORE
Summary: SCF(FBXO3) containing RBX1 destabilises FBXL2 and thereby raises TRAF levels and cytokine output.
Reason: Receptor-specific inflammatory output; non-core.
Supporting Evidence:
PMID:23542741
The SCF apparatus contains Rbx1 and Cullin1, which form a scaffold to link the E2 conjugating enzyme (Ubc) with a substrate specificity module 14–16.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0050727 regulation of inflammatory response
NAS
PMID:35127719
Diverse Roles of F-BoxProtein3 in Regulation of Various Cell...
KEEP AS NON CORE
Summary: SCF(FBXO3) containing RBX1 destabilises FBXL2 and thereby raises TRAF levels and cytokine output.
Reason: Receptor-specific inflammatory output; non-core.
Supporting Evidence:
PMID:35127719
The ubiquitin protein ligase complex Skp1-Cullin1-F-Box (SCF) is composed of four subunits: F-box protein, SKP1, CULLIN1, and RBX1 (Skaar et al., 2014).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0051298 centrosome duplication
NAS
PMID:34388369
Structure of the human signal peptidase complex reveals the ...
MODIFY
Summary: NAS row for centrosome duplication; the cited reference is the cryo-EM structure of the human signal peptidase complex, which does not concern RBX1.
Reason: The identifier does not support the claim, and even on the real evidence (SCF(cyclin F) degrading CP110, SCF(FBXL13) degrading CEP192) RBX1 restrains rather than executes centrosome duplication. Regulation of centrosome duplication (GO:0010824), already annotated, is the defensible term.
Supporting Evidence:
PMID:34388369
Structure of the human signal peptidase complex reveals the determinants for signal peptide cleavage.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0051726 regulation of cell cycle
NAS
PMID:33234069
The FBXL family of F-box proteins: variations on a theme.
MARK AS OVER ANNOTATED
Summary: NAS row from a review of the FBXL family.
Reason: Over-annotation: too broad for the shared catalytic subunit, and redundant with the SCF-dependent proteolysis and G1/S annotations.
Supporting Evidence:
PMID:33234069
Rbx1 engages an E2 enzyme conjugated to activated ubiquitin, thus enabling the direct transfer of ubiquitin to the substrate (figure 1).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0060090 molecular adaptor activity
EXP
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin liga...
MODIFY
Summary: From the SCF(SKP2) crystal structure: CUL1 holds the SKP1-F-box receptor module and RBX1 more than 100 A apart, with RBX1 forming the two-subunit catalytic core that recruits the ubiquitin-conjugating enzyme.
Reason: 'Molecular adaptor activity' understates and mistypes RBX1's role: the scaffolding is done by CUL1 (GO:0160072), while RBX1 recruits and activates the E2. Ubiquitin conjugating enzyme binding captures what the structure shows; the catalytic consequence is already annotated as GO:0061630.
Supporting Evidence:
PMID:11961546
Structure of the Cul1-Rbx1-Skp1-F boxSkp2 SCF ubiquitin ligase complex.
file:human/RBX1/RBX1-uniprot.txt
Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate.
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0060173 limb development
NAS
PMID:10471509
A novel member of the F-box/WD40 gene family, encoding dacty...
MARK AS OVER ANNOTATED
Summary: NAS row citing the positional cloning of mouse dactylaplasia (Dac/Fbxw4), an F-box/WD40 gene required for maintenance of the apical ectodermal ridge.
Reason: Over-annotation: the reference concerns a mouse F-box protein, not RBX1, and limb development is far downstream of the shared RING's activity.
Supporting Evidence:
PMID:10471509
We report here the positional cloning of Dac and show that it belongs to the F-box/WD40 gene family, which encodes adapters that target specific proteins for destruction by presenting them to the ubiquitination machinery.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0060271 cilium assembly
NAS
PMID:34368969
SCF(Fbxw5) targets kinesin-13 proteins to facilitate cilioge...
KEEP AS NON CORE
Summary: SCF(FBXW5) containing RBX1 degrades kinesin-13 proteins (MCAK, KIF2A/B) in G2, permitting ciliogenesis in the following G1/G0.
Reason: Genuine but FBXW5-specific; non-core for the shared RING.
Supporting Evidence:
PMID:34368969
SCFFbxw5 complexes for all ubiquitylation experiments were prepared by mixing equimolar amounts of Fbxw5/Skp1 and Cul1˜Nedd8/Rbx1 sub‐complexes.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0060964 regulation of miRNA-mediated gene silencing
NAS
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase dur...
KEEP AS NON CORE
Summary: CRL4-DCAF12-mediated turnover of MOV10, a RISC-associated helicase, links RBX1-dependent proteolysis to miRNA-mediated silencing.
Reason: Indirect, receptor-specific effect; kept as non-core.
Supporting Evidence:
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
IPI
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A u...
REMOVE
Summary: IPI row pairing RBX1 with c-Jun (JUN) in the study that defined the CUL4A-DDB1-DET1-COP1-ROC1 ligase for c-Jun.
Reason: c-Jun is the substrate of this ligase, and it is recruited by COP1/DET1, not by RBX1; RBX1 contributes the catalytic RING. Annotating RBX1 with transcription factor binding attributes the receptor's specificity to the shared catalytic subunit. The informative statements from this paper (protein ubiquitination, CRL4A complex membership) are annotated separately.
Supporting Evidence:
PMID:14739464
Human De-etiolated-1 regulates c-Jun by assembling a CUL4A ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 supplies catalytic E2 recruitment but ordinarily does **not** select protein substrates by itself.
GO:0061630 ubiquitin protein ligase activity
IBA
GO_REF:0000033
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000129805 Β· PANTHER:PTN000129805 SUPPORTS TRANSFER
RING-box family node spanning RBX1, RBX2/RNF7 and APC11; the descendant experimental evidence includes human RBX1 itself, mouse Rbx1, fly Roc1a/Roc1b and yeast Hrt1/Rbx1 and Apc11, so the function is inherited rather than lineage-specific.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IC
PMID:24936062
F-box only protein 31 (FBXO31) negatively regulates p38 mito...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:24936062
Here we report that the accumulation of F-box only protein 31 (FBXO31), a component of Skp1 Β· Cul1 Β· F-box protein E3 ligase, negatively regulated p38 activation in cancer cells upon genotoxic stresses.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IC
PMID:26124108
F-box protein FBXO31 directs degradation of MDM2 to facilita...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:26124108
Following DNA damage, MDM2 is degraded rapidly, resulting in increased p53 stability.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IC
PMID:30171069
The SCF(FBXO46) ubiquitin ligase complex mediates degradatio...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:30171069
The SCF(FBXO46) ubiquitin ligase complex mediates degradation of the tumor suppressor FBXO31 and thereby prevents premature cellular senescence.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin part...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for effic...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor N...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:15601839
BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:16482215
Two E3 ubiquitin ligases, SCF-Skp2 and DDB1-Cul4, target hum...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:16482215
This suggests that SCF-Skp2 is a major degradation pathway in this cell line.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:17636018
ASB4 is a hydroxylation substrate of FIH and promotes vascul...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:17636018
Like other SOCS box-containing proteins, ASB4 is the substrate recognition molecule of an elongin B/elongin C/cullin/Roc ubiquitin ligase complex that mediates the ubiquitination and degradation of substrate protein(s).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:18498745
The CUL7 E3 ubiquitin ligase targets insulin receptor substr...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:18498745
Recent genetic studies have documented a pivotal growth-regulatory role played by the Cullin 7 (CUL7) E3 ubiquitin ligase complex containing the Fbw8-substrate-targeting subunit, Skp1, and the ROC1 RING finger protein.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:19782033
Cullin mediates degradation of RhoA through evolutionarily c...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:19782033
BACURDs form ubiquitin ligase complexes, which selectively ubiquitinate RhoA, with Cul3.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:20870715
HIV-1 Vpr loads uracil DNA glycosylase-2 onto DCAF1, a subst...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:20870715
To date, three of the four HIV-1 accessory proteins, including Vpr, have been found to interact with cullin-RING finger E3 ubiquitin ligases (CRLs).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:22017875
mTOR drives its own activation via SCF(Ξ²TrCP)-dependent degr...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:22017875
To purify SCFΞ²-TRCP complex, 293T cells were transfected with vectors encoding GST-Ξ²-TRCP1, Myc-Cul-1, Myc-Skp1, and HA-Rbx1.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:22017876
DEPTOR, an mTOR inhibitor, is a physiological substrate of S...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:22017876
Here we report that DEPTOR is a physiological substrate of SCF(Ξ²TrCP) E3 ligase for targeted degradation.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:22405651
The glomuvenous malformation protein Glomulin binds Rbx1 and...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:22405651
The glomuvenous malformation protein Glomulin binds Rbx1 and regulates cullin RING ligase-mediated turnover of Fbw7.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:23453970
Impaired KLHL3-mediated ubiquitination of WNK4 causes human ...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:23453970
Impaired KLHL3-mediated ubiquitination of WNK4 causes human hypertension.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:27626656
Hepatitis B Virus X Protein Promotes Degradation of SMC5/6 t...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:27626656
These findings suggest that HBx may assemble an HBx-DDB1-CUL4-ROC1 E3 ligase complex (referred to as CRL4HBx hereafter) to target host proteins that antagonize HBV replication for ubiquitylation and degradation.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:29779948
The Eukaryotic Proteome Is Shaped by E3Β Ubiquitin Ligases Ta...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:29779948
We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complex adaptors that regulate C-terminal degrons, including six CRL2 and two CRL4 complexes, and computationally implicate multiple non-CRLs in end recognition.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:34526721
Structural basis of human transcription-DNA repair coupling.
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:34526721
RBX1 and the E2 enzyme–donor ubiquitin complex were modelled as described in the Methods.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:35687106
ARMC5 is part of an RPB1-specific ubiquitin ligase implicate...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:35687106
ARMC5-CUL3-RBX1 as an RPB1-specific E3 based on in vivo and in vitro ubiquitination.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:36608670
A central role for regulated protein stability in the contro...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:36608670
The pulse reaction was quenched for 5 minutes on ice with 50 mM EDTA, and *ubiquitin was chased from UBE2D2 to SCF substrates.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:37844242
Molecular basis for C-degron recognition by CRL2(APPBP2) ubi...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:37844242
Cryo-EM samples were generated by mixing two complexes, APPBP2-EB-EC-Peptide and NEDD8-CUL2Δ·RBX1, in a 1:1 ratio.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:38225631
ARMC5 controls the degradation of most Pol II subunits, and ...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:38225631
ARMC5-CUL3-RBX1 was a novel dominant E3 controlling the degradation of all 12 Pol II subunits under physiological conditions.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:39504960
Redundant pathways for removal of defective RNA polymerase I...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:39504960
Tellingly, CUL3 E3 ligase relies on BTB domain-containing proteins as adaptors to recognize substrates for ubiquitylation75, suggesting that ARMC5 might connect CUL3 to RNAPII.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form parallel mechanisms to control early stages of RNA Pol II transcription.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IDA
PMID:39880951
C-terminal amides mark proteins for degradation via SCF-FBXO...
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
PMID:39880951
FBXO31 is a substrate receptor for the SKP1-CUL1-F-box protein (SCF) ubiquitin ligase SCF-FBXO31, which ubiquitylates CTAPs for subsequent proteasomal degradation.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
IEA
GO_REF:0000003
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
ISS
GO_REF:0000024
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-1504190
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
Reactome:R-HSA-1504190
CUL3:KLHL12:RBX1 polyubiquitinates Dishevelled, targeting it for degradation by the proteasome (Angers et al, 2006).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-5635856
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
Reactome:R-HSA-5635856
The transcriptional activity of full-length activated Ci/GLI proteins is restricted by their rapid ubiquitin-mediated degradation after initiation of Hh signaling (Ohlmeyer et al, 1998; Humke et al, 2010; Tukachinsky et al, 2010; Wen et al, 2010).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-5658424
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
Reactome:R-HSA-5658424
NF1 levels are controlled by proteasomal degradation in response to stimulation by some growth factors (Cichowski et al, 2003).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-9755505
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
Reactome:R-HSA-9755505
The KEAP1:CUL3:RBX1 E3-ubiquitin ligase complex is a negative regulator of Nuclear factor erythroid 2-related (NFE2L2).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-9759172
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
Reactome:R-HSA-9759172
SQSTM1 is an adaptor protein that mediates aggregation of target proteins for selective autophagy (reviewed in Lamark et al, 2017).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-9762091
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
Reactome:R-HSA-9762091
GSK3-dependent phosphorylation of NFE2L2 promotes its subsequent ubiquitination by a BTRC:CUL1 E3 ligase complex (Salazar et al, 2006; Rada et al, 2011; Rada et al, 2012; Rojo et al, 2012; reviewed in Baird and Yamamoto, 2020; Yamamoto et al, 2018).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061630 ubiquitin protein ligase activity
TAS
Reactome:R-HSA-9766645
ACCEPT
Summary: Core molecular function: RBX1 is the RING E3 of cullin-RING ligases, binding ubiquitin-charged E2s (CDC34/UBE2R, UBE2D) and positioning them for transfer onto substrates recruited by the cullin's receptor module.
Reason: This is the central, repeatedly reconstituted activity of RBX1: RING mutations abolish ligase activity of ROC1 immunocomplexes without disturbing complex assembly, and every CRL reconstitution cited here depends on RBX1 for ubiquitin transfer.
Supporting Evidence:
Reactome:R-HSA-9766645
KEAP1 is ubiquitinated by the CUL3:RBX1 complex in an SQSTM1-dependent manner (Zhang et al, 2005).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0061663 NEDD8 ligase activity
IDA
PMID:19250909
E2-RING expansion of the NEDD8 cascade confers specificity t...
ACCEPT
Summary: NEDD8 ligase activity of the RBX1-UBE2M pair that activates cullin-RING ligases by neddylating the cullin C-terminal domain.
Reason: Core function; the EC 2.3.2.32 mapping and the IDA from the UBE2M/UBE2F specificity study agree, and cullin neddylation is what couples RBX1's two catalytic roles (it neddylates the cullin that in turn reorients its own RING for ubiquitin transfer).
Supporting Evidence:
PMID:19250909
The largest ubiquitin E3 subclass consists of cullin-RING ligases (CRLs), which contain one each of several cullins (CUL1, -2, -3, -4, or -5) and RING proteins (RBX1 or -2).
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0061663 NEDD8 ligase activity
IEA
GO_REF:0000003
ACCEPT
Summary: NEDD8 ligase activity of the RBX1-UBE2M pair that activates cullin-RING ligases by neddylating the cullin C-terminal domain.
Reason: Core function; the EC 2.3.2.32 mapping and the IDA from the UBE2M/UBE2F specificity study agree, and cullin neddylation is what couples RBX1's two catalytic roles (it neddylates the cullin that in turn reorients its own RING for ubiquitin transfer).
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
file:human/RBX1/RBX1-deep-research-falcon.md
RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.
GO:0062197 cellular response to chemical stress
TAS
Reactome:R-HSA-9711123
KEEP AS NON CORE
Summary: Reactome assigns RBX1-containing CRL3(KEAP1) activity to the cellular response to chemical stress (the NRF2 pathway).
Reason: Defensible as pathway context; non-core for the shared RING, whose direct role is NRF2 ubiquitination.
Supporting Evidence:
Reactome:R-HSA-9711123
Cells are equipped with versatile physiological stress responses to prevent hazardous consequences resulting from exposure to chemical insults of endogenous and exogenous origin.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0070534 protein K63-linked ubiquitination
IDA
PMID:29358211
The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrie...
ACCEPT
Summary: The CUL3-RBX1-KCTD10 ligase attaches K63-linked chains to RhoB, targeting it to lysosomes rather than the proteasome.
Reason: Core chemistry in a non-degradative mode; the linkage type is set by the E2 and assembly geometry, not by a different RBX1 activity.
Supporting Evidence:
PMID:29358211
The Cullin-3-Rbx1-KCTD10 complex controls endothelial barrier function via K63 ubiquitination of RhoB.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0070936 protein K48-linked ubiquitination
IC
PMID:36646384
E3 ligase adaptor FBXO7 contributes to ubiquitination and pr...
ACCEPT
Summary: K48-linked polyubiquitination by RBX1-containing CRLs - shown for c-Myc (SCF(FBXW7)), TIAM1 (CRL3(KBTBD6/7)), p85alpha (CRL3(KBTBD2)) and NRF2 (CUL3-KEAP1-RBX1, where arsenite binding to the RBX1 RING blocks it).
Reason: Core process and the predominant chain type built by CRLs; the arsenite study is direct evidence that the RBX1 RING is the catalytic element for this linkage.
Supporting Evidence:
PMID:36646384
For example, the SCF–FBXO7 interaction mediates the ubiquitination and degradation of PINK1 (21).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0070936 protein K48-linked ubiquitination
IDA
PMID:15103331
Phosphorylation-dependent degradation of c-Myc is mediated b...
ACCEPT
Summary: K48-linked polyubiquitination by RBX1-containing CRLs - shown for c-Myc (SCF(FBXW7)), TIAM1 (CRL3(KBTBD6/7)), p85alpha (CRL3(KBTBD2)) and NRF2 (CUL3-KEAP1-RBX1, where arsenite binding to the RBX1 RING blocks it).
Reason: Core process and the predominant chain type built by CRLs; the arsenite study is direct evidence that the RBX1 RING is the catalytic element for this linkage.
Supporting Evidence:
PMID:15103331
The SCF complex consists of four components: the invariable subunits Skp1, Cul1 (also known as Cdc53) and Rbx1 (Roc1, Hrt1) and a variable F-box protein that serves as a receptor for target proteins and thereby determines target specificity ( Elledge and Harper, 1998 ;
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0070936 protein K48-linked ubiquitination
IDA
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP ...
ACCEPT
Summary: K48-linked polyubiquitination by RBX1-containing CRLs - shown for c-Myc (SCF(FBXW7)), TIAM1 (CRL3(KBTBD6/7)), p85alpha (CRL3(KBTBD2)) and NRF2 (CUL3-KEAP1-RBX1, where arsenite binding to the RBX1 RING blocks it).
Reason: Core process and the predominant chain type built by CRLs; the arsenite study is direct evidence that the RBX1 RING is the catalytic element for this linkage.
Supporting Evidence:
PMID:25684205
CUL3-KBTBD6/KBTBD7 ubiquitin ligase cooperates with GABARAP proteins to spatially restrict TIAM1-RAC1 signaling.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0070936 protein K48-linked ubiquitination
IDA
PMID:27708159
Insulin resistance and diabetes caused by genetic or diet-in...
ACCEPT
Summary: K48-linked polyubiquitination by RBX1-containing CRLs - shown for c-Myc (SCF(FBXW7)), TIAM1 (CRL3(KBTBD6/7)), p85alpha (CRL3(KBTBD2)) and NRF2 (CUL3-KEAP1-RBX1, where arsenite binding to the RBX1 RING blocks it).
Reason: Core process and the predominant chain type built by CRLs; the arsenite study is direct evidence that the RBX1 RING is the catalytic element for this linkage.
Supporting Evidence:
PMID:27708159
Kbtbd2 encodes a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0070936 protein K48-linked ubiquitination
IDA
PMID:29658272
Arsenite Targets the RING Finger Domain of Rbx1 E3 Ubiquitin...
ACCEPT
Summary: K48-linked polyubiquitination by RBX1-containing CRLs - shown for c-Myc (SCF(FBXW7)), TIAM1 (CRL3(KBTBD6/7)), p85alpha (CRL3(KBTBD2)) and NRF2 (CUL3-KEAP1-RBX1, where arsenite binding to the RBX1 RING blocks it).
Reason: Core process and the predominant chain type built by CRLs; the arsenite study is direct evidence that the RBX1 RING is the catalytic element for this linkage.
Supporting Evidence:
PMID:29658272
It is well established that Nrf2 is ubiquitinated by the Keap1–Cul3–Rbx1 E3 ligase complex.36 When endogenous Rbx1 was depleted using siRNA, the ubiquitination level of Nrf2 was dramatically decreased (Figure 5c, lanes 1–2).
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0070936 protein K48-linked ubiquitination
IEA
GO_REF:0000117
ACCEPT
Summary: K48-linked polyubiquitination by RBX1-containing CRLs - shown for c-Myc (SCF(FBXW7)), TIAM1 (CRL3(KBTBD6/7)), p85alpha (CRL3(KBTBD2)) and NRF2 (CUL3-KEAP1-RBX1, where arsenite binding to the RBX1 RING blocks it).
Reason: Core process and the predominant chain type built by CRLs; the arsenite study is direct evidence that the RBX1 RING is the catalytic element for this linkage.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
The RING-type zinc finger domain is essential for ubiquitin ligase activity
GO:0071230 cellular response to amino acid stimulus
IDA
PMID:29769719
KLHL22 activates amino-acid-dependent mTORC1 signalling to p...
KEEP AS NON CORE
Summary: The same CUL3-KLHL22-RBX1 event is triggered by amino-acid stimulation.
Reason: Context-specific stimulus response mediated by a single receptor; non-core.
Supporting Evidence:
PMID:29769719
Here we find that in response to amino acids, the CUL3-KLHL22 E3 ubiquitin ligase promotes K48-linked polyubiquitination and degradation of DEPDC5, an essential subunit of GATOR1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
IDA
PMID:32355176
The cooperative action of CSB, CSA, and UVSSA target TFIIH t...
ACCEPT
Summary: RBX1 is the RING subunit of CUL4-RING ligases at the family level (the parent of the CUL4A- and CUL4B-specific terms).
Reason: Core complex membership, directly observed in the CSA/ERCC8 and CRL4 structures.
Supporting Evidence:
PMID:32355176
Immunoprecipitation of RNAPIIo revealed a UV-specific association with the CSB and CSA proteins, as well as with CUL4, DDB1 and RBX1, which are subunits of a DDB1-CUL4 (CRL4) E3 ubiquitin ligase complex that associates with CSA24,27.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0080008 Cul4-RING E3 ubiquitin ligase complex
IDA
PMID:34526721
Structural basis of human transcription-DNA repair coupling.
ACCEPT
Summary: RBX1 is the RING subunit of CUL4-RING ligases at the family level (the parent of the CUL4A- and CUL4B-specific terms).
Reason: Core complex membership, directly observed in the CSA/ERCC8 and CRL4 structures.
Supporting Evidence:
PMID:34526721
RBX1 and the E2 enzyme–donor ubiquitin complex were modelled as described in the Methods.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0080135 regulation of cellular response to stress
NAS
PMID:31586112
TFEB activates Nrf2 by repressing its E3 ubiquitin ligase DC...
MARK AS OVER ANNOTATED
Summary: NAS row from a TFEB/DCAF11-NRF2 study.
Reason: Over-annotation: too broad and indirect for the shared RING; the supportable claim is CRL4(DCAF11)-dependent ubiquitination of NRF2.
Supporting Evidence:
PMID:31586112
DCAF11 and DDB1-Cul4/Roc1 bind to the DIDLID sequence of the Neh2 domain of Nrf2 to mediate its degradation19.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0090090 negative regulation of canonical Wnt signaling pathway
TAS
Reactome:R-HSA-4641258
KEEP AS NON CORE
Summary: CUL3-KLHL12-RBX1 ubiquitinates DVL, and SCF(beta-TrCP) degrades phospho-beta-catenin, both negative inputs to canonical Wnt signalling.
Reason: Pathway-level consequence of two receptor-specific ligases; kept as non-core.
Supporting Evidence:
Reactome:R-HSA-4641258
DVL protein levels are regulated by both proteasomal and lysosomal degradation (reviewed in Gao and Chen, 2010).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0090734 site of DNA damage
IDA
PMID:34526721
Structural basis of human transcription-DNA repair coupling.
ACCEPT
Summary: The CRL4(CSA) ligase containing RBX1 is recruited to DNA damage-stalled RNA polymerase II, where it ubiquitinates RPB1/POLR2A at Lys1268.
Reason: A defined site of RBX1 catalysis established by cryo-EM of the transcription-coupled repair complex; the RBX1 RING and its E2 are part of the modelled assembly.
Supporting Evidence:
PMID:34526721
RBX1 and the E2 enzyme–donor ubiquitin complex were modelled as described in the Methods.
file:human/RBX1/RBX1-uniprot.txt
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
GO:0097602 cullin family protein binding
IBA
GO_REF:0000033
ACCEPT
Summary: RBX1 binds the C-terminal domain of all cullins through an intermolecular beta-sheet; ROC1/ROC2 interact with cullins generally, whereas the paralogue APC11 is restricted to the cullin-like APC2.
Reason: Core molecular function and the basis of RBX1's promiscuity across CRL families; supported by IDA, by the SCF and CRL2/CRL3/CRL4 structures, and by the PAINT inference at the RING-box family node.
Propagation Review
Root cause: NO FAILURE CORE
Sources checked:
PANTHER:PTN000129805 Β· PANTHER:PTN000129805 SUPPORTS TRANSFER
RING-box family node spanning RBX1, RBX2/RNF7 and APC11; the descendant experimental evidence includes human RBX1 itself, mouse Rbx1, fly Roc1a/Roc1b and yeast Hrt1/Rbx1 and Apc11, so the function is inherited rather than lineage-specific.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0097602 cullin family protein binding
IDA
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin part...
ACCEPT
Summary: RBX1 binds the C-terminal domain of all cullins through an intermolecular beta-sheet; ROC1/ROC2 interact with cullins generally, whereas the paralogue APC11 is restricted to the cullin-like APC2.
Reason: Core molecular function and the basis of RBX1's promiscuity across CRL families; supported by IDA, by the SCF and CRL2/CRL3/CRL4 structures, and by the PAINT inference at the RING-box family node.
Supporting Evidence:
PMID:10230407
ROC1, a homolog of APC11, represents a family of cullin partners with an associated ubiquitin ligase activity.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0097602 cullin family protein binding
IPI
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi...
ACCEPT
Summary: RBX1 binds the C-terminal domain of all cullins through an intermolecular beta-sheet; ROC1/ROC2 interact with cullins generally, whereas the paralogue APC11 is restricted to the cullin-like APC2.
Reason: Core molecular function and the basis of RBX1's promiscuity across CRL families; supported by IDA, by the SCF and CRL2/CRL3/CRL4 structures, and by the PAINT inference at the RING-box family node.
Supporting Evidence:
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
IDA
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase dur...
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:34065512
CRL4-DCAF12 Ubiquitin Ligase Controls MOV10 RNA Helicase during Spermatogenesis and T Cell Activation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
IDA
PMID:37844242
Molecular basis for C-degron recognition by CRL2(APPBP2) ubi...
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:37844242
Cryo-EM samples were generated by mixing two complexes, APPBP2-EB-EC-Peptide and NEDD8-CUL2Δ·RBX1, in a 1:1 ratio.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
NAS
PMID:15601820
VHL-box and SOCS-box domains determine binding specificity f...
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:15601820
VHL-box and SOCS-box domains determine binding specificity for Cul2-Rbx1 and Cul5-Rbx2 modules of ubiquitin ligases.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
NAS
PMID:21822215
The tumour antigen PRAME is a subunit of a Cul2 ubiquitin li...
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:21822215
The tumour antigen PRAME is a subunit of a Cul2 ubiquitin ligase and associates with active NFY promoters.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
NAS
PMID:22649776
The Role of Elongin BC-Containing Ubiquitin Ligases.
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:22649776
The S phase kinase-associated protein 1 (Skp1)–Cullin 1 (Cul1)–F box protein (SCF) family is a member of the RING finger-containing ubiquitin ligase family (Lipkowitz and Weissman, 2011).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
NAS
PMID:29779948
The Eukaryotic Proteome Is Shaped by E3Β Ubiquitin Ligases Ta...
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:29779948
We characterize eight Cullin-RING E3 ubiquitin ligase (CRL) complex adaptors that regulate C-terminal degrons, including six CRL2 and two CRL4 complexes, and computationally implicate multiple non-CRLs in end recognition.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
NAS
PMID:33398168
Molecular basis for arginine C-terminal degron recognition b...
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:33398168
Recently, a few classes of C-terminal degrons (C-degrons) that are recognized by dedicated cullin-RING ligases (CRLs) have been identified.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
NAS
PMID:34743205
CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptos...
ACCEPT
Summary: C-end degron (C-degron) pathways: CRL2 receptors (FEM1A/B/C, KLHDC2/3, APPBP2) and CRL4(DCAF12) recognise C-terminal degrons, and RBX1 provides the ligase activity of these complexes.
Reason: Core process for the shared RING within a well-defined branch of CRL-dependent proteolysis; the CRL2(APPBP2) cryo-EM structures include NEDD8-CUL2-RBX1.
Supporting Evidence:
PMID:34743205
CRL2-KLHDC3 E3 ubiquitin ligase complex suppresses ferroptosis through promoting p14(ARF) degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0160240 RNA polymerase II transcription initiation surveillance
IDA
PMID:39504960
Redundant pathways for removal of defective RNA polymerase I...
KEEP AS NON CORE
Summary: CRL3(ARMC5) containing RBX1 ubiquitinates Ser5-phosphorylated RPB1, removing excessive or defective RNA polymerase II at the promoter-proximal checkpoint.
Reason: A precise, well-supported process in which RBX1 performs the ubiquitination, but it is specific to the ARMC5 receptor; kept as non-core for the shared RING.
Supporting Evidence:
PMID:39504960
Tellingly, CUL3 E3 ligase relies on BTB domain-containing proteins as adaptors to recognize substrates for ubiquitylation75, suggesting that ARMC5 might connect CUL3 to RNAPII.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0160240 RNA polymerase II transcription initiation surveillance
IDA
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form...
KEEP AS NON CORE
Summary: CRL3(ARMC5) containing RBX1 ubiquitinates Ser5-phosphorylated RPB1, removing excessive or defective RNA polymerase II at the promoter-proximal checkpoint.
Reason: A precise, well-supported process in which RBX1 performs the ubiquitination, but it is specific to the ARMC5 receptor; kept as non-core for the shared RING.
Supporting Evidence:
PMID:39667934
CRL3(ARMC5) ubiquitin ligase and Integrator phosphatase form parallel mechanisms to control early stages of RNA Pol II transcription.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:0160276 negative regulation of beige fat cell differentiation
ISS
GO_REF:0000024
KEEP AS NON CORE
Summary: Ortholog-based transfer from mouse Rbx1: the CRL2(APPBP2) ligase polyubiquitinates PRDM16, restraining beige-fat biogenesis.
Reason: The mouse evidence is sound and RBX1 is 100% identical between human and mouse, so the transfer is safe; the process is nonetheless a receptor-specific metabolic output and non-core.
Supporting Evidence:
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1900076 regulation of cellular response to insulin stimulus
IC
PMID:27708159
Insulin resistance and diabetes caused by genetic or diet-in...
KEEP AS NON CORE
Summary: Curator inference from CRL3(KBTBD2), which degrades the PI3K regulatory subunit p85alpha; its loss causes insulin resistance in mice.
Reason: Defensible receptor-specific output; non-core for the shared catalytic subunit.
Supporting Evidence:
PMID:27708159
Kbtbd2 encodes a BTB-Kelch family substrate recognition subunit of the Cullin-3-based E3 ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1901524 regulation of mitophagy
NAS
PMID:36135912
Mitochondrial Fission and Fusion: Molecular Mechanisms, Biol...
MARK AS OVER ANNOTATED
Summary: NAS row citing a review of mitochondrial fission and fusion, in which FBXL4-containing CRL1 is mentioned.
Reason: Over-annotation: the cited review does not assay RBX1, and mitophagy regulation by one F-box receptor does not generalise to the shared catalytic subunit.
Supporting Evidence:
PMID:36135912
Post-translational phosphorylation, SUMOylation, and ubiquitination regulate DNM1L on the mitochondria [29].
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1901525 negative regulation of mitophagy
IC
PMID:17636018
ASB4 is a hydroxylation substrate of FIH and promotes vascul...
KEEP AS NON CORE
Summary: Curator inference that elongin BC-cullin-ROC ligases containing RBX1 limit mitophagy.
Reason: Inference-level and receptor-specific; kept as non-core.
Supporting Evidence:
PMID:17636018
Like other SOCS box-containing proteins, ASB4 is the substrate recognition molecule of an elongin B/elongin C/cullin/Roc ubiquitin ligase complex that mediates the ubiquitination and degradation of substrate protein(s).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1901987 regulation of cell cycle phase transition
NAS
PMID:16861906
L2DTL/CDT2 interacts with the CUL4/DDB1 complex and PCNA and...
MARK AS OVER ANNOTATED
Summary: NAS rows from CRL4(CDT2) and AMBRA1 studies, where CRL-dependent turnover of licensing and autophagy factors affects phase transitions.
Reason: Over-annotation for RBX1: the direct process is CRL-dependent ubiquitination; the phase-transition effect is downstream and receptor-specific.
Supporting Evidence:
PMID:16861906
Our studies suggest that L2DTL and PCNA interact with CUL4/DDB1 complexes and are involved in CDT1 degradation after DNA damage.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1901987 regulation of cell cycle phase transition
NAS
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates ...
MARK AS OVER ANNOTATED
Summary: NAS rows from CRL4(CDT2) and AMBRA1 studies, where CRL-dependent turnover of licensing and autophagy factors affects phase transitions.
Reason: Over-annotation for RBX1: the direct process is CRL-dependent ubiquitination; the phase-transition effect is downstream and receptor-specific.
Supporting Evidence:
PMID:25499913
AMBRA1 interplay with cullin E3 ubiquitin ligases regulates autophagy dynamics.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1902412 regulation of mitotic cytokinesis
NAS
PMID:34758320
Phosphorylation at Ser68 facilitates DCAF11-mediated ubiquit...
KEEP AS NON CORE
Summary: CRL4(DCAF11) containing RBX1 degrades Ser68-phosphorylated CENP-A during the cell cycle.
Reason: Receptor-specific; kept as non-core.
Supporting Evidence:
PMID:34758320
Furthermore, we find that DCAF11 (DDB1 and CUL4 associated factor 11/WDR23) is the E3 ligase that specifically mediates the observed polyubiquitination.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1902499 positive regulation of protein autoubiquitination
IMP
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubi...
ACCEPT
Summary: RBX1 stimulates autoubiquitination of the E2 CDC34 with which it works, an activity traced to the RING domain.
Reason: A direct consequence of RBX1 activating the E2~ubiquitin conjugate; UniProt records the same property.
Supporting Evidence:
PMID:14528312
Targeting of protein ubiquitination by BTB-Cullin 3-Roc1 ubiquitin ligases.
file:human/RBX1/RBX1-uniprot.txt
Probably also stimulates CDC34 autoubiquitination.
GO:1902883 negative regulation of response to oxidative stress
IDA
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for effic...
KEEP AS NON CORE
Summary: By supporting KEAP1-CUL3-RBX1-dependent degradation of NRF2, RBX1 restrains the antioxidant response, and disabling the CUL1/ROC1 module diminishes CRL ligase activity toward such substrates.
Reason: Defensible as a downstream consequence of CRL3(KEAP1) activity; kept as non-core because the sign of the effect is set by the receptor and substrate, not by RBX1.
Supporting Evidence:
PMID:11027288
The CUL1 C-terminal sequence and ROC1 are required for efficient nuclear accumulation, NEDD8 modification, and ubiquitin ligase activity of CUL1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1904178 negative regulation of adipose tissue development
NAS
PMID:27113764
The antiobesity factor WDTC1 suppresses adipogenesis via the...
KEEP AS NON CORE
Summary: The CRL4(WDTC1) ligase containing RBX1 suppresses adipogenesis, in part through H2AK119 monoubiquitination.
Reason: Receptor-specific metabolic output; non-core.
Supporting Evidence:
PMID:27113764
Here, we demonstrate that WDTC1 is a component of a DDB1-CUL4-ROC1 (CRL4) E3 ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1904263 positive regulation of TORC1 signaling
IDA
PMID:29769719
KLHL22 activates amino-acid-dependent mTORC1 signalling to p...
KEEP AS NON CORE
Summary: CUL3-KLHL22-RBX1 ubiquitinates DEPDC5 in response to amino acids, relieving GATOR1 inhibition and activating mTORC1.
Reason: Genuine, mechanistically defined contribution through one BTB receptor; kept as non-core.
Supporting Evidence:
PMID:29769719
Here we find that in response to amino acids, the CUL3-KLHL22 E3 ubiquitin ligase promotes K48-linked polyubiquitination and degradation of DEPDC5, an essential subunit of GATOR1.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1904415 regulation of xenophagy
NAS
PMID:34515398
FBXO2/SCF ubiquitin ligase complex directs xenophagy through...
KEEP AS NON CORE
Summary: SCF(FBXO2) containing RBX1 ubiquitinates group A Streptococcus surface glycans to direct xenophagy; SKP1, CUL1 and ROC1 are all required.
Reason: Genuine but receptor-specific defence output; non-core.
Supporting Evidence:
PMID:34515398
Furthermore, SCF components such as SKP1, CUL1, and ROC1 are required for ubiquitin-mediated xenophagy against GAS.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process
NAS
PMID:33909987
Convergence of mammalian RQC and C-end rule proteolytic path...
KEEP AS NON CORE
Summary: RBX1-containing CRL2 ligases (ZYG11B/ZER1-type C-degron receptors) participate in degradation of alanine-tailed ribosome-associated quality-control substrates.
Reason: Receptor-specific branch of CRL-dependent proteolysis; kept as non-core.
Supporting Evidence:
PMID:33909987
Incompletely synthesized nascent chains obstructing large ribosomal subunits are targeted for degradation by ribosome-associated quality control (RQC).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:2000001 regulation of DNA damage checkpoint
NAS
PMID:33784509
FBX4 mediates rapid cyclin D1 proteolysis upon DNA damage in...
KEEP AS NON CORE
Summary: SCF ligases containing RBX1 (via FBX4/FBXO31) degrade cyclin D1 after DNA damage, contributing to checkpoint responses.
Reason: Receptor-specific and downstream; kept as non-core.
Supporting Evidence:
PMID:33784509
Much focus has been placed on identifying the E3 ligases responsible for mediating cyclin D1 degradation.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:2000036 regulation of stem cell population maintenance
NAS
PMID:29691401
Methylated DNMT1 and E2F1 are targeted for proteolysis by L3...
KEEP AS NON CORE
Summary: CRL4(DCAF5) ligases containing RBX1 degrade methylated SOX2 and DNMT1, influencing stem-cell maintenance.
Reason: Receptor-specific output; kept as non-core.
Supporting Evidence:
PMID:29691401
The cullin-RING ubiquitin ligases (CRLs) comprise the largest families of ubiquitin E3 ligases23.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:2000036 regulation of stem cell population maintenance
NAS
PMID:30442713
Proteolysis of methylated SOX2 protein is regulated by L3MBT...
KEEP AS NON CORE
Summary: CRL4(DCAF5) ligases containing RBX1 degrade methylated SOX2 and DNMT1, influencing stem-cell maintenance.
Reason: Receptor-specific output; kept as non-core.
Supporting Evidence:
PMID:30442713
Proteolysis of methylated SOX2 protein is regulated by L3MBTL3 and CRL4(DCAF5) ubiquitin ligase.
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors
GO:2000104 negative regulation of DNA-templated DNA replication
NAS
PMID:22649776
The Role of Elongin BC-Containing Ubiquitin Ligases.
KEEP AS NON CORE
Summary: Elongin BC-containing CRL2 ligases with RBX1 act on replication-licensing and other substrates, limiting re-replication.
Reason: Author-statement-level and receptor-specific; kept as non-core.
Supporting Evidence:
PMID:22649776
The S phase kinase-associated protein 1 (Skp1)–Cullin 1 (Cul1)–F box protein (SCF) family is a member of the RING finger-containing ubiquitin ligase family (Lipkowitz and Weissman, 2011).
file:human/RBX1/RBX1-uniprot.txt
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
file:human/RBX1/RBX1-deep-research-falcon.md
Specificity is chiefly imposed by modular receptors

Core Functions

Catalytic RING subunit of cullin-RING ubiquitin ligases: RBX1 binds the cullin C-terminal domain and recruits a ubiquitin-charged E2 (CDC34/UBE2R, UBE2D), activating the E2~ubiquitin conjugate so that ubiquitin is transferred directly onto a lysine of the substrate held by the cullin's receptor module. Mostly K48-linked chains are built, committing the substrate to the proteasome.

Supporting Evidence:
  • PMID:10230407
    ROC1 mutations completely abolished their ligase activity without noticeable changes in associated proteins.
  • PMID:11961546
    The globular domain binds the RING finger protein Rbx1 through an intermolecular beta-sheet, forming a two-subunit catalytic core that recruits the ubiquitin-conjugating enzyme.
  • PMID:36372232
    RBX1 is a RING protein that recruits a ubiquitin-charged E2 to the E3 ligase.
  • file:human/RBX1/RBX1-uniprot.txt
    Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate.
  • file:human/RBX1/RBX1-deep-research-falcon.md
    Its N-terminal region binds the C terminus of a cullin scaffold, whereas its RING domain recruits a modifier-loaded E2 enzyme.

NEDD8 E3 for cullin neddylation: with the NEDD8-conjugating E2 UBE2M/UBC12, and assisted by DCN-type co-E3s, RBX1 transfers NEDD8 onto the conserved lysine of the CUL1-CUL4 C-terminal domain, the modification that reorients the cullin-RING arm, displaces CAND1 and switches the ligase into its active, ubiquitin-transferring conformation.

Molecular Function:
NEDD8 transferase activity
Directly Involved In:
Cellular Locations:
Supporting Evidence:
  • PMID:24949976
    Nonetheless, RING E3 mechanisms matching a specific UBL and acceptor lysine remain elusive, including for RBX1, which mediates NEDD8 ligation to cullins and >10% of all ubiquitination.
  • PMID:21765416
    We propose RING domain rotation as a general mechanism for UBL transfer for the largest family of E3s.
  • PMID:19250909
    The E2s have distinct functions, with UBE2M/RBX1 and UBE2F/RBX2 displaying different target cullin specificities.
  • file:human/RBX1/RBX1-uniprot.txt
    Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M.
  • file:human/RBX1/RBX1-deep-research-falcon.md
    RBX1 also works with UBE2M~NEDD8 to neddylate cullins and activate CRLs.

Catalytic module of SCF (SKP1-CUL1-F-box-RBX1) ligases in cell-cycle proteolysis: within SCF, RBX1 and CUL1 form the invariant core onto which interchangeable F-box receptors dock, and RBX1 performs the ubiquitin transfer that destroys Thr187-phosphorylated p27/CDKN1B via SCF(SKP2) at the G1/S transition and other cell-cycle regulators via SCF(beta-TrCP), SCF(FBXW7) and SCF(cyclin F).

Supporting Evidence:
  • PMID:15520277
    The CUL1/RBX1 complex functions as a scaffold to assemble the E2 ubiquitin conjugating enzyme with the substrate specificity module
  • PMID:33234069
    Rbx1 engages an E2 enzyme conjugated to activated ubiquitin, thus enabling the direct transfer of ubiquitin to the substrate
  • PMID:10230407
    YeastROC1 encodes an essential gene whose reduced expression resulted in multiple, elongated buds and accumulation of Sic1p and Cln2p.
  • file:human/RBX1/RBX1-deep-research-falcon.md
    Specificity is chiefly imposed by modular receptors

References

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Suggested Questions for Experts

Q: Should the ~55 GO:0005515 rows recording RBX1 with individual cullins, substrate receptors and CRL substrates be re-curated as cullin family protein binding (GO:0097602) plus complex membership, or captured in GO-CAM as has_input relations on the receptor and RBX1 activity nodes, rather than as bare protein binding on the shared catalytic subunit?

Q: Which receptor-specific pathway outputs (circadian rhythm, iron homeostasis, TORC1, BMP, xenophagy, ciliogenesis, spermatogenesis, beige-fat differentiation) should be annotated to RBX1 at all, given that RBX1 is shared by every CRL and that the same subunit supports opposite-sign outputs through different receptors?

Q: How should the division of labour between RBX1 and ARIH1 be annotated? Neddylated CUL1-RBX1 activates ARIH1, which primes many CRL substrates with the first ubiquitin while the RBX1-E2 pair elongates the chain - a distinction that current terms (GO:0061630 versus GO:0034450) only partly express.

Suggested Experiments

Experiment: Reconstitute neddylated CUL1-RBX1 and CUL3-RBX1 ligases carrying RING linchpin and E2-interface mutations, and compare priming versus elongation kinetics on SCF(beta-TrCP), SCF(FBXW7) and CUL3(KEAP1) substrates with and without ARIH1, reading out chain length by ubiquitin-remnant mass spectrometry.

Hypothesis: The RBX1 RING is required for chain elongation but dispensable for ARIH1-mediated priming of a defined subset of CRL substrates.

Type: structure-guided mutational reconstitution with ubiquitination kinetics

Experiment: Rescue RBX1-depleted human cells with alleles selectively impaired in UBE2M binding versus in ubiquitin-charged E2 binding, then measure cullin neddylation state, accumulation of canonical substrates (p27, CDT1, NRF2, DEPTOR) and proliferation/senescence, comparing each to NEDD8-E1 inhibition.

Hypothesis: RBX1's neddylation and ubiquitination activities can be separated in cells, so that loss of cullin neddylation accounts for only part of the RBX1-null phenotype.

Type: separation-of-function rescue in cells

Experiment: Quantify RBX1 and RBX2 occupancy on CUL5 complexes across cell types and receptor classes (SOCS-box versus elongin A) by targeted proteomics of endogenous CUL5 pulldowns in RBX2-null and RBX1-degron cells.

Hypothesis: RBX1 associates with CUL5 only in defined contexts, whereas RBX2/RNF7 is the default CUL5 partner.

Type: quantitative interaction proteomics with genetic controls

Deep Research

Falcon

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πŸ“š Additional Documentation

Notes

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