Protein / target
E3 ubiquitin-protein ligase RBX1
Protein at a glance
Biological role
Ubiquitin-protein transferase activity
Primary system
Immune system
Strongest disease association
plasma cell myeloma
Therapeutic maturity
Clinically validated target
Druggability
Small molecule
Clinical development
3 approved · 1 in clinical development
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function
E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase (CRLs) complexes which mediate the ubiquitination and subsequent proteasomal degradation of target proteins, including proteins involved in cell cycle progression, signal transduction, transcription and transcription-coupled nucleotide excision repair (PubMed:10230407, PubMed:10579999, PubMed:11961546, PubMed:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:22748924, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:32355176, PubMed:33417871, PubMed:37844242, PubMed:38326650, PubMed:39504960, PubMed:39667934, PubMed:38316879). CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets (PubMed:27565346). The functional specificity of the E3 ubiquitin-protein ligase complexes depends on the variable substrate recognition components. As a component of the CSA complex mediates ubiquitination of Pol II subunit POLR2A at 'Lys-1268', a critical TC-NER checkpoint (PubMed:32355176, PubMed:34526721). Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:35982156). Core component of a Cul9-RING ubiquitin ligase complex composed of CUL9 and RBX1, which mediates mono-ubiquitination of p53/TP53 (PubMed:38605244). Recruits the E2 ubiquitin-conjugating enzyme CDC34 to the complex and brings it into close proximity to the substrate. Probably also stimulates CDC34 autoubiquitination. May be required for histone H3 and histone H4 ubiquitination in response to ultraviolet and for subsequent DNA repair. Promotes the neddylation of CUL1, CUL2, CUL4 and CUL4 via its interaction with UBE2M. Involved in the ubiquitination of KEAP1, ENC1 and KLHL41. In concert with ATF2 and CUL3, promotes degradation of KAT5 thereby attenuating its ability to acetylate and activate ATM. As part of a multisubunit complex composed of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5; polyubiquitinates monoubiquitinated POLR2A (PubMed:19920177)
Subcellular location
Domains and Gene Ontology detail (100)Hide
Gene Ontology
- Ccentrosome
- CCul2-RING ubiquitin ligase complex
- CCul3-RING ubiquitin ligase complex
- CCul4-RING E3 ubiquitin ligase complex
- CCul4A-RING E3 ubiquitin ligase complex
- CCul4B-RING E3 ubiquitin ligase complex
- CCul5-RING ubiquitin ligase complex
- CCul7-RING ubiquitin ligase complex
- Ccullin-RING ubiquitin ligase complex
- Ccytoplasm
- Ccytosol
- CGolgi apparatus
Biological roles
What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.
View supporting evidenceHide supporting evidence
Transcriptional regulation
- ·E3 ubiquitin ligase component of multiple cullin-RING-based E3 ubiquitin-protein ligase…
- ·RNA polymerase II-specific DNA-binding transcription factor binding
- ·epigenetic regulation of gene expression
- ·negative regulation of transcription by RNA polymerase II
Immune signalling
- ·negative regulation of beige fat cell differentiation
- ·neural crest cell differentiation
- ·regulation of inflammatory response
- ·regulation of mitotic cytokinesis
Metabolic enzyme activity
- ·NEDD8 transferase activity
- ·ubiquitin-protein transferase activity
Apoptosis & cell death
- ·regulation of apoptotic process
View underlying pathways (25)Hide underlying pathways
Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.
Interaction neighbourhood
Proteins with the strongest functional or physical association. Node size and line weight reflect STRING confidence; hover or select a partner to inspect one association.
Functional and physical associations from STRING v12.0. Only associations with this protein are drawn — partner-to-partner links are not part of this evidence.
Drugs targeting this protein
Whether each drug engages this protein directly or through a complex, and how many other targets are recorded for it. Direct binders with few recorded targets are listed first.
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Appears in clinical studies involving plasma cell myeloma, immune system disorder, prostate cancer, non-small cell lung carcinoma
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Appears in clinical studies involving anemia, mantle cell lymphoma, myelodysplastic syndrome, plasma cell myeloma
ChEMBL mechanism, action type and target identity. Open Targets clinical status and indications.
Translational evidence
Why this target matters therapeutically — disease associations, drugs in development, tractability and safety, from Open Targets.
Highest-confidence therapeutic associations
Diseases where a drug acting on this target has already reached clinical development.
Highest overall evidence
Remaining associations by Open Targets' aggregated evidence score.
Show all associationsHide all associations
Open Targets ranks 364 associations for this target and we store the top 10 by aggregated score. The long tail is largely literature co-mention and RNA-expression evidence, not evidence that this target drives those diseases.
Known drugs · 4 total
plasma cell myeloma · sarcoidosis · systemic lupus erythematosus
plasma cell myeloma · immune system disorder · prostate cancer
anemia · mantle cell lymphoma · myelodysplastic syndrome
plasma cell myeloma · systemic sclerosis · immune system disorder
Tractability
Safety liabilities
Clinical trials
Trials of drugs that target this protein — reached indirectly through those drugs, so a trial listed here studies the drug, not the protein.
Show remaining trials (24)Hide
ClinicalTrials.gov via the drug-target graph.
Forefront confidence
Our own weighting of the evidence behind each disease association. Human genetics and clinical evidence count for most; literature co-mention counts for little, because two entities sharing an abstract is not evidence that one drives the other.
The evidence agreement range shows how closely the independent evidence families agree — it is not a statistical confidence interval, and nothing here is fitted to outcome data. Derived from Open Targets evidence types under Forefront weighting; the underlying per-type scores are shown above so the calculation can be checked.
What's happening now
Recent activity around this target, drawn from one canonical event stream. Every item is reached through 2 drugs that target this protein, so each event is news about that drug rather than about the protein directly.
- Label change
Label change: LENALIDOMIDE (NDA021880)
- Industry developmentAdvanced hierarchical ZnFe-LDH@MnO₂ nanostructures for sensitive voltammetric determination of lenalidomide
- Label change
Label change: LENALIDOMIDE (ANDA201452)
- Label change
Label change: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (NDA021880)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (NDA021880)
- Regulatory approval
Approval: LENALIDOMIDE (ANDA201452)
- Regulatory approval
Approval: Thalidomide Lipomed (EMA)
- Label change
Label change: LENALIDOMIDE (NDA021880)
- Label change
Label change: LENALIDOMIDE (NDA021880)
Objective event titles are shown unmodified; the event kind and significance line are derived from structured fields. Forefront AttentionEvent stream aggregating Europe PMC Regulatory filings ClinicalTrials.gov.