Protein / target
E3 ubiquitin-protein ligase RBX1
Protein at a glance
Biological role
Ubiquitin-protein transferase
Strongest disease association
Multiple Myeloma
Therapeutic position
Established drug target
Derived from structured UniProt, Open Targets and literature data on this page.
Protein profile
Canonical identity and biological annotation from UniProt.
Function overview
E3 ubiquitin 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 transcrip…
View complete UniProt function annotationHide complete annotation
E3 ubiquitin 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
Cell-cycle regulation
- ·G1/S transition of mitotic cell cycle
- ·regulation of cell cycle phase transition
- ·regulation of mitotic cell cycle
Cell proliferation & survival
- ·cell population proliferation
- ·regulation of cell population proliferation
Oncogenic signalling
- ·Loss of Function of FBXW7 in Cancer and NOTCH1 Signaling
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
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.
Approved medicines with mapped indications
Approved therapies targeting this protein, grouped by what they are approved to treat — the disease-first view of the medicines below. Relationships come from the canonical approved-indication graph (ChEMBL phase-4), the same source as the drug cards.
Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.
Drugs targeting this protein
How approved and investigational drugs engage this protein — mechanism and action type, direct vs complex targeting, and how broadly each acts across other targets. A drug-first view (the section above groups the approved ones disease-first); direct binders with few recorded targets are listed first.
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Indicated for Immune System Diseases, Multiple Myeloma
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Indicated for Anemia, Immune System Diseases, Lymphoma, Mantle-Cell, Multiple Myeloma
CRL4(CRBN) E3 ubiquitin ligase inhibitor
Indicated for Immune System Diseases, Multiple Myeloma
ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.
Translational evidence
Why this target matters therapeutically, strongest evidence first. Disease associations are gene-level (via the gene that encodes this protein) and open into the full confidence synthesis; the development universe, tractability and safety annotations are target-level, from Open Targets.
Strongest disease associations · via encoding gene RBX1
Gene-level evidence surfaced through the gene RBX1that encodes this protein — not a direct protein–disease relationship. Ranked by Forefront's causal-directness weighting, so genetically- and clinically-evidenced diseases lead over ones that merely share the literature.
View evidence synthesis (4)Hide
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 per-type scores above show the calculation.
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Drug development
4 compounds recorded · 3 approved · 1 in clinical development
View all recorded compounds (4)Hide
Open Targets known-drugs universe. Drug name and highest clinical stage only — the disease relationship is NOT read from this slice (it carries trial-context noise); approved indications come from the canonical graph above.
Tractability
Small molecules — Strong
Protein degraders — Emerging
View underlying tractability evidence (5)Hide
Raw Open Targets tractability assessment buckets, by modality.
Safety-related annotations
Terms indexed against this target in Open Targets' safety data, with their datasource. These are annotations, not causal claims: the direction of effect (whether activation or inhibition is implicated), species and evidence strength are not captured here, so an entry does not mean that modulating this target is known to cause that condition.
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. Ranked by active status, then clinical phase and recency, and spread across the targeting drugs.
View all trials (26)Hide
ClinicalTrials.gov via the drug-target graph.
What's happening now
Recent therapeutic activity around this target — regulatory actions, clinical trials and safety signals for 2 drugs that target this protein, plus publications where such a drug is a genuine subject. Every item is reached indirectly through the drug, not the protein itself; incidental mentions (a paper that merely measures a drug) and press items are excluded.
- Trial status changed
A Phase 3b, Multicenter, Open-label, Daratumumab Long-term Extension Study
- Trial status changed
64407564MMY3009: A Phase 3 Randomized Study Comparing Talquetamab in Combination With Pomalidomide (Tal-P), Talquetamab in Combination With Teclistamab (Tal-Tec), and Investigator's Choice of Either Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pom
- Label change
Label change: LENALIDOMIDE (NDA021880)
- Trial status changed
A Phase II Trial of Tafasitamab and Lenalidomide Followed by Tafasitamab and ICE as Salvage Therapy for Transplant Eligible Patients With Relapsed/ Refractory Large B-Cell Lymphoma
- Label change
Label change: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (ANDA201452)
- Supplemental approval
Supplemental approval: LENALIDOMIDE (NDA021880)
- New publicationSafety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection.
- Safety communication
Drug Safety Update: Pomalidomide (Imnovid▼): risk of hepatitis B reactivation
- Safety communication
Drug Safety Update: Lenalidomide (Revlimid): risk of serious hepatic adverse drug reactions
- Safety communication
Drug Safety Update: Lenalidomide (Revlimid▼): update on risk of second primary malignancy
- Safety communication
Drug Safety Update: Lenalidomide: risk of thrombosis and thromboembolism
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.