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Protein / target

E3 ubiquitin-protein ligase RBX1

Encoded byRBX1P62877Homo sapiensSwiss-Prot
Clinically validated
Therapeutic maturity
3
Approved medicines
Open Targets target-level
View by indication →
30
Clinical trials
Small-molecule tractable
Druggability
Approved Drug

Protein at a glance

Biological role

Ubiquitin-protein transferase

Strongest disease association

Multiple Myeloma

Via encoding gene RBX1 · Clinical evidence · score 0.62

Therapeutic position

Established drug target

Small molecules

Derived from structured UniProt, Open Targets and literature data on this page.

Protein profile

UniProt 2026_02

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 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

CytoplasmNucleus
Domains and Gene Ontology detail (100)

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

108 aa · 12 kDa

Biological roles

Reactome v97

What this protein does, drawn together from its UniProt function, Gene Ontology terms and Reactome pathways.

Cell-cycle regulationGOCell proliferation & survivalGOOncogenic signallingReactomeTranscriptional regulationUniProt · GO · ReactomeImmune signallingGOMetabolic enzyme activityGO
View 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)

Concepts derived from UniProt GO Reactome — each badge above shows which sources supported that role.

Interaction neighbourhood

STRING v12.0

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.

UBE2D2SKP1CUL7CAND1CUL4AGLMNUBE2D1FBXW8SKP2NEDD8RBX1

10 strongest partners — larger node and heavier line mean higher confidence

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

3 medicines · 5 areas

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.

Immune System Diseases3 medicines
Multiple Myeloma3 medicines
Anemia1 medicine
Lymphoma, Mantle-Cell1 medicine
Myelodysplastic Syndromes1 medicine

Approved indications from ChEMBL (phase-4), via the canonical drug→disease graph.

Drugs targeting this protein

3

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.

Thalidomide
ApprovedInhibitor

CRL4(CRBN) E3 ubiquitin ligase inhibitor

Indicated for Immune System Diseases, Multiple Myeloma

Acts on a complex — shared with CRBN, DDB1, CUL4A · 1 of 4 recorded protein targets

lenalidomide
ApprovedInhibitor

CRL4(CRBN) E3 ubiquitin ligase inhibitor

Indicated for Anemia, Immune System Diseases, Lymphoma, Mantle-Cell, Multiple Myeloma

Acts on a complex — shared with CRBN, DDB1, CUL4A · 1 of 4 recorded protein targets

pomalidomide
ApprovedInhibitor

CRL4(CRBN) E3 ubiquitin ligase inhibitor

Indicated for Immune System Diseases, Multiple Myeloma

Acts on a complex — shared with CRBN, DDB1, CUL4A · 1 of 4 recorded protein targets

ChEMBL mechanism, action type, target identity and approved indications. Open Targets clinical status.

Translational evidence

Open Targets 26

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.

Multiple Myeloma
0.77Well supported

Clinical evidence dominant · Open Targets 0.62

Myelodysplastic syndrome
0.69Moderately supported

Clinical evidence dominant · Open Targets 0.56

Neoplasms
0.48Limited support

Pathway evidence dominant · Open Targets 0.54

HIV Infections
0.34Preliminary

Pathway evidence dominant · Open Targets 0.50 · no direct causal or clinical evidence

View evidence synthesis (4)
Multiple MyelomaWell supported
0.77
agreement 0.610.92
Clinical90%Literature10%

Open Targets aggregate 0.62 · 2 independent evidence families

Myelodysplastic syndromeModerately supported
0.69
agreement 0.540.85
Clinical100%Literature0%

Open Targets aggregate 0.56 · 2 independent evidence families

NeoplasmsLimited support
0.48
agreement 0.350.61
Pathway58%Clinical22%Literature20%

Open Targets aggregate 0.54 · 3 independent evidence families

HIV InfectionsPreliminary
0.34
agreement 0.160.51
Pathway97%Literature3%

Open Targets aggregate 0.50 · 2 independent evidence families · no direct causal or clinical evidence

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.

Show all associations
Multiple Myeloma0.62
Myelodysplastic syndrome0.56
Neoplasms0.54
HIV Infections0.50

Drug development

4 compounds recorded · 3 approved · 1 in clinical development

Open Targets' development universe — every compound recorded against the target at any stage, not all approved medicines. Distinct from the 3 drugs that target this protein in Forefront's canonical graph (3 with a mapped approved indication, shown above): these count different sets and are not a subset relation.

View all recorded compounds (4)
IBERDOMIDEPhase 3
THALIDOMIDEApproval
LENALIDOMIDEApproval
POMALIDOMIDEApproval

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 moleculesStrong

Approved Drug and Structure with Ligand support this modality.

Protein degradersEmerging

Feasibility evidence (database ubiquitination and half-life data) — no clinical-stage drug of this modality recorded.

View underlying tractability evidence (5)
SM · Approved DrugSM · Structure with LigandSM · High-Quality PocketPR · Database UbiquitinationPR · Half-life Data

Raw Open Targets tractability assessment buckets, by modality.

Safety-related annotations

neutropeniaClinPGx

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

30

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)

ClinicalTrials.gov via the drug-target graph.

What's happening now

12

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.

  1. Trial status changed2026-07-31

    A Phase 3b, Multicenter, Open-label, Daratumumab Long-term Extension Study

    Status changed to Active, not recruiting · ClinicalTrials.gov · via lenalidomide

  2. Trial status changed2026-07-30

    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

    Status changed to Active, not recruiting · ClinicalTrials.gov · via pomalidomide

  3. Label change2026-07-22

    Label change: LENALIDOMIDE (NDA021880)

    fda · regulatory · fda · via lenalidomide

  4. Trial status changed2026-07-20

    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

    Status changed to Active, not recruiting · ClinicalTrials.gov · via lenalidomide

  5. Label change2026-06-15

    Label change: LENALIDOMIDE (ANDA201452)

    fda · regulatory · fda · via lenalidomide

  6. Supplemental approval2026-04-27

    Supplemental approval: LENALIDOMIDE (ANDA201452)

    fda · regulatory · fda · via lenalidomide

  7. Supplemental approval2026-04-27

    Supplemental approval: LENALIDOMIDE (NDA021880)

    fda · regulatory · fda · via lenalidomide

  8. New publication2022-03-01
    Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection.

    Clinical cancer research : an official journal of the American Association for Cancer Research · 2022 · 38 citations · Europe PMC · via pomalidomide

  9. Safety communication2016-05-10

    Drug Safety Update: Pomalidomide (Imnovid▼): risk of hepatitis B reactivation

    mhra · safety · mhra · via pomalidomide

  10. Safety communication2014-12-11

    Drug Safety Update: Lenalidomide (Revlimid): risk of serious hepatic adverse drug reactions

    mhra · safety · mhra · via lenalidomide

  11. Safety communication2014-12-11

    Drug Safety Update: Lenalidomide (Revlimid▼): update on risk of second primary malignancy

    mhra · safety · mhra · via lenalidomide

  12. Safety communication2014-12-11

    Drug Safety Update: Lenalidomide: risk of thrombosis and thromboembolism

    mhra · safety · mhra · via lenalidomide

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.