E3 ubiquitin-protein ligase RBX1
Also known as: RBX1, RNF75, ROC1
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. CRLs complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins, ARIH1 mediating addition of the first ubiquitin on CRLs targets. 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. Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Core component of a Cul9-RING ubiquitin ligase complex composed of CUL9 and RBX1, which mediates mono-ubiquitination of p53/TP53. 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.
Classification
- Family (Pfam)
- PF12678 zf-rbx1
- InterPro
- RING-box_E3_Ubiquitin_Ligase, Znf_RING, Znf_RING/FYVE/PHD, Znf_RING_H2
- Functional cluster
- Mixed Regulatory & Membrane Proteins
Experimental structures · PDB · 81
- 1LDJ X-ray 3.00A
- 1LDK X-ray 3.10A
- 1U6G X-ray 3.10A
- 2HYE X-ray 3.10A
- 2LGV NMR
- 3DPL X-ray 2.60A
- 3DQV X-ray 3.00A
- 3RTR X-ray 3.21A
- 4F52 X-ray 3.00A
- 4P5O X-ray 3.11A
- 5N4W X-ray 3.90A
- 6R6H EM 8.40A
- … and 69 more
A predicted model is available from AlphaFold.
Gene Ontology · 100
- GO:0005813 centrosome
- GO:0031462 Cul2-RING ubiquitin ligase complex
- GO:0031463 Cul3-RING ubiquitin ligase complex
- GO:0080008 Cul4-RING E3 ubiquitin ligase complex
- GO:0031464 Cul4A-RING E3 ubiquitin ligase complex
- GO:0031465 Cul4B-RING E3 ubiquitin ligase complex
- GO:0031466 Cul5-RING ubiquitin ligase complex
- GO:0031467 Cul7-RING ubiquitin ligase complex
- GO:0031461 cullin-RING ubiquitin ligase complex
- GO:0005737 cytoplasm
- GO:0005829 cytosol
- GO:0005794 Golgi apparatus
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:0019005 SCF ubiquitin ligase complex
- GO:0090734 site of DNA damage
- GO:0030891 VCB complex
- GO:0097602 cullin family protein binding
- GO:0060090 molecular adaptor activity
- GO:0061663 NEDD8 ligase activity
- GO:0019788 NEDD8 transferase activity
- GO:0044877 protein-containing complex binding
- GO:0061629 RNA polymerase II-specific DNA-binding transcription factor binding
- GO:0061630 ubiquitin protein ligase activity
- GO:0031625 ubiquitin protein ligase binding
- GO:0004842 ubiquitin-protein transferase activity
- GO:0034450 ubiquitin-ubiquitin ligase activity
- GO:0008270 zinc ion binding
- GO:0008283 cell population proliferation
- GO:0071230 cellular response to amino acid stimulus
- GO:0062197 cellular response to chemical stress
- GO:0034599 cellular response to oxidative stress
- GO:0034644 cellular response to UV
- GO:0051298 centrosome duplication
- GO:0060271 cilium assembly
- GO:0006974 DNA damage response
- GO:0040029 epigenetic regulation of gene expression
- GO:0000082 G1/S transition of mitotic cell cycle
- GO:0006879 intracellular iron ion homeostasis
- GO:0060173 limb development
- GO:0000165 MAPK cascade
- GO:1904178 negative regulation of adipose tissue development
- GO:0160276 negative regulation of beige fat cell differentiation
- GO:0043124 negative regulation of canonical NF-kappaB signal transduction
- GO:0090090 negative regulation of canonical Wnt signaling pathway
- GO:2000104 negative regulation of DNA-templated DNA replication
- GO:0046627 negative regulation of insulin receptor signaling pathway
- GO:1901525 negative regulation of mitophagy
- GO:1902883 negative regulation of response to oxidative stress
- GO:0000122 negative regulation of transcription by RNA polymerase II
- GO:0032480 negative regulation of type I interferon production
- GO:0014033 neural crest cell differentiation
- GO:0006289 nucleotide-excision repair
- GO:0043123 positive regulation of canonical NF-kappaB signal transduction
- GO:0032436 positive regulation of proteasomal ubiquitin-dependent protein catabolic process
- GO:1902499 positive regulation of protein autoubiquitination
- GO:0045732 positive regulation of protein catabolic process
- GO:1904263 positive regulation of TORC1 signaling
- GO:0043687 post-translational protein modification
- GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process
- GO:0044314 protein K27-linked ubiquitination
- GO:0070936 protein K48-linked ubiquitination
- GO:0006513 protein monoubiquitination
- GO:0045116 protein neddylation
- GO:0000209 protein polyubiquitination
- GO:0016567 protein ubiquitination
- GO:0042981 regulation of apoptotic process
- GO:0010506 regulation of autophagy
- GO:0030510 regulation of BMP signaling pathway
- GO:0051726 regulation of cell cycle
- GO:1901987 regulation of cell cycle phase transition
- GO:0010564 regulation of cell cycle process
- GO:0042127 regulation of cell population proliferation
- GO:1900076 regulation of cellular response to insulin stimulus
- GO:0080135 regulation of cellular response to stress
- GO:0010824 regulation of centrosome duplication
- GO:0042752 regulation of circadian rhythm
- GO:2000001 regulation of DNA damage checkpoint
- GO:0030174 regulation of DNA-templated DNA replication initiation
- GO:0006355 regulation of DNA-templated transcription
- GO:0045995 regulation of embryonic development
- GO:0050727 regulation of inflammatory response
- GO:0060964 regulation of miRNA-mediated gene silencing
- GO:1901524 regulation of mitophagy
- GO:0007346 regulation of mitotic cell cycle
- GO:1902412 regulation of mitotic cytokinesis
- GO:0032814 regulation of natural killer cell activation
- GO:2000036 regulation of stem cell population maintenance
- GO:0032006 regulation of TOR signaling
- GO:1904415 regulation of xenophagy
- GO:0031297 replication fork processing
- GO:1990116 ribosome-associated ubiquitin-dependent protein catabolic process
- GO:0160240 RNA polymerase II transcription initiation surveillance
- GO:0031146 SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
- GO:0042770 signal transduction in response to DNA damage
- GO:0007283 spermatogenesis
- GO:0042110 T cell activation
- GO:0006283 transcription-coupled nucleotide-excision repair
- GO:0006511 ubiquitin-dependent protein catabolic process
- GO:0140627 ubiquitin-dependent protein catabolic process via the C-end degron rule pathway
Drugs targeting this protein · 5
- IBERDOMIDE modulator
- POMALIDOMIDE inhibitor
- THALIDOMIDE inhibitor
- LENALIDOMIDE HYDROCHLORIDE MONOHYDRATE modulator
- LENALIDOMIDE inhibitor
Related proteins · sequence + function similarity
- E3 ubiquitin-protein ligase RBX1 1.00
- E3 ubiquitin-protein ligase RBX1 1.00
- RING-box protein 1A 0.97
- RING-box protein 1a 0.94
- RING-box protein 1 0.89
- RING-box protein 1b 0.83
- RING-box protein 1 0.82
- E3 ubiquitin-protein ligase rbx1 0.75
- Eukaryotic translation initiation factor 1A, X-chromosomal 0.67
- Eukaryotic translation initiation factor 1A 0.67
- Eukaryotic translation initiation factor 1A, X-chromosomal 0.67
- Eukaryotic translation initiation factor 1A, X-chromosomal 0.67
Co-cited proteins · studied together in the literature
- E3 ubiquitin-protein ligase RBX1 3 shared papers
- RING-box protein HRT1 3 shared papers
- Armadillo repeat-containing protein 5 4 shared papers
- Cullin-1 15 shared papers
- Cullin-3 15 shared papers
- Ubiquitin-conjugating enzyme E2 R1 1 shared papers
- Kelch repeat and BTB domain-containing protein 4 1 shared papers
- Armadillo repeat-containing protein 5 2 shared papers
- Elongin-C 1 shared papers
- S-phase kinase-associated protein 1 6 shared papers
- DNA excision repair protein ERCC-8 5 shared papers
- Cullin-2 9 shared papers
Literature · 58 cited papers
- C-terminal amides mark proteins for degradation via SCF-FBXO31. Nature · 2025
- CRL3ARMC5 ubiquitin ligase and Integrator phosphatase form parallel mechanisms to control early stages of RNA Pol II transcription. Mol. Cell · 2024
- Redundant pathways for removal of defective RNA polymerase II complexes at a promoter-proximal pause checkpoint. Mol. Cell · 2024
- Noncanonical assembly, neddylation and chimeric cullin-RING/RBR ubiquitylation by the 1.8 MDa CUL9 E3 ligase complex. Nat. Struct. Mol. Biol. · 2024
- Mechanism of millisecond Lys48-linked poly-ubiquitin chain formation by cullin-RING ligases. Nat. Struct. Mol. Biol. · 2024
- Structural basis for RNA polymerase II ubiquitylation and inactivation in transcription-coupled repair. Nat. Struct. Mol. Biol. · 2024
- ARMC5 controls the degradation of most Pol II subunits, and ARMC5 mutation increases neural tube defect risks in mice and humans. Genome Biol. · 2024
- Molecular basis for C-degron recognition by CRL2APPBP2 ubiquitin ligase. Proc. Natl. Acad. Sci. U.S.A. · 2023
- Structure of CRL7FBXW8 reveals coupling with CUL1-RBX1/ROC1 for multi-cullin-RING E3-catalyzed ubiquitin ligation. Nat. Struct. Mol. Biol. · 2022
- ARMC5 is part of an RPB1-specific ubiquitin ligase implicated in adrenal hyperplasia. Nucleic Acids Res. · 2022
- A conserved mechanism for regulating replisome disassembly in eukaryotes. Nature · 2021
- Structural basis of human transcription-DNA repair coupling. Nature · 2021
- … and 46 more in the literature graph