P62877 · RBX1_HUMAN
- ProteinE3 ubiquitin-protein ligase RBX1
- GeneRBX1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids108 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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:33417871).
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 promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:35982156).
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).
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 promotes the ubiquitination of ERCC6 resulting in proteasomal degradation. Core component of the Cul7-RING(FBXW8) ubiquitin ligase complex, which mediates the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:35982156).
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).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 42 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 45 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 53 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 56 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 68 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 75 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 77 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 80 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 82 | Zn2+ 2 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 83 | Zn2+ 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 94 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 97 | Zn2+ 3 (UniProtKB | ChEBI) | ||||
Sequence: D |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameE3 ubiquitin-protein ligase RBX1
- EC number
- Alternative names
- Cleaved into 1 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP62877
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 53 | Strong reduction in ligase activity; when associated with A-56. | ||||
Sequence: C → A | ||||||
Mutagenesis | 56 | Strong reduction in ligase activity; when associated with A-53. | ||||
Sequence: C → A | ||||||
Mutagenesis | 75 | Strong reduction in ligase activity; when associated with A-77. | ||||
Sequence: C → A | ||||||
Mutagenesis | 77 | Strong reduction in ligase activity; when associated with A-75. | ||||
Sequence: H → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 49 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed; alternate | ||||
Sequence: M | |||||||
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000423264 | 1-108 | UniProt | E3 ubiquitin-protein ligase RBX1 | |||
Sequence: MAAAMDVDTPSGTNSGAGKKRFEVKKWNAVALWAWDIVVDNCAICRNHIMDLCIECQANQASATSEECTVAWGVCNHAFHFHCISRWLKTRQVCPLDNREWEFQKYGH | |||||||
Modified residue | 2 | UniProt | N-acetylalanine; in E3 ubiquitin-protein ligase RBX1, N-terminally processed | ||||
Sequence: A | |||||||
Chain | PRO_0000056013 | 2-108 | UniProt | E3 ubiquitin-protein ligase RBX1, N-terminally processed | |||
Sequence: AAAMDVDTPSGTNSGAGKKRFEVKKWNAVALWAWDIVVDNCAICRNHIMDLCIECQANQASATSEECTVAWGVCNHAFHFHCISRWLKTRQVCPLDNREWEFQKYGH | |||||||
Modified residue | 9 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 9 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 13 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
Part of a SCF complex consisting of CUL1, RBX1, SKP1 and SKP2 (PubMed:10230406, PubMed:11961546).
Part of CBC(VHL) complexes with elongin BC complex (ELOB and ELOC), CUL2 or CUL5 and VHL (PubMed:10213691).
Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II (PubMed:12732143).
Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1 (PubMed:11384984, PubMed:12149480).
Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), SOCS1 or WSB1 and CUL5. Part of a multisubunit ubiquitin ligase complex consisting of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5 (PubMed:19920177).
Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7 (PubMed:10230407, PubMed:12481031).
Interacts with CDC34 (PubMed:22748924).
Interacts with GLMN. GLMN competes for the binding site of the E2 ubiquitin-conjugating enzyme CDC34 and disrupts CDC34 binding (PubMed:22748924).
Interacts with COPS6 (PubMed:11337588).
Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1 (PubMed:14739464).
Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B (PubMed:16678110).
Interacts with UBE2M (PubMed:19250909).
Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3 (PubMed:18809579).
Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF (PubMed:20596027).
Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34 (PubMed:19112177).
Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein (PubMed:15983046).
Part of the BCR(ENC1) complex containing ENC1 (PubMed:15983046).
Part of the BCR(GAN) complex containing GAN (PubMed:15983046).
Part of the BCR(KLHL41) complex containing KLHL41 (PubMed:15983046).
Part of the BCR(KEAP1) complex containing KEAP1 (PubMed:15983046).
Interacts with SESN1 and SESN2 (PubMed:23274085).
Interacts with NOTCH2 (PubMed:29149593).
Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (PubMed:23455478).
Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5 (PubMed:24192928, PubMed:25349211, PubMed:26906416).
Component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7 (PubMed:25684205).
Component of the ECS(LRR1) complex with the substrate recognition component LRR1 (PubMed:34700328).
Component of the BCR(KBTBD4) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD4 and RBX1 (PubMed:33417871).
Component of the Cul7-RING(FBXW8) complex consisting of CUL7, RBX1, SKP1 and FBXW8; within the complex interacts with CUL7 (PubMed:12481031, PubMed:35982156).
Part of CBC(VHL) complexes with elongin BC complex (ELOB and ELOC), CUL2 or CUL5 and VHL (PubMed:10213691).
Part of the CSA complex (DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II (PubMed:12732143).
Part of multisubunit E3 ubiquitin ligase complexes with elongin BC complex (ELOB and ELOC), CUL2 and MED8; elongin BC complex (ELOB and ELOC), CUL5 and MUF1 (PubMed:11384984, PubMed:12149480).
Part of multisubunit complexes with elongin BC complex (ELOB and ELOC), SOCS1 or WSB1 and CUL5. Part of a multisubunit ubiquitin ligase complex consisting of elongin BC complex (ELOB and ELOC), elongin A/ELOA, RBX1 and CUL5 (PubMed:19920177).
Interacts directly with CUL1 and probably also with CUL2, CUL3, CUL4A, CUL4B, CUL5 and CUL7 (PubMed:10230407, PubMed:12481031).
Interacts with CDC34 (PubMed:22748924).
Interacts with GLMN. GLMN competes for the binding site of the E2 ubiquitin-conjugating enzyme CDC34 and disrupts CDC34 binding (PubMed:22748924).
Interacts with COPS6 (PubMed:11337588).
Component of the DCX DET1-COP1 ubiquitin ligase complex at least composed of RBX1, DET1, DDB1, CUL4A and COP1 (PubMed:14739464).
Part of an E3 ligase complex composed of RBX1, DDB1, DDB2 and CUL4A or CUL4B (PubMed:16678110).
Interacts with UBE2M (PubMed:19250909).
Part of a SCF complex consisting of CUL1, FBXO3, RBX1 and SKP1; this complex interacts with PML via FBXO3 (PubMed:18809579).
Component of the SCF(Cyclin F) complex consisting of CUL1, RBX1, SKP1 and CCNF (PubMed:20596027).
Identified in a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin ligase complex together with HINT1 and CDC34 (PubMed:19112177).
Component of multiple BCR (BTB-CUL3-RBX1) E3 ubiquitin-protein ligase complexes formed of CUL3, RBX1 and a variable BTB domain-containing protein (PubMed:15983046).
Part of the BCR(ENC1) complex containing ENC1 (PubMed:15983046).
Part of the BCR(GAN) complex containing GAN (PubMed:15983046).
Part of the BCR(KLHL41) complex containing KLHL41 (PubMed:15983046).
Part of the BCR(KEAP1) complex containing KEAP1 (PubMed:15983046).
Interacts with SESN1 and SESN2 (PubMed:23274085).
Interacts with NOTCH2 (PubMed:29149593).
Component of the BCR(KLHL22) E3 ubiquitin ligase complex, at least composed of CUL3, KLHL22 and RBX1 (PubMed:23455478).
Interacts with DCUN1D1, DCUN1D2, DCUN1D3, DCUN1D4 and DCUN1D5 (PubMed:24192928, PubMed:25349211, PubMed:26906416).
Component of a BCR3 (BTB-CUL3-RBX1) E3 ubiquitin ligase complex, also named Cul3-RING ubiquitin ligase complex CUL3(KBTBD6/7), composed of CUL3, RBX1, KBTBD6 and KBTBD7 (PubMed:25684205).
Component of the ECS(LRR1) complex with the substrate recognition component LRR1 (PubMed:34700328).
Component of the BCR(KBTBD4) E3 ubiquitin ligase complex, at least composed of CUL3, KBTBD4 and RBX1 (PubMed:33417871).
Component of the Cul7-RING(FBXW8) complex consisting of CUL7, RBX1, SKP1 and FBXW8; within the complex interacts with CUL7 (PubMed:12481031, PubMed:35982156).
(Microbial infection) Interacts with human adenovirus 5 protein E1A; this interaction inhibits RBX1-CUL1-dependent elongation reaction of ubiquitin chains by the SCF(FBW7) complex.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P62877 | CUL1 Q13616 | 31 | EBI-398523, EBI-359390 | |
BINARY | P62877 | CUL2 Q13617 | 9 | EBI-398523, EBI-456179 | |
BINARY | P62877 | CUL3 Q13618 | 5 | EBI-398523, EBI-456129 | |
BINARY | P62877 | CUL4B Q13620 | 8 | EBI-398523, EBI-456067 | |
BINARY | P62877 | CUL5 Q93034 | 3 | EBI-398523, EBI-1057139 | |
BINARY | P62877 | GLMN Q92990 | 7 | EBI-398523, EBI-726150 | |
BINARY | P62877 | KRTAP12-2 P59991 | 3 | EBI-398523, EBI-10176379 | |
BINARY | P62877 | PBX4 Q9BYU1 | 3 | EBI-398523, EBI-10302990 | |
BINARY | P62877 | SESN2 P58004 | 3 | EBI-398523, EBI-3939642 | |
BINARY | P62877 | SKP2 Q13309 | 4 | EBI-398523, EBI-456291 | |
BINARY | P62877 | UBE2M P61081 | 7 | EBI-398523, EBI-1041660 |
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for zinc finger.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Zinc finger | 53-98 | RING-type | ||||
Sequence: CIECQANQASATSEECTVAWGVCNHAFHFHCISRWLKTRQVCPLDN |
Domain
The RING-type zinc finger domain is essential for ubiquitin ligase activity (PubMed:10230407).
It coordinates an additional third zinc ion (PubMed:11961546, PubMed:22748924).
It coordinates an additional third zinc ion (PubMed:11961546, PubMed:22748924).
Sequence similarities
Belongs to the RING-box family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length108
- Mass (Da)12,274
- Last updated2004-08-16 v1
- Checksum30FC5ADF66096C0E
Sequence caution
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 18 | in Ref. 9; AAM21718 | ||||
Sequence: G → S |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF142059 EMBL· GenBank· DDBJ | AAD30146.1 EMBL· GenBank· DDBJ | mRNA | ||
AF140598 EMBL· GenBank· DDBJ | AAD29715.1 EMBL· GenBank· DDBJ | mRNA | ||
CR456560 EMBL· GenBank· DDBJ | CAG30446.1 EMBL· GenBank· DDBJ | mRNA | ||
AK315722 EMBL· GenBank· DDBJ | BAG38078.1 EMBL· GenBank· DDBJ | mRNA | ||
AL080242 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471095 EMBL· GenBank· DDBJ | EAW60403.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001466 EMBL· GenBank· DDBJ | AAH01466.1 EMBL· GenBank· DDBJ | mRNA | ||
BC017370 EMBL· GenBank· DDBJ | AAH17370.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
AY099360 EMBL· GenBank· DDBJ | AAM21718.1 EMBL· GenBank· DDBJ | mRNA |