E3 ubiquitin-protein ligase RBX1 (RBX1)
The protein contains 108 amino acids for an estimated molecular weight of 12274 Da.
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:15983046, PubMed:16678110, PubMed:19112177, PubMed:19679664, PubMed:23455478, PubMed:27565346, PubMed:29769719, PubMed:11961546, PubMed:22748924). 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. 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. (updated: Nov. 7, 2018)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Cellular response to hypoxia
DNA damage response, detection of DNA damage
DNA repair
Global genome nucleotide-excision repair
Interleukin-1-mediated signaling pathway
MAPK cascade
Negative regulation of canonical Wnt signaling pathway
Negative regulation of G2/M transition of mitotic cell cycle
Notch signaling pathway
Nucleotide-excision repair, DNA damage recognition
Nucleotide-excision repair, DNA duplex unwinding
Nucleotide-excision repair, DNA incision
Nucleotide-excision repair, DNA incision, 3'-to lesion
Nucleotide-excision repair, DNA incision, 5'-to lesion
Nucleotide-excision repair, preincision complex assembly
Nucleotide-excision repair, preincision complex stabilization
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Positive regulation of protein autoubiquitination
Post-translational protein modification
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein monoubiquitination
Protein neddylation
Protein polyubiquitination
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Regulation of transcription from RNA polymerase II promoter in response to hypoxia
SCF complex assembly
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Transcription-coupled nucleotide-excision repair
Ubiquitin-dependent protein catabolic process
Viral process
Wnt signaling pathway
Cellular Component
Cul2-RING ubiquitin ligase complex
Cul3-RING ubiquitin ligase complex
Cul4-RING E3 ubiquitin ligase complex
Cul4A-RING E3 ubiquitin ligase complex
Cul4B-RING E3 ubiquitin ligase complex
Cul5-RING ubiquitin ligase complex
Cul7-RING ubiquitin ligase complex
Cullin-RING ubiquitin ligase complex
Cytosol
Nuclear SCF ubiquitin ligase complex
Nucleoplasm
Nucleus
SCF ubiquitin ligase complex
VCB complex
Molecular Function
Cullin family protein binding
Ligase activity
NEDD8 ligase activity
NEDD8 transferase activity
Protein complex binding
Protein-containing complex binding
Transcription factor binding
Ubiquitin protein ligase activity
Ubiquitin protein ligase binding
Ubiquitin-protein transferase activity
Ubiquitin-ubiquitin ligase activity
Zinc ion binding
The reference OMIM entry for this protein is 603814
Ring-box 1; rbx1
Regulator of cullins 1; roc1
CLONING
The VHL protein (VHL; 608537) is part of a complex that includes elongin B (600787), elongin C (600788), and cullin-2 (CUL2; 603135), proteins associated with transcriptional elongation and ubiquitination. Components of the VCB (VHL-elongin C/elongin B) complex share sequence similarities with the E3 ubiquitin ligase complexes, SCF (SKP1 (601434)-CUL1 (603134)-F-box protein) and APC (anaphase promoting complex, see 603462). F-box proteins, such as S. cerevisiae Cdc4 and Grr1, are adaptor proteins that recruit different binding partners to SCF (Tyers and Willems, 1999). Kamura et al. (1999) purified the endogenous VHL complex from rat liver and determined the partial protein sequence of a 16-kD protein component. By searching an EST database with the peptide sequences, these authors identified human and mouse cDNAs encoding a predicted 108-amino acid protein. They designated the protein RBX1 (RING-box protein-1) because it contained a RING-H2 finger-like motif. The mouse and human RBX1 proteins are identical, and there are RBX1 homologs in Drosophila, C. elegans, and S. cerevisiae. Kamura et al. (1999) demonstrated that RBX1 interacts with both CUL1 and CUL2. They found that yeast Rbx1 is a subunit and a potent activator of the SCF-Cdc4 complex that is required for ubiquitination of the cyclin-dependent kinase inhibitor Sic1 and for the G1-to-S cell cycle transition. Mammalian RBX1 rescued the viability defect in yeast rbx1 mutants. The authors concluded that the presence of RBX1 as a component of both the VHL and SCF-Cdc4 complexes extends the structural similarity between these 2 complexes and raises the possibility that the VHL complex may function as a ubiquitin ligase for target proteins. Skowyra et al. (1999) found that Rbx1 is part of the yeast SCF-Grr1 complex, which ubiquitinates the phosphorylated G1 cyclin cln1. Using mouse cullin-4A (603137) as bait in a yeast 2-hybrid screen of a human HeLa pGAD cDNA library, Ohta et al. (1999) identified 2 highly conserved RING finger proteins, which they referred to as ROC1 and ROC2 (603863), which are homologous to APC11 (ANAPC11; 614534), a subunit of the APC. The ROC1 and ROC2 proteins commonly interact with all cullins. Yeast ROC1 encodes an essential gene whose reduced expression resulted in multiple, elongated buds and accumulation of Sic1 and Cln2 proteins. ROC1 and APC11 immunocomplexes can catalyze isopeptide ligations to form polyubiquitin chains in an E1 (314370)- and E2 (see 602961)-dependent manner. ROC1 mutations completely abolished their ligase activity without noticeable changes in associated proteins. Ubiquitination of phosphorylated I-kappa-B-alpha (164008) can be catalyzed by the ROC1 immunocomplex in vitro. Hence, combinations of ROC/APC11 and cullin proteins potentially constitute a wide variety of ubiquitin ligases.GENE FUNCTION
Tan et al. (1999) showed that ROC1 is recruited by cullin-1 to form a quaternary SCF(HOS)-ROC1 holoenzyme (with SKP1 and the BTRCP (603482) homolog HOS). SCF(HOS)-ROC1 binds IKK-beta (603258)-phosphorylated I-kappa-B-alpha and catalyzes its ubiquitination in the presence of ubiquitin, E1, and CDC34 (116948). ROC1 plays a unique role in the ubiquitination reaction by heterodimerizing with cullin-1 to catalyze ubiquitin polymerization. Wertz et al. (2004) reported that human DET1 (608727) promotes ubiquitination and degradation of the protooncogenic transcription factor c-Jun (165160) by assembling a multisubunit ... More on the omim web site
Nov. 16, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603814 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed