E3 ubiquitin-protein ligase RNF126 (RNF126)
The protein contains 326 amino acids for an estimated molecular weight of 35585 Da.
E3 ubiquitin-protein ligase that mediates ubiquitination oF target proteins (PubMed:23277564, PubMed:24275455, PubMed:24981174). Depending on the associated E2 ligase, mediates 'Lys-48'- and 'Lys-63'-linked polyubiquitination of substrates (By similarity). Part of a BAG6-dependent quality control process ensuring that proteins of the secretory pathway that are mislocalized to the cytosol are degraded by the proteasome. Probably acts by providing the ubiquitin ligase activity associated with the BAG6 complex and be responsible for ubiquitination of the hydrophobic mislocalized proteins and their targeting to the proteasome (PubMed:24981174, PubMed:29042515). May also play a role in the endosomal recycling of IGF2R, the cation-independent mannose-6-phosphate receptor (PubMed:24275455). May play a role in the endosomal sorting and degradation of several membrane receptors including EGFR, FLT3, MET and CXCR4, by mediating their ubiquitination (PubMed:23418353). By ubiquitinating CDKN1A/p21 and targeting it for degradation, may also promote cell proliferation (PubMed:23026136). May monoubiquitinate AICDA (PubMed:23277564). (updated: June 20, 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.
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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| Variant | Description |
|---|---|
| dbSNP:rs2285751 |
Biological Process
Cytoplasm protein quality control by the ubiquitin-proteasome system
Negative regulation of epidermal growth factor receptor signaling pathway
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein K63-linked ubiquitination
Protein monoubiquitination
Protein polyubiquitination
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Regulation of cell population proliferation
Retrograde transport, endosome to Golgi
Ubiquitin-dependent protein catabolic process
Ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway
The reference OMIM entry for this protein is 615177
Ring finger protein 126; rnf126
DESCRIPTION
RNF126 is an E3 ubiquitin ligase that ubiquitinates proteins and thereby targets them for proteasome-mediated degradation (Zhi et al., 2012).CLONING
Using a small interfering RNA library to screen for E3 ubiquitin ligases that, upon knockdown, reduced the viability of MDA-MB-231 breast cancer and PC3 prostate cancer cell lines, Zhi et al. (2012) identified RNF126. The deduced 311-amino acid protein has an N-terminal zinc finger domain and a C-terminal RING finger domain. Analysis of 48 human tissues showed that RNF126 mRNA was highly expressed in liver and testis. Epitope-tagged RNF126 localized to both the cytoplasm and nucleus of transfected PC3 cells and TSU-Pr1 bladder cancer cells.GENE FUNCTION
Zhi et al. (2012) found that RNF126 was highly expressed in a subset of breast cancer cell lines and that its upregulation negatively correlated with expression of the cell cycle regulator p21 (CDKN1A; 116899). Knockdown of RNF126 reduced viability in several human cancer cell lines, increased p21 protein stability, caused G1 cell cycle arrest, and reduced tumorigenicity following injection in nude mice. Protein interaction assays revealed that the N-terminal and middle domains of RNF126, but not the C-terminal RING domain, interacted directly with p21 in a p53 (TP53 191170)-independent manner. RNF126 ubiquitinated p21 in vitro in the presence of E1 (see 314370), UBCH5B (602962), ATP, and ubiquitin (191339). RNF126 was heavily ubiquitinated in cells and was subject to autoubiquitination in vitro; however, RNF126 had a long half-life, and ubiquitination did not appear to cause its instability.MAPPING
Hartz (2013) mapped the RNF126 gene to chromosome 19p13.3 based on an alignment of the RNF126 sequence (GenBank GENBANK AK000559) with the genomic sequence (GRCh37). ... More on the omim web site
July 2, 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 615177 was added.