E3 ubiquitin-protein ligase RNF114 (RNF114)
The protein contains 228 amino acids for an estimated molecular weight of 25694 Da.
E3 ubiquitin-protein ligase that promotes the ubiquitination of various substrates (PubMed:23645206, PubMed:25165885). In turn, participates in the regulation of many biological processes including cell cycle, apoptosis, osteoclastogenesis as well as innate or adaptive immunity (PubMed:25165885, PubMed:28708287). Acts as negative regulator of NF-kappa-B-dependent transcription by promoting the ubiquitination and stabilization of the NF-kappa-B inhibitor TNFAIP3 (PubMed:25165885). May promote the ubiquitination of TRAF6 as well (PubMed:28708287). Acts also as a negative regulator of T-cell activation (PubMed:25165885). Inhibits cellular dsRNA responses and interferon production by targeting MAVS component for proteasomal degradation (PubMed:25165885). Ubiquitinates the CDK inhibitor CDKN1A leading to its degradationand probably also CDKN1B and CDKN1C (PubMed:23645206). This activity stimulates cell cycle G1-to-S phase transition and suppresses cellular senescence. May play a role in spermatogenesis. (updated: Oct. 16, 2019)
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.
This protein is annotated as membranous in Gene Ontology.
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The reference OMIM entry for this protein is 612451
Ring finger protein 114; rnf114
Zinc finger protein 313; znf313
CLONING
Capon et al. (2008) identified RNF114, which they called ZNF313, in a region of chromosome 20 associated with psoriasis (see 177900). The deduced 25.7-kD protein belongs to a family of RING domain E3 ubiquitin ligases characterized by 3 zinc fingers and a ubiquitin-interacting motif. Real-time PCR detected high ZNF313 expression in testis and much lower expression in all other tissues examined. ZNF313 was also expressed in skin, CD4 (186940)-positive T cells, and immature and mature dendritic cells.GENE STRUCTURE
Capon et al. (2008) determined that the RNF114 gene contains 6 exons.MAPPING
By genomic sequence analysis, Capon et al. (2008) mapped the RNF114 gene to chromosome 20q13.GENE FUNCTION
Using a protein pull-down assay, Capon et al. (2008) showed that ZNF313 bound ubiquitin via its ubiquitin-interaction motif. Bijlmakers et al. (2011) noted that the RNF114 paralog RNF125 (610432) regulates the RIGI (DDX58; 609631)/MDA5 (IFIH1; 606951) innate antiviral response after double-stranded RNA (dsRNA) activation within the cytoplasm. This signaling cascade induces production of type I IFN (e.g., IFNB1; 147640) through activation of IRF3 (603734) and NFKB (see 164011) transcription factors. Bijlmakers et al. (2011) showed that human RNF114 associated with ubiquitinated proteins and that it was a soluble protein induced by IFNs and synthetic dsRNA. Overexpression of RNF114 enhanced NFKB and IRF3 reporter activity and increased type I and type III (IL29; 607403) IFN mRNA levels. Bijlmakers et al. (2011) concluded that RNF114 regulates a positive-feedback loop that enhances dsRNA-induced type I IFN production and that dysregulation of RIGI/MDA5 signaling leads to overproduction of type I IFN, an early mediator of epithelial inflammation.MOLECULAR GENETICS
For discussion of a possible association between variation in the RNF114 gene and psoriasis, see PSORS12 (612950). Onoufriadis et al. (2012) analyzed the RNF114 gene in 485 psoriasis patients and 842 controls and identified 4 disease-associated variants in the RNF114 promoter, each of which was present in a single patient. electrophoretic mobility shift analysis showed that 2 of the variants, -41C-T and -64C-A, were associated with reduced SP1 (189906)-binding activity and reduced RNF114 gene expression. ... More on the omim web site
Oct. 27, 2019: 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 612451 was added.