E3 ubiquitin-protein ligase rififylin (RFFL)
The protein contains 363 amino acids for an estimated molecular weight of 40514 Da.
E3 ubiquitin-protein ligase that regulates several biological processes through the ubiquitin-mediated proteasomal degradation of various target proteins. Mediates 'Lys-48'-linked polyubiquitination of PRR5L and its subsequent proteasomal degradation thereby indirectly regulating cell migration through the mTORC2 complex. Ubiquitinates the caspases CASP8 and CASP10, promoting their proteasomal degradation, to negatively regulate cell death downstream of death domain receptors in the extrinsic pathway of apoptosis. Negatively regulates the tumor necrosis factor-mediated signaling pathway through targeting of RIPK1 to ubiquitin-mediated proteasomal degradation. Negatively regulates p53/TP53 through its direct ubiquitination and targeting to proteasomal degradation. Indirectly, may also negatively regulate p53/TP53 through ubiquitination and degradation of SFN. May also play a role in endocytic recycling. (updated: March 4, 2015)
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.
- 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.
- 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.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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, is annotated as membranous in UniProt.
(right-click above to access to more options from the contextual menu)
Biological Process
Apoptotic process
Intracellular protein transport
Negative regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis
Negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
Negative regulation of signal transduction by p53 class mediator
Negative regulation of tumor necrosis factor-mediated signaling pathway
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Regulation of fibroblast migration
Regulation of signal transduction by p53 class mediator
Regulation of TOR signaling
Ubiquitin-dependent protein catabolic process
The reference OMIM entry for this protein is 609735
Ring finger and fyve-like domain containing 1; rffl
Rififylin
CLONING
By EST database searching, Coumailleau et al. (2004) identified and subsequently cloned rififylin (RING finger and FYVE-like domain-containing) from mouse testis cDNA. The mouse Rffl cDNA encodes 2 proteins of 336 and 364 amino acids, generated by alternative splicing. The N-terminal region contains a domain related to the FYVE double zinc finger domain that mediates binding to phosphatidylinositol 3-phosphate (PIK3; see 171834), and the C-terminal region contains a consensus sequence for a C3HC4 RING finger domain. Northern blot analysis revealed a ubiquitously expressed transcript of approximately 4 kb and a smaller transcript of about 2 kb at a very high level in testis and at a moderate level in liver. RT-PCR indicated that both proteins are ubiquitously expressed, with the larger isoform almost exclusively expressed in adult mouse liver and kidney cells and in HeLa cells.GENE FUNCTION
Coumailleau et al. (2004) found that Rffl-GFP localized to globular structures at the perinuclear region. Coexpression of Rffl-GFP with various endosomal markers demonstrated that the Rffl-positive structures belonged to the endocytic recycling compartment (ERC). Morphologic analysis of HeLa cells overexpressing Rffl revealed an aggregation of perinuclear transferrin receptor-positive tubules. Pulse-chase experiments showed that overexpression of Rffl significantly slowed recycling from the ERC to the plasma membrane. Deletion mutant experiments demonstrated that the Rffl N-terminal FYVE domain is necessary and sufficient for targeting Rffl to the ERC and for inhibiting transferrin recycling. In contrast, the C-terminal zinc finger domain is dispensable for the effect mediated by Rffl overexpression on recycling endosomes. Using inhibitors of phosphatidylinositol 3-kinases, Coumailleau et al. (2004) found that Rffl acts mainly on a PIK3-independent pathway.MAPPING
The International Radiation Hybrid Mapping Consortium mapped the RFFL gene to chromosome 17 (TMAP WI-15077). Coumailleau et al. (2004) identified the mouse Rffl gene on chromosome 11. ... More on the omim web site
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 25, 2017: Additional information
No protein expression data in P. Mayeux work for RFFL
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609735 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed