F-box only protein 4 (FBXO4)
The protein contains 387 amino acids for an estimated molecular weight of 44136 Da.
Substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex that mediates the ubiquitination and subsequent proteasomal degradation of target proteins. Promotes ubiquitination of CCND1 and its subsequent proteasomal degradation. Recognizes TERF1 and promotes its ubiquitination together with UBE2D1. (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.
- 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.
- 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
Aging
Cellular homeostasis
Cellular response to ionizing radiation
Common myeloid progenitor cell proliferation
Negative regulation of fibroblast proliferation
Negative regulation of protein localization to nucleus
Positive regulation of protein polyubiquitination
Positive regulation of protein ubiquitination
Positive regulation of telomere maintenance via telomerase
Post-translational protein modification
Posttranscriptional regulation of gene expression
Protein destabilization
Protein polyubiquitination
Protein ubiquitination
Regulation of DNA damage checkpoint
Regulation of protein stability
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Telomere maintenance
Ubiquitin-dependent protein catabolic process
Cellular Component
Cytoplasm
Cytosol
Obsolete cell
SCF ubiquitin ligase complex
Ubiquitin ligase complex
The reference OMIM entry for this protein is 609090
F-box only protein 4; fbxo4
Fbx4
DESCRIPTION
Members of the F-box protein family, such as FBXO4, are characterized by an approximately 40-amino acid F-box motif. SCF complexes, formed by SKP1 (601434), cullin (see CUL1; 603134), and F-box proteins, act as protein-ubiquitin ligases. F-box proteins interact with SKP1 through the F box, and they interact with ubiquitination targets through other protein interaction domains (Jin et al., 2004).CLONING
Using SKP1 as bait in a yeast 2-hybrid screen and by searching DNA databases, Cenciarelli et al. (1999) identified FBXO4, which they designated FBX4. The deduced protein contains an F box in its N-terminal half. Northern blot analysis detected nearly ubiquitous expression of a 4.4-kb FBX4 transcript. Immunofluorescence localization detected epitope-tagged FBX4 in the cytoplasm and nucleus of transfected HeLa cells. By PCR, Winston et al. (1999) found expression of FBX4 in heart, kidney, liver, lung, pancreas, and placenta, but not in brain and skeletal muscle.GENE FUNCTION
By coexpression and immunoprecipitation in HeLa cells, Cenciarelli et al. (1999) demonstrated that FBX4 interacts with CUL1 and SKP1, but not with CUL2 (603135). The FBX4 F box was required for this interaction. FBX4 supported ubiquitin ligase activity in HeLa cells when cotransfected with CUL1 and SKP1.MAPPING
By FISH, Chiaur et al. (2000) mapped the FBXO4 gene to chromosome 5p12. Jin et al. (2004) stated that the mouse Fbxo4 gene maps to chromosome 15A1. ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
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
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 609090 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed