Cullin-5 (CUL5)
The protein contains 780 amino acids for an estimated molecular weight of 90955 Da.
Core component of multiple SCF-like ECS (Elongin-Cullin 2/5-SOCS-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination and subsequent proteasomal degradation of target proteins. As a scaffold protein may contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The functional specificity of the E3 ubiquitin-protein ligase complex depends on the variable substrate recognition component. ECS(SOCS1) seems to direct ubiquitination of JAK2. Seems to be involved in proteosomal degradation of p53/TP53 stimulated by adenovirus E1B-55 kDa protein. May form a cell surface vasopressin receptor. (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.
- 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.
- 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.
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Biological Process
Calcium ion transmembrane transport
Cell cycle arrest
Cell population proliferation
Cellular response to DNA damage stimulus
ERBB2 signaling pathway
G1/S transition of mitotic cell cycle
Intrinsic apoptotic signaling pathway
Negative regulation of cell population proliferation
Post-translational protein modification
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Regulation of cytosolic calcium ion concentration
Response to osmotic stress
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Ubiquitin-dependent protein catabolic process
Viral process
The reference OMIM entry for this protein is 601741
Cullin 5; cul5
Vasopressin-activated calcium-mobilizing receptor 1; vacm1
CLONING
Arginine vasopressin (AVP)-activated calcium-mobilizing receptor-1 (VACM1) is a cell surface protein involved in intracellular signal transduction. The gene encoding rabbit Vacm1 was isolated by Burnatowska-Hledin et al. (1995) from a renal medullary cDNA library by expression cloning in Xenopus laevis oocytes. While searching for expressed genes in the ataxia-telangiectasia (208900) gene (ATM; 607585) region on chromosome 11q22-q23, Byrd et al. (1997) identified the gene encoding the human homolog of rabbit Vacm1 and determined the complete amino acid sequence for the protein. The 780-amino acid predicted polypeptide differs from the rabbit sequence by only 7 residues. Northern hybridization analysis showed expression in a wide range of human tissues. Byrd et al. (1997) noted that the human VACM1 gene shares homology with the C. elegans gene Cul5, a member of the family of cullin genes that are involved in cell cycle regulation.GENE STRUCTURE
An et al. (2007) determined that the CUL5 gene contains 19 exons and spans about 100 kb.MAPPING
Byrd et al. (1997) mapped the CUL5 gene to chromosome 11q22-q23.MOLECULAR GENETICS
Since human immunodeficiency virus (HIV)-1 viral infectivity factor (Vif) interacts with CUL5 to mediate degradation of the anti-HIV-1 enzyme APOBEC3G (607113), An et al. (2007) investigated whether genetic variation in CUL5 affects the course of HIV-1 infection. SNP analysis showed that CUL5 genetic variation did not affect susceptibility to HIV-1 infection. Some CUL5 haplotypes were associated with a rapid loss of CD4 (186940)-positive T cells and increased viral loads after infection, whereas other CUL5 haplotypes showed a delayed CD4-positive T-cell depletion. Gel-shift analysis suggested that there may be differential nuclear protein binding efficiencies between the CUL5 haplotypes. An et al. (2007) proposed that inhibitors that block interaction between HIV-1 Vif and CUL5 may have potential as an anti-HIV-1 therapeutic strategy. ... 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 16, 2016: Protein entry updated
Automatic update: OMIM entry 601741 was added.
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed