Cullin-1 (CUL1)
The protein contains 776 amino acids for an estimated molecular weight of 89679 Da.
Core component of multiple cullin-RING-based SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes, which mediate the ubiquitination of proteins involved in cell cycle progression, signal transduction and transcription. SCF complexes and ARIH1 collaborate in tandem to mediate ubiquitination of target proteins (PubMed:27565346). In the SCF complex, serves as a rigid scaffold that organizes the SKP1-F-box protein and RBX1 subunits. May contribute to catalysis through positioning of the substrate and the ubiquitin-conjugating enzyme. The E3 ubiquitin-protein ligase activity of the complex is dependent on the neddylation of the cullin subunit and exchange of the substrate recognition component is mediated by TIP120A/CAND1. The functional specificity of the SCF complex depends on the F-box protein as substrate recognition component. SCF(BTRC) and SCF(FBXW11) direct ubiquitination of CTNNB1 and participate in Wnt signaling. SCF(FBXW11) directs ubiquitination of phosphorylated NFKBIA. SCF(BTRC) directs ubiquitination of NFKBIB, NFKBIE, ATF4, SMAD3, SMAD4, CDC25A, FBXO5 and probably NFKB2. SCF(BTRC) and/or SCF(FBXW11) direct ubiquitination of CEP68 (PubMed:25704143, PubMed:25503564). SCF(SKP2) directs ubiquitination of phosphorylated CDKN1B/p27kip and is involved in regulation of G1/S transition. SCF(SKP2) directs ubiquitination of ORC1, CDT1, RBL2, ELF4, CDKN1A, RAG2, FOXO1A, and probably MYC and TAL1. SCF(FBXW7) directs ubiquitination of CCNE1, NOTCH1 released notch (updated: Nov. 7, 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.
- 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
Anaphase-promoting complex-dependent catabolic process
Animal organ morphogenesis
Cell cycle arrest
Cell population proliferation
Cellular iron ion homeostasis
Circadian rhythm
Fc-epsilon receptor signaling pathway
G1/S transition of mitotic cell cycle
G2/M transition of mitotic cell cycle
Interleukin-1-mediated signaling pathway
Intrinsic apoptotic signaling pathway
Mitotic cell cycle
Negative regulation of cell population proliferation
Negative regulation of G2/M transition of mitotic cell cycle
NIK/NF-kappaB signaling
Notch signaling pathway
Obsolete positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition
Obsolete regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle
Post-translational protein modification
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein monoubiquitination
Protein polyubiquitination
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Regulation of mitotic cell cycle phase transition
SCF complex assembly
SCF-dependent proteasomal ubiquitin-dependent protein catabolic process
Stimulatory C-type lectin receptor signaling pathway
Stress-activated MAPK cascade
T cell receptor signaling pathway
Ubiquitin-dependent protein catabolic process
Viral process
Wnt signaling pathway
The reference OMIM entry for this protein is 603134
Cullin 1; cul1
CLONING
Kipreos et al. (1996) found that mutations in the cullin-1 (cul1) gene of C. elegans cause hyperplasia of all tissues. They determined that cul1 is a negative regulator of the cell cycle; in cul1 mutants, the G1-to-S-phase progression is accelerated, overriding mechanisms for mitotic arrest and producing abnormally small cells. Searches of EST databases revealed that cul1 is a member of a conserved gene family, with at least 5 members in nematodes, 6 in humans, and 3 in S. cerevisiae. Human CUL1 is an ortholog of nematode cul1.GENE FUNCTION
Michel and Xiong (1998) stated that CUL1 has homology to yeast Cdc53, which is part of a complex known as SCF that mediates the ubiquitin-dependent degradation of G1 cycles and cyclin-dependent kinase inhibitors. SCF complexes are composed of SKP1 (601434), Cdc53, and an F box-containing protein, which may confer substrate specificity. These authors found that interaction of the predicted 776-amino acid human CUL1 protein with SKP1 is mediated through the N-terminal domains of both proteins. Immunoprecipitation studies and Western blot analysis revealed that the steady-state levels of both CUL1 and SKP1, as well as their association with one another, remain relatively constant throughout the cell cycle and in postmitotic cells. However, none of the other human cullins tested interacted with SKP1. Michel and Xiong (1998) determined that via SKP1, CUL1 forms a complex with SKP2 (601436), an F box-containing protein, and cyclin A (123835). The authors concluded that the SCF proteolytic pathway is evolutionarily conserved and is used by mammalian CUL1, while the other cullin proteins may use a SKP1/F-box-independent pathway to mediate protein degradation. Maniatis (1999) reviewed the work of Winston et al. (1999) and others concerning the SCF ubiquitin ligase complex. CUL1 acts as a scaffold for SKP1 and the F-box-containing BTRC protein (603482) in the SCF complex, which regulates the function of nuclear factor kappa-B (see 164011) and beta-catenin (see 116806). Yu et al. (1998) reported studies suggesting that the p19 (SKP1)/p45 (SKP2)/CUL1 complex is likely to function as a conserved ubiquitin E3 enzyme that regulates the mammalian G1/S transition by specifically targeting mammalian G1 cell cycle regulators, such as p21 and cyclin D proteins, for ubiquitin-dependent degradation. The sequential timing of cell cycle transitions is primarily governed by the availability and activity of key cell cycle proteins. Studies in yeast identified a class of ubiquitin ligases (E3 enzymes) called SCF complexes, which regulate the abundance of proteins that promote and inhibit cell cycle progression at the transition between G1 and S phases. SCF complexes consist of 3 invariable components, SKP1, CUL1 (CDC53 in yeast), and RBX1 (603814), and a variable F-box protein that recruits a specific cellular protein to the ubiquitin pathway for degradation. To study the role of CUL1 in mammalian development and cell cycle regulation, Dealy et al. (1999) generated mice deficient for Cul1 and analyzed null embryos and heterozygous cell lines. They showed that Cul1 is required for early mouse development and that Cul1 mutants fail to regulate the abundance of the G1 cyclin, cyclin E (CCNE1; 123837), during embryogenesis. COP9 signalosome cleaves the ubiquitin-like protein NEDD8 (603171) from the CUL1 subunit of SCF ubiquitin ligases. Cope et al. (2002) found that the JAB1/MPN domain metalloenzyme ... More on the omim web site
Nov. 16, 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 603134 was added.