Ubiquitin-conjugating enzyme E2 R1 (CDC34)
The protein contains 236 amino acids for an estimated molecular weight of 26737 Da.
Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-48'-linked polyubiquitination (PubMed:22496338). Cooperates with the E2 UBCH5C and the SCF(FBXW11) E3 ligase complex for the polyubiquitination of NFKBIA leading to its subsequent proteasomal degradation. Performs ubiquitin chain elongation building ubiquitin chains from the UBE2D3-primed NFKBIA-linked ubiquitin. UBE2D3 acts as an initiator E2, priming the phosphorylated NFKBIA target at positions 'Lys-21' and/or 'Lys-22' with a monoubiquitin. Cooperates with the SCF(SKP2) E3 ligase complex to regulate cell proliferation through ubiquitination and degradation of MYBL2 and KIP1. Involved in ubiquitin conjugation and degradation of CREM isoform ICERIIgamma and ATF15 resulting in abrogation of ICERIIgamma- and ATF5-mediated repression of cAMP-induced transcription during both meiotic and mitotic cell cycles. Involved in the regulation of the cell cycle G2/M phase through its targeting of the WEE1 kinase for ubiquitination and degradation. Also involved in the degradation of beta-catenin. Is target of human herpes virus 1 protein ICP0, leading to ICP0-dependent dynamic interaction with proteasomes (PubMed:10329681, PubMed:10373550, PubMed:10871850, PubMed:11675391, PubMed:12037680, PubMed:15652359, PubMed:17461777, PubMed:17698585, PubMed:19112177, PubMed:19126550, PubMed:19945379, PubMed:20061386, PubMed:20347421). (updated: Oct. 25, 2017)
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.
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| Variant | Description |
|---|---|
| dbSNP:rs16990650 |
Biological Process
Cellular protein modification process
Cellular response to interferon-beta
DNA replication initiation
G1/S transition of mitotic cell cycle
Negative regulation of cAMP-mediated signaling
Positive regulation of inclusion body assembly
Positive regulation of neuron apoptotic process
Proteasome-mediated ubiquitin-dependent protein catabolic process
Protein K48-linked ubiquitination
Protein polyubiquitination
Protein ubiquitination
Response to growth factor
Ubiquitin-dependent protein catabolic process
The reference OMIM entry for this protein is 116948
Cell division cycle 34, s. cerevisiae, homolog of; cdc34
Ubiquitin-conjugating enzyme cdc34
Ubc3; ubch3
Ubiquitin-conjugating enzyme e2r 1; ube2r1
CLONING
Normal eukaryotes from yeasts to humans have a conserved checkpoint mechanism in cell division for maintenance of genomic stability. After DNA strand breaks, checkpoint genes induce rest in the G1 and G2 phases of the cell cycle until the damage is repaired. Plon et al. (1993) isolated a putative human G2 checkpoint gene, a homolog of the CDC34 gene of Saccharomyces cerevisiae. Human CDC34 could substitute efficiently for yeast CDC34.GENE FUNCTION
Using deletion and site-directed mutagenesis experiments, Semplici et al. (2002) demonstrated that CK2 (see 115440) phosphorylated CDC34 and UBC3B (UBE2R2; 612506) at a corresponding serine residue in the C terminus of each protein. In vitro binding experiments demonstrated that phosphorylated UBC3B and CDC34 bound specifically to the F-box protein beta-TRCP (BTRC; 603482), which resulted in enhanced degradation of beta-catenin (116806), a substrate of BTRC. Semplici et al. (2002) suggested that CK2-dependent phosphorylation of CDC34 and UBC3B functions by regulating BTRC substrate recognition. Pierce et al. (2009) developed a quantitative framework based on product distribution that predicted that the really interesting new gene (RING) E3 enzymes SCF(Cdc4) (606278) and SCF-beta-TrCP (603482) work with the E2 Cdc34 to build polyubiquitin chains on substrates by sequential transfers of single ubiquitins. Measurements with millisecond time resolution directly demonstrated that substrate polyubiquitylation proceeds sequentially. Pierce et al. (2009) concluded that their results presented an unprecedented glimpse into the mechanism of RING ubiquitin ligases and illuminated the quantitative parameters that underlie the rate and pattern of ubiquitin chain assembly.MAPPING
Plon et al. (1993) demonstrated by in situ hybridization that the CDC34 gene is located in the far telomeric region of 19p13.3, in a region of syntenic homology between human 19p and mouse 11. ... More on the omim web site
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
June 20, 2017: Protein entry updated
Automatic update: comparative model was added.
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 116948 was added.