Ubiquitin-conjugating enzyme E2 L3 (UBE2L3)
The protein contains 154 amino acids for an estimated molecular weight of 17862 Da.
Ubiquitin-conjugating enzyme E2 that specifically acts with HECT-type and RBR family E3 ubiquitin-protein ligases. Does not function with most RING-containing E3 ubiquitin-protein ligases because it lacks intrinsic E3-independent reactivity with lysine: in contrast, it has activity with the RBR family E3 enzymes, such as PRKN and ARIH1, that function like RING-HECT hybrids. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. In vitro catalyzes 'Lys-11'-linked polyubiquitination. Involved in the selective degradation of short-lived and abnormal proteins. Down-regulated during the S-phase it is involved in progression through the cell cycle. Regulates nuclear hormone receptors transcriptional activity. May play a role in myelopoiesis. (updated: June 2, 2021)
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.
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
Cell cycle phase transition
Cell population proliferation
Cellular protein modification process
Cellular response to glucocorticoid stimulus
Cellular response to steroid hormone stimulus
Positive regulation of protein targeting to mitochondrion
Positive regulation of protein ubiquitination
Positive regulation of ubiquitin-protein transferase activity
Protein K11-linked ubiquitination
Protein polyubiquitination
Protein ubiquitination
Protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Regulation of transcription, DNA-templated
Transcription, DNA-templated
Ubiquitin-dependent protein catabolic process
Cellular Component
Cytoplasm
Cytosol
Extracellular exosome
Nucleoplasm
Nucleus
Ubiquitin ligase complex
The reference OMIM entry for this protein is 603721
Ubiquitin-conjugating enzyme e2l 3; ube2l3
Ubiquitin-conjugating enzyme ubch7; ubch7
DESCRIPTION
Ubiquitin-conjugating enzymes (E2s or UBCs) are essential components of the posttranslational protein ubiquitination pathway, mediating the transfer of activated ubiquitin to substrate proteins.CLONING
The S. cerevisiae UBC1, UBC4, and UBC5 enzymes appear to participate in the degradation of short-lived and abnormal proteins. Human UBE2L1 (600012) is a homolog of yeast UBC4 and UBC5. By screening a genomic library with a UBE2L1 probe, Moynihan et al. (1996) isolated clones corresponding to a novel gene, UBE2L3. Nuber et al. (1996) cloned human keratinocyte cDNAs encoding UBE2L3, which they referred to as UBCH7. The predicted 154-amino acid protein has 64% sequence similarity to UBCH5. UBCH7 efficiently mediated E6AP (UBE3A; 601623)-dependent ubiquitination in an in vitro assay. By RT-PCR, Moynihan et al. (1998) determined that UBE2L3 is expressed as 4 mRNAs that differ in the length of the 3-prime untranslated region (UTR). Sequence comparisons revealed that the human and mouse UBE2L3 cDNAs share 97% DNA sequence identity in the coding region and 93% identity for 287 nucleotides extending into the 3-prime UTR. The predicted mouse and human UBE2L3 proteins are identical.GENE STRUCTURE
Moynihan et al. (1996) demonstrated that the UBE2L3 and UBE2L1 genes are identical except that the UBE2L1 gene is intronless, while the UBE2L3 coding sequence is interrupted by 3 introns. Moynihan et al. (1998) determined that the UBE2L3 gene spans approximately 57 kb.MAPPING
By analysis of somatic cell hybrids and by FISH, Moynihan et al. (1996) mapped the UBE2L3 gene to chromosome 22q11.2-q13.1. They also mapped a pseudogene, UBE2L2, to 12q12. Ardley et al. (1997) found that another pseudogene, UBE2L4, was located at 19q13.1-q13.2.GENE FUNCTION
Shimura et al. (2001) hypothesized that alpha-synuclein (163890) and parkin (602544) interact functionally, namely, that parkin ubiquitinates alpha-synuclein normally and that this process is altered in autosomal recessive Parkinson disease (600116). Shimura et al. (2001) identified a protein complex in normal human brain that includes parkin as the E3 ubiquitin ligase, UBCH7 as its associated E2 ubiquitin-conjugating enzyme, and a novel 22-kD glycosylated form of alpha-synuclein (alpha-Sp22) as its substrate. In contrast to normal parkin, mutant parkin associated with autosomal recessive Parkinson disease failed to bind alpha-Sp22. In an in vitro ubiquitination assay, alpha-Sp22 was modified by normal, but not mutant, parkin into polyubiquitinated, high molecular weight species. Accordingly, alpha-Sp22 accumulated in a nonubiquitinated form in parkin-deficient Parkinson disease brains. Shimura et al. (2001) concluded that alpha-Sp22 is a substrate for parkin's ubiquitin ligase activity in normal human brain and that loss of parkin function causes pathologic accumulation of alpha-Sp22. These findings demonstrated a critical biochemical reaction between the 2 Parkinson disease-linked gene products and suggested that this reaction underlies the accumulation of ubiquitinated alpha-synuclein in conventional Parkinson disease. Carrano et al. (2009) identified the E3 ubiquitin ligase Wwp1 (602307) as a positive regulator of life span in C. elegans in response to dietary restriction. Overexpression of Wwp1 in worms extended life span by up to 20% under conditions of ad libitum feeding. Conversely, reduction of Wwp1 completely suppressed the extended lo ... More on the omim web site
July 1, 2021: 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
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603721 was added.