Ubiquitin-conjugating enzyme E2 variant 2 (UBE2V2)
The protein contains 145 amino acids for an estimated molecular weight of 16363 Da.
Has no ubiquitin ligase activity on its own. The UBE2V2/UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through 'Lys-63'. This type of poly-ubiquitination does not lead to protein degradation by the proteasome. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. (updated: April 1, 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.
- 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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| Variant | Description |
|---|---|
| dbSNP:rs11557776 | |
| dbSNP:rs14890 | |
| dbSNP:rs11557786 |
Biological Process
Cell population proliferation
DNA double-strand break processing
Double-strand break repair
Double-strand break repair via nonhomologous end joining
Error-free postreplication DNA repair
Global genome nucleotide-excision repair
Negative regulation of neuron apoptotic process
Positive regulation of DNA repair
Positive regulation of neuron projection development
Positive regulation of proteasomal ubiquitin-dependent protein catabolic process
Positive regulation of synapse assembly
Postreplication repair
Protein K63-linked ubiquitination
Protein polyubiquitination
Protein ubiquitination
Regulation of DNA repair
The reference OMIM entry for this protein is 603001
Ubiquitin-conjugating enzyme e2 variant 2; ube2v2
Uev2
1-alpha,25-@dihydroxyvitamin d3-inducible transcript 1; ddvit1
Enterocyte differentiation-promoting factor 1; edpf1
Methyl methanesulfonate sensitive 2, s. cerevisiae, homolog of; mms2
CLONING
By mRNA differential display, RACE PCR, and library screening, Fritsche et al. (1997) isolated human monocyte and macrophage cDNAs encoding UBE2V2, which they called DDVIT1. The nucleotide sequence of DDVIT1 is identical to that of the EDPF1 cDNA (GenBank GENBANK U62136). Northern blot analysis detected DDVIT1 transcripts in all human tissues and cell lines examined. The authors demonstrated that the 1.4-kb DDVIT1 mRNA was induced in freshly isolated blood monocytes by short-term incubation with vitamin D3. The predicted 145-amino acid DDVIT1 protein (see GenBank GENBANK X98091) does not have hydrophobic regions, and therefore the authors suggested that it is soluble. Sancho et al. (1998) found that the UBE2V2 protein, which they named UEV2, has 90% sequence identity to the C-terminal 140 amino acids of the 221- and 170-amino acid UEV1 isoforms (UBE2V1; 602995). The authors stated that the UEV1 and UEV2 proteins are similar in sequence and in predicted structure to the ubiquitin-conjugating enzymes, or E2s (e.g., UBE2D1; 602961), but lack a critical cysteine residue essential for the catalytic activity of E2 enzymes.GENE FUNCTION
In yeast, Hofmann and Pickart (1999) showed that the MMS2 protein formed a specific heteromeric complex with UBC13-encoded E2 (603679) and was required for the UBC13-dependent assembly of polyubiquitin chains linked through lysine 63. A ubc13 yeast strain was UV sensitive, and single, double, and triple mutants of the UBC13, MMS2, and ubiquitin genes displayed a similar phenotype. The findings supported a model in which an MMS2/UBC13 protein complex assembles novel polyubiquitin chains for signaling in DNA repair, and suggested that UEV proteins may act to increase diversity and selectivity in ubiquitin conjugation. The RAD6 (179095) pathway is central to postreplicative DNA repair in eukaryotic cells. Two principal elements of this pathway are the ubiquitin-conjugating enzymes RAD6 and the MMS2-UBC13 heterodimer, which are recruited to chromatin by the RING finger proteins RAD18 (605256) and RAD5 (608048), respectively. Hoege et al. (2002) showed that UBC9 (601661), a small ubiquitin-related modifier (SUMO)-conjugating enzyme, is also affiliated with this pathway and that proliferating cell nuclear antigen (PCNA; 176740), a DNA polymerase sliding clamp involved in DNA synthesis and repair, is a substrate. PCNA is monoubiquitinated through RAD6 and RAD18, modified by lys63-linked multiubiquitination, which additionally requires MMS2, UBC13, and RAD5, and is conjugated to SUMO by UBC9. All 3 modifications affect the same lysine residue of PCNA, K164, suggesting that they label PCNA for alternative functions. Hoege et al. (2002) demonstrated that these modifications differentially affect resistance to DNA damage, and that damage-induced PCNA ubiquitination is elementary for DNA repair and occurs at the same conserved residue in yeast and humans. ... 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
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for UBE2V2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 603001 was added.
Jan. 28, 2016: Protein entry updated
Automatic update: model status changed
Jan. 25, 2016: Protein entry updated
Automatic update: model status changed