Alternative titles; symbols
HGNC Approved Gene Symbol: UBE2V2
Cytogenetic location: 8q11.21 Genomic coordinates (GRCh38): 8:47,997,437-48,064,708 (from NCBI)
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 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 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.
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.
Fritsche, J., Rehli, M., Krause, S. W., Andreesen, R., Kreutz, M. Molecular cloning of a 1-alpha,25-dihydroxyvitamin D3-inducible transcript (DDVit 1) in human blood monocytes. Biochem. Biophys. Res. Commun. 235: 407-412, 1997. [PubMed: 9199207] [Full Text: https://doi.org/10.1006/bbrc.1997.6798]
Hoege, C., Pfander, B., Moldovan, G.-L., Pyrowolakis, G., Jentsch, S. RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin and SUMO. Nature 419: 135-141, 2002. [PubMed: 12226657] [Full Text: https://doi.org/10.1038/nature00991]
Hofmann, R. M., Pickart, C. M. Noncanonical MMS2-encoded ubiquitin-conjugating enzyme functions in assembly of novel polyubiquitin chains for DNA repair. Cell 96: 645-653, 1999. [PubMed: 10089880] [Full Text: https://doi.org/10.1016/s0092-8674(00)80575-9]
Sancho, E., Vila, M. R., Sanchez-Pulido, L., Lozano, J. J., Paciucci, R., Nadal, M., Fox, M., Harvey, C., Bercovich, B., Loukili, N., Ciechanover, A., Lin, S. L., Sanz, F., Estivill, X., Valencia, A., Thomson, T. M. Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. Molec. Cell. Biol. 18: 576-589, 1998. [PubMed: 9418904] [Full Text: https://doi.org/10.1128/MCB.18.1.576]