Alternative titles; symbols
HGNC Approved Gene Symbol: UBE2L1
Cytogenetic location: 14q22.3 Genomic coordinates (GRCh38): 14:55,229,193-55,229,936 (from NCBI)
Robinson et al. (1995) identified a gene encoding a human ubiquitin-conjugating enzyme (E2) designated L-UBC by them. The gene is highly homologous to yeast UBC4 and a human gene they called UBCH5 (602961). The function of these genes is to ubiquitinate specific proteins targeted for degradation. The accumulation of specific proteins that have undergone aberrant processing in neurofibrillary tangles and amyloid plaques is a classic pathologic feature in Alzheimer disease (see 104300) brain. Abnormal ubiquitination has been suggested to play a role in that disorder.
Moynihan et al. (1996) stated that the L-UBC cDNA reported by Robinson et al. (1995) was probably derived from transcription of the nearly identical UBE2L3 (603721) gene. They noted that, unlike the UBE2L3 gene, the UBE2L1 gene is intronless, and contains a 'G' rather than an 'A' at position 162.
The ubiquitination pathway is a cyclical 4-step process that functions to target specific cellular proteins for degradation and also regulates their activity. The system is also required for the processing of MHC-restricted class 1 antigens. Robinson et al. (1995) noted that this pathway operates in all cell types. Many proteins, such as p53 (191170), are resistant to proteolysis in the absence of ubiquitination. In the first step of the pathway, the alpha-carboxyl group of the C terminus of ubiquitin is bound to a ubiquitin-activating enzyme through a thiol-ester bond in an ATP-dependent step. A limited number of genes code for this class of enzymes, e.g., UBE1 (314370) on the X chromosome, UBE1L (191325) on chromosome 3, and UBE1Y (489000), which is on the Y chromosome in rodents and probably in man. In the second step of the pathway, the 'activated' carboxyl group is transferred to one of a number of E2s (UBCs) by transthiolation. A large number of E2 genes have been identified in yeast (UBCs 1-10). Different E1 proteins may interact with specific ubiquitin-conjugating enzymes (UBCs or E2s). E2s may be the proteins that give the ubiquitination pathway its target protein specificity. In yeast, specific biologic functions have been ascribed to some of the UBCs by the analysis of mutants. In the third step of the pathway, E2s catalyze substrate ubiquitination at epsilon amino groups of lysine residues in target proteins either directly or with the assistance of ubiquitin-protein ligases (the E3 family). Robinson et al. (1995) stated that, in human, there are 2 closely related UBC-2 genes, RAD6A (312180) and RAD6B (179095), which map to the X chromosome and chromosome 5, respectively.
Moynihan et al. (1996) noted that the UBE2L1 gene is intronless.
By PCR analysis of somatic cell hybrid panels and by fluorescence in situ hybridization, Robinson et al. (1995) mapped the UBE2L1 gene to chromosome 14q24.3.
Moynihan, T. P., Ardley, H. C., Leek, J. P., Thompson, J., Brindle, N. S., Markham, A. F., Robinson, P. A. Characterization of a human ubiquitin-conjugating enzyme gene UBE2L3. Mammalian Genome 7: 520-525, 1996. [PubMed: 8672131] [Full Text: https://doi.org/10.1007/s003359900155]
Robinson, P. A., Leek, J. P., Thompson, J., Carr, I. M., Bailey, A., Moynihan, T. P., Coletta, P. L., Lench, N. J., Markham, A. F. A human ubiquitin conjugating enzyme, L-UBC, maps in the Alzheimer's disease locus on chromosome 14q24.3. Mammalian Genome 6: 725-731, 1995. [PubMed: 8563171] [Full Text: https://doi.org/10.1007/BF00354295]