Alternative titles; symbols
HGNC Approved Gene Symbol: ENO2
Cytogenetic location: 12p13.31 Genomic coordinates (GRCh38): 12:6,914,580-6,923,697 (from NCBI)
The enolases (phosphopyruvate hydratase; EC 4.2.1.11) catalyze the interconversion of 2-phosphoglycerate to phosphoenolpyruvate in the glycolytic pathway. The functional enzyme is a dimer made up of subunits referred to as alpha, beta, and gamma. In mammals there are at least 3 isoforms of enolase characterized by different tissue distributions as well as by distinct biochemical and immunologic properties. The gamma-, or neuron-specific, enolase (ENO2) is the major form found in mature neurons and in cells of neuronal origin. The alpha-, or nonneuronal, enolase (ENO1; 172430) is a nearly ubiquitous form, found in almost all tissues, and its expression precedes that of the other isoforms in the early stage of embryonic development. The beta-, or muscle-specific, enolase (ENO3; 131370) is present in adult skeletal muscle (summary by Oliva et al., 1991).
Muller et al. (2012) proposed that homozygous deletions in passenger genes in cancer deletions can expose cancer-specific therapeutic vulnerabilities when the collaterally deleted gene is a member of a functionally redundant family of genes carrying out an essential function. The glycolytic gene ENO1 in the 1p36 locus is deleted in glioblastoma, which is tolerated by the expression of ENO2. Muller et al. (2012) showed that short hairpin RNA-mediated silencing of ENO2 selectively inhibits growth, survival, and the tumorigenic potential of ENO1-deleted GBM cells, and that the enolase inhibitor phosphonoacetohydroxamate is selectively toxic to ENO1-deleted GBM cells relative to ENO1-intact GBM cells or normal astrocytes. Muller et al. (2012) suggested that the principle of collateral vulnerability should be applicable to other passenger-deleted genes encoding functionally redundant essential activities and provide an effective treatment strategy for cancers containing such genomic events.
Enolase-2 is determined by a gene on chromosome 12 (Grzeschik, 1976). Herbschleb-Voogt et al. (1978) confirmed assignment to chromosome 12 by showing synteny with LDHB and PEPB in man-mouse hybrids. Mattei et al. (1982) assigned ENO2 to 12p11-qter by study of cells trisomic for 12pter-p11. Law and Kao (1982) also assigned the gene to chromosome 12. By in situ hybridization, Craig et al. (1989, 1990) localized ENO2 to 12p13. Oliva et al. (1991) demonstrated that the ENO2 gene contains 12 exons distributed over 9,213 nucleotides. The putative promoter region lacks canonical TATA and CAAT boxes, is very G+C-rich, and contains several potential regulatory sequences.
Craig, S. P., Day, I. N. M., Thompson, R. J., Craig, I. W. Localization of human neurone-specific enolase to chromosome 12p13. (Abstract) Cytogenet. Cell Genet. 51: 980 only, 1989.
Craig, S. P., Day, I. N. M., Thompson, R. J., Craig, I. W. Localisation of neurone-specific enolase (ENO2) to 12p13. Cytogenet. Cell Genet. 54: 71-73, 1990. [PubMed: 2249478] [Full Text: https://doi.org/10.1159/000132960]
Grzeschik, K.-H. Assignment of human genes: beta-glucuronidase to chromosome 7, adenylate kinase-1 to 9, a second enzyme with enolase activity to 12, and mitochondrial IDH to 15. Cytogenet. Cell Genet. 16: 142-148, 1976. Note: Alternate: Birth Defects Orig. Art. Ser. 12(7): 142-148, 1976. [PubMed: 185011] [Full Text: https://doi.org/10.1159/000130576]
Herbschleb-Voogt, E., Monteba-van Heuvel, M., Wijnen, L. M. M., Westerveld, A., Pearson, P. L., Meera Khan, P. Chromosomal assignment and regional localization of CS, ENO-2, GAPDH, LDH-B, PEP-B and TPI in man-rodent cell hybrids. Cytogenet. Cell Genet. 22: 482-486, 1978. [PubMed: 318158] [Full Text: https://doi.org/10.1159/000131003]
Hinks, L. J., Day, I. N. M. Further studies of enolase loci. (Abstract) Cytogenet. Cell Genet. 58: 1854 only, 1991.
Law, M. L., Kao, F. Regional mapping of the gene coding for enolase-2 on human chromosome 12. J. Cell Sci. 53: 245-254, 1982. [PubMed: 6953074] [Full Text: https://doi.org/10.1242/jcs.53.1.245]
Mattei, J. F., Baeteman, M. A., Mattei, M. G., Ardissonne, J. P., Giraud, F. Regional assignments of CS and ENO2 on chromosome 12. (Abstract) Cytogenet. Cell Genet. 32: 297 only, 1982.
Muller, F. L., Colla, S., Aquilanti, E., Manzo, V. E., Genovese, G., Lee, J., Eisenson, D., Narurkar, R., Deng, P., Nezi, L., Lee, M. A., Hu, B., and 10 others. Passenger deletions generate therapeutic vulnerabilities in cancer. Nature 488: 337-342, 2012. Note: Erratum: Nature 525: 278 only, 2015. [PubMed: 22895339] [Full Text: https://doi.org/10.1038/nature11331]
Oliva, D., Cali, L., Feo, S., Giallongo, A. Complete structure of the human gene encoding neuron-specific enolase. Genomics 10: 157-165, 1991. [PubMed: 2045099] [Full Text: https://doi.org/10.1016/0888-7543(91)90496-2]