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HGNC Approved Gene Symbol: ENO1
Cytogenetic location: 1p36.23 Genomic coordinates (GRCh38) : 1:8,861,000-8,878,686 (from NCBI)
Enolase is a glycolytic enzyme (2-phospho-D-glycerate hydrolyase; EC 4.2.1.11). Each of the 3 ENO isoenzymes is a homodimer composed of 2 alpha (ENO1), 2 gamma (ENO2; 131360), or 2 beta (ENO3; 131370) subunits. Isoenzyme alpha (ENO1) is present in most tissues, whereas the beta form (ENO3) is localized to muscle and the gamma form (ENO2) is found only in nervous tissue (summary by Giallongo et al., 1986).
Giallongo et al. (1986) cloned and sequenced a full-length cDNA for human alpha-enolase. Its coding region was found to be 1,299 bases long. The 433-amino acid protein shows 67% homology to yeast enolase and 94% homology to rat nonneural enolase.
Wistow et al. (1988) presented evidence for the remarkable conclusion that alpha-enolase is encoded by the same gene that encodes tau-crystallin, a lens structural protein.
Giallongo et al. (1990) determined that the ENO1 gene contains 12 exons.
Giblett et al. (1974) observed an electrophoretic variant of red cell PPH among Cree Indians. Linkage was found with the Rhesus locus. Since the Rh locus has been assigned to chromosome 1 and since cell hybridization studies assign the PPH locus to chromosome 1, the new data are consistent. The Goss-Harris method of mapping combines features of recombinational study in families and synteny tests in hybrid cells. As applied to chromosome 1, the method shows that AK2 and UMPK are distal to PGM1 and that the order of the loci is PGM1: UMPK: (AK2, alpha-FUC): ENO1 (Goss and Harris, 1977). Comings (1972) and Ohno (1973) suggested that during vertebrate evolution tetraploidization occurred 2-3 hundred million years ago and that chromosomal events that tend to preserve ancestral linkage groups, such as Robertsonian fusions, inversions and gene duplications, have been favored. Demonstration of linkage of homologous genes supports this hypothesis.
D'Ancona et al. (1977) regionalized ENO1 to 1pter-p36.13. Lalley et al. (1978) demonstrated synteny of enolase, PGD (172200), PGM1 (171900), and AK2 (103020) on chromosome 4 of the mouse; they are on 1p of man.
Gross (2023) mapped the ENO1 gene to chromosome 1p36.23 based on an alignment of the ENO1 sequence (GenBank BC001810) with the genomic sequence (GRCh38).
Pseudogene
Feo et al. (1990) concluded that there is a single alpha-enolase pseudogene in the human genome. This intronless, processed pseudogene was mapped to chromosome 1 by Southern blot analysis of rodent-human hybrid cell DNAs; thus, it is on the same chromosome as the functional gene. Ribaudo et al. (1996) confirmed the assignment of ENO1P to chromosome 1. By fluorescence in situ hybridization, they found that it is located on 1q41-q42, whereas the functional gene is located on the short arm of that chromosome.
Lachant et al. (1986) and Lachant and Tanaka (1987) reported 4 generations of a Caucasian family with hereditary red cell enolase deficiency. Partial deficiency in this kindred behaved as an autosomal dominant and was associated with a spherocytic phenotype, although a normal acidified glycerol lysis test suggested that the spherocytes of enolase deficiency are different from those of hereditary spherocytosis (see 182900). Clinical expression of enolase deficiency varied in this family. Some had slightly low hematocrit with elevated reticulocytes, while others had no evidence of anemia or hemolysis.
MBP1, an isoform of ENO1 produced through alternative splicing, is a transcriptional repressor that negatively regulates MYC (190080) promoter activity and suppresses cell growth. Using a yeast 2-hybrid screen of a HeLa cell cDNA library, Ghosh et al. (2001) identified human TRAPPC2B (620472), which they called MIP2A, as an MBP1-interacting protein. In vitro and in vivo analyses confirmed that MIP2A and MBP1 specifically interacted to form a complex in the perinuclear region of cells. Mutation analysis identified the first 95 amino acids of MBP1 as an MIP2A-binding domain. Binding of MIP2A to MBP1 relieved transcriptional repression by MBP1, especially MBP1-mediated transcriptional repression of the MYC promoter, and thereby antagonized MBP1-mediated cell growth suppression.
To identify the autoantigens related to Hashimoto encephalopathy, a rare autoimmune disease associated with Hashimoto thyroiditis (140300), Ochi et al. (2002) developed a human brain proteome map using 2-dimensional electrophoresis and applied it to the immunoscreening of brain proteins that react with autoantibodies in affected patients. They thereby identified alpha-enolase as the autoantigen in that disorder.
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 (131360). 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.
Comings, D. E. Evidence for ancient tetraploidy and conservation of linkage groups in mammalian chromosomes. Nature 238: 455-457, 1972. [PubMed: 4561854] [Full Text: https://doi.org/10.1038/238455a0]
D'Ancona, G. G., Chern, C. J., Benn, P., Croce, C. M. Assignment of the human gene for enolase 1 to region pter-p36 of chromosome 1. Cytogenet. Cell Genet. 18: 327-332, 1977. [PubMed: 884968] [Full Text: https://doi.org/10.1159/000130779]
D'Ancona, G. G., Croce, C. M. Assignment of the gene for enolase to mouse chromosome 4 using somatic cell hybrids. Cytogenet. Cell Genet. 19: 1-6, 1977. [PubMed: 891258] [Full Text: https://doi.org/10.1159/000130788]
Feo, S., Oliva, D., Arico, B., Barba, G., Cali, L., Giallongo, A. The human genome contains a single processed pseudogene for alpha enolase located on chromosome 1. DNA Seq. 1: 79-83, 1990. [PubMed: 2132962] [Full Text: https://doi.org/10.3109/10425179009041350]
Ghosh, A. K., Majumder, M., Steele, R., White, R. A., Ray, R. B. A novel 16-kilodalton cellular protein physically interacts with and antagonizes the functional activity of c-myc promoter-binding protein 1. Molec. Cell. Biol. 21: 655-662, 2001. [PubMed: 11134351] [Full Text: https://doi.org/10.1128/MCB.21.2.655-662.2001]
Giallongo, A., Feo, S., Moore, R., Croce, C. M., Showe, L. C. Molecular cloning and nucleotide sequence of a full-length cDNA for human alpha enolase. Proc. Nat. Acad. Sci. 83: 6741-6745, 1986. [PubMed: 3529090] [Full Text: https://doi.org/10.1073/pnas.83.18.6741]
Giallongo, A., Oliva, D., Cali, L., Barba, G., Barbieri, G., Feo, S. Structure of the human gene for alpha-enolase. Europ. J. Biochem. 190: 567-573, 1990. [PubMed: 2373081] [Full Text: https://doi.org/10.1111/j.1432-1033.1990.tb15611.x]
Giblett, E. R., Chen, S.-H., Anderson, J. E., Lewis, M. A family study suggesting genetic linkage of phosphopyruvate hydratase (enolase) to the Rh blood group system. Cytogenet. Cell Genet. 13: 91-92, 1974. [PubMed: 4208018] [Full Text: https://doi.org/10.1159/000130243]
Goss, S. J., Harris, H. Gene transfer by means of cell fusion. II. The mapping of 8 loci on human chromosome 1 by statistical analysis of gene assortment in somatic cell hybrids. J. Cell Sci. 25: 39-57, 1977. [PubMed: 561097] [Full Text: https://doi.org/10.1242/jcs.25.1.39]
Gross, M. B. Personal Communication. Baltimore, Md. 8/11/2023.
Lachant, N. A., Jennings, M. A., Tanaka, K. R. Partial erythrocyte enolase deficiency: a hereditary disorder with variable clinical expression. (Abstract) Blood 68: 55a only, 1986.
Lachant, N. A., Tanaka, K. R. Enolase kinetic properties in partial erythrocyte enolase deficiency. (Abstract) Clin. Res. 35: 426A only, 1987.
Lalley, P. A., Francke, U., Minna, J. D. Homologous genes for enolase, phosphogluconate dehydrogenase, phosphoglucomutase, and adenylate kinase are syntenic on mouse chromosome 4 and human chromosome 1p. Proc. Nat. Acad. Sci. 75: 2382-2386, 1978. [PubMed: 209463] [Full Text: https://doi.org/10.1073/pnas.75.5.2382]
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]
Ochi, H., Horiuchi, I., Araki, N., Toda, T., Araki, T., Sato, K., Murai, H., Osoegawa, M., Yamada, T., Okamura, K., Ogino, T., Mizumoto, K., Yamashita, H., Saya, H., Kira, J. Proteomic analysis of human brain identifies alpha-enolase as a novel autoantigen in Hashimoto's encephalopathy. FEBS Lett. 528: 197-202, 2002. [PubMed: 12297304] [Full Text: https://doi.org/10.1016/s0014-5793(02)03307-0]
Ohno, S. Ancient linkage groups and frozen accidents. Nature 244: 259-262, 1973. [PubMed: 4200792] [Full Text: https://doi.org/10.1038/244259a0]
Ribaudo, M. R., Di Leonardo, A., Rubino, P., Giallongo, A., Feo, S. Assignment of enolase processed pseudogene (ENO1P) to human chromosome 1 bands 1q41-q42. Cytogenet. Cell Genet. 74: 201-202, 1996. [PubMed: 8941374] [Full Text: https://doi.org/10.1159/000134414]
Van Cong, N., Weil, D., Rebourcet, R., Frezal, J. Localisation des enolases 1 et 2 respectivement sur les chromosomes 1 et 12 par l'analyse des hybrids homme-souris. Ann. Genet. 20: 153-157, 1977. [PubMed: 304697]
Wistow, G. J., Lietman, T., Williams, L. A., Stapel, S. O., de Jong, W. W., Horwitz, J., Piatigorsky, J. Tau-crystallin/alpha-enolase: one gene encodes both an enzyme and a lens structural protein. J. Cell Biol. 107: 2729-2736, 1988. [PubMed: 2462567] [Full Text: https://doi.org/10.1083/jcb.107.6.2729]