Alternative titles; symbols
HGNC Approved Gene Symbol: CELA1
Cytogenetic location: 12q13.13 Genomic coordinates (GRCh38): 12:51,328,442-51,346,679 (from NCBI)
Elastase (EC 3.4.21.36; formerly EC 3.4.4.7) is a member of the serine protease family, which are characterized by the reactivity of a serine residue in the active site of the enzyme. Elastase breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin (summary by Talas et al., 2000). Elastase-1 is functionally silent in human pancreas but is expressed in skin (Talas et al., 2000).
Tani et al. (1987) isolated the human ELA1 gene by screening human genomic libraries with the porcine elastase-1 cDNA as a probe. Southern blot analysis of total DNA showed conservation of the gene among the porcine, rat, calf, and human genomes. Northern blot analysis, however, indicated that the ELA1 gene is not expressed in the human adult pancreas, even though abundant expression is observed in the rat and porcine pancreas.
The human ELA1 gene is evolutionarily silenced in pancreatic acinar cells, which appears to be due to mutations that inactivate enhancer and promoter elements that are crucial for pancreas-specific transcription (summary by Talas et al., 2000).
Rose and MacDonald (1997) examined the question of why the human ELA1 gene is transcriptionally silent despite the apparent integrity of the structural gene. The transcriptional regulatory sequences necessary and sufficient for transcription of the active rat homolog localized within 205 bp of the transcriptional start and comprise a pancreas-specific transcriptional enhancer of 134 bp immediately upstream of a 71-bp nonspecific promoter. The human gene, they found, has 58 nucleotide differences within this region, 13 of which are in the 3 functional elements (A, B, and C) that constitute the enhancer. Through cell transfection analyses with a pancreatic acinar tumor cell line, they showed that the nucleotide differences in the human 5-prime flanking gene sequences inactivated both the enhancer and the promoter. The changes in the 3 elements of the human enhancer alone are sufficient to inactivate the enhancer; conversely, restoring these to the rat configuration partially restored the activity of the human enhancer. Replacing the active 71-bp rat promoter with the human promoter also prevented expression. Therefore, Rose and MacDonald (1997) concluded that the evolutionary silencing of the human ELA1 gene was due to mutations that inactivated crucial enhancer and promoter elements.
Talas et al. (2000) detected ELA1 mRNA expression in cultured human primary keratinocytes. Antibody staining localized the protein to the basal cell layer of the human epidermis at a number of sites including the palmoplanta. Sequencing of genomic DNA from individuals with and without keratoderma (NEPPK; 600962) revealed a sequence variant, an insertion of a single C, that would result in premature termination of the protein. This sequence variant did not segregate with the disorder and occurred at a relatively high frequency among 80 additional unrelated normal individuals (heterozygously in 31 and homozygously in 6). Individuals homozygous for the variant did not have any obvious skin abnormalities.
Tani et al. (1987) determined that the human elastase-1 gene contains 8 exons.
Using a rat cDNA probe, Honey et al. (1984) found that a 15.9-kb DNA fragment containing human elastase-1 gene sequences cosegregated with chromosome 12 in mouse-man somatic hybridization experiments.
O'Connell et al. (1985) localized the ELA1 locus to proximal 12p by family linkage studies using RFLP markers.
By fluorescence in situ hybridization, Davies et al. (1995) mapped ELA1 to 12q13 to a region between D12S361 and D12S347. The physical mapping was achieved by study of chromosome 12-specific YACs.
Davies, R. L., Yoon, S. J., Weissenbach, J., Ward, D., Krauter, K., Kucherlapati, R. Physical mapping of the human ELA1 gene between D12S361 and D12S347 on chromosome 12q13. Genomics 29: 766-768, 1995. [PubMed: 8575772] [Full Text: https://doi.org/10.1006/geno.1995.9939]
Honey, N. K., Sakaguchi, A. Y., Quinto, C., MacDonald, R. J., Rutter, W. J., Naylor, S. L. Assignment of the human genes for elastase to chromosome 12, and for trypsin and carboxypeptidase A to chromosome 7. (Abstract) Cytogenet. Cell Genet. 37: 492 only, 1984.
O'Connell, P., Leppert, M., Hoff, M., Kumlin, E., Thomas, W., Cai, G., Law, M., White, R. A linkage map for human chromosome 12. (Abstract) Am. J. Hum. Genet. 37: A169 only, 1985.
Rose, S. D., MacDonald, R. J. Evolutionary silencing of the human elastase I gene (ELA1). Hum. Molec. Genet. 6: 897-903, 1997. [PubMed: 9175736] [Full Text: https://doi.org/10.1093/hmg/6.6.897]
Talas, U., Dunlop, J., Khalaf, S., Leigh, I. M., Kelsell, D. P. Human elastase 1: evidence for expression in the skin and the identification of a frequent frameshift polymorphism. J. Invest. Derm. 114: 165-170, 2000. [PubMed: 10620133] [Full Text: https://doi.org/10.1046/j.1523-1747.2000.00825.x]
Tani, T., Kawashima, I., Furukawa, H., Ohmine, T., Takiguchi, Y. Characterization of a silent gene for human pancreatic elastase I: structure of the 5-prime-flanking region. J. Biochem. 101: 591-599, 1987. [PubMed: 3648024] [Full Text: https://doi.org/10.1093/jb/101.3.591]