Roger Stephen Holmes^1,2 , Laura A. Cox ¹

1. Department of Genetics and Southwest National Primate Research Center, Texas Biomedical Research Institute, San Antonio, TX, USA
2. Eskitis Institute for Cell and Molecular Therapies and School of Biomolecular and Physical Sciences, Griffith University, Nathan, QLD, Australia
Author    Correspondence author
Genomics and Applied Biology, 2013, Vol. 4, No. 3   
Received: 10 Feb., 2013    Accepted: 16 Feb., 2013    Published: 01 Jan., 1970

This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Endothelin-converting enzyme-1 (ECE1) is a key enzyme responsible for generating the vasoconstrictive peptide (endothelin-1) which has been linked to several diseases, including systemic and pulmonary hypertension, stroke, asthma and heart failure. Genetic deficiency of this protein results in developmental defects of various neural crest-derived tissues. Comparative ECE1 amino acid sequences and structures and ECE1 gene locations were examined. Vertebrate ECE1 sequences shared 66-99% identity as compared with 30-37% sequence identities with other ECE-like family members, ECE2, ECEL1 and MME. Ten N-glycosylation sites were conserved for most vertebrate ECE1 proteins examined. Sequence alignments, key amino acid residues and conserved predicted secondary and tertiary structures were also studied, including cytoplasmic, transmembrane and extracellular sequences, and active site residues. Vertebrate ECE1 genes usually contained 18 coding exons. The human ECE1 gene promoter and first coding exon contained a large CpG island (CpG68) and several transcription factor binding sites, whereas the 3'-UTR region contained 11 miRNA target sites, which may contribute to the regulation of ECE1 gene expression in cardiac and other tissues of the body. Human ECE1 was located within blood pressure and disease phenotype QTLs on chromosome 1 previously described for essential hypertension and Hirschsprung disease. Phylogenetic analyses examined the relationships and potential evolutionary origins of the vertebrate ECE1 gene with other vertebrate neutral endopeptidase M13 ECE-like genes. These suggested that ECE1 forms a gene cluster with ECE2 and KEL which may have originated in an invertebrate ancestral genome from a gene duplication event of an ancestral neutral endopeptidase M13-like gene.

Comparative biochemistry; Genomics; Evolution