Organization of the Gene Encoding the Human Endothelin-converting Enzyme (ECE-1)

doi:10.1074/jbc.270.50.29794

Organization of the Gene Encoding the Human Endothelin-converting Enzyme (ECE-1) (*)

From the From F. Hoffmann-La Roche Ltd., Pharma Division, Preclinical Research, Grenzacherstrasse 124, CH-4002 Basel, Switzerland and
INSERM U406, Faculté de Médecine Timone, Bd Jean Moulin, 13385 Marseille Cedex 05, France

^§ To whom correspondence should be addressed:
F. Hoffmann-La Roche Ltd., Pharma Division, Preclinical Research, PRPV 69/348, Grenzacherstrasse 124, CH-4002 Basel, Switzerland.
Tel.: 41-61-6880405; Fax: 41-61-6882438.

Abstract

The two human endothelin-converting enzyme (ECE-1) isoforms, which differ by their N-terminal region, are encoded by a single gene. The gene is composed of 19 exons that span more than 68 kilobases and has been mapped to the 1p36 band of the human genome. The two isoform mRNAs display different tissue distributions. Their precursors are transcribed from two distinct start sites, upstream from exon 1 and exon 3, respectively. Sequence analysis of the two putative promoters revealed the presence of motifs characteristic for several transcription factors. Comparison of the ECE-1 gene structure with those of other zinc metalloproteases, as well as a phylogenetic study, confirm the existence of a metalloprotease subfamily composed of ECE-1, ECE-2, neutral endopeptidase, Kell blood group protein, and two bacterial enzymes.

Footnotes

↵* The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The nucleotide sequence(s) reported in this paper has been submitted to the GenBank(TM)/EMBL Data Bank with accession number(s) X91922[GenBank]-X91939[GenBank].
↵¹ The abbreviations used are:

ET-1

endothelin-1

ECE

endothelin-converting enzyme

kb

kilobase(s)

PCR

polymerase chain reaction

HUVEC

(primary cultures of) human umbilical vein endothelial cells

NEP

neutral endopeptidase 3.4.24.11

MOPS

morpholinopropanesulfonic acid.
↵²O. Valdenaire, B. Kalina, W. Fischli, and B. M. Loeffler, personal communication.
↵³Position of nucleotides on ECE-1 cDNA sequence common to both isoforms is given relative to isoform ECE-1a sequence, which can be found in (16).
↵⁴P. E. Kolenbrander, unpublished data.
↵⁵S. L. Naylor, R. B. Chinn, D. K. Garcia, and R. J. Leach, personal communication.
- Received July 19, 1995.