CLONING AND SEQUENCING OF A HUMAN ENDOTHELIN-CONVERTING ENZYME IN RENAL ADENOCARCINOMA (ACHN) CELLS PRODUCING ENDOTHELIN-2

Endothelin (ET)-2 is a 21 residue vasoactive peptide which is biosynthesized from big ET-2(1-38) by a specific cleavage at Trp(21)-Val(22) with an ET converting enzyme (ECE). To identify an ECE in ACHN (human renal adenocarcinoma) cells which produce ET-2, we have cloned and sequenced a novel cDNA encoding a human ECE in ACHN (hAECE). It encodes a 770 amino acid protein with a zinc-binding motif and a single membrane spanning region. The sequences of nucleic acids and amino acids from Leu(45) to Trp(770) of hAECE are identical to those from Leu(33) to Trp(758) Of a human ECE in HUVEC (hHECE). The sequences in the amino-terminal moiety are divergent between hAECE and hHECE. Based on the difference of the amino-terminal amino acid sequences, ECEs reported so far, can be classified into two isoforms. These results strongly suggest that an alternative splicing might occur in the 5'-terminal region of the ECE pre-mRNA. (C) 1995 Academic Press, Inc.