Identification and characterisation of the angiotensin converting enzyme-3 (ACE3) gene: a novel mammalian homologue of ACE.
BACKGROUND
Mammalian angiotensin converting enzyme (ACE) plays a key role in blood pressure regulation. Although multiple ACE-like proteins exist in non-mammalian organisms, to date only one other ACE homologue, ACE2, has been identified in mammals.


RESULTS
Here we report the identification and characterisation of the gene encoding a third homologue of ACE, termed ACE3, in several mammalian genomes. The ACE3 gene is located on the same chromosome downstream of the ACE gene. Multiple sequence alignment and molecular modelling have been employed to characterise the predicted ACE3 protein. In mouse, rat, cow and dog, the predicted protein has mutations in some of the critical residues involved in catalysis, including the catalytic Glu in the HEXXH zinc binding motif which is Gln, and ESTs or reverse-transcription PCR indicate that the gene is expressed. In humans, the predicted ACE3 protein has an intact HEXXH motif, but there are other deletions and insertions in the gene and no ESTs have been identified.


CONCLUSIONS
In the genomes of several mammalian species there is a gene that encodes a novel, single domain ACE-like protein, ACE3. In mouse, rat, cow and dog ACE3, the catalytic Glu is replaced by Gln in the putative zinc binding motif, indicating that in these species ACE3 would lack catalytic activity as a zinc metalloprotease. In humans, no evidence was found that the ACE3 gene is expressed and the presence of deletions and insertions in the sequence indicate that ACE3 is a pseudogene.
Rella
Monika
M
Institute of Molecular and Cellular Biology, Faculty of Biological Sciences, University of Leeds, Leeds, UK. monika.rella@qmail.com <monika.rella@qmail.com>
Elliot
Joann L
JL
Revett
Timothy J
TJ
Lanfear
Jerry
J
Phelan
Anne
A
Jackson
Richard M
RM
Turner
Anthony J
AJ
Hooper
Nigel M
NM
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D004285:Dogs; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D023281:Genomics / Q000379:methods*; D006801:Humans; D045726:Metalloproteases / Q000737:chemistry; D051379:Mice; D008969:Molecular Sequence Data; D007703:Peptidyl-Dipeptidase A / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity
D045726:Metalloproteases; C522402:Ace3 protein, mouse; D007703:Peptidyl-Dipeptidase A