Mammalian Glutamyl Aminopeptidase Genes (ENPEP) and Proteins: Comparative Studies of a Major Contributor to Arterial Hypertension

Abstract

Glutamyl aminopeptidase (ENPEP) is a member of the M1 family of endopeptidases which are mammalian type II integral membrane zinc-containing endopeptidases. ENPEP is involved in the catabolic pathway of the renin-angiotensin system forming angiotensin III, which participates in blood pressure regulation and blood vessel formation. Comparative ENPEP amino acid sequences and structures and ENPEP gene locations were examined using data from several mammalian genome projects. Mammalian ENPEP sequences shared 71-98% identities. Five N-glycosylation sites were conserved for all mammalian ENPEP proteins examined although 9-18 sites were observed, in each case. Sequence alignments, key amino acid residues and predicted secondary and tertiary structures were also studied, including transmembrane and cytoplasmic sequences and active site residues. Highest levels of human ENPEP expression were observed in the terminal ileum of the small intestine and in the kidney cortex. Mammalian ENPEP genes contained 20 coding exons. The human ENPEP gene promoter and first coding exon contained a CpG island (CpG27) and at least 6 transcription factor binding sites, whereas the 3′-UTR region contained 7 miRNA target sites, which may contribute to the regulation of ENPEP gene expression in tissues of the body. Phylogenetic analyses examined the relationships of mammalian ENPEP genes and proteins, including primate, other eutherian, marsupial and monotreme sources, using chicken ENPEP as a primordial sequence for comparative purposes.

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

“…ENPEP, Glutamyl Aminopeptidase, belongs to the peptidase M1 family which is the mammalian type II integral membrane zinc-containing endopeptidases. ENPEP regulates blood pressure regulation and blood vessel formation through the catabolic pathway of the renin-angiotensin system [23]. The relationship between ENPEP and viral infection is unknown.…”

Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses

“…ENPEP, Glutamyl Aminopeptidase, belongs to the peptidase M1 family which is the mammalian type II integral membrane zinc-containing endopeptidases. ENPEP regulates blood pressure regulation and blood vessel formation through the catabolic pathway of the renin-angiotensin system [26]. The relationship between ENPEP and viral infection is unknown.…”

Why do we die? Uncovering the genetic connections causing COVID-19 disease severity 

“…In fact, COVID-19 associated nephritis may serve as a marker of disease severity and capillary leak syndrome; a predictor of uid overload, respiratory failure, and death [34]. Additionally, ENPEP receptors are suggested to play an important role in the RAS system in the brain [12,16,17] populations. This study may serve as a building block for future genetic studies to further investigate the role these variants as well as other variants may play in the severity of this disease.…”

“…Reports suggest glutamyl aminopeptidase (ENPEP), alanine aminopeptidase (ANPEP), and DPP4 may serve as co-receptors [8]. ENPEP is involved with the RAS system, associated with hypertension, and has higher expression in the kidneys [12][13][14][15]. Cardiac and kidney complications have been reported with SARS-CoV-2 patients.…”

“…Cardiac and kidney complications have been reported with SARS-CoV-2 patients. ENPEP receptors are suggested to play an important role in the RAS system in the brain [12,16,17]. Neurological and central nervous system complications in patients have been reported [18].…”