Angiotensin-Converting Enzyme 2 (ACE2)

Angiotensin-converting enzyme 2 (ACE2), a first homolog of ACE, regulates the renin angiotensin system (RAS) by counterbalancing ACE activity. Accumulating evidence in recent years has demonstrated a physiological and pathological role of ACE2 in the cardiovascular, renal and respiratory systems. ACE2 also has an important role in blood pressure control. This enzyme, an homolog of ACE, hydrolyzes angiotensin (Ang) I to produce Ang-(1-9), which is subsequently converted into Ang-(1-7) by a neutral endopeptidase and ACE. ACE2 releases Ang-(1-7) more efficiently than its catalysis of Ang-(1-9) by cleavage of Pro(7)-Phe(8) bound in Ang II. Thus, the major biologically active product of ACE2 is Ang-(1-7), which is considered to be a beneficial peptide of the RAS cascade in the cardiovascular system. A physiological role for ACE2 has been implicated in hypertension, cardiac function, heart function and diabetes, and as a receptor of the severe acute respiratory syndrome coronavirus. In the acute respiratory distress syndrome (ARDS), ACE, AngII, and AT1R promote the disease pathogenesis, whereas ACE2 and the AT2R protect from ARDS. Importantly, ACE2 has been identified as a key SARS-coronavirus receptor and plays a protective role in severe acute respiratory syndrome (SARS) pathogenesis. Furthermore, the recent explosion of research into the ACE2 homolog, collectrin, has revealed a new physiological function of ACE2 as an amino acid transporter, which explains the pathogenic role of gene mutations in Hartnup disorder. This review summarizes and discusses the recently unveiled roles for ACE2 in disease pathogenesis.

Angiotensin-Converting Enzyme 2 (ACE2) Related Areas

Cardiovascular>>Blood Pressure Regulation>>ACE2

Enzyme>>Protease & Regulator>>Metalloprotease & Regulator>>ACE2

Angiotensin-Converting Enzyme 2 (ACE2) Alternative Names

ACE2, ACEH, DKFZp434A014 [Homo sapiens]

Ace2, RP23-330O24.1, 2010305L05Rik [Mus musculus]

Summaries for Angiotensin-Converting Enzyme 2 (ACE2)

Entrez Gene summary for Angiotensin-Converting Enzyme 2 (ACE2):

The protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidases and has considerable homology to human angiotensin 1 converting enzyme. This secreted protein catalyzes the cleavage of angiotensin I into angiotensin 1-9, and angiotensin II into the vasodilator angiotensin 1-7. The organ- and cell-specific expression of this gene suggests that it may play a role in the regulation of cardiovascular and renal function, as well as fertility. In addition, the encoded protein is a functional receptor for the spike glycoprotein of the human coronaviruses SARS and HCoV-NL63.

OMIM - description for Angiotensin-Converting Enzyme 2 (ACE2):

By EST database searching for sequences showing homology to the zinc metalloprotease angiotensin-I converting enzyme (ACE; 106180) and by screening a human lymphoma cDNA library, Tipnis et al. (2000) cloned a full-length ACE2 cDNA, which they called ACEH, encoding a deduced 805-amino acid protein that shares approximately 40% identity with the N- and C-terminal domains of ACE. ACE2 contains a potential 17-amino acid N-terminal signal peptide and a putative 22-amino acid C-terminal membrane anchor. It has a conserved zinc metalloprotease consensus sequence (HEXXH) and a conserved glutamine residue that is predicted to serve as a third zinc ligand. Northern blot analysis detected high expression of ACE2 in kidney, testis, and heart, and moderate expression in colon, small intestine, and ovary. By quantitative RT-PCR, Harmer et al. (2002) found ACE2 expressed in all 72 human tissues and cells examined except red blood cells. Highest expression was detected in testis, renal and cardiovascular tissues, and in all portions of the gastrointestinal tract, particularly the ilium. Central nervous system and lymphoid tissues expressed relatively low ACE2 levels.

Wikipedia summary for Angiotensin-Converting Enzyme 2 (ACE2):

AngiotensinI-converting enzyme 2 (ACE 2) is an exopeptidase that catalyses the conversion of angiotensin I to the nonapeptide angiotensin[1-9],[1] or the conversion of angiotensin II to angiotensin 1-7.[2] ACE 2 has direct effects on cardiac functiona, and is expressed predominantly in vascular endothelial cells of the heart and the kidneys.[3] ACE 2 is also receptor for SARS virus.

Human Angiotensin-Converting Enzyme 2 (ACE2) Protein General Information

 

• Protein names: Recommended name: Angiotensin-converting enzyme 2
• Sequence length: 805 AA.
• Domain: Signal Transmembrane Transmembrane helix
• Sequence similarities: Belongs to the peptidase M2 family.
• Post-translational modification: N-glycosylation on Asn-90 may limit SARS infectivity.
• Subunit structure: Interacts with ITGB1. Interacts with SARS-CoV and HCoV-NL63 spike glycoprotein.
• Subcellular location: Processed angiotensin-converting enzyme 2: Secreted Ref.3. Cell membrane; Single-pass type I membrane protein
• Tissue specificity: Expressed in endothelial cells from small and large arteries, and in arterial smooth muscle cells. Expressed in lung alveolar epithelial cells, enterocytes of the small intestine, Leydig cells and Sertoli cells (at protein level). Expressed in heart, kidney, testis, and gastrointestinal system
• Enzyme regulation: Activated by chloride and fluoride, but not bromide. Inhibited by MLN-4760, cFP_Leu, and EDTA, but not by the ACE inhibitors linosipril, captopril and enalaprilat

General information above from UniProt

Function for Angiotensin-Converting Enzyme 2 (ACE2) Protein

UniProtKB:

Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin-13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses.

Genatlas:

• Angiotensin-Converting Enzyme 2 (ACE2) functions as a carboxypeptidase, converting angiotensin I to angiotensin II and degrading bradykinin
• Angiotensin-Converting Enzyme 2 (ACE2) protects from severe acute lung injury induced by acid aspiration or sepsis
• Angiotensin-Converting Enzyme 2 (ACE2) is implicated in the regulation of heart and renal function where it is proposed to control the levels of angiotensin II relative to its hypotensive metabolite, angiotensin-(1-7)