Angiotensin Converting Enzyme, Human (ACE, ACE1, DCP1, Dipeptidyl carboxypeptidase-1)

Renin-Angiotensin System (RAS) is a crtical regulator of blood pressure homeostasis. The protease renin cleaves angiotensinogen into inactive decameric peptide angiotensin-I (Ang-I). Angiotensin-converting enzyme (ACE) then cleaves C-terminal dipeptide from Ang-I to form an active octamer angiotensin-II (Ang-II), which can contribute to hypertension by promoting vascular smooth muscle vasocontriction and renal tubule sodium reabsorption. ACE can also cleave many other small peptides including the vasodialating peptide bradykinin into inactive fragment, cleave Alzheimer amyloid beta-peptide (Abeta), retard Abeta aggregation, deposition and fibril formation. ACE mutant mice display spontaneous hypotension, partial male infertility and kidney malformations. ACE is found in somatic (s-ACE) and testicular/germinal (t-ACE) isoforms. The products of renin and ACE catalysis, namely Ang1-10 and Ang1-8 can also be by another peptidase, ACE-2 to Ang1-9 and Ang1-7, respectively. ACE-2 and ACE (s-ACE and t-ACE) are made as transmembrane (TM) proteins but these enzymes also exist as soluble, truncated forms lacking the TM and cytosolic domains.\n\nACE (also known as dipeptidyl carboxypeptidase-1, DCP1; Kininase-II, ACE1) gene has been mapped at human chromosome 17q23. The s-ACE and t-ACE isoforms are generated by alternative splicing of ACE-2 gene. Somatic-ACE, a Zn (II) containing dipeptidyl carboxy peptidase is a single chain glycoprotein with a molecular mass of ~140kDa. The s-ACE enzymes from mouse (1312aa), rat (1313aa) and human (1306aa) contain two large areas of homologous sequence, each containing catalytic site and a Zn-binding region. These homologous regions are approximately half the size of whole s-ACE. The s-ACE is expressed in many somatic tissue tissues, including vascular endothelial cells, renal epithelial cells, and testicular Leydig cells. In contrast to s-ACE, the t-ACE enzymes (~80kD) from mouse (732aa), rat (775aa) and human (732aa) contain only one active site and are expressed only in sperms. The soluble ACE is present present in serum and seminal, amniotic and cerebrospinal fluids. The t-ACE is identical, from residue 37 to its C-terminus, to the second half or C-terminus of s-ACE. The t-ACE from mouse, rat and human are ~72% identical to each other in their aa seq.\n\nSource: Human somatic-ACE (MW ~170kD)was isolated from human kidney membranes by lisinopril-affinity chromatography to (same/more than)95% purity (SDS-PGE). The human samples have been shown by certified tests to be negative for HbsAg and HIV and HCV. However, all precautions must be taken to avoid contamination. \n\nSpecific Activity: ~250mU\n\nUnit Definition:\nOne unit produces 1umole of hippuric acid or His-Leu from Hippuril-His-Leu per min in 0.1M phosphate buffer-300mM NaCl, pH 8.3 at 37 degrees C. A recent lot has specific activity of 13.3mU/ug of protein. Lot specific activity is supplied with each vial.\n\nOptimum pH: 7.5-8.5\n\nForm: Supplied as a liquid in 5mM potassium phosphate, 10uM zinc sulfate, pH 8.3, 10% glycerol.\n\nApplication: Western Blot +positive control

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SPECIFICATIONS

Catalog Number

A2295-01Q

Size

250mU

Applications

WB

References

1. Crackower, M.A., Nature 417: 822 (2002). 2. Sibinga, N.E.S. & Ware, J.A., Circ. Res. 87: e1-e9 (2000). 3. Bernstein, K.E., et al., JBC 264: 11,945 (1989). 4. Tinis, S.R., et al., JBC 275: 33,238 (2000). 5. Donoghue, M., et al., Circ. Res. 87: e1-e9 (2000).