Neprilysin
https://www.uniprot.org/uniprotkb/P08473/entry
Function
Thermolysin-like specificity, but is almost confined on acting on polypeptides of up to 30 amino acids (PubMed:6349683, PubMed:6208535, PubMed:15283675, PubMed:8168535).
Biologically important in the destruction of opioid peptides such as Met- and Leu-enkephalins by cleavage of a Gly-Phe bond (PubMed:6349683, PubMed:17101991).
Catalyzes cleavage of bradykinin, substance P and neurotensin peptides (PubMed:6208535).
Able to cleave angiotensin-1, angiotensin-2 and angiotensin 1-9 (PubMed:6349683, PubMed:15283675).
Involved in the degradation of atrial natriuretic factor (ANF) and brain natriuretic factor (BNP(1-32)) (PubMed:2531377, PubMed:2972276, PubMed:16254193).
Displays UV-inducible elastase activity toward skin preelastic and elastic fibers (PubMed:20876573).8 Publications
Miscellaneous
Important cell surface marker in the diagnostic of human acute lymphocytic leukemia.3 Publications
Catalytic activity
Preferential cleavage of polypeptides between hydrophobic residues, particularly with Phe or Tyr at P1'.5 Publications
EC:3.4.24.11 (UniProtKB | ENZYME | Rhea)
Furin
https://www.uniprot.org/uniprotkb/P09958/entry
Function
function
Ubiquitous endoprotease within constitutive secretory pathways capable of cleavage at the RX(K/R)R consensus motif (PubMed:11799113, PubMed:1629222, PubMed:1713771, PubMed:2251280, PubMed:24666235, PubMed:25974265, PubMed:7592877, PubMed:7690548, PubMed:9130696).
Mediates processing of TGFB1, an essential step in TGF-beta-1 activation (PubMed:7737999).
Converts through proteolytic cleavage the non-functional Brain natriuretic factor prohormone into its active hormone BNP(1-32) (PubMed:20489134, PubMed:21763278).
By mediating processing of accessory subunit ATP6AP1/Ac45 of the V-ATPase, regulates the acidification of dense-core secretory granules in islets of Langerhans cells (By similarity).By Similarity12 Publications
(Microbial infection) Cleaves and activates diphtheria toxin DT.1 Publication
(Microbial infection) Cleaves and activates anthrax toxin protective antigen (PA).2 Publications
(Microbial infection) Cleaves and activates HIV-1 virus Envelope glycoprotein gp160.1 Publication
(Microbial infection) Required for H7N1 and H5N1 influenza virus infection probably by cleaving hemagglutinin.1 Publication
(Microbial infection) Able to cleave S.pneumoniae serine-rich repeat protein PsrP.1 Publication
(Microbial infection) Facilitates human coronaviruses EMC and SARS-CoV-2 infections by proteolytically cleaving the spike protein at the monobasic S1/S2 cleavage site. This cleavage is essential for spike protein-mediated cell-cell fusion and entry into human lung cells.2 Publications
(Microbial infection) Facilitates mumps virus infection by proteolytically cleaving the viral fusion protein F.1 Publication
Catalytic activity
Release of mature proteins from their proproteins by cleavage of -Arg-Xaa-Yaa-Arg-|-Zaa- bonds, where Xaa can be any amino acid and Yaa is Arg or Lys. Releases albumin, complement component C3 and von Willebrand factor from their respective precursors.16 Publications
EC:3.4.21.75 (UniProtKB | ENZYME | Rhea)
Cofactor
Ca2+ (UniProtKB | Rhea| CHEBI:29108 )4 Publications
Note: Binds 3 calcium ions per subunit.3 Publications
Activity regulation
Inhibited by the not secondly cleaved propeptide (PubMed:9130696, PubMed:11799113).
Inhibited by m-guanidinomethyl-phenylacetyl-Arg-Val-Arg-(amidomethyl)-benzamidine (m-guanidinomethyl-Phac-RVR-Amb) and 4-guanidinomethyl-phenylacetyl-Arg-Tle-Arg-4-amidinobenzylamide (MI-1148) (PubMed:24666235, PubMed:25974265).
Inhibited by Decanoyl-Arg-Val-Lys-Arg-chloromethylketone (decanoyl-RVKR-CMK) (PubMed:32362314).
Inhibited by heparin/heparan sulfate-binding (PubMed:2408021).6 Publications
pH Dependence
Optimum pH is 6.0.1 Publication
Atrial natriuretic peptide-converting enzyme
https://www.uniprot.org/uniprotkb/Q9Y5Q5/entry
Alternative names
Corin
Heart-specific serine proteinase ATC2
Pro-ANP-converting enzyme
Transmembrane protease serine 10
Function
function
Serine-type endopeptidase involved in atrial natriuretic peptide (NPPA) and brain natriuretic peptide (NPPB) processing (PubMed:10880574, PubMed:21288900, PubMed:20489134, PubMed:21763278).
Converts through proteolytic cleavage the non-functional propeptides NPPA and NPPB into their active hormones, ANP and BNP(1-32) respectively, thereby regulating blood pressure in the heart and promoting natriuresis, diuresis and vasodilation (PubMed:10880574, PubMed:21288900, PubMed:20489134, PubMed:21763278).
Proteolytic cleavage of pro-NPPA also plays a role in female pregnancy by promoting trophoblast invasion and spiral artery remodeling in uterus (PubMed:22437503).
Also acts as a regulator of sodium reabsorption in kidney (By similarity).By Similarity5 Publications
Isoform 2
Has weaker endopeptidase activity compared to isoform 1.
Miscellaneous
Initially named CORIN due to its abundant expression in the heart.1 Publication
Activity regulation
Inhibited in a dose-dependent manner by non-specific trypsin-like serine protease inhibitors including benzamidine.
