CPN, CPB2 cleave C3a, C5a

Stable Identifier
Reaction [transition]
Homo sapiens
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Carboxypeptidase N (CPN) is able to inactivate the complement anaphylatoxins C3a, C4a, and C5a (Bokisch & Müller-Eberhard 1970), 74-77 amino acid peptides that are released during complement activation. They mediate smooth muscle contraction, vasodilation, release of histamine from mast cells, and chemotaxis of selective bone marrow derived myeloid cells. C3a and C5a mediate their activities by binding the C3a receptor (C3AR1) and C5a receptor (C5AR1), respectively. CPN regulates these anaphylatoxins by removing their carboxy-terminal arginines, which reduces their biological activities 10-100-fold (Ember et al. 1998).
Carboxypeptidase B2 (Plasma carboxypeptidase B, Thrombin-activable fibrinolysis inhibitor, TAF1, CPB2) also can convert C3a and C5a to C3a-desArg and C5a-desArg (Campbell et al. 2002). C3a-desArg cannot bind C3AR1, and C5a-desArg has a 90% decrease in pro-inflammatory activity compared to C5a (Sayah et al. 2003).

CPN is a tetramer comprised of two heterodimers each consisting of a CPN1 and CPN2 subunit (Levin et al. 1982, Keil et al. 2007). The catalytic CPN1 subunit ranges in size from 48 kDa to 55 kDa. This reflects processing by trypsin or plasmin, which can remove a C-terminal segment to produce the 48 kDa form, and cleave at Arg218-Arg219 to produce two peptide chains held together in an active conformation by non-covalent bonds (Levin et al. 1982, Quagraine et al. 2005). This step increases the catalytic activity of CPN towards chromogenic substrates.

Literature References
PubMed ID Title Journal Year
4098172 Anaphylatoxin inactivator of human plasma: its isolation and characterization as a carboxypeptidase

Müller-Eberhard, HJ, Bokisch, VA

J. Clin. Invest. 1970
11939578 Inactivation of C3a and C5a octapeptides by carboxypeptidase R and carboxypeptidase N

Okada, H, Okada, N, Campbell, WD, Lazoura, E

Microbiol. Immunol. 2002
Catalyst Activity

metallocarboxypeptidase activity of CPN, CBP2 [extracellular region]

Orthologous Events
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