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Gene Review

CPN1  -  carboxypeptidase N, polypeptide 1

Homo sapiens

Synonyms: ACBP, Anaphylatoxin inactivator, Arginine carboxypeptidase, CPN, Carboxypeptidase N catalytic chain, ...
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Disease relevance of CPN1


Psychiatry related information on CPN1

  • This paper outlines the development and piloting of a measure of professional stress for community mental health nurses, the CPN Stress Questionnaire (Revised) [6].
  • The measures used included the Maslach Human Services Survey, the CPN Stress Questionnaire, the Psychnurse Methods of Coping Questionnaire, the Rosenberg Self-Esteem Scale and the General Health Questionnaire GHQ-12 [7].
  • The CPN and eating disorders [8].
  • This paper is based on the author's experience of using the Q sort technique with BA Social Sciences (BASS) students, and the community psychiatric nursing (CPN, ENB No 811 course) [9].

High impact information on CPN1

  • VPE activity induced by RGP-1 was augmented by kininase inhibitors, inhibited by a kallikrein inhibitor and unaffected by an antihistamine drug [10].
  • The kininase activity of endothelial cells was partially inhibited by antibody to human lung converting enzyme [11].
  • The chemotactic factor inactivator (CFI) isolated from human serum contains a kininase activity that causes extensive hydrolysis of bradykinin [12].
  • Using a new biochemical assay for measuring the carboxy-terminal cleavage activity, we purified from serum and plasma a peptidase that specifically removes the carboxy-terminal lysine from SDF-1alpha and identified it as carboxypeptidase N (CPN, also known as kininase I, arginine carboxypeptidase, and anaphylotoxin inactivator) [13].
  • We tested the hypothesis that the copper present in bile--the major route of elimination of the metal from the body--is derived exclusively from hepatocytes by administering radiocopper (64Cu or 67Cu)-labeled ionic Cu, desialylated (AsCPN) or intact human ceruloplasmin (CPN), intravenously, to rats with cannulated bile ducts [14].

Chemical compound and disease context of CPN1


Biological context of CPN1

  • We have prepared and crystallized the recombinant C-terminally truncated catalytic domain of human CPN1, and have determined and refined its 2.1 A crystal structure [18].
  • Modeling of the Pro-Phe-Arg C-terminal end of the natural substrate bradykinin into the active site shows that the S1' pocket of CPN1 might better accommodate P1'-Lys than Arg residues, in agreement with CPN's preference for cleaving off C-terminal Lys residues [18].
  • In tetrameric CPN, each CPN1 subunit might interact with the central leucine-rich repeat tandem of the cognate CPN2 subunit via a unique hydrophobic surface patch wrapping around the catalytic domain-TT interface, exposing the two active centers [18].
  • In an in-vivo complement activation model in guinea pigs, BX 528 showed minimal inhibition of plasma CPN activity up to 60 mg/kg with peak plasma concentrations up to 250 micro M [19].
  • The third level of control of eosinophil chemotaxis is composed of inactivators and inhibitors of chemotactic stimuli and is exemplified by degradation of C5a by anaphylatoxin inactivator or chemotactic factor inactivator and of ECF-A by carboxypeptidase-A or aminopeptidases [20].

Anatomical context of CPN1


Associations of CPN1 with chemical compounds

  • Three Thr residues at the distal TT edge of CPN1 are O-linked to N-acetyl glucosamine sugars; equivalent sites in the membrane-anchored CPM are occupied by basic residues probably involved in membrane interaction [18].
  • Human carboxypeptidase N (CPN), a member of the CPN/E subfamily of "regulatory" metallo-carboxypeptidases, is an extracellular glycoprotein synthesized in the liver and secreted into the blood, where it controls the activity of vasoactive peptide hormones, growth factors and cytokines by specifically removing C-terminal basic residues [18].
  • CPN is a member of a larger family of carboxypeptidases, many of which also cleave arginine and lysine [25].
  • The C5a degradation product, C5a des Arg, is rapidly formed after exposure of C5a to serum carboxypeptidase N and may represent the relevant C5-derived inflammatory peptide in vivo [26].
  • Endothelial cells also possess enzymatic activities, in particular ACE/kininase activity, which can alter local levels of angiotensin II and bradykinin [27].

Regulatory relationships of CPN1

  • The kinin activity from incubated HAE plasma was susceptible to kininase inactivation and was blocked by a Bk2 receptor antagonist [28].

Other interactions of CPN1


Analytical, diagnostic and therapeutic context of CPN1

  • Alterations in activities of anaphylatoxin inactivator and chemotactic factor inactivator during hemodialysis [22].
  • Ninety-nine neurotic patients from a controlled trial of CPN v. psychiatric out-patient aftercare were followed up seven years later [34].
  • TETR-PCR for C. pneumoniae with primer set CPN 90-CPN 91 was 90% sensitive and 93.3% specific compared with a nested PCR with primer set CP1/2-CPC/D for clinical respiratory samples [35].
  • Arginine carboxypeptidase (CPR) is a labile enzyme present in human serum which is unrelated to carboxypeptidase N. In this study we demonstrate that CPR exists in a precursor form in plasma and can be converted to the active form by trypsin and presumable trypsin-like enzymes [36].
  • Treatment of rat plasma with an excess of trypsin in the presence of a kininase inhibitor generated T-kinin immunoreactivity equivalent to 455 +/- 71 pmol/ml (mean +/- S.E.M.; n = 9) and this immunoreactivity was eluted from a reversed-phase HPLC column as a single peak with the same retention time as synthetic T-kinin [37].


  1. Pharmacologic intervention with angiotensin II and kininase inhibitor enhanced efficacy of radioimmunotherapy in human colon cancer xenografts. Kinuya, S., Yokoyama, K., Kawashima, A., Hiramatsu, T., Konishi, S., Shuke, N., Watanabe, N., Takayama, T., Michigishi, T., Tonami, N. J. Nucl. Med. (2000) [Pubmed]
  2. Decreased synthesis of serum carboxypeptidase N (SCPN) in familial SCPN deficiency. Mathews, K.P., Curd, J.G., Hugli, T.E. J. Clin. Immunol. (1986) [Pubmed]
  3. Blood kallikrein. Kinin system in acute pancreatitis. Orlov, V., Belyakov, N. Am. J. Gastroenterol. (1978) [Pubmed]
  4. Activation of the kallikrein kinin system in interstitial cystitis. Rosamilia, A., Clements, J.A., Dwyer, P.L., Kende, M., Campbell, D.J. J. Urol. (1999) [Pubmed]
  5. Characterization of the carboxypeptidase involved in the proteolytic cleavage of the influenza haemagglutinin. Garten, W., Klenk, H.D. J. Gen. Virol. (1983) [Pubmed]
  6. Stress and the community mental health nurse: the development of a measure. Brown, D., Leary, J., Carson, J., Bartlett, H., Fagin, L. Journal of psychiatric and mental health nursing. (1995) [Pubmed]
  7. Stressors, moderators and stress outcomes: findings from the All-Wales Community Mental Health Nurse Study. Edwards, D., Burnard, P., Coyle, D., Fothergill, A., Hannigan, B. Journal of psychiatric and mental health nursing. (2000) [Pubmed]
  8. The CPN and eating disorders. Burgoyne, G. Nursing. (1990) [Pubmed]
  9. The Q sort theory and technique. Nyatanga, L. Nurse education today. (1989) [Pubmed]
  10. Pathogenesis of periodontitis: a major arginine-specific cysteine proteinase from Porphyromonas gingivalis induces vascular permeability enhancement through activation of the kallikrein/kinin pathway. Imamura, T., Pike, R.N., Potempa, J., Travis, J. J. Clin. Invest. (1994) [Pubmed]
  11. Metabolism of vasoactive peptides by human endothelial cells in culture. Angiotensin I converting enzyme (kininase II) and angiotensinase. Johnson, A.R., Erdös, E.G. J. Clin. Invest. (1977) [Pubmed]
  12. Characterization of the protease activity in the chemotactic factor inactivator. Ward, P.A., Ozols, J. J. Clin. Invest. (1976) [Pubmed]
  13. Identification of carboxypeptidase N as an enzyme responsible for C-terminal cleavage of stromal cell-derived factor-1alpha in the circulation. Davis, D.A., Singer, K.E., De La Luz Sierra, M., Narazaki, M., Yang, F., Fales, H.M., Yarchoan, R., Tosato, G. Blood (2005) [Pubmed]
  14. Origins of biliary copper. Kressner, M.S., Stockert, R.J., Morell, A.G., Sternlieb, I. Hepatology (1984) [Pubmed]
  15. Bradykinin promotes ischemic norepinephrine release in guinea pig and human hearts. Hatta, E., Maruyama, R., Marshall, S.J., Imamura, M., Levi, R. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  16. Umbilical plasma kininase I activity in fetal hypoxia. Tsukahara, Y., Itakura, A., Ohno, Y., Ando, H., Mizutani, S. Horm. Metab. Res. (2003) [Pubmed]
  17. Aldosterone, kallikrein, kininase I and II in normal and hypertension complicated pregnancy. Ferrazzani, S., Leardi, P., Magnotti, D.L., De Carolis, S., Moneta, E., Porcelli, G., Volpe, A.R., Menini, E., Liberale, I. Adv. Exp. Med. Biol. (1989) [Pubmed]
  18. Crystal structure of the human carboxypeptidase N (kininase I) catalytic domain. Keil, C., Maskos, K., Than, M., Hoopes, J.T., Huber, R., Tan, F., Deddish, P.A., Erdös, E.G., Skidgel, R.A., Bode, W. J. Mol. Biol. (2007) [Pubmed]
  19. A novel inhibitor of activated thrombin-activatable fibrinolysis inhibitor (TAFIa) - Part I: Pharmacological characterization. Wang, Y.X., Zhao, L., Nagashima, M., Vincelette, J., Sukovich, D., Li, W., Subramanyam, B., Yuan, S., Emayan, K., Islam, I., Hrvatin, P., Bryant, J., Light, D.R., Vergona, R., Morser, J., Buckman, B.O. Thromb. Haemost. (2007) [Pubmed]
  20. Modulation of human eosinophil polymorphonuclear leukocyte migration and function. Goetzl, E.J. Am. J. Pathol. (1976) [Pubmed]
  21. Kininase I-type carboxypeptidases enhance nitric oxide production in endothelial cells by generating bradykinin B1 receptor agonists. Sangsree, S., Brovkovych, V., Minshall, R.D., Skidgel, R.A. Am. J. Physiol. Heart Circ. Physiol. (2003) [Pubmed]
  22. Alterations in activities of anaphylatoxin inactivator and chemotactic factor inactivator during hemodialysis. McCormick, J.R., Kreutzer, D.L., Keating, H.J., Hupp, J., Despins, A., Moore, M. Am. J. Pathol. (1982) [Pubmed]
  23. Kininase II-type enzymes. Their putative role in muscle energy metabolism. Dragović, T., Minshall, R., Jackman, H.L., Wang, L.X., Erdös, E.G. Diabetes (1996) [Pubmed]
  24. Human nasal mucosal carboxypeptidase: activity, location, and release. Ohkubo, K., Baraniuk, J.N., Merida, M., Hausfeld, J.N., Okada, H., Kaliner, M.A. J. Allergy Clin. Immunol. (1995) [Pubmed]
  25. Carboxypeptidase N: a pleiotropic regulator of inflammation. Matthews, K.W., Mueller-Ortiz, S.L., Wetsel, R.A. Mol. Immunol. (2004) [Pubmed]
  26. A direct in vivo comparison of the inflammatory properties of human C5a and C5a des Arg in human skin. Swerlick, R.A., Yancey, K.B., Lawley, T.J. J. Immunol. (1988) [Pubmed]
  27. Paracrine modulation of heart cell function by endothelial cells. Shah, A.M. Cardiovasc. Res. (1996) [Pubmed]
  28. Hereditary angioneurotic oedema: characterization of plasma kinin and vascular permeability-enhancing activities. Shoemaker, L.R., Schurman, S.J., Donaldson, V.H., Davis, A.E. Clin. Exp. Immunol. (1994) [Pubmed]
  29. Chromosomal localization of the genes for human carboxypeptidase D (CPD) and the active 50-kilodalton subunit of human carboxypeptidase N (CPN1). Riley, D.A., Tan, F., Miletich, D.J., Skidgel, R.A. Genomics (1998) [Pubmed]
  30. Characterization of a prolyl endopeptidase (kininase) from human urine using fluorogenic quenched substrates. Quinto, B.M., Juliano, M.A., Hirata, I., Carmona, A.K., Juliano, L., Casarini, D.E. Int. J. Biochem. Cell Biol. (2000) [Pubmed]
  31. Bradykinin and des-Arg(9)-bradykinin metabolic pathways and kinetics of activation of human plasma. Cyr, M., Lepage, Y., Blais, C., Gervais, N., Cugno, M., Rouleau, J.L., Adam, A. Am. J. Physiol. Heart Circ. Physiol. (2001) [Pubmed]
  32. Angiotensin converting enzyme (ACE) and neprilysin hydrolyze neuropeptides: a brief history, the beginning and follow-ups to early studies. Skidgel, R.A., Erdös, E.G. Peptides (2004) [Pubmed]
  33. Kallikrein-like esteroprotease activity and kininase activity in submandibular gland from a mutant mouse with human cystic fibrosis like alterations. Dodera Martínez, G., Vila, S.B., Catanzaro, O.L., Pivetta, O.H. Life Sci. (1988) [Pubmed]
  34. Care of chronic neurotic out-patients by community psychiatric nurses. A long-term follow-up study. Burns, T., Paykel, E.S., Ezekiel, A., Lemon, S. The British journal of psychiatry : the journal of mental science. (1991) [Pubmed]
  35. Touchdown enzyme time release-PCR for detection and identification of Chlamydia trachomatis, C. pneumoniae, and C. psittaci using the 16S and 16S-23S spacer rRNA genes. Madico, G., Quinn, T.C., Boman, J., Gaydos, C.A. J. Clin. Microbiol. (2000) [Pubmed]
  36. Pro-carboxypeptidase R cleaves bradykinin following activation. Shinohara, T., Sakurada, C., Suzuki, T., Takeuchi, O., Campbell, W., Ikeda, S., Okada, N., Okada, H. Int. Arch. Allergy Immunol. (1994) [Pubmed]
  37. Measurement of T-kinin in rat plasma using a specific radioimmunoassay. O'Harte, F., Smith, D.D., Lanspa, S.J., Conlon, J.M. Regul. Pept. (1992) [Pubmed]
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