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Gene Review

CPD  -  carboxypeptidase D

Homo sapiens

Synonyms: Carboxypeptidase D, GP180, Metallocarboxypeptidase D, gp180
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Disease relevance of CPD

  • In contrast to the restricted expression in the normal adenohypophysis, CPD appeared to be widespread in the majority of adenomas, suggesting that CPD levels are increased in adenomas [1].
  • This study evaluated the expression patterns of CPE, CPD, and CPZ immunoreactivity in 48 pituitary adenomas [1].
  • Luciferase reporter assays with various size constructs containing the promoter region upstream of the start sites showed that it was active in three different cell lines, especially in the human hepatoma cell line HepG2 and the human monocytic cell line THP-1, which have high constitutive expression of CPD [2].
  • The sequence is similar (75% identity) to duck gp180, a protein that was isolated, cloned and sequenced as a hepatitis B virus-binding protein but not characterized as a carboxypeptidase [3].
  • Apparent toxicity thresholds were associated with large increases in steady-state CPD levels [4].

Psychiatry related information on CPD


High impact information on CPD

  • Substrate specificity is altered by DNA damage, such that AfXPB unwinds dsDNA with 3' extensions, but not blunt-ended dsDNA, unless it contains a lesion, as shown for CPD or (6-4) photoproducts [6].
  • The CD8+CD28- subset of IEC-activated CD8+ T cells, which express CD101 and CD103, interacts with IECs through gp180 and has regulatory function [7].
  • In contrast, gp-180-deficient neutrophils interacted in a normal fashion with endothelial monolayers, attaching to their surfaces and migrating between cell junctions to spread between the monolayers and the subjacent plastic [8].
  • Compared with normal neutrophils. gp-180-deficient neutrophils showed decreased adhesion to cold-insoluble globulin-coated plastic surfaces, and their ability to spread on this substratum was greatly impaired [8].
  • We conclude that the abnormal function of gp-180-deficient cells is unlikely to be caused by a faulty interaction with the vascular endothelium [8].

Chemical compound and disease context of CPD

  • Blood was collected into CPD or heparin immediately before and 15 min after an intravenous dose of 0.2 micrograms/kg body weight of DDAVP [9].
  • In addition, dietary supplements of anti-oxidant, alpha-tocopherol, fed to LBAM larvae were successful in reducing the toxicity of CPD [10].
  • For the purpose of understanding better the mode of action of alkanes on insects, the relationship between mortality, weight loss in oxygen enriched atmospheres and dietary antioxidants was examined using an alkane, C15 Ampol CPD and a spray oil, C23 DC-Tron NR, on lightbrown apple moth, Epiphyas postvittana Walker, (LBAM) [10].
  • We show here that gE/gI and a second glycoprotein, gB, TGN46, and another cellular protein, carboxypeptidase D, all moved to cell junctions after infection with an HSV mutant unable to produce cytoplasmic capsids [11].

Biological context of CPD


Anatomical context of CPD


Associations of CPD with chemical compounds

  • CPD is a B-type (or kininase I-type) carboxypeptidase that cleaves C-terminal basic residues from proteins and peptides, such as Arg9 from bradykinin [2].
  • Some of the constructs contained the three Cys residues present in the CPD transmembrane region, while other constructs contained Ala in place of the Cys [17].
  • Thus, the covalent attachment of palmitic acid to the Cys residues of CPD has a functional significance in the trafficking of the protein [17].
  • A construct containing the Cys residues of the CPD transmembrane domain was soluble in Triton X-100 as was endogenous palmitoylated CPD, indicating that palmitoylation does not target CPD to detergent-resistant membrane rafts [17].
  • The internalization of CPD is not substantially affected by treatment of the AtT-20 cells with brefeldin A [16].

Regulatory relationships of CPD

  • PRL/E2-induced cell-surface CPD released Arg from extracellular substrates, increased intracellular NO, promoted survival and inhibited apoptosis of MCF-7 cells [18].

Other interactions of CPD

  • Aplysia CPE and the CPD-related enzyme are candidate processing enzymes that may play a role in the processing of the ELH prohormone and other Aplysia prohormones [19].
  • A novel neuronal Aplysia enzyme was also identified by the polymerase chain reaction that was most closely related to the carboxypeptidase D (CPD)-related duck protein gp180 and the Drosophila silver gene carboxypeptidases [19].
  • Chromosomal localization of the genes for human carboxypeptidase D (CPD) and the active 50-kilodalton subunit of human carboxypeptidase N (CPN1) [20].
  • We have constructed a 1 Mb YAC and PAC contig which harbours both the SLC6A4 and the carboxypeptidase D (CPD) genes [21].
  • Highly selective expression of CPD in corticotrophs suggests that CPD plays a particularly important role in prohormone (POMC) processing in corticotrophs, with minimal or no significant roles in non-corticotrophs [22].

Analytical, diagnostic and therapeutic context of CPD


  1. Immunohistochemical localization of carboxypeptidases D, E, and Z in pituitary adenomas and normal human pituitary. Fan, X., Olson, S.J., Blevins, L.S., Allen, G.S., Johnson, M.D. J. Histochem. Cytochem. (2002) [Pubmed]
  2. Structural characterization of the human carboxypeptidase D gene and its promoter. Timblin, B., Rehli, M., Skidgel, R.A. Int. Immunopharmacol. (2002) [Pubmed]
  3. Sequence of human carboxypeptidase D reveals it to be a member of the regulatory carboxypeptidase family with three tandem active site domains. Tan, F., Rehli, M., Krause, S.W., Skidgel, R.A. Biochem. J. (1997) [Pubmed]
  4. UVB Dose-toxicity Thresholds and Steady-state DNA-photoproduct Levels During Chronic Irradiation of Inbred Xenopus laevis Tadpoles. Pandelova, I., Hewitt, S.R., Rollins-Smith, L.A., Hays, J.B. Photochem. Photobiol. (2006) [Pubmed]
  5. The utility of CPD for older adult mental health nurses. Bush, T., Meadows-Smith, D., Snowdon-Carr, V., Rao, V.B., Collishaw, H. Nursing times. (2005) [Pubmed]
  6. Conserved XPB core structure and motifs for DNA unwinding: implications for pathway selection of transcription or excision repair. Fan, L., Arvai, A.S., Cooper, P.K., Iwai, S., Hanaoka, F., Tainer, J.A. Mol. Cell (2006) [Pubmed]
  7. Expansion of CD8+ T cells with regulatory function after interaction with intestinal epithelial cells. Allez, M., Brimnes, J., Dotan, I., Mayer, L. Gastroenterology (2002) [Pubmed]
  8. Studies on the interaction between GP-18-0-deficient neutrophils and vascular endothelium. Buchanan, M.R., Crowley, C.A., Rosin, R.E., Gimbrone, M.A., Babior, B.M. Blood (1982) [Pubmed]
  9. Accumulative effect of DDAVP and heparin in increasing plasma factor VIII levels. Rock, G., Palmer, D.S. Vox Sang. (1981) [Pubmed]
  10. Evidence for oil-induced oxidative stress to larvae of the lightbrown apple moth, Epiphyas postvittana Walker (Lepidoptera: Tortricidae). Taverner, P.D., Bailey, P.T., Roush, R.T. Pest Manag. Sci. (2002) [Pubmed]
  11. Redistribution of cellular and herpes simplex virus proteins from the trans-golgi network to cell junctions without enveloped capsids. Wisner, T.W., Johnson, D.C. J. Virol. (2004) [Pubmed]
  12. Carboxypeptidase D is up-regulated in raw 264.7 macrophages and stimulates nitric oxide synthesis by cells in arginine-free medium. Hadkar, V., Skidgel, R.A. Mol. Pharmacol. (2001) [Pubmed]
  13. Mechanism of novel vitamin K analog induced growth inhibition in human hepatoma cell line. Osada, S., Carr, B.I. J. Hepatol. (2001) [Pubmed]
  14. 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]
  15. Immunohistochemical localization of carboxypeptidases E and D in the human placenta and umbilical cord. Reznik, S.E., Salafia, C.M., Lage, J.M., Fricker, L.D. J. Histochem. Cytochem. (1998) [Pubmed]
  16. Intracellular trafficking of metallocarboxypeptidase D in AtT-20 cells: localization to the trans-Golgi network and recycling from the cell surface. Varlamov, O., Fricker, L.D. J. Cell. Sci. (1998) [Pubmed]
  17. Palmitoylation of carboxypeptidase D. Implications for intracellular trafficking. Kalinina, E.V., Fricker, L.D. J. Biol. Chem. (2003) [Pubmed]
  18. Prolactin and estrogen up-regulate carboxypeptidase-d to promote nitric oxide production and survival of mcf-7 breast cancer cells. Abdelmagid, S.A., Too, C.K. Endocrinology (2008) [Pubmed]
  19. Molecular cloning of Aplysia neuronal cDNAs that encode carboxypeptidases related to mammalian prohormone processing enzymes. Fan, X., Nagle, G.T. DNA Cell Biol. (1996) [Pubmed]
  20. 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]
  21. Refined mapping of the human serotonin transporter (SLC6A4) gene within 17q11 adjacent to the CPD and NF1 genes. Shen, S., Battersby, S., Weaver, M., Clark, E., Stephens, K., Harmar, A.J. Eur. J. Hum. Genet. (2000) [Pubmed]
  22. Immunohistochemical localization and comparison of carboxypeptidases D, E, and Z, alpha-MSH, ACTH, and MIB-1 between human anterior and corticotroph cell "basophil invasion" of the posterior pituitary. Fan, X., Olson, S.J., Johnson, M.D. J. Histochem. Cytochem. (2001) [Pubmed]
  23. Diversity of ACTH-Immunoreactive Cells in the Human Adenohypophysis: An Immunohistochemical Study with Special Reference to Cluster Formation and Follicular Cell Association. Yamashita, M., Sano, T., Qian, Z.R., Kovacs, K., Horvath, E. Endocr. Pathol. (2006) [Pubmed]
  24. Preservation of neutrophils in CPD-adenine. Strauss, R.G., Crouch, J. Transfusion (1981) [Pubmed]
  25. Fetal cheek-to-cheek diameter in the prediction of mode of delivery. Abramowicz, J.S., Rana, S., Abramowicz, S. Am. J. Obstet. Gynecol. (2005) [Pubmed]
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