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Cpn1  -  carboxypeptidase N, polypeptide 1

Mus musculus

Synonyms: 0610011F20Rik, 50 kDa, CPN, Carboxypeptidase N catalytic chain, Carboxypeptidase N polypeptide 1, ...
 
 
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Disease relevance of Cpn1

  • We have purified a 50-kDa heparanase from human hepatoma and placenta, and now report cloning of the cDNA and gene encoding this enzyme [1].
  • A 50-kDa cellular factor, E4F, has been implicated in mediating trans activation of the adenovirus E4 gene by the 289R E1A(13S) protein [2].
  • In this report, we compare the 50-kDa protein with that found in pp60v-src-hsp90-p50 complexes immunoprecipitated from Rous sarcoma virus-transformed cells with antibodies to pp60v-src [3].
  • Furthermore, D-1 fusion protein induced in mice antibodies that immunoprecipitated a 50-kDa component from cultured human melanoma cells [4].
  • Binding of the carboxy-terminal 50 kDa HC fragment of tetanus toxin to polysialogangliosides is important for this initial cell binding step [5].
 

High impact information on Cpn1

 

Chemical compound and disease context of Cpn1

  • Groups of mice were immunized i.n. with the nontoxic C-terminal 50-kDa portion of tetanus toxin (fragment C [Frg C]) either alone or mixed with PT-9K/129G, PTX, or cholera toxin (CT) or were immunized subcutaneously (s.c.) with an equivalent amount of Frg C adsorbed to alhydrogel [11].
 

Biological context of Cpn1

 

Anatomical context of Cpn1

  • These antibodies react on immunoblots with one major mast cell protein band of 50 kDa [14].
  • Interestingly, zymosan and PMA induce the myristoylation of the 50-kDa protein in C3H/HeJ macrophages, but not the acylation of the 68-kDa and 42-kDa doublet species [15].
  • Here, we examined the processing of membrane form of Pref-1A to release the 50-kDa soluble form that inhibits adipocyte differentiation [16].
  • The 50-kDa protein apparently makes a major contribution to the total copper-binding activity of the mouse hepatic cytosol and may play a significant role in intracellular copper metabolism [17].
  • The most reactive platelet protein, however, is the 50-kDa protein, which is either absent or nonreactive in fibroblast membranes [18].
 

Associations of Cpn1 with chemical compounds

  • Carboxypeptidase R (EC 3.4.17.20; CPR) and carboxypeptidase N (EC 3. 4.17.3; CPN) cleave carboxyl-terminal arginine and lysine residues from biologically active peptides such as kinins and anaphylatoxins, resulting in regulation of their biological activity [19].
  • We demonstrate that SDF-1alpha in serum and plasma lacks the carboxy terminal lysine, and depletion of CPN from serum and plasma significantly reduces the SDF-1alpha carboxypeptidase activity [20].
  • CSPG-I has a mass of approximately 970 kDa with multiple chondroitin sulfate chains (average of 50 kDa each) and a core protein of approximately 370 kDa including oligosaccharides [21].
  • Furthermore, treatment of the 80- and 50-kDa subunits, synthesized in the presence of tunicamycin, with chondroitinase ABC, neuraminidase, and endo-alpha-N-acetyl galactosaminidase reduced their apparent molecular masses to 60 and 25 kDa, respectively [22].
  • Hexokinases are comprised of two highly homologous approximately 50-kDa halves and are product-inhibited by glucose-6-P [23].
 

Physical interactions of Cpn1

 

Enzymatic interactions of Cpn1

  • This 50-kDa product was highly phosphorylated as compared to the bulk of the normal 55-kDa form of vimentin [27].
 

Co-localisations of Cpn1

  • No role has been assigned to the 66-, 44-, or 13-kDa proteins but the 50-kDa band comigrates with tubulin and the 18-kDa band comigrates with calmodulin [28].
  • Using an anti-arylacetamide antiserum the primary protein adduct detected following administration of 3'-hydroxyacetanilide (300 and 600 mg/kg) to mice was a 50 kDa microsomal protein that co-migrated with cytochrome P450 2E1 [29].
 

Regulatory relationships of Cpn1

 

Other interactions of Cpn1

 

Analytical, diagnostic and therapeutic context of Cpn1

  • The ligand binding subunit of this complex is a protein with an apparent molecular mass of approximately 50 kDa as judged by gel permeation chromatography [7].
  • In this study, we investigated a novel 50-kDa ERK-like protein (ERK-50) that is up-regulated significantly in addition to ERK1,2 after treatment with the dual APL [38].
  • The antibody specifically labels two proteins of approximately 70 and 50 kDa in Western blot analysis [39].
  • Immunoprecipitation and SDS-PAGE analysis demonstrated KCA-3 to have a m.w. of approximately 50 kDa under both reducing and nonreducing conditions [40].
  • Lysine binding fragments of plasmin, isolated from macrophage-conditioned media utilizing affinity chromatography, appeared as a major (48 kDa) and two minor bands (42 and 50 kDa) in SDS-polyacrylamide gel electrophoresis and were immunoreactive with anti-kringle 1-3 IgG [41].

References

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  2. The adenovirus E1A-regulated transcription factor E4F is generated from the human homolog of nuclear factor phiAP3. Fernandes, E.R., Rooney, R.J. Mol. Cell. Biol. (1997) [Pubmed]
  3. A 50-kDa cytosolic protein complexed with the 90-kDa heat shock protein (hsp90) is the same protein complexed with pp60v-src hsp90 in cells transformed by the Rous sarcoma virus. Whitelaw, M.L., Hutchison, K., Perdew, G.H. J. Biol. Chem. (1991) [Pubmed]
  4. Cloning and in vitro expression of a melanoma-associated antigen immunogenic in patients with melanoma. Hayashibe, K., Mishima, Y., Ferrone, S. J. Immunol. (1991) [Pubmed]
  5. Analysis of mutants of tetanus toxin Hc fragment: ganglioside binding, cell binding and retrograde axonal transport properties. Sinha, K., Box, M., Lalli, G., Schiavo, G., Schneider, H., Groves, M., Siligardi, G., Fairweather, N. Mol. Microbiol. (2000) [Pubmed]
  6. A brain detoxifying enzyme for organophosphorus nerve poisons. Nomura, D.K., Leung, D., Chiang, K.P., Quistad, G.B., Cravatt, B.F., Casida, J.E. Proc. Natl. Acad. Sci. U.S.A. (2005) [Pubmed]
  7. A 12(S)-hydroxyeicosatetraenoic acid receptor interacts with steroid receptor coactivator-1. Kurahashi, Y., Herbertsson, H., Söderström, M., Rosenfeld, M.G., Hammarström, S. Proc. Natl. Acad. Sci. U.S.A. (2000) [Pubmed]
  8. Characterization of mammalian translocase of inner mitochondrial membrane (Tim44) isolated from diabetic newborn mouse kidney. Wada, J., Kanwar, Y.S. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  9. Surface protein phosphorylation by ecto-protein kinase is required for the maintenance of hippocampal long-term potentiation. Chen, W., Wieraszko, A., Hogan, M.V., Yang, H.A., Kornecki, E., Ehrlich, Y.H. Proc. Natl. Acad. Sci. U.S.A. (1996) [Pubmed]
  10. Exon-intron organization and sequence comparison of human and murine T11 (CD2) genes. Diamond, D.J., Clayton, L.K., Sayre, P.H., Reinherz, E.L. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  11. A mutant pertussis toxin molecule that lacks ADP-ribosyltransferase activity, PT-9K/129G, is an effective mucosal adjuvant for intranasally delivered proteins. Roberts, M., Bacon, A., Rappuoli, R., Pizza, M., Cropley, I., Douce, G., Dougan, G., Marinaro, M., McGhee, J., Chatfield, S. Infect. Immun. (1995) [Pubmed]
  12. Characterization of mouse carboxypeptidase N small active subunit gene structure. Matthews, K.W., Wetsel, R.A. J. Immunol. (2001) [Pubmed]
  13. Expression of the third complement component (C3) and carboxypeptidase N small subunit (CPN1) during mouse embryonic development. Matthews, K.W., Drouin, S.M., Liu, C., Martin, J.F., Skidgel, R.A., Wetsel, R.A. Dev. Comp. Immunol. (2004) [Pubmed]
  14. Identification, purification, and characterization of a mast cell-associated cytolytic factor related to tumor necrosis factor. Young, J.D., Liu, C.C., Butler, G., Cohn, Z.A., Galli, S.J. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  15. Bacterial lipopolysaccharides, phorbol myristate acetate, and zymosan induce the myristoylation of specific macrophage proteins. Aderem, A.A., Keum, M.M., Pure, E., Cohn, Z.A. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  16. Ectodomain shedding of preadipocyte factor 1 (Pref-1) by tumor necrosis factor alpha converting enzyme (TACE) and inhibition of adipocyte differentiation. Wang, Y., Sul, H.S. Mol. Cell. Biol. (2006) [Pubmed]
  17. Identification and purification of a self-associating copper-binding protein from mouse hepatic cytosols. Seo, H.C., Ettinger, M.J. J. Biol. Chem. (1993) [Pubmed]
  18. Identification of platelet membrane proteins that interact with amino-terminal peptides of pp60c-src. Feder, D., Bishop, J.M. J. Biol. Chem. (1991) [Pubmed]
  19. Pro-carboxypeptidase R is an acute phase protein in the mouse, whereas carboxypeptidase N is not. Sato, T., Miwa, T., Akatsu, H., Matsukawa, N., Obata, K., Okada, N., Campbell, W., Okada, H. J. Immunol. (2000) [Pubmed]
  20. 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]
  21. Differentiation of 3T3-L1 preadipocytes with 3-isobutyl-1-methylxanthine and dexamethasone stimulates cell-associated and soluble chondroitin 4-sulfate proteoglycans. Calvo, J.C., Rodbard, D., Katki, A., Chernick, S., Yanagishita, M. J. Biol. Chem. (1991) [Pubmed]
  22. The predominant form of secreted colony stimulating factor-1 is a proteoglycan. Price, L.K., Choi, H.U., Rosenberg, L., Stanley, E.R. J. Biol. Chem. (1992) [Pubmed]
  23. Structure/function relationships in hexokinase. Site-directed mutational analyses and characterization of overexpressed fragments implicate different functions for the N- and C-terminal halves of the enzyme. Arora, K.K., Filburn, C.R., Pedersen, P.L. J. Biol. Chem. (1993) [Pubmed]
  24. Metabolic activation and immunochemical localization of liver protein adducts of the nonsteroidal anti-inflammatory drug diclofenac. Hargus, S.J., Amouzedeh, H.R., Pumford, N.R., Myers, T.G., McCoy, S.C., Pohl, L.R. Chem. Res. Toxicol. (1994) [Pubmed]
  25. Deoxyribonucleic acid-protein interactions associated with transcriptional initiation of the mouse testis-specific cytochrome c gene. Yiu, G.K., Murray, M.T., Hecht, N.B. Biol. Reprod. (1997) [Pubmed]
  26. Two distinct porcine natural killer lytic trigger molecules as PNK-E/G7 molecular complex. Wierda, W.G., Johnson, B.D., Dato, M.E., Kim, Y.B. Cell. Immunol. (1993) [Pubmed]
  27. Vimentin phosphorylation by p37mos protein kinase in vitro and generation of a 50-kDa cleavage product in v-mos-transformed cells. Singh, B., Arlinghaus, R.B. Virology (1989) [Pubmed]
  28. The in vivo biosynthesis of embryonic proteins after maternal administration of phenytoin in the mouse. Hicks, H.E., Banes, A.J. Proc. Soc. Exp. Biol. Med. (1985) [Pubmed]
  29. The acetaminophen regioisomer 3'-hydroxyacetanilide inhibits and covalently binds to cytochrome P450 2E1. Halmes, N.C., Samokyszyn, V.M., Hinton, T.W., Hinson, J.A., Pumford, N.R. Toxicol. Lett. (1998) [Pubmed]
  30. Asb6, an adipocyte-specific ankyrin and SOCS box protein, interacts with APS to enable recruitment of elongins B and C to the insulin receptor signaling complex. Wilcox, A., Katsanakis, K.D., Bheda, F., Pillay, T.S. J. Biol. Chem. (2004) [Pubmed]
  31. Separate elements in the 3' untranslated region of the mouse protamine 1 mRNA regulate translational repression and activation during murine spermatogenesis. Fajardo, M.A., Haugen, H.S., Clegg, C.H., Braun, R.E. Dev. Biol. (1997) [Pubmed]
  32. Effects of recombinant insulin-like growth factor-binding protein-4 on bone formation parameters in mice. Miyakoshi, N., Richman, C., Qin, X., Baylink, D.J., Mohan, S. Endocrinology (1999) [Pubmed]
  33. Gene 33/RALT is induced by hypoxia in cardiomyocytes, where it promotes cell death by suppressing phosphatidylinositol 3-kinase and extracellular signal-regulated kinase survival signaling. Xu, D., Patten, R.D., Force, T., Kyriakis, J.M. Mol. Cell. Biol. (2006) [Pubmed]
  34. Characterization of transforming growth factors produced by the insulin-independent teratoma-derived cell line 1246-3A. Yamada, Y., Serrero, G. J. Cell. Physiol. (1989) [Pubmed]
  35. Structure of the gene encoding mouse adipose differentiation-related protein (ADRP). Eisinger, D.P., Serrero, G. Genomics (1993) [Pubmed]
  36. Cytochrome P450 isoforms in human fetal tissues related to phenobarbital-inducible forms in the mouse. Mäenpää, J., Rane, A., Raunio, H., Honkakoski, P., Pelkonen, O. Biochem. Pharmacol. (1993) [Pubmed]
  37. Further characterization of the interaction between L-selectin and its endothelial ligands. Imai, Y., Lasky, L.A., Rosen, S.D. Glycobiology (1992) [Pubmed]
  38. A 50-kDa ERK-like protein is up-regulated by a dual altered peptide ligand that suppresses myasthenia gravis-associated responses. Ben-David, H., Aruna, B.V., Seger, R., Sela, M., Mozes, E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  39. Identification of a 30-base pair regulatory element and novel DNA binding protein that regulates the human GLUT4 promoter in transgenic mice. Oshel, K.M., Knight, J.B., Cao, K.T., Thai, M.V., Olson, A.L. J. Biol. Chem. (2000) [Pubmed]
  40. Anti-KCA-3, a monoclonal antibody reactive with a rat complement C3 receptor, distinguishes Kupffer cells from other macrophages. Maruiwa, M., Mizoguchi, A., Russell, G.J., Narula, N., Stronska, M., Mizoguchi, E., Rabb, H., Arnaout, M.A., Bhan, A.K. J. Immunol. (1993) [Pubmed]
  41. Macrophage formation of angiostatin during inflammation. A byproduct of the activation of plasminogen. Falcone, D.J., Khan, K.M., Layne, T., Fernandes, L. J. Biol. Chem. (1998) [Pubmed]
 
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