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CNDP2  -  CNDP dipeptidase 2 (metallopeptidase M20...

Homo sapiens

Synonyms: CN2, CNDP dipeptidase 2, CPGL, Cytosolic non-specific dipeptidase, FLJ10830, ...
 
 
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Disease relevance of CNDP2

  • Crigler-Najjar syndrome types I and II (CN1 and CN2) are usually inherited as autosomal recessive conditions and are characterized by non-hemolytic unconjugated hyperbilirubinaemia [1].
  • High CN1 activities were found in sera of patients with sarcoidosis, and elevated CN2 activities were found in lung cancer [2].
  • Efficacy of haemodiafiltration treatment with PEPA dialysis membranes in plasma free light chain removal in a patient with primary amyloidosis [3].
  • A recent study of patients with lymphoma has shown that patients in the PEPA program can tolerate higher doses of chemotherapy than can control patients and that they have lower frequency of complications caused by infection [4].
 

High impact information on CNDP2

  • Three peptides, CN1, CN2, and CN4, which represent approximately 85% of the total amino acids of H315 were isolated and further characterized by electrophoresis and paper chromatography [5].
  • The NH2-terminal cyanogen bromide peptide, CN2, of in vivo and in vitro H315 co-migrated exactly on gel electrophoresis under conditions which completely resolved two proteins differing in size by only 14 amino acids [5].
  • With computational analysis, CPGL was located at chromosome 18q22.3 and was a homologue of peptidase family M20 [6].
  • RESULTS: From our previous cDNA transfection screening, we identified a gene named CPGL and its isoform, CPGL-B [6].
  • CPGL was expressed in all adult and fetal tissues, whereas its isoform, CPGL-B, lacking exons 3 and 4, was expressed in all fetal tissues but only in liver and placenta of adult tissues [6].
 

Biological context of CNDP2

 

Anatomical context of CNDP2

  • Electrophysiological studies suggested that PEPA activates the neural network much more potently in the medial prefrontal cortex (mPFC) than in the basolateral amygdala and hippocampal CA1 field [10].
 

Associations of CNDP2 with chemical compounds

  • The Michaelis-Menten constants are: CN1 4.59 +/- 0.03 mmol/l; CN2 37.26 +/- 3.49 mmol/l. CN2 can be inhibited by EDTA (76%), dimercaprolum (97%) and phenanthroline (98%) [2].
  • Kininase I (carboxypeptidase N; EC 3.4.17.3) consists of carboxypeptidase N1 (CN1) and carboxypeptidase N2 (CN2); these two enzymes can be differentiated by their activities towards hippuryl-L-arginine and hippuryl-L-lysine, respectively [2].
  • Only 1-methyl-4-phenyl-4-propionoxypiperidine (MPPP) and 1-[2-phenylethyl]-4-phenyl-4-acetoxypiperidine (PEPAP) interacted significantly (Ki 1.6 microM and 0.3 microM, respectively) [7].
  • The horizontal cell AMPA current was enhanced by cyclothiazide but not by PEPA, indicating the presence of the flip receptor variant [11].
  • RESULTS: Two tumor-targeting prodrugs CNF1 and CNF2 bearing 5-FdUrd conjugated with a common cyclic peptide CNGRC by succinate and glutarate linkers, respectively, and their control compounds CN1 and CN2 without 5-FdUrd moiety were synthesized and identified [12].
 

Other interactions of CNDP2

  • CN2 presents intermediate levels of hyperbilirubinaemia as a result of an incomplete deficiency of hepatic UGT1A1 activity [1].
 

Analytical, diagnostic and therapeutic context of CNDP2

  • Sequence analysis showed that anserinase is a member of the M20A metallopeptidase subfamily in MEROPS peptidase database, to which 'serum' carnosinase (EC 3.4.13.20) and cytosolic nonspecific dipeptidase (EC 3.4.13.18, CNDP) belong [13].
  • Intraperitoneal injection of PEPA 15 min before extinction training remarkably reduced the duration of freezing responses during the extinction training and test, compared with the vehicle-injected control mice [10].
  • Quantitative PCR studies suggested the pronounced expression of PEPA-preferring AMPA receptor subunits (GluR3 and GluR4) and a splice variant (flop) in the mPFC [10].

References

  1. Spectrum of UGT1A1 mutations in Crigler-Najjar (CN) syndrome patients: identification of twelve novel alleles and genotype-phenotype correlation. Servedio, V., d'Apolito, M., Maiorano, N., Minuti, B., Torricelli, F., Ronchi, F., Zancan, L., Perrotta, S., Vajro, P., Boschetto, L., Iolascon, A. Hum. Mutat. (2005) [Pubmed]
  2. A simple spectrophotometric assay of carboxypeptidase N (kininase I) in human serum. Schweisfurth, H., Reinhart, E., Heinrich, J., Brugger, E. J. Clin. Chem. Clin. Biochem. (1983) [Pubmed]
  3. Efficacy of haemodiafiltration treatment with PEPA dialysis membranes in plasma free light chain removal in a patient with primary amyloidosis. Machiguchi, T., Tamura, T., Yoshida, H. Nephrol. Dial. Transplant. (2002) [Pubmed]
  4. Antibiotic prophylaxis in cancer patients: regimens of oral, nonabsorbable antibiotics for prevention of infection during induction of remission. Bodey, G.P. Rev. Infect. Dis. (1981) [Pubmed]
  5. Initiation and translation in vitro of mRNA for MOPC 315 immunoglobulin heavy chain and characterization of translation product. Bedard, D.L., Huang, R.C. J. Biol. Chem. (1977) [Pubmed]
  6. Identification of carboxypeptidase of glutamate like-B as a candidate suppressor in cell growth and metastasis in human hepatocellular carcinoma. Zhang, P., Chan, D.W., Zhu, Y., Li, J.J., Ng, I.O., Wan, D., Gu, J. Clin. Cancer Res. (2006) [Pubmed]
  7. Designer drugs that are potent inhibitors of CYP2D6. Pritzker, D., Kanungo, A., Kilicarslan, T., Tyndale, R.F., Sellers, E.M. Journal of clinical psychopharmacology. (2002) [Pubmed]
  8. A Hong Kong influenza hemagglutinin light chain: amino acid sequence of cyanogen bromide fragment CN2. Ward, C.W., Dopheide, T.A. Virology (1979) [Pubmed]
  9. Confirmation of the regional assignment of peptidase A (PEPA) to 18q23 by gene dosage studies. Junien, C., de Grouchy, J., Turleau, C., Serville, F. Ann. Genet. (1980) [Pubmed]
  10. Facilitation of extinction learning for contextual fear memory by PEPA: a potentiator of AMPA receptors. Zushida, K., Sakurai, M., Wada, K., Sekiguchi, M. J. Neurosci. (2007) [Pubmed]
  11. Glutamate receptor subtypes in human retinal horizontal cells. Shen, W., Finnegan, S.G., Slaughter, M.M. Vis. Neurosci. (2004) [Pubmed]
  12. A new class of 5-fluoro-2'-deoxyuridine prodrugs conjugated with a tumor-homing cyclic peptide CNGRC by ester linkers: synthesis, reactivity, and tumor-cell-selective cytotoxicity. Zhang, Z., Hatta, H., Tanabe, K., Nishimoto, S. Pharm. Res. (2005) [Pubmed]
  13. Purification and sequence identification of anserinase. Yamada, S., Tanaka, Y., Ando, S. FEBS J. (2005) [Pubmed]
 
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