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Gene Review

ENPEP  -  glutamyl aminopeptidase (aminopeptidase A)

Homo sapiens

Synonyms: AP-A, APA, Aminopeptidase A, CD249, Differentiation antigen gp160, ...
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Disease relevance of ENPEP


Psychiatry related information on ENPEP

  • This paper examines existing statutes and the APA resource document, considers the variety of ways in which the goals of reform can be achieved, and recommends approaches that balance desires for public safety with the legitimate needs and concerns of the mental health professions [6].
  • Concerns about APA questionnaire on personality disorders [7].
  • Comments on the APA Panic Disorder Guideline. American Psychiatric Association [8].
  • Pathological gambling was officially defined as a psychiatric illness by APA in 1980 [9].
  • IgG to gp160 and to four peptides (gp41 immunodominant DI domain, gp41/Id; EDLKWA epitope of DIII domain, gp41/K; gp120 C-terminus, gp120/Ct; V3 loop, gp120/V3) were evaluated in all samples [10].

High impact information on ENPEP


Chemical compound and disease context of ENPEP


Biological context of ENPEP


Anatomical context of ENPEP

  • The APA was strongly immunolocalized in pericytes [19].
  • Enzymatic assays on human RCC cell lines indicated a 100% concordance between APA activity and gp160 expression [2].
  • The gp160 cDNA possesses 78% homology to the murine BP-1/6C3 antigen, a B-lymphocyte differentiation protein that exhibits aminopeptidase A (APA; EC activity [2].
  • Immunohistochemical staining in high-grade CIN and SCC tissues showed that APA was strongly expressed at the edge of lesions adjacent to cervical stromal cells [18].
  • Furthermore, APA expression and enzymatic activity were enhanced by addition of the conditioned medium (CM) from fibroblast culture, but not by heat-treated CM [18].

Associations of ENPEP with chemical compounds

  • These data indicate that the gp160 human kidney/RCC glycoprotein is human APA [2].
  • HIgher concentrations (1-10 microM) of aldosterone (ALD) stimulated APA activity to a lesser extent (x 1.25) [20].
  • APA activity was calcium-dependent and was inhibited by amastatin [20].
  • Treatment of HGECs by dexamethasone (DEX) increased ecto-APA activity in a dose- and time-dependent manner [20].
  • These results suggested the importance of tumor-stromal interaction for the regulation of APA expression in the microenvironment of cervical carcinoma and the potential role for this peptidase in regulating tumor invasion through inactivation of Ang II activity [18].

Physical interactions of ENPEP

  • In cells expressing recombinant human immunodeficiency virus (HIV) envelope glycoprotein, gp160 bound transiently to calreticulin with a peak at 10 min after its synthesis [21].
  • Here we show that CD4 binding to gp120 induces the formation and/or exposure of the gp41 HR1 coiled coil in a process that does not involve gp120 shedding and that depends on the proteolytic maturation of the gp160 envelope glycoprotein precursor [22].
  • The gp120 and gp160 specifically recognize the C-terminal heparin-binding domain of Fn (Fn-CTHBD) with a calculated KD of 2.8 x 10(-7) M for gp160 [23].
  • There was, however, a temporal association between CD4 down-modulation and the accumulation of intracellular HIV-1 gp 160/120; in addition, intracellular CD4-gp 160 complexes were identifiable in OM-10.1 cell lysates at time points following TNF-alpha induction after surface CD4 was no longer detectable [24].
  • These results provide supporting evidence that envelope-specific, complement-activating antibodies induced by infection or gp160 immunization can target HIV-1 immune complexes to CR1 [25].

Regulatory relationships of ENPEP


Other interactions of ENPEP


Analytical, diagnostic and therapeutic context of ENPEP


  1. Altered levels of acid, basic, and neutral peptidase activity and expression in human clear cell renal cell carcinoma. Varona, A., Blanco, L., López, J.I., Gil, J., Agirregoitia, E., Irazusta, J., Larrinaga, G. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  2. Molecular cloning of the human kidney differentiation antigen gp160: human aminopeptidase A. Nanus, D.M., Engelstein, D., Gastl, G.A., Gluck, L., Vidal, M.J., Morrison, M., Finstad, C.L., Bander, N.H., Albino, A.P. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  3. A phase I evaluation of the safety and immunogenicity of vaccination with recombinant gp160 in patients with early human immunodeficiency virus infection. Military Medical Consortium for Applied Retroviral Research. Redfield, R.R., Birx, D.L., Ketter, N., Tramont, E., Polonis, V., Davis, C., Brundage, J.F., Smith, G., Johnson, S., Fowler, A. N. Engl. J. Med. (1991) [Pubmed]
  4. Endoproteolytic cleavage of gp160 is required for the activation of human immunodeficiency virus. McCune, J.M., Rabin, L.B., Feinberg, M.B., Lieberman, M., Kosek, J.C., Reyes, G.R., Weissman, I.L. Cell (1988) [Pubmed]
  5. Protection of chimpanzees from infection by HIV-1 after vaccination with recombinant glycoprotein gp120 but not gp160. Berman, P.W., Gregory, T.J., Riddle, L., Nakamura, G.R., Champe, M.A., Porter, J.P., Wurm, F.M., Hershberg, R.D., Cobb, E.K., Eichberg, J.W. Nature (1990) [Pubmed]
  6. Statutory approaches to limiting psychiatrists' liability for their patients' violent acts. Appelbaum, P.S., Zonana, H., Bonnie, R., Roth, L.H. The American journal of psychiatry. (1989) [Pubmed]
  7. Concerns about APA questionnaire on personality disorders. Braude, M. The American journal of psychiatry. (1986) [Pubmed]
  8. Comments on the APA Panic Disorder Guideline. American Psychiatric Association. Pyles, R.L., Fox, R.P., Rosenblitt, D. The American journal of psychiatry. (1998) [Pubmed]
  9. Refining prevalence estimates of pathological gambling. Volberg, R.A., Steadman, H.J. The American journal of psychiatry. (1988) [Pubmed]
  10. Compartmentalization of the IgG immune response to HIV-1 in breast milk. Becquart, P., Hocini, H., Garin, B., Sépou, A., Kazatchkine, M.D., Bélec, L. AIDS (1999) [Pubmed]
  11. A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS. Zagury, D., Bernard, J., Cheynier, R., Desportes, I., Leonard, R., Fouchard, M., Reveil, B., Ittele, D., Lurhuma, Z., Mbayo, K. Nature (1988) [Pubmed]
  12. Primary aldosteronism: hypertension with a genetic basis. Gordon, R.D., Klemm, S.A., Tunny, T.J., Stowasser, M. Lancet (1992) [Pubmed]
  13. Intensive preoperative chemotherapy with colony-stimulating factor for resectable adenocarcinoma of the esophagus or gastroesophageal junction. Ajani, J.A., Roth, J.A., Ryan, M.B., Putnam, J.B., Pazdur, R., Levin, B., Gutterman, J.U., McMurtrey, M. J. Clin. Oncol. (1993) [Pubmed]
  14. The APA Task Force report on benzodiazepine dependence, toxicity, and abuse. Salzman, C. The American journal of psychiatry. (1991) [Pubmed]
  15. Enhancement of aminopeptidase A expression during angiotensin II-induced choriocarcinoma cell proliferation through AT1 receptor involving protein kinase C- and mitogen-activated protein kinase-dependent signaling pathway. Ino, K., Uehara, C., Kikkawa, F., Kajiyama, H., Shibata, K., Suzuki, T., Khin, E.E., Ito, M., Takeuchi, M., Itakura, A., Mizutani, S. J. Clin. Endocrinol. Metab. (2003) [Pubmed]
  16. High-resolution genetic map of the human glutamyl aminopeptidase gene (ENPEP). Li, L., Wu, Q., Barnoski, B.L., Cooper, M.D. Genomics (1997) [Pubmed]
  17. Proteolytic fragmentation reveals the oligomeric and domain structure of porcine aminopeptidase A. Hesp, J.R., Hooper, N.M. Biochemistry (1997) [Pubmed]
  18. Regulation of aminopeptidase A expression in cervical carcinoma: role of tumor-stromal interaction and vascular endothelial growth factor. Suganuma, T., Ino, K., Shibata, K., Nomura, S., Kajiyama, H., Kikkawa, F., Tsuruoka, N., Mizutani, S. Lab. Invest. (2004) [Pubmed]
  19. Localization of angiotensin II, the AT1 receptor, angiotensin-converting enzyme, aminopeptidase A, adipocyte-derived leucine aminopeptidase, and vascular endothelial growth factor in the human ovary throughout the menstrual cycle. Harata, T., Ando, H., Iwase, A., Nagasaka, T., Mizutani, S., Kikkawa, F. Fertil. Steril. (2006) [Pubmed]
  20. Receptor-mediated induction of aminopeptidase A (APA) of human glomerular epithelial cells (HGEC) by glucocorticoids. Stefanovic, V., Vlahovic, P., Ardaillou, N., Ardaillou, R. FEBS Lett. (1991) [Pubmed]
  21. Calreticulin interacts with newly synthesized human immunodeficiency virus type 1 envelope glycoprotein, suggesting a chaperone function similar to that of calnexin. Otteken, A., Moss, B. J. Biol. Chem. (1996) [Pubmed]
  22. Small-molecule inhibitors of HIV-1 entry block receptor-induced conformational changes in the viral envelope glycoproteins. Si, Z., Madani, N., Cox, J.M., Chruma, J.J., Klein, J.C., Schön, A., Phan, N., Wang, L., Biorn, A.C., Cocklin, S., Chaiken, I., Freire, E., Smith, A.B., Sodroski, J.G. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  23. Heparin-binding domain of human fibronectin binds HIV-1 gp120/160 and reduces virus infectivity. Bozzini, S., Falcone, V., Conaldi, P.G., Visai, L., Biancone, L., Dolei, A., Toniolo, A., Speziale, P. J. Med. Virol. (1998) [Pubmed]
  24. Oscillation of the human immunodeficiency virus surface receptor is regulated by the state of viral activation in a CD4+ cell model of chronic infection. Butera, S.T., Perez, V.L., Wu, B.Y., Nabel, G.J., Folks, T.M. J. Virol. (1991) [Pubmed]
  25. Complement-activating antibodies in sera from infected individuals and vaccinated volunteers that target human immunodeficiency virus type 1 to complement receptor type 1 (CR1, CD35). Zhou, J., Montefiori, D.C. Virology (1996) [Pubmed]
  26. HIV-1 envelope glycoproteins induce activation of activated protein-1 in CD4+ T cells. Chirmule, N., Goonewardena, H., Pahwa, S., Pasieka, R., Kalyanaraman, V.S., Pahwa, S. J. Biol. Chem. (1995) [Pubmed]
  27. gp160 of HIV or anti-CD4 monoclonal antibody ligation of CD4 induces inhibition of JNK and ERK-2 activities in human peripheral CD4+ T lymphocytes. Jabado, N., Pallier, A., Jauliac, S., Fischer, A., Hivroz, C. Eur. J. Immunol. (1997) [Pubmed]
  28. Adhesion mediated by intercellular adhesion molecule 1 attenuates the potency of antibodies that block HIV-1 gp160-dependent syncytium formation. Berman, P.W., Nakamura, G.R. AIDS Res. Hum. Retroviruses (1994) [Pubmed]
  29. HIV-1 gp160 induces transforming growth factor-beta production in human PBMC. Hu, R., Oyaizu, N., Than, S., Kalyanaraman, V.S., Wang, X.P., Pahwa, S. Clin. Immunol. Immunopathol. (1996) [Pubmed]
  30. Brain aminopeptidases and hypertension. Banegas, I., Prieto, I., Vives, F., Alba, F., Gasparo, M., Segarra, A.B., Hermoso, F., Dur??n, R., Ram??rez, M. Journal of the renin-angiotensin-aldosterone system : JRAAS (2006) [Pubmed]
  31. Ultrastructural localization of aminopeptidase A/angiotensinase and placental leucine aminopeptidase/oxytocinase in chorionic villi of human placenta. Ito, N., Nomura, S., Iwase, A., Ito, T., Ino, K., Nagasaka, T., Tsujimoto, M., Kobayashi, M., Mizutani, S. Early Hum. Dev. (2003) [Pubmed]
  32. Purification and characterization of human placental microsomal aminopeptidase: immunological difference between placental microsomal aminopeptidase and pregnancy serum cystyl-aminopeptidase. Kurauchi, O., Mizutani, S., Okano, K., Narita, O., Tomoda, Y. Enzyme (1986) [Pubmed]
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