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Gene Review

LNPEP  -  leucyl/cystinyl aminopeptidase

Homo sapiens

Synonyms: CAP, Cystinyl aminopeptidase, IRAP, Insulin-regulated membrane aminopeptidase, Insulin-responsive aminopeptidase, ...
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Disease relevance of LNPEP


High impact information on LNPEP

  • PLAP is not secreted by SRD-12B cells, cholesterol auxotrophs that lack S1P [2].
  • In sterol-deprived cells, cleavage by both proteases leads to PLAP secretion [2].
  • Grb2 binds with its COOH-terminal SH3 domain to a PLAP motif within TNFR-I and with its NH2-terminal SH3 domain to SOS (son of sevenless) [3].
  • Infection by HIV-PLAP of peripheral blood mononuclear cells (PBMCs) and T cell lines leads to rapid depletion of CD4(+) T cells and induction of apoptosis [4].
  • A monoclonal antibody (H17E2) against placental alkaline phosphatase (PLAP) and testicular placental-like alkaline phosphatase was labelled with indium-111 and used in radioimmunoscintigraphy of 15 patients known or suspected to have germ-cell carcinoma of the testis or carcinoma of the ovary or cervix [5].

Chemical compound and disease context of LNPEP


Biological context of LNPEP


Anatomical context of LNPEP


Associations of LNPEP with chemical compounds


Physical interactions of LNPEP

  • The 5'-flanking region of human P-LAP gene contained DNA-binding motifs for several ubiquitous transcription factors such as SP1 and AP2 [19].

Regulatory relationships of LNPEP


Other interactions of LNPEP


Analytical, diagnostic and therapeutic context of LNPEP


  1. Placental leucine aminopeptidase (P-LAP) and glucose transporter 4 (GLUT4) expression in benign, borderline, and malignant ovarian epithelia. Shibata, K., Kajiyama, H., Mizokami, Y., Ino, K., Nomura, S., Mizutani, S., Terauchi, M., Kikkawa, F. Gynecol. Oncol. (2005) [Pubmed]
  2. Molecular identification of the sterol-regulated luminal protease that cleaves SREBPs and controls lipid composition of animal cells. Sakai, J., Rawson, R.B., Espenshade, P.J., Cheng, D., Seegmiller, A.C., Goldstein, J.L., Brown, M.S. Mol. Cell (1998) [Pubmed]
  3. Identification of Grb2 as a novel binding partner of tumor necrosis factor (TNF) receptor I. Hildt, E., Oess, S. J. Exp. Med. (1999) [Pubmed]
  4. HIV-1 directly kills CD4+ T cells by a Fas-independent mechanism. Gandhi, R.T., Chen, B.K., Straus, S.E., Dale, J.K., Lenardo, M.J., Baltimore, D. J. Exp. Med. (1998) [Pubmed]
  5. Indium-111 labelled monoclonal antibody to placental alkaline phosphatase in in the detection of neoplasms of testis, ovary, and cervix. Epenetos, A.A., Snook, D., Hooker, G., Begent, R., Durbin, H., Oliver, R.T., Bodmer, W.F., Lavender, J.P. Lancet (1985) [Pubmed]
  6. P-LAP/IRAP-induced cell proliferation and glucose uptake in endometrial carcinoma cells via insulin receptor signaling. Shibata, K., Kajiyama, H., Ino, K., Nawa, A., Nomura, S., Mizutani, S., Kikkawa, F. BMC Cancer (2007) [Pubmed]
  7. Lipid domain structure of the plasma membrane revealed by patching of membrane components. Harder, T., Scheiffele, P., Verkade, P., Simons, K. J. Cell Biol. (1998) [Pubmed]
  8. Possible role of placental leucine aminopeptidase in the antiproliferative effect of oxytocin in human endometrial adenocarcinoma. Suzuki, Y., Shibata, K., Kikkawa, F., Kajiyama, H., Ino, K., Nomura, S., Tsujimoto, M., Mizutani, S. Clin. Cancer Res. (2003) [Pubmed]
  9. A novel role for placental leucine aminopeptidase (P-LAP) as a determinant of chemoresistance in endometrial carcinoma cells. Kondo, C., Shibata, K., Terauchi, M., Kajiyama, H., Ino, K., Nomura, S., Nawa, A., Mizutani, S., Kikkawa, F. Int. J. Cancer (2006) [Pubmed]
  10. Expression of placental leucine aminopeptidase is associated with a poor outcome in endometrial endometrioid adenocarcinoma. Shibata, K., Kikkawa, F., Suzuki, Y., Mizokami, Y., Kajiyama, H., Ino, K., Nomura, S., Nagasaka, T., Mizutani, S. Oncology (2004) [Pubmed]
  11. Existence of placental leucine aminopeptidase/oxytocinase/insulin-regulated membrane aminopeptidase in human endometrial epithelial cells. Toda, S., Ando, H., Nagasaka, T., Tsukahara, S., Nomura, M., Kotani, Y., Nomura, S., Kikkawa, F., Tsujimoto, M., Mizutani, S. J. Clin. Endocrinol. Metab. (2002) [Pubmed]
  12. Structure of the human oxytocinase/insulin-regulated aminopeptidase gene and localization to chromosome 5q21. Rasmussen, T.E., Pedraza-Díaz, S., Hardré, R., Laustsen, P.G., Carríon, A.G., Kristensen, T. Eur. J. Biochem. (2000) [Pubmed]
  13. The oxytocinase subfamily of M1 aminopeptidases. Tsujimoto, M., Hattori, A. Biochim. Biophys. Acta (2005) [Pubmed]
  14. The Formin family protein, formin homolog overexpressed in spleen, interacts with the insulin-responsive aminopeptidase and profilin IIa. Tojo, H., Kaieda, I., Hattori, H., Katayama, N., Yoshimura, K., Kakimoto, S., Fujisawa, Y., Presman, E., Brooks, C.C., Pilch, P.F. Mol. Endocrinol. (2003) [Pubmed]
  15. Separation of insulin signaling into distinct GLUT4 translocation and activation steps. Funaki, M., Randhawa, P., Janmey, P.A. Mol. Cell. Biol. (2004) [Pubmed]
  16. Evidence that the angiotensin IV (AT(4)) receptor is the enzyme insulin-regulated aminopeptidase. Albiston, A.L., McDowall, S.G., Matsacos, D., Sim, P., Clune, E., Mustafa, T., Lee, J., Mendelsohn, F.A., Simpson, R.J., Connolly, L.M., Chai, S.Y. J. Biol. Chem. (2001) [Pubmed]
  17. Interaction of the Akt Substrate, AS160, with the Glucose Transporter 4 Vesicle Marker Protein, Insulin-Regulated Aminopeptidase. Peck, G.R., Ye, S., Pham, V., Fernando, R.N., Macaulay, S.L., Chai, S.Y., Albiston, A.L. Mol. Endocrinol. (2006) [Pubmed]
  18. Angiotensin AT4 ligands are potent, competitive inhibitors of insulin regulated aminopeptidase (IRAP). Lew, R.A., Mustafa, T., Ye, S., McDowall, S.G., Chai, S.Y., Albiston, A.L. J. Neurochem. (2003) [Pubmed]
  19. Structural organization of the 5'-end and chromosomal assignment of human placental leucine aminopeptidase/insulin-regulated membrane aminopeptidase gene. Horio, J., Nomura, S., Okada, M., Katsumata, Y., Nakanishi, Y., Kumano, Y., Takami, S., Kinoshita, M., Tsujimoto, M., Nakazato, H., Mizutani, S. Biochem. Biophys. Res. Commun. (1999) [Pubmed]
  20. Placental leucine aminopeptidase might regulate the effects of oxytocin with resolution in endothelial cells. Sano, M., Itakura, A., Ito, M., Takeuchi, M., Okada, M., Kotani, T., Mizutani, S., Kikkawa, F. Med. Sci. Monit. (2005) [Pubmed]
  21. Ap-2 and Ikaros regulate transcription of human placental leucine aminopeptidase/oxytocinase gene. Ito, T., Nomura, S., Okada, M., Katsumata, Y., Kikkawa, F., Rogi, T., Tsujimoto, M., Mizutani, S. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  22. Human leukocyte-derived arginine aminopeptidase. The third member of the oxytocinase subfamily of aminopeptidases. Tanioka, T., Hattori, A., Masuda, S., Nomura, Y., Nakayama, H., Mizutani, S., Tsujimoto, M. J. Biol. Chem. (2003) [Pubmed]
  23. Distribution of adipocyte-derived leucine aminopeptidase (A-LAP)/ER-aminopeptidase (ERAP)-1 in human uterine endometrium. Shibata, D., Ando, H., Iwase, A., Nagasaka, T., Hattori, A., Tsujimoto, M., Mizutani, S. J. Histochem. Cytochem. (2004) [Pubmed]
  24. The insulin-regulated aminopeptidase: a companion and regulator of GLUT4. Keller, S.R. Front. Biosci. (2003) [Pubmed]
  25. Placental leucine aminopeptidase/oxytocinase in maternal serum and placenta during normal pregnancy. Yamahara, N., Nomura, S., Suzuki, T., Itakura, A., Ito, M., Okamoto, T., Tsujimoto, M., Nakazato, H., Mizutani, S. Life Sci. (2000) [Pubmed]
  26. Immunoaffinity purification and characterization of native placental leucine aminopeptidase/oxytocinase from human placenta. Nakanishi, Y., Nomura, S., Okada, M., Ito, T., Katsumata, Y., Kikkawa, F., Hattori, A., Tsujimoto, M., Mizutani, S. Placenta (2000) [Pubmed]
  27. Interleukin-1beta stimulates placental leucine aminopeptidase/oxytocinase expression in BeWo choriocarcinoma cells. Ikoma, Y., Nomura, S., Ito, T., Katsumata, Y., Nakata, M., Iwanaga, K., Okada, M., Kikkawa, F., Tamakoshi, K., Nagasaka, T., Tsujimoto, M., Mizutani, S. Mol. Hum. Reprod. (2003) [Pubmed]
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