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Gene Review

MME  -  membrane metallo-endopeptidase

Homo sapiens

Synonyms: Atriopeptidase, CALLA, CD10, Common acute lymphocytic leukemia antigen, EPN, ...
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Disease relevance of MME


Psychiatry related information on MME


High impact information on MME


Chemical compound and disease context of MME


Biological context of MME


Anatomical context of MME

  • We find that CRI-positive cells and CD5 B cells both co-express slgD but fail to bind peanut agglutinin or MAbs specific for CD10, indicating that both cell types reside in the mantle zones of secondary B cell follicles [19].
  • This is probably due to a lack of sensitivity of this method, the level of NEP activity in Jurkat T cells being 3-5% of that measured in B cell lines [20].
  • Anti-CD10 monoclonal antibodies (mAbs) recognized the CD10+ B cell line Raji, but not Jurkat cells as assessed by FACS analysis [20].
  • CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation [21].
  • Recently, inhibition of CD10/NEP was found to reduce the concentration of metenkephalin needed to activate human and invertebrate granulocytes by several orders of magnitude [21].

Associations of MME with chemical compounds

  • We investigated the mechanisms of NEP regulation of cell migration in PC cells, including regulation of phosphorylation on tyrosine of focal adhesion kinase (FAK) [1].
  • The CD10 cell surface enzyme is known to hydrolyze a variety of biologically active peptides including met-enkephalin, formyl-met-leu-phe (f-MLP), and substance P [21].
  • Bradykinin (0.1 mmol/l) was inactivated in the presence and absence of inhibitors by rat skeletal muscle NEP, as measured by high-performance liquid chromatography [22].
  • Here we describe the crystal structure of the extracellular domain (residues 52-749) of human NEP complexed with the generic metalloproteinase inhibitor phosphoramidon at 2.1 A resolution [23].
  • Similarly, (S)-[[1-[(2-biphenyl-4-ylethyl)carbamoyl]-4-(2-fluorophenyl)but-3- yny l]amino]methyl]phosphonic acid (56), an arylacetylene amino phosphonate amide, had IC50's of 33 nM and 6.5 microM for ECE-1 and NEP, respectively [24].

Physical interactions of MME


Enzymatic interactions of MME


Regulatory relationships of MME

  • The effects of neurokinin A (NKA) and human hemokinin-1 (hHK-1) in tissues from pregnant but not from nonpregnant women were enhanced by the inhibition of neprilysin [32].
  • The present data suggest that NEP may be involved in the circulation control by degrading PAMP as well as ANP [33].
  • Soluble recombinant neprilysin induces aggrecanase-mediated cleavage of aggrecan in cartilage explant cultures [34].
  • Stimulation of the expression or activity of alpha-secretase or neprilysin has been shown to enhance Abeta degradation [35].
  • These data indicate that neprilysin proteolytically inactivates fibroblast growth factor-2, resulting in negative regulation of angiogenesis [36].

Other interactions of MME

  • Lineage commitment of the CD34+ cells into the erythroid lineage was assessed by the coexpression of high levels of the CD71 antigen, the myeloid lineage by coexpression of the CD33 antigen and the B-lymphoid lineage by the CD10 antigen [37].
  • The expression of aminopeptidase-N and neutral endopeptidase in human ovarian tissue was examined using specific monoclonal antibodies for each of these peptidases and histochemical staining for enzyme activity [38].
  • To better understand the nature of the signal responsible for the targeting of ECE-1b to the intracellular compartment, we have constructed several ECE/NEP chimaeric proteins and expressed them by transfection into Madin-Darby canine kidney (MDCK) cells [25].
  • However, there was a highly significant augmentation in the NEP-inhibited segments, consistent with an inhibition of ET-1 degradation (median difference, 16.8; 95% CI, -23.5, -10.4; P =.002, Wilcoxon) [39].
  • RESULTS: Reduced DPP IV activity in serum and reduced NEP activity in BAL fluid were found in healthy smokers compared with non-smokers [40].

Analytical, diagnostic and therapeutic context of MME


  1. Neutral endopeptidase inhibits prostate cancer cell migration by blocking focal adhesion kinase signaling. Sumitomo, M., Shen, R., Walburg, M., Dai, J., Geng, Y., Navarro, D., Boileau, G., Papandreou, C.N., Giancotti, F.G., Knudsen, B., Nanus, D.M. J. Clin. Invest. (2000) [Pubmed]
  2. Organization of the gene encoding common acute lymphoblastic leukemia antigen (neutral endopeptidase 24.11): multiple miniexons and separate 5' untranslated regions. D'Adamio, L., Shipp, M.A., Masteller, E.L., Reinherz, E.L. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  3. Effects of recombinant neutral endopeptidase (EC on the growth of lung cancer cell lines in vitro and in vivo. Bunn, P.A., Helfrich, B.A., Brenner, D.G., Chan, D.C., Dykes, D.J., Cohen, A.J., Miller, Y.E. Clin. Cancer Res. (1998) [Pubmed]
  4. Endothelin-converting enzyme-1 inhibition and growth of human glioblastoma cells. Berger, Y., Dehmlow, H., Blum-Kaelin, D., Kitas, E.A., Löffler, B.M., Aebi, J.D., Juillerat-Jeanneret, L. J. Med. Chem. (2005) [Pubmed]
  5. Increased expression of profibrotic neutral endopeptidase and bradykinin type 1 receptors in stenotic aortic valves. Helske, S., Laine, M., Kupari, M., Lommi, J., Turto, H., Nurmi, L., Tikkanen, I., Werkkala, K., Lindstedt, K.A., Kovanen, P.T. Eur. Heart J. (2007) [Pubmed]
  6. Distinct subcellular expression patterns of neutral endopeptidase (CD10) in prostate cancer predict diverging clinical courses in surgically treated patients. Fleischmann, A., Schlomm, T., Huland, H., Köllermann, J., Simon, P., Mirlacher, M., Salomon, G., Chun, F.H., Steuber, T., Simon, R., Sauter, G., Graefen, M., Erbersdobler, A. Clin. Cancer Res. (2008) [Pubmed]
  7. Neprylisin decreases uniformly in Alzheimer's disease and in normal aging. Russo, R., Borghi, R., Markesbery, W., Tabaton, M., Piccini, A. FEBS Lett. (2005) [Pubmed]
  8. Association of the Neprilysin gene with susceptibility to late-onset Alzheimer's disease. Sakai, A., Ujike, H., Nakata, K., Takehisa, Y., Imamura, T., Uchida, N., Kanzaki, A., Yamamoto, M., Fujisawa, Y., Okumura, K., Kuroda, S. Dementia and geriatric cognitive disorders. (2004) [Pubmed]
  9. Neuronal neprilysin overexpression is associated with attenuation of Abeta-related spatial memory deficit. Poirier, R., Wolfer, D.P., Welzl, H., Tracy, J., Galsworthy, M.J., Nitsch, R.M., Mohajeri, M.H. Neurobiol. Dis. (2006) [Pubmed]
  10. Novel selective inhibitors of neutral endopeptidase for the treatment of female sexual arousal disorder. Synthesis and activity of functionalized glutaramides. Pryde, D.C., Maw, G.N., Planken, S., Platts, M.Y., Sanderson, V., Corless, M., Stobie, A., Barber, C.G., Russell, R., Foster, L., Barker, L., Wayman, C., Van Der Graaf, P., Stacey, P., Morren, D., Kohl, C., Beaumont, K., Coggon, S., Tute, M. J. Med. Chem. (2006) [Pubmed]
  11. Relationship of serum neutral endopeptidase E.C. activity to alcohol consumption. Frette, C., Pezet, S., El Nabout, R.A., Bertrand, J.P., Pham, Q.T., Kauffmann, F., Lafuma, C. Alcohol. Clin. Exp. Res. (1998) [Pubmed]
  12. Racecadotril in the treatment of acute watery diarrhea in children. Salazar-Lindo, E., Santisteban-Ponce, J., Chea-Woo, E., Gutierrez, M. N. Engl. J. Med. (2000) [Pubmed]
  13. Neutral endopeptidase 24.11 loss in metastatic human prostate cancer contributes to androgen-independent progression. Papandreou, C.N., Usmani, B., Geng, Y., Bogenrieder, T., Freeman, R., Wilk, S., Finstad, C.L., Reuter, V.E., Powell, C.T., Scheinberg, D., Magill, C., Scher, H.I., Albino, A.P., Nanus, D.M. Nat. Med. (1998) [Pubmed]
  14. Molecular cloning of the common acute lymphoblastic leukemia antigen (CALLA) identifies a type II integral membrane protein. Shipp, M.A., Richardson, N.E., Sayre, P.H., Brown, N.R., Masteller, E.L., Clayton, L.K., Ritz, J., Reinherz, E.L. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  15. Differential expression of the CD10 antigen (neutral endopeptidase) in primary versus metastatic malignant melanomas of the skin. Kanitakis, J., Narvaez, D., Claudy, A. Melanoma Res. (2002) [Pubmed]
  16. Vasopeptidase inhibition: a new concept in blood pressure management. Burnett, J.C. Journal of hypertension. Supplement : official journal of the International Society of Hypertension. (1999) [Pubmed]
  17. cDNA arrays and immunohistochemistry identification of CD10/CALLA expression in hepatocellular carcinoma. Xiao, S.Y., Wang, H.L., Hart, J., Fleming, D., Beard, M.R. Am. J. Pathol. (2001) [Pubmed]
  18. Down-regulation and inactivation of neutral endopeptidase 24.11 (enkephalinase) in human neutrophils. Erdös, E.G., Wagner, B., Harbury, C.B., Painter, R.G., Skidgel, R.A., Fa, X.G. J. Biol. Chem. (1989) [Pubmed]
  19. Relationship of the CD5 B cell to human tonsillar lymphocytes that express autoantibody-associated cross-reactive idiotypes. Kipps, T.J., Duffy, S.F. J. Clin. Invest. (1991) [Pubmed]
  20. Jurkat T cells express a functional neutral endopeptidase activity (CALLA) involved in T cell activation. Mari, B., Checler, F., Ponzio, G., Peyron, J.F., Manie, S., Farahifar, D., Rossi, B., Auberger, P. EMBO J. (1992) [Pubmed]
  21. CD10 (CALLA)/neutral endopeptidase 24.11 modulates inflammatory peptide-induced changes in neutrophil morphology, migration, and adhesion proteins and is itself regulated by neutrophil activation. Shipp, M.A., Stefano, G.B., Switzer, S.N., Griffin, J.D., Reinherz, E.L. Blood (1991) [Pubmed]
  22. Kininase II-type enzymes. Their putative role in muscle energy metabolism. Dragović, T., Minshall, R., Jackman, H.L., Wang, L.X., Erdös, E.G. Diabetes (1996) [Pubmed]
  23. Structure of human neutral endopeptidase (Neprilysin) complexed with phosphoramidon. Oefner, C., D'Arcy, A., Hennig, M., Winkler, F.K., Dale, G.E. J. Mol. Biol. (2000) [Pubmed]
  24. Design and synthesis of potent, selective inhibitors of endothelin-converting enzyme. Wallace, E.M., Moliterni, J.A., Moskal, M.A., Neubert, A.D., Marcopulos, N., Stamford, L.B., Trapani, A.J., Savage, P., Chou, M., Jeng, A.Y. J. Med. Chem. (1998) [Pubmed]
  25. The N-terminal segment of endothelin-converting enzyme (ECE)-1b contains a di-leucine motif that can redirect neprilysin to an intracellular compartment in Madin-Darby canine kidney (MDCK) cells. Cailler, F., Zappulla, J.P., Boileau, G., Crine, P. Biochem. J. (1999) [Pubmed]
  26. Detection of the p110 beta subunit of phosphatidylinositol 3-kinase complexed with neutral endopeptidase. Shen, R., Milowsky, M.I., Ozaki, N., Navarro, D., Sumitomo, M., Xu, Y., Nanus, D.M. Anticancer Res. (2002) [Pubmed]
  27. Clearance of brain natriuretic peptide in patients with chronic heart failure: indirect evidence for a neutral endopeptidase mechanism but against an atrial natriuretic peptide clearance receptor mechanism. Lang, C.C., Motwani, J.G., Coutie, W.J., Struthers, A.D. Clin. Sci. (1992) [Pubmed]
  28. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP-27, but not PACAP-38) degradation by the neutral endopeptidase EC Gourlet, P., Vandermeers, A., Robberecht, P., Deschodt-Lanckman, M. Biochem. Pharmacol. (1997) [Pubmed]
  29. CD10/neutral endopeptidase 24.11 is phosphorylated by casein kinase II and coassociates with other phosphoproteins including the lyn src-related kinase. Ganju, R.K., Shpektor, R.G., Brenner, D.G., Shipp, M.A. Blood (1996) [Pubmed]
  30. Receptors mediating the effects of substance P and neurokinin A on mucus secretion and smooth muscle tone of the ferret trachea: potentiation by an enkephalinase inhibitor. Webber, S.E. Br. J. Pharmacol. (1989) [Pubmed]
  31. Angiotension-(1-7) and antihypertensive mechanisms. Ferrario, C.M. J. Nephrol. (1998) [Pubmed]
  32. Regulation of the stimulant actions of neurokinin a and human hemokinin-1 on the human uterus: a comparison with histamine. Pennefather, J.N., Patak, E., Ziccone, S., Lilley, A., Pinto, F.M., Page, N.M., Story, M.E., Grover, S., Candenas, M.L. Biol. Reprod. (2006) [Pubmed]
  33. Proadrenomedullin N-terminal 20 peptide is rapidly cleaved by neutral endopeptidase. Nagatomo, Y., Kitamura, K., Kangawa, K., Fujimoto, Y., Eto, T. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  34. Soluble recombinant neprilysin induces aggrecanase-mediated cleavage of aggrecan in cartilage explant cultures. Chevrier, A., Mort, J.S., Crine, P., Hoemann, C.D., Buschmann, M.D. Arch. Biochem. Biophys. (2001) [Pubmed]
  35. Disease-modifying therapies in Alzheimer's disease : how far have we come? H??ll, M., Berger, M., Heneka, M. Drugs (2006) [Pubmed]
  36. Neprilysin Inhibits Angiogenesis via Proteolysis of Fibroblast Growth Factor-2. Goodman, O.B., Febbraio, M., Simantov, R., Zheng, R., Shen, R., Silverstein, R.L., Nanus, D.M. J. Biol. Chem. (2006) [Pubmed]
  37. Sequential generations of hematopoietic colonies derived from single nonlineage-committed CD34+CD38- progenitor cells. Terstappen, L.W., Huang, S., Safford, M., Lansdorp, P.M., Loken, M.R. Blood (1991) [Pubmed]
  38. Differential expression of aminopeptidase-N on human ovarian granulosa and theca cells. Fujiwara, H., Maeda, M., Imai, K., Fukuoka, M., Yasuda, K., Horie, K., Takakura, K., Taii, S., Mori, T. J. Clin. Endocrinol. Metab. (1992) [Pubmed]
  39. Inhibition of neointima formation in an organ culture of human saphenous vein: a comparison of dual endothelin-converting enzyme/neutral endopeptidase and selective neutral endopeptidase inhibition. Porter, K.E., Dickinson, T., London, N.J. J. Vasc. Surg. (2001) [Pubmed]
  40. Peptidase activities in serum and bronchoalveolar lavage fluid from allergic asthmatics--comparison with healthy non-smokers and smokers and effects of inhaled glucocorticoids. Van Der Velden, V.H., Naber, B.A., Van Hal, P.T., Overbeek, S.E., Hoogsteden, H.C., Versnel, M.A. Clin. Exp. Allergy (1999) [Pubmed]
  41. Cell specific expression of CD10/neutral endopeptidase 24.11 gene in human prostatic tissue and cells. Song, J., Aumüller, G., Xiao, F., Wilhelm, B., Albrecht, M. Prostate (2004) [Pubmed]
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