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Gene Review

Enpp2  -  ectonucleotide pyrophosphatase/phosphodies...

Mus musculus

Synonyms: ATX, Autotaxin, E-NPP 2, Ectonucleotide pyrophosphatase/phosphodiesterase family member 2, Extracellular lysophospholipase D, ...
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Disease relevance of Enpp2

  • Up-regulations of ATX expression with adipocyte differentiation and genetic obesity suggest a possible involvement of this released protein in the development of adipose tissue and obesity-associated pathologies [1].
  • These findings provide novel insights into understanding the functions of ATX as a key regulator of bioactive phospholipids and suggest interventions to correct dysfunction in conditions of tumor cell growth and metastasis [2].
  • Furthermore, at E8.5, ATX-deficient embryos showed allantois malformation, neural tube defects, and asymmetric headfolds [3].
  • A circulating thymic factor (FTS) is able to restore the contact sensitivity response to DNFB when injected 3 to 9 weeks after ATX but not 16 weeks later [4].
  • Autotaxin (ATX) is a tumor cell motility-stimulating factor originally isolated from melanoma cell supernatant that has been implicated in regulation of invasive and metastatic properties of cancer cells [5].
  • These results identify a novel pathway in which LPA production by autotaxin/lysoPLD regulates murine hemostasis and thrombosis and suggest that binding of autotaxin/lysoPLD to activated platelets may provide a mechanism to localize LPA production [6].

High impact information on Enpp2


Chemical compound and disease context of Enpp2


Biological context of Enpp2

  • Differentiation-dependent up-regulation of ATX expression was also observed in a primary culture of mouse preadipocytes [1].
  • Treatment of 3T3F442A-preadipocytes with concentrated conditioned medium from ATX-expressing COS-7 cells led to an increase in cell number as compared with concentrated conditioned medium from ATX non-expressing COS-7 cells [1].
  • Localization of murine ATX was first observed in the floor plate of the neural tube at day 9.5 of mouse embryonic development [9].
  • One HEF was from intron 2 of Enpp2, a gene highly upregulated in these cells and has been implicated in cell motility [10].
  • Using Enpp2 as a candidate direct target, we identified three additional HEFs upstream of the transcription start site [10].

Anatomical context of Enpp2

  • In situ hybridization (ISH) validated microarray data and it also showed that Fox M1, cyclin D2, and CDK4 were highly expressed in CNS germinal zones and ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2) was highly expressed in choroid plexus where stem/progenitor cells are possibly located [11].
  • ATX mRNA expression was highly up-regulated during adipocyte differentiation of 3T3F442A-preadipocytes [1].
  • To delineate a potential role for ATX in osteo-/chondrogenic development, its expression pattern during murine embryogenesis was examined in comparison with Col1a1 and Col2a1, a marker either of osteoblast, odontoblast and tendon or of chondrocyte development, respectively [9].
  • We demonstrate herein that ATX is a key regulator of extracellular lysophosphatidic acid (LPA) that can act as survival factor, in addition to its mitogenic activity in mouse fibroblasts [2].
  • Mouse CD4+ T cells repopulated T/NK cell-depleted, ATX IIKO mice after grafting with FP THY/LIV, indicating that pig MHC can positively select mouse CD4 cells [12].

Associations of Enpp2 with chemical compounds


Other interactions of Enpp2


Analytical, diagnostic and therapeutic context of Enpp2

  • The contact sensitivity response to DNFB is decreased after adult thymectomy (ATX) [4].
  • To deplete T cells in vivo, rat anti-Lyt-2 or anti-L3T4 monoclonal antibodies (mAb) were administered to adult-thymectomized (ATX) recipient mice prior to transplantation [17].
  • BACKGROUND: Donor-specific xenograft tolerance can be achieved by grafting fetal porcine thymus tissue to thymectomized (ATX) mice treated with natural killer (NK) and T-cell-depleting monoclonal antibodies plus 3 Gy of total body irradiation (TBI) [18].
  • Although the survival of fully allogeneic skin grafts was prominently prolonged by adult thymectomy in anti-T-cell receptor-alpha beta monoclonal antibody (TCR-alpha beta mAb)-treated mice compared with that of non-adult thymectomized (ATX) mice, the skin allografts were eventually rejected [19].
  • Upon intraventricular injection in mice, ATX II causes acute, short-lasting hyperexcitation and convulsions [20].


  1. Autotaxin is released from adipocytes, catalyzes lysophosphatidic acid synthesis, and activates preadipocyte proliferation. Up-regulated expression with adipocyte differentiation and obesity. Ferry, G., Tellier, E., Try, A., Grés, S., Naime, I., Simon, M.F., Rodriguez, M., Boucher, J., Tack, I., Gesta, S., Chomarat, P., Dieu, M., Raes, M., Galizzi, J.P., Valet, P., Boutin, J.A., Saulnier-Blache, J.S. J. Biol. Chem. (2003) [Pubmed]
  2. Autotaxin (lysoPLD/NPP2) protects fibroblasts from apoptosis through its enzymatic product, lysophosphatidic acid, utilizing albumin-bound substrate. Song, J., Clair, T., Noh, J.H., Eun, J.W., Ryu, S.Y., Lee, S.N., Ahn, Y.M., Kim, S.Y., Lee, S.H., Park, W.S., Yoo, N.J., Lee, J.Y., Nam, S.W. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  3. Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development. van Meeteren, L.A., Ruurs, P., Stortelers, C., Bouwman, P., van Rooijen, M.A., Pradère, J.P., Pettit, T.R., Wakelam, M.J., Saulnier-Blache, J.S., Mummery, C.L., Moolenaar, W.H., Jonkers, J. Mol. Cell. Biol. (2006) [Pubmed]
  4. Regulation of contact sensitivity to DNFB in the mouse: effects of adult thymectomy and thymic factor. Erard, D., Charreire, J., Auffredou, M.T., Galanaud, P., Bach, J.F. J. Immunol. (1979) [Pubmed]
  5. Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1. Hama, K., Aoki, J., Fukaya, M., Kishi, Y., Sakai, T., Suzuki, R., Ohta, H., Yamori, T., Watanabe, M., Chun, J., Arai, H. J. Biol. Chem. (2004) [Pubmed]
  6. Autotaxin/lysopholipase D and lysophosphatidic acid regulate murine hemostasis and thrombosis. Pamuklar, Z., Federico, L., Liu, S., Umezu-Goto, M., Dong, A., Panchatcharam, M., Fulkerson, Z., Fulerson, Z., Berdyshev, E., Natarajan, V., Fang, X., van Meeteren, L.A., Moolenaar, W.H., Mills, G.B., Morris, A.J., Smyth, S.S. J. Biol. Chem. (2009) [Pubmed]
  7. Autotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate. Clair, T., Aoki, J., Koh, E., Bandle, R.W., Nam, S.W., Ptaszynska, M.M., Mills, G.B., Schiffmann, E., Liotta, L.A., Stracke, M.L. Cancer Res. (2003) [Pubmed]
  8. Hepatitis B virus X protein acts as a tumor promoter in development of diethylnitrosamine-induced preneoplastic lesions. Madden, C.R., Finegold, M.J., Slagle, B.L. J. Virol. (2001) [Pubmed]
  9. Developmental expression analysis of murine autotaxin (ATX). Bächner, D., Ahrens, M., Betat, N., Schröder, D., Gross, G. Mech. Dev. (1999) [Pubmed]
  10. A genomic approach to the identification and characterization of HOXA13 functional binding elements. McCabe, C.D., Innis, J.W. Nucleic Acids Res. (2005) [Pubmed]
  11. Temporal expression changes during differentiation of neural stem cells derived from mouse embryonic stem cell. Ahn, J.I., Lee, K.H., Shin, D.M., Shim, J.W., Kim, C.M., Kim, H., Lee, S.H., Lee, Y.S. J. Cell. Biochem. (2004) [Pubmed]
  12. Positive and negative selection of functional mouse CD4 cells by porcine MHC in pig thymus grafts. Zhao, Y., Sergio, J.J., Swenson, K., Arn, J.S., Sachs, D.H., Sykes, M. J. Immunol. (1997) [Pubmed]
  13. Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression. Boucher, J., Quilliot, D., Pradères, J.P., Simon, M.F., Grès, S., Guigné, C., Prévot, D., Ferry, G., Boutin, J.A., Carpéné, C., Valet, P., Saulnier-Blache, J.S. Diabetologia (2005) [Pubmed]
  14. Bmp-2 downstream targets in mesenchymal development identified by subtractive cloning from recombinant mesenchymal progenitors (C3H10T1/2). Bächner, D., Ahrens, M., Schröder, D., Hoffmann, A., Lauber, J., Betat, N., Steinert, P., Flohé, L., Gross, G. Dev. Dyn. (1998) [Pubmed]
  15. Genetic loci that control the angiogenic response to basic fibroblast growth factor. Rogers, M.S., Rohan, R.M., Birsner, A.E., D'Amato, R.J. FASEB J. (2004) [Pubmed]
  16. Substrate-specifying determinants of the nucleotide pyrophosphatases/phosphodiesterases NPP1 and NPP2. Cimpean, A., Stefan, C., Gijsbers, R., Stalmans, W., Bollen, M. Biochem. J. (2004) [Pubmed]
  17. Cellular pathways for rejection of class-I-MHC--disparate skin and tumor allografts. Smith, D.M., Stuart, F.P., Wemhoff, G.A., Quintáns, J., Fitch, F.W. Transplantation (1988) [Pubmed]
  18. Enhanced CD4 reconstitution by grafting neonatal porcine tissue in alternative locations is associated with donor-specific tolerance and suppression of preexisting xenoreactive T cells. Rodriguez-Barbosa, J.I., Zhao, Y., Barth, R., Zhao, G., Arn, J.S., Sachs, D.H., Sykes, M. Transplantation (2001) [Pubmed]
  19. Sensitization of T-cell receptor-alpha beta+ T cells recovered from long-term T-cell receptor downmodulation. Omoto, K., Kong, Y.Y., Nomoto, K., Umesue, M., Murakami, Y., Eto, M., Nomoto, K. Immunology (1996) [Pubmed]
  20. Iodine labelling of sea anemone toxin II, and binding to normal and denervated diaphragm. Habermann, E., Beress, L. Naunyn Schmiedebergs Arch. Pharmacol. (1979) [Pubmed]
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