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Gene Review

ENPP2  -  ectonucleotide pyrophosphatase/phosphodies...

Homo sapiens

Synonyms: ATX, ATX-X, AUTOTAXIN, Autotaxin, E-NPP 2, ...
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Disease relevance of ENPP2


Psychiatry related information on ENPP2


High impact information on ENPP2

  • Autotaxin (ATX) is a tumor cell motility-stimulating factor, originally isolated from melanoma cell supernatants [6].
  • Moreover, we demonstrate that several cancer cell lines release significant amounts of LPC, a substrate for ATX, into the culture medium [6].
  • The demonstration that ATX and lysoPLD are identical suggests that autocrine or paracrine production of LPA contributes to tumor cell motility, survival, and proliferation [6].
  • The Km value of ATX for LPC was 25-fold lower than that for the synthetic nucleoside substrate, p-nitrophenyl-tri-monophosphate [6].
  • Recombinant ATX, particularly in the presence of LPC, dramatically increased chemotaxis and proliferation of multiple different cell lines [6].

Chemical compound and disease context of ENPP2


Biological context of ENPP2


Anatomical context of ENPP2


Associations of ENPP2 with chemical compounds


Physical interactions of ENPP2


Enzymatic interactions of ENPP2

  • N-terminal sequencing of the secreted autotaxin revealed that it was cleaved at two N-terminal sites that match the consensus sequences for cleavage by a signal peptidase and furin [1].

Regulatory relationships of ENPP2


Other interactions of ENPP2


Analytical, diagnostic and therapeutic context of ENPP2


  1. The N-terminal hydrophobic sequence of autotaxin (ENPP2) functions as a signal peptide. Koike, S., Keino-Masu, K., Ohto, T., Masu, M. Genes Cells (2006) [Pubmed]
  2. Autotaxin is overexpressed in glioblastoma multiforme and contributes to cell motility of glioblastoma by converting lysophosphatidylcholine to lysophosphatidic acid. Kishi, Y., Okudaira, S., Tanaka, M., Hama, K., Shida, D., Kitayama, J., Yamori, T., Aoki, J., Fujimaki, T., Arai, H. J. Biol. Chem. (2006) [Pubmed]
  3. Identification of large-scale molecular changes 1 of Autotaxin(ENPP2) knock-down by small interfering RNA in breast cancer cells. Noh, J.H., Ryu, S.Y., Eun, J.W., Song, J., Ahn, Y.M., Kim, S.Y., Lee, S.H., Park, W.S., Yoo, N.J., Lee, J.Y., Lee, S.N., Nam, S.W. Mol. Cell. Biochem. (2006) [Pubmed]
  4. Induction of autotaxin by the Epstein-Barr virus promotes the growth and survival of Hodgkin lymphoma cells. Baumforth, K.R., Flavell, J.R., Reynolds, G.M., Davies, G., Pettit, T.R., Wei, W., Morgan, S., Stankovic, T., Kishi, Y., Arai, H., Nowakova, M., Pratt, G., Aoki, J., Wakelam, M.J., Young, L.S., Murray, P.G. Blood (2005) [Pubmed]
  5. Autotaxin expression is enhanced in frontal cortex of Alzheimer-type dementia patients. Umemura, K., Yamashita, N., Yu, X., Arima, K., Asada, T., Makifuchi, T., Murayama, S., Saito, Y., Kanamaru, K., Goto, Y., Kohsaka, S., Kanazawa, I., Kimura, H. Neurosci. Lett. (2006) [Pubmed]
  6. Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production. Umezu-Goto, M., Kishi, Y., Taira, A., Hama, K., Dohmae, N., Takio, K., Yamori, T., Mills, G.B., Inoue, K., Aoki, J., Arai, H. J. Cell Biol. (2002) [Pubmed]
  7. cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. Murata, J., Lee, H.Y., Clair, T., Krutzsch, H.C., Arestad, A.A., Sobel, M.E., Liotta, L.A., Stracke, M.L. J. Biol. Chem. (1994) [Pubmed]
  8. Autotaxin is an N-linked glycoprotein but the sugar moieties are not needed for its stimulation of cellular motility. Stracke, M.L., Arestad, A., Levine, M., Krutzsch, H.C., Liotta, L.A. Melanoma Res. (1995) [Pubmed]
  9. Carba analogs of cyclic phosphatidic acid are selective inhibitors of autotaxin and cancer cell invasion and metastasis. Baker, D.L., Fujiwara, Y., Pigg, K.R., Tsukahara, R., Kobayashi, S., Murofushi, H., Uchiyama, A., Murakami-Murofushi, K., Koh, E., Bandle, R.W., Byun, H.S., Bittman, R., Fan, D., Murph, M., Mills, G.B., Tigyi, G. J. Biol. Chem. (2006) [Pubmed]
  10. Integrin alpha6beta4 promotes expression of autotaxin/ENPP2 autocrine motility factor in breast carcinoma cells. Chen, M., O'Connor, K.L. Oncogene (2005) [Pubmed]
  11. Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Nam, S.W., Clair, T., Kim, Y.S., McMarlin, A., Schiffmann, E., Liotta, L.A., Stracke, M.L. Cancer Res. (2001) [Pubmed]
  12. Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid. Tanaka, M., Okudaira, S., Kishi, Y., Ohkawa, R., Iseki, S., Ota, M., Noji, S., Yatomi, Y., Aoki, J., Arai, H. J. Biol. Chem. (2006) [Pubmed]
  13. Target genes of the WNT/beta-catenin pathway in Wilms tumors. Zirn, B., Samans, B., Wittmann, S., Pietsch, T., Leuschner, I., Graf, N., Gessler, M. Genes Chromosomes Cancer (2006) [Pubmed]
  14. Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities. Clair, T., Lee, H.Y., Liotta, L.A., Stracke, M.L. J. Biol. Chem. (1997) [Pubmed]
  15. Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. van Meeteren, L.A., Ruurs, P., Christodoulou, E., Goding, J.W., Takakusa, H., Kikuchi, K., Perrakis, A., Nagano, T., Moolenaar, W.H. J. Biol. Chem. (2005) [Pubmed]
  16. Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2). Kawagoe, H., Soma, O., Goji, J., Nishimura, N., Narita, M., Inazawa, J., Nakamura, H., Sano, K. Genomics (1995) [Pubmed]
  17. Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. Stracke, M.L., Krutzsch, H.C., Unsworth, E.J., Arestad, A., Cioce, V., Schiffmann, E., Liotta, L.A. J. Biol. Chem. (1992) [Pubmed]
  18. Autotaxin stimulates urokinase-type plasminogen activator expression through phosphoinositide 3-kinase-Akt-necrosis factor kappa B signaling cascade in human melanoma cells. Lee, J., Duk Jung, I., Gyo Park, C., Han, J.W., Young Lee, H. Melanoma Res. (2006) [Pubmed]
  19. The candidate tumor suppressor CST6 alters the gene expression profile of human breast carcinoma cells: down-regulation of the potent mitogenic, motogenic, and angiogenic factor autotaxin. Song, J., Jie, C., Polk, P., Shridhar, R., Clair, T., Zhang, J., Yin, L., Keppler, D. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  20. Mechanical loading stimulates ecto-ATPase activity in human tendon cells. Tsuzaki, M., Bynum, D., Almekinders, L., Faber, J., Banes, A.J. J. Cell. Biochem. (2005) [Pubmed]
  21. Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells. Lee, H.Y., Murata, J., Clair, T., Polymeropoulos, M.H., Torres, R., Manrow, R.E., Liotta, L.A., Stracke, M.L. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  22. Distinctive gene expression of prostatic stromal cells cultured from diseased versus normal tissues. Zhao, H., Ramos, C.F., Brooks, J.D., Peehl, D.M. J. Cell. Physiol. (2007) [Pubmed]
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