Autotaxin

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Ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin)
Identifiers
Symbol(s) ENPP2; ATX; ATX-X; FLJ26803; LysoPLD; NPP2; PD-IALPHA; PDNP2
External IDs OMIM: 601060 MGI: 1321390 HomoloGene: 4526
EC number 3.6.1.9 3.1.4.1, 3.6.1.9
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 5168 18606
Ensembl ENSG00000136960 ENSMUSG00000022425
Uniprot Q13822 Q6PDE0
Refseq NM_001040092 (mRNA)
NP_001035181 (protein)		 NM_015744 (mRNA)
NP_056559 (protein)
Location Chr 8: 120.64 - 120.72 Mb Chr 15: 54.67 - 54.75 Mb
Pubmed search [1] [2]

Ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin), also known as ENPP2, is a human gene.[1]

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or ENPP2), is a secreted enzyme important for generating the lipid signaling molecule lysophosphatidic acid (LPA). Autotaxin has lysophospholipase D activity that converts lysophosphatidylcholine into LPA.

Autotaxin was originally identified as a tumor cell-motility-stimulating factor; later it was shown to be LPA (which signals through Lysophospholipid receptors), the lipid product of the reaction catalyzed by autotaxin, which is responsible for its effects on cell-proliferation.

The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and as a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells, has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined.[1]

Contents

[edit] See also

[edit] References

  1. ^ a b Entrez Gene: ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin).

[edit] Further reading

  • Stracke ML, Krutzsch HC, Unsworth EJ, et al. (1992). "Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein.". J. Biol. Chem. 267 (4): 2524–9. PMID 1733949. 
  • Stracke ML, Arestad A, Levine M, et al. (1996). "Autotaxin is an N-linked glycoprotein but the sugar moieties are not needed for its stimulation of cellular motility.". Melanoma Res. 5 (4): 203–9. PMID 7496154. 
  • Murata J, Lee HY, Clair T, et al. (1994). "cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases.". J. Biol. Chem. 269 (48): 30479–84. PMID 7982964. 
  • Lee HY, Murata J, Clair T, et al. (1996). "Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells.". Biochem. Biophys. Res. Commun. 218 (3): 714–9. doi:10.1006/bbrc.1996.0127. PMID 8579579. 
  • Kawagoe H, Soma O, Goji J, et al. (1996). "Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2).". Genomics 30 (2): 380–4. doi:10.1006/geno.1995.0036. PMID 8586446. 
  • Lee HY, Clair T, Mulvaney PT, et al. (1996). "Stimulation of tumor cell motility linked to phosphodiesterase catalytic site of autotaxin.". J. Biol. Chem. 271 (40): 24408–12. PMID 8798697. 
  • Clair T, Lee HY, Liotta LA, Stracke ML (1997). "Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities.". J. Biol. Chem. 272 (2): 996–1001. PMID 8995394. 
  • Dias Neto E, Correa RG, Verjovski-Almeida S, et al. (2000). "Shotgun sequencing of the human transcriptome with ORF expressed sequence tags.". Proc. Natl. Acad. Sci. U.S.A. 97 (7): 3491–6. PMID 10737800. 
  • Nam SW, Clair T, Kim YS, et al. (2001). "Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor.". Cancer Res. 61 (18): 6938–44. PMID 11559573. 
  • Umezu-Goto M, Kishi Y, Taira A, et al. (2002). "Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production.". J. Cell Biol. 158 (2): 227–33. doi:10.1083/jcb.200204026. PMID 12119361. 
  • Tokumura A, Majima E, Kariya Y, et al. (2002). "Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase.". J. Biol. Chem. 277 (42): 39436–42. doi:10.1074/jbc.M205623200. PMID 12176993. 
  • Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932. 
  • Jung ID, Lee J, Yun SY, et al. (2003). "Cdc42 and Rac1 are necessary for autotaxin-induced tumor cell motility in A2058 melanoma cells.". FEBS Lett. 532 (3): 351–6. PMID 12482591. 
  • Yang SY, Lee J, Park CG, et al. (2003). "Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells.". Clin. Exp. Metastasis 19 (7): 603–8. PMID 12498389. 
  • Gijsbers R, Aoki J, Arai H, Bollen M (2003). "The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site.". FEBS Lett. 538 (1-3): 60–4. PMID 12633853. 
  • Koh E, Clair T, Woodhouse EC, et al. (2003). "Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities.". Cancer Res. 63 (9): 2042–5. PMID 12727817. 
  • Kehlen A, Englert N, Seifert A, et al. (2004). "Expression, regulation and function of autotaxin in thyroid carcinomas.". Int. J. Cancer 109 (6): 833–8. doi:10.1002/ijc.20022. PMID 15027116. 
  • Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMID 15489334. 
  • Boucher J, Quilliot D, Pradères JP, et al. (2005). "Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression.". Diabetologia 48 (3): 569–77. doi:10.1007/s00125-004-1660-8. PMID 15700135. 
  • van Meeteren LA, Ruurs P, Christodoulou E, et al. (2005). "Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate.". J. Biol. Chem. 280 (22): 21155–61. doi:10.1074/jbc.M413183200. PMID 15769751. 

[edit] References

  • Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K (2002). "Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase". J. Biol. Chem. 277 (42): 39436–42. doi:10.1074/jbc.M205623200. PMID 12176993. 
  • Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H (2002). "Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production". J. Cell Biol. 158 (2): 227–33. doi:10.1083/jcb.200204026. PMID 12119361.