{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} '''Autotaxin''', also known as '''ectonucleotide pyrophosphatase/phosphodiesterase family member 2''' ('''E-NPP 2'''), is an enzyme that in humans is encoded by the ''ENPP2'' gene.<ref name="Kawagoe_1995">{{cite journal | vauthors = Kawagoe H, Soma O, Goji J, Nishimura N, Narita M, Inazawa J, Nakamura H, Sano K | title = Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2) | journal = Genomics | volume = 30 | issue = 2 | pages = 380–384 | date = November 1995 | pmid = 8586446 | doi = 10.1006/geno.1995.0036 | hdl = 20.500.14094/D1001481 | hdl-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin) | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5168 }}</ref>
== Structure == Autotaxin is a multi-domain protein with a modular architecture. From the N- to the C-terminus, it comprises two consecutive N-terminal cysteine-rich somatomedin B-like (SMB) domains, followed by a central catalytic phosphodiesterase (PDE) domain and a C-terminal nuclease-like (NUC) domain. The two SMB domains mediate protein–protein interactions, particularly through integrin-dependent binding to cell surfaces. The catalytic PDE domain, which is structurally related to alkaline phosphatases, harbors the enzyme's lysophospholipase D activity responsible for converting lysophosphatidylcholine into lysophosphatidic acid (LPA). The C-terminal NUC domain, although catalytically inactive, is structurally linked to the PDE domain and contributes to substrate binding and overall protein stability. A region at the extreme C-terminus, sometimes referred to as the MORFO domain, overlaps with the NUC region and has been associated with oligodendrocyte remodeling. Thus, the domain organization from N- to C-terminus is: SMB1–SMB2–PDE–NUC, with the MORFO domain often considered part of or overlapping with the NUC domain.<ref name="pmid18485925">{{cite journal | vauthors = Yuelling LM, Fuss B | title = Autotaxin (ATX): a multi-functional and multi-modular protein possessing enzymatic lysoPLD activity and matricellular properties | journal = Biochimica et Biophysica Acta | volume = 1781 | issue = 9 | pages = 525–30 | date = September 2008 | pmid = 18485925 | pmc = 2564869 | doi = 10.1016/j.bbalip.2008.04.009 }}</ref><ref name="pmid23069371">{{cite journal | vauthors = Hausmann J, Perrakis A, Moolenaar WH | title = Structure-function relationships of autotaxin, a secreted lysophospholipase D | journal = Advances in Biological Regulation | volume = 53 | issue = 1 | pages = 112–7 | date = January 2013 | pmid = 23069371 | doi = 10.1016/j.jbior.2012.09.010 }}</ref>
The crystal structures of rat and mouse autotaxin have been determined,<ref name="Nishimasu_2011">{{cite journal | vauthors = Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O | title = Crystal structure of autotaxin and insight into GPCR activation by lipid mediators | journal = Nature Structural & Molecular Biology | volume = 18 | issue = 2 | pages = 205–212 | date = February 2011 | pmid = 21240269 | doi = 10.1038/nsmb.1998 | s2cid = 6336916 }}</ref> including both apo and ligand-bound forms. Each structure reveals four domains: two N-terminal somatomedin-B-like domains likely involved in cell-surface localization, the catalytic PDE domain containing a deep hydrophobic pocket for lipid substrate binding, and the C-terminal inactive NUC domain, which appears to stabilize the overall structure.
== Function == Autotaxin 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 a phosphodiesterase. Autotaxin is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants have been identified. Autotaxin is able to cleave the phosphodiester bond between the α and the β position of triphosphate nucleotides, acting as an ectonucleotide phosphodiesterase producing pyrophosphate, as most members of the ENPP family.<ref>{{Cite journal | vauthors = Borza R, Salgado-Polo F, Moolenaar WH, Perrakis A | title = Structure and function of the ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family: Tidying up diversity | journal = Journal of Biological Chemistry | volume = 298 | issue = 2 | date = 2022-02-01 | pmid = 34958798 | pmc = 8808174 | doi = 10.1016/j.jbc.2021.101526 | language = English | article-number = 101526 | doi-access = free | issn = 0021-9258 }}</ref> Importantly, autotaxin also acts as phospholipase, catalyzing the removal of the head group of various lysolipids. The physiological function of autotaxin is the production of the signalling lipid 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 up-regulated in several kinds of tumours.<ref name="entrez" /> Also, autotaxin and LPA are involved in numerous inflammatory-driven diseases such as asthma and arthritis.<ref>{{cite journal | vauthors = Benesch MG, Ko YM, McMullen TP, Brindley DN | title = Autotaxin in the crosshairs: taking aim at cancer and other inflammatory conditions | journal = FEBS Letters | volume = 588 | issue = 16 | pages = 2712–2727 | date = August 2014 | pmid = 24560789 | doi = 10.1016/j.febslet.2014.02.009 | s2cid = 35544825 | bibcode = 2014FEBSL.588.2712B }}</ref> Physiologically, LPA helps promote wound healing responses to tissue damage. Under normal circumstances, LPA negatively regulates autotaxin transcription, but in the context of wound repair, cytokines induce autotaxin expression to increase overall LPA concentrations.<ref>{{cite journal | vauthors = Benesch MG, Zhao YY, Curtis JM, McMullen TP, Brindley DN | title = Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate | journal = Journal of Lipid Research | volume = 56 | issue = 6 | pages = 1134–1144 | date = June 2015 | pmid = 25896349 | pmc = 4442871 | doi = 10.1194/jlr.M057661 | doi-access = free }}</ref>
== As a drug target ==
Autotaxin contains a tripartite binding site composed of a zinc-dependent catalytic center, a hydrophilic groove, and a hydrophobic pocket.<ref>{{Cite journal | vauthors = Salgado-Polo F, Perrakis A | title = The Structural Binding Mode of the Four Autotaxin Inhibitor Types that Differentially Affect Catalytic and Non-Catalytic Functions | journal = Cancers | volume = 11 | issue = 10 | pages = 1577 | date = 2019-10-16 | pmid = 31623219 | pmc = 6826961 | doi = 10.3390/cancers11101577 | language = en | doi-access = free | issn = 2072-6694 }}</ref> Based on how inhibitors interact with this site, ATX inhibitors can be classified into six types: '''Type I''' compounds occupy the orthosteric site, mimicking the LPC substrate binding;<ref>{{Cite journal | vauthors = Baker DL, Fujiwara Y, Pigg KR, Tsukahara R, Kobayashi S, Murofushi H, Uchiyama A, Murakami-Murofushi K, Koh E, Bandle RW, Byun HS, Bittman R, Fan D, Murph M, Mills GB | title = Carba analogs of cyclic phosphatidic acid are selective inhibitors of autotaxin and cancer cell invasion and metastasis | journal = The Journal of Biological Chemistry | volume = 281 | issue = 32 | pages = 22786–22793 | date = 2006-08-11 | pmid = 16782709 | pmc = 3505596 | doi = 10.1074/jbc.M512486200 | doi-access = free | issn = 0021-9258 | bibcode = 2006JBiCh.28122786B }}</ref><ref>{{Cite journal | vauthors = Nikitopoulou I, Kaffe E, Sevastou I, Sirioti I, Samiotaki M, Madan D, Prestwich GD, Aidinis V | title = A Metabolically-Stabilized Phosphonate Analog of Lysophosphatidic Acid Attenuates Collagen-Induced Arthritis | journal = PLOS ONE | volume = 8 | issue = 7 | date = 2013-07-29 | pmid = 23923032 | pmc = 3726599 | doi = 10.1371/journal.pone.0070941 | language = en | article-number = e70941 | doi-access = free | issn = 1932-6203 | bibcode = 2013PLoSO...870941N }}</ref> '''Type II''' inhibitors bind solely to the hydrophobic pocket, blocking LPC accommodation;<ref name="molpharm.aspetjournals.org">{{Cite journal | vauthors = Stein AJ, Bain G, Prodanovich P, Santini AM, Darlington J, Stelzer NM, Sidhu RS, Schaub J, Goulet L, Lonergan D, Calderon I, Evans JF, Hutchinson JH | title = Structural Basis for Inhibition of Human Autotaxin by Four Potent Compounds with Distinct Modes of Binding | journal = Molecular Pharmacology | volume = 88 | issue = 6 | pages = 982–992 | date = 2015-12-01 | pmid = 26371182 | doi = 10.1124/mol.115.100404 | url = https://molpharm.aspetjournals.org/article/S0026-895X(24)03209-7/abstract | language = English | issn = 0026-895X | url-access = subscription }}</ref><ref>{{Cite journal | vauthors = Jiang G, Madan D, Prestwich GD | title = Aromatic phosphonates inhibit the lysophospholipase D activity of autotaxin | journal = Bioorganic & Medicinal Chemistry Letters | volume = 21 | issue = 17 | pages = 5098–5101 | date = 2011-09-01 | pmid = 21489790 | pmc = 3140587 | doi = 10.1016/j.bmcl.2011.03.068 | series = Tetrahedron Young Investigator Award 2011: Carolyn R. Bertozzi | issn = 0960-894X }}</ref> '''Type III''' inhibitors occupy the allosteric regulatory tunnel, modulating ATX activity non-competitively;<ref name="molpharm.aspetjournals.org"/><ref>{{Cite journal | vauthors = Miller LM, Keune WJ, Castagna D, Young LC, Duffy EL, Potjewyd F, Salgado-Polo F, Engel García P, Semaan D, Pritchard JM, Perrakis A, Macdonald SJ, Jamieson C, Watson AJ | title = Structure–Activity Relationships of Small Molecule Autotaxin Inhibitors with a Discrete Binding Mode | journal = Journal of Medicinal Chemistry | volume = 60 | issue = 2 | pages = 722–748 | date = 2017-01-26 | pmid = 27982588 | doi = 10.1021/acs.jmedchem.6b01597 | issn = 0022-2623 }}</ref> '''Type IV''' compounds occupy both the binding pocket and the tunnel without contacting the catalytic site;<ref>{{Cite journal | vauthors = Keune WJ, Potjewyd F, Heidebrecht T, Salgado-Polo F, Macdonald SJ, Chelvarajan L, Abdel Latif A, Soman S, Morris AJ, Watson AJ, Jamieson C, Perrakis A | title = Rational Design of Autotaxin Inhibitors by Structural Evolution of Endogenous Modulators | journal = Journal of Medicinal Chemistry | volume = 60 | issue = 5 | pages = 2006–2017 | date = 2017-03-09 | pmid = 28165241 | doi = 10.1021/acs.jmedchem.6b01743 | issn = 0022-2623 }}</ref><ref name="SalgadoPolo_2023">{{Cite journal | vauthors = Salgado-Polo F, Borza R, Matsoukas MT, Marsais F, Jagerschmidt C, Waeckel L, Moolenaar WH, Ford P, Heckmann B, Perrakis A | title = Autotaxin facilitates selective LPA receptor signaling | journal = Cell Chemical Biology | volume = 30 | issue = 1 | pages = 69–84.e14 | date = 2023-01-19 | pmid = 36640760 | doi = 10.1016/j.chembiol.2022.12.006 | url = https://www.cell.com/cell-chemical-biology/abstract/S2451-9456(22)00456-1 | language = English | issn = 2451-9456 | doi-access = free }}</ref> '''Type V''' inhibitors occupy the allosteric tunnel and the orthosteric site;<ref>{{Cite journal | vauthors = Clark JM, Salgado-Polo F, Macdonald SJ, Barrett TN, Perrakis A, Jamieson C | title = Structure-Based Design of a Novel Class of Autotaxin Inhibitors Based on Endogenous Allosteric Modulators | journal = Journal of Medicinal Chemistry | volume = 65 | issue = 8 | pages = 6338–6351 | date = 2022-04-28 | pmid = 35440138 | pmc = 9059126 | doi = 10.1021/acs.jmedchem.2c00368 | issn = 0022-2623 }}</ref> and '''Type VI''' compounds engage all three regions—the orthosteric site, allosteric tunnel, and hydrophobic pocket.<ref>{{Cite journal | vauthors = Desroy N, Borza R, Heiermann J, Triballeau N, Joncour A, Bienvenu N, Hengeveld WJ, Springer J, Galien R, Joosten RP, Perrakis A, Heckmann B | title = Design, Synthesis, and Biological Implications of Autotaxin inhibitors with a Three-Point lock binding mode | journal = Bioorganic & Medicinal Chemistry | volume = 124 | date = 2025-07-01 | pmid = 40233422 | doi = 10.1016/j.bmc.2025.118181 | url = https://www.sciencedirect.com/science/article/pii/S0968089625001221 | article-number = 118181 | issn = 0968-0896 | doi-access = free }}</ref>
A type IV inhibitor, Ziritaxestat (GLPG1690), against idiopathic pulmonary fibrosis<ref name="SalgadoPolo_2023" /> showed promising results in a phase II trial that ended in May 2018.<ref>{{ClinicalTrialsGov|NCT02738801|Study to Assess Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Properties of GLPG1690}}</ref> It has been shown that THC is also a partial autotaxin inhibitor, with an apparent IC50 of 407 ± 67 nM for the ATX-gamma isoform.<ref>{{cite journal | vauthors = Eymery MC, McCarthy AA, Hausmann J | title = Linking medicinal cannabis to autotaxin-lysophosphatidic acid signaling | journal = Life Science Alliance | volume = 6 | issue = 2 | date = February 2023 | pmid = 36623871 | pmc = 9834664 | doi = 10.26508/lsa.202201595 | article-number = e202201595 }}</ref> THC was also co-crystallized with autotaxin, deciphering the binding interface of the complex. These results might explain some of the effects of THC on inflammation and neurological diseases, since autotaxin is responsible of LPA generation, a key lipid mediator involved in numerous diseases and physiological processes. However, clinical trials need to be performed in order to assess the importance of ATX inhibition by THC during medicinal cannabis consumption. Development of cannabinoid inspired autotaxin inhibitors could also be an option in the future. A DNA aptamer inhibitor of Autotaxin has also been described.<ref>{{cite journal | vauthors = Kato K, Ikeda H, Miyakawa S, Futakawa S, Nonaka Y, Fujiwara M, Okudaira S, Kano K, Aoki J, Morita J, Ishitani R, Nishimasu H, Nakamura Y, Nureki O | title = Structural basis for specific inhibition of Autotaxin by a DNA aptamer | journal = Nature Structural & Molecular Biology | volume = 23 | issue = 5 | pages = 395–401 | date = May 2016 | pmid = 27043297 | doi = 10.1038/nsmb.3200 | s2cid = 24948842 }}</ref>
== See also == * Lysophosphatidic acid * Lysophospholipid receptors * Lipid signaling * Phospholipases
== References == {{reflist}} {{Clear}}
== Further reading == {{refbegin | 2}} * {{cite journal | vauthors = Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K | title = Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase | journal = The Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39436–39442 | date = October 2002 | pmid = 12176993 | doi = 10.1074/jbc.M205623200 | doi-access = free }} * {{cite journal | vauthors = Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H | title = Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production | journal = The Journal of Cell Biology | volume = 158 | issue = 2 | pages = 227–233 | date = July 2002 | pmid = 12119361 | pmc = 2173129 | doi = 10.1083/jcb.200204026 }} * {{cite journal | vauthors = Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA | title = Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein | journal = The Journal of Biological Chemistry | volume = 267 | issue = 4 | pages = 2524–2529 | date = February 1992 | pmid = 1733949 | doi = 10.1016/S0021-9258(18)45911-X | doi-access = free }} * {{cite journal | vauthors = Stracke ML, Arestad A, Levine M, Krutzsch HC, Liotta LA | title = Autotaxin is an N-linked glycoprotein but the sugar moieties are not needed for its stimulation of cellular motility | journal = Melanoma Research | volume = 5 | issue = 4 | pages = 203–209 | date = August 1995 | pmid = 7496154 | doi = 10.1097/00008390-199508000-00001 | s2cid = 8300784 | url = https://zenodo.org/record/1234826 }} * {{cite journal | vauthors = Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA, Stracke ML | title = cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases | journal = The Journal of Biological Chemistry | volume = 269 | issue = 48 | pages = 30479–30484 | date = December 1994 | pmid = 7982964 | doi = 10.1016/S0021-9258(18)43838-0 | doi-access = free }} * {{cite journal | vauthors = Lee HY, Murata J, Clair T, Polymeropoulos MH, Torres R, Manrow RE, Liotta LA, Stracke ML | title = Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells | journal = Biochemical and Biophysical Research Communications | volume = 218 | issue = 3 | pages = 714–719 | date = January 1996 | pmid = 8579579 | doi = 10.1006/bbrc.1996.0127 | bibcode = 1996BBRC..218..714L | url = https://zenodo.org/record/1229470 }} * {{cite journal | vauthors = Lee HY, Clair T, Mulvaney PT, Woodhouse EC, Aznavoorian S, Liotta LA, Stracke ML | title = Stimulation of tumor cell motility linked to phosphodiesterase catalytic site of autotaxin | journal = The Journal of Biological Chemistry | volume = 271 | issue = 40 | pages = 24408–24412 | date = October 1996 | pmid = 8798697 | doi = 10.1074/jbc.271.40.24408 | doi-access = free }} * {{cite journal | vauthors = Clair T, Lee HY, Liotta LA, Stracke ML | title = Autotaxin is an exoenzyme possessing 5'-nucleotide phosphodiesterase/ATP pyrophosphatase and ATPase activities | journal = The Journal of Biological Chemistry | volume = 272 | issue = 2 | pages = 996–1001 | date = January 1997 | pmid = 8995394 | doi = 10.1074/jbc.272.2.996 | doi-access = free }} * {{cite journal | vauthors = Dias Neto E, Correa RG, Verjovski-Almeida S, Briones MR, Nagai MA, da Silva W, Zago MA, Bordin S, Costa FF, Goldman GH, Carvalho AF, Matsukuma A, Baia GS, Simpson DH, Brunstein A, de Oliveira PS, Bucher P, Jongeneel CV, O'Hare MJ, Soares F, Brentani RR, Reis LF, de Souza SJ, Simpson AJ | title = Shotgun sequencing of the human transcriptome with ORF expressed sequence tags | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 97 | issue = 7 | pages = 3491–3496 | date = March 2000 | pmid = 10737800 | pmc = 16267 | doi = 10.1073/pnas.97.7.3491 | bibcode = 2000PNAS...97.3491D | doi-access = free }} * {{cite journal | vauthors = Nam SW, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA, Stracke ML | title = Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor | journal = Cancer Research | volume = 61 | issue = 18 | pages = 6938–6944 | date = September 2001 | pmid = 11559573 }} * {{cite journal | vauthors = Umezu-Goto M, Kishi Y, Taira A, Hama K, Dohmae N, Takio K, Yamori T, Mills GB, Inoue K, Aoki J, Arai H | title = Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production | journal = The Journal of Cell Biology | volume = 158 | issue = 2 | pages = 227–233 | date = July 2002 | pmid = 12119361 | pmc = 2173129 | doi = 10.1083/jcb.200204026 }} * {{cite journal | vauthors = Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K | title = Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase | journal = The Journal of Biological Chemistry | volume = 277 | issue = 42 | pages = 39436–39442 | date = October 2002 | pmid = 12176993 | doi = 10.1074/jbc.M205623200 | doi-access = free }} * {{cite journal | vauthors = Jung ID, Lee J, Yun SY, Park CG, Choi WS, Lee HW, Choi OH, Han JW, Lee HY | title = Cdc42 and Rac1 are necessary for autotaxin-induced tumor cell motility in A2058 melanoma cells | journal = FEBS Letters | volume = 532 | issue = 3 | pages = 351–356 | date = December 2002 | pmid = 12482591 | doi = 10.1016/S0014-5793(02)03698-0 | s2cid = 19821754 | doi-access = free | bibcode = 2002FEBSL.532..351J }} * {{cite journal | vauthors = Yang SY, Lee J, Park CG, Kim S, Hong S, Chung HC, Min SK, Han JW, Lee HW, Lee HY | title = Expression of autotaxin (NPP-2) is closely linked to invasiveness of breast cancer cells | journal = Clinical & Experimental Metastasis | volume = 19 | issue = 7 | pages = 603–608 | year = 2003 | pmid = 12498389 | doi = 10.1023/A:1020950420196 | s2cid = 25181446 }} * {{cite journal | vauthors = Gijsbers R, Aoki J, Arai H, Bollen M | title = The hydrolysis of lysophospholipids and nucleotides by autotaxin (NPP2) involves a single catalytic site | journal = FEBS Letters | volume = 538 | issue = 1–3 | pages = 60–64 | date = March 2003 | pmid = 12633853 | doi = 10.1016/S0014-5793(03)00133-9 | bibcode = 2003FEBSL.538...60G | s2cid = 38206060 }} * {{cite journal | vauthors = Koh E, Clair T, Woodhouse EC, Schiffmann E, Liotta L, Stracke M | title = Site-directed mutations in the tumor-associated cytokine, autotaxin, eliminate nucleotide phosphodiesterase, lysophospholipase D, and motogenic activities | journal = Cancer Research | volume = 63 | issue = 9 | pages = 2042–2045 | date = May 2003 | pmid = 12727817 }} * {{cite journal | vauthors = Kehlen A, Englert N, Seifert A, Klonisch T, Dralle H, Langner J, Hoang-Vu C | title = Expression, regulation and function of autotaxin in thyroid carcinomas | journal = International Journal of Cancer | volume = 109 | issue = 6 | pages = 833–838 | date = May 2004 | pmid = 15027116 | doi = 10.1002/ijc.20022 | s2cid = 25281125 }} * {{cite journal | vauthors = Boucher J, Quilliot D, Pradères JP, Simon MF, Grès S, Guigné C, Prévot D, Ferry G, Boutin JA, Carpéné C, Valet P, Saulnier-Blache JS | title = Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression | journal = Diabetologia | volume = 48 | issue = 3 | pages = 569–577 | date = March 2005 | pmid = 15700135 | pmc = 1885462 | doi = 10.1007/s00125-004-1660-8 }} {{refend}}
==External links== * {{UCSC gene info|ENPP2}} {{Esterases}} {{Enzymes}} {{Portal bar|Biology|border=no}}
Category:EC 3.1.4