Q13822A8UHA1E9PHP7Q13827Q14555Q15117Q9UCQ8Q9UCR0Q9UCR1Q9UCR2Q9UCR3Q9UCR4ENPP2_HUMANEctonucleotide pyrophosphatase/phosphodiesterase family member 2E-NPP 23.1.4.39AutotaxinExtracellular lysophospholipase DLysoPLDENPP2ATXPDNP2Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomocDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2)PARTIAL PROTEIN SEQUENCECHARACTERIZATIONVARIANT PRO-493Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2).NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-45TISSUE SPECIFICITYVARIANT PRO-493Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)TISSUE SPECIFICITYVARIANT PRO-493Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1)CATALYTIC ACTIVITYSUBCELLULAR LOCATIONACTIVITY REGULATIONVARIANT PRO-493Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3)PROTEIN SEQUENCE OF 36-42 AND 49-54CATALYTIC ACTIVITYACTIVITY REGULATIONBIOPHYSICOCHEMICAL PROPERTIESTISSUE SPECIFICITYVARIANT PRO-493DNA sequence and analysis of human chromosome 8.NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1)VARIANT PRO-493Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase.PROTEIN SEQUENCE OF 36-49; 318-330; 335-344; 440-450 AND 854-863FUNCTIONCATALYTIC ACTIVITYSUBCELLULAR LOCATIONTISSUE SPECIFICITYBIOPHYSICOCHEMICAL PROPERTIESIdentification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein.PROTEIN SEQUENCE OF 256-266; 370-392; 457-463; 481-496; 501-510; 545-554; 639-643; 706-710 AND 829-840FUNCTIONSUBCELLULAR LOCATIONVARIANT PRO-493Autotaxin (NPP-2), a metastasis-enhancing mitogen, is an angiogenic factor.FUNCTION IN ANGIOGENESISSerum lysophosphatidic acid is produced through diverse phospholipase pathways.FUNCTIONAutotaxin hydrolyzes sphingosylphosphorylcholine to produce the regulator of migration, sphingosine-1-phosphate.FUNCTIONCATALYTIC ACTIVITYBIOPHYSICOCHEMICAL PROPERTIESMUTAGENESIS OF THR-210; HIS-316 AND HIS-360Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression.INDUCTIONPOSSIBLE FUNCTION IN OBESITYThe phospholipase A1 activity of lysophospholipase A-I links platelet activation to LPA production during blood coagulation.FUNCTIONCATALYTIC ACTIVITYBIOPHYSICOCHEMICAL PROPERTIESStructural basis of substrate discrimination and integrin binding by autotaxin.FUNCTIONCATALYTIC ACTIVITYACTIVITY REGULATIONMUTAGENESIS OF THR-210; PHE-211; ALA-218; ASN-231 AND TYR-307Structural Basis for Inhibition of Human Autotaxin by Four Potent Compounds with Distinct Modes of Binding.X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 55-860 IN COMPLEX WITH SYNTHETIC INHIBITOR; CALCIUM AND ZINCFUNCTIONCATALYTIC ACTIVITYCOFACTORSUBCELLULAR LOCATIONTISSUE SPECIFICITYGLYCOSYLATION AT ASN-525DISULFIDE BONDSDiscovery of 2-[[2-Ethyl-6-[4-[2-(3-hydroxyazetidin-1-yl)-2-oxoethyl]piperazin-1-yl]-8-methylimidazo[1,2-a]pyridin-3-yl]methylamino]-4-(4-fluorophenyl)thiazole-5-carbonitrile (GLPG1690), a First-in-Class Autotaxin Inhibitor Undergoing Clinical Evaluation for the Treatment of Idiopathic Pulmonary Fibrosis.X-RAY CRYSTALLOGRAPHY (2.43 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR; CALCIUM AND ZINCCOFACTORDISULFIDE BONDSSelective Inhibition of Autotaxin Is Efficacious in Mouse Models of Liver Fibrosis.X-RAY CRYSTALLOGRAPHY (2.59 ANGSTROMS) IN COMPLEX WITH SYNTHETIC INHIBITOR; CALCIUM AND ZINCCATALYTIC ACTIVITYFUNCTIONCOFACTORSUBCELLULAR LOCATIONDISULFIDE BONDSHydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:15769751, PubMed:26371182, PubMed:27754931, PubMed:14500380, PubMed:12354767). Major substrate is lysophosphatidylcholine (PubMed:12176993, PubMed:27754931, PubMed:14500380). Can also act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:14500380). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:15769751, PubMed:12176993). Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation (PubMed:11559573). Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein (PubMed:1733949). May have a role in induction of parturition (PubMed:12176993). Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor (PubMed:1733949, PubMed:11559573). Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids (PubMed:21393252). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (PubMed:21393252).1-O-alkyl-sn-glycero-3-phosphoethanolamine + H2O = 1-O-alkyl-sn-glycero-3-phosphate + ethanolamine + H(+)1-O-(9Z-octadecenyl)-sn-glycero-3-phosphocholine + H2O = 1-O-(9Z-octadecenyl)-sn-glycero-3-phosphate + choline + H(+)a 2-acyl-sn-glycero-3-phosphocholine + H2O = a 2-acyl-sn-glycerol 3-phosphate + choline + H(+)a 2-acyl-sn-glycero-3-phospho-L-serine + H2O = a 2-acyl-sn-glycerol 3-phosphate + H(+) + L-serine1-dodecanoyl-sn-glycero-3-phosphocholine + H2O = 1-dodecanoyl-sn-glycerol 3-phosphate + choline + H(+)H2O + sphing-4-enine-phosphocholine = choline + H(+) + sphing-4-enine 1-phosphate1-(9Z-octadecenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + choline + H(+)1-tetradecanoyl-sn-glycero-3-phosphocholine + H2O = 1-tetradecanoyl-sn-glycerol 3-phosphate + choline + H(+)1-decanoyl-sn-glycero-3-phosphocholine + H2O = 1-decanoyl-sn-glycero-3-phosphate + choline + H(+)1-hexadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexadecanoyl-sn-glycero-3-phosphate + choline + H(+)1-octadecanoyl-sn-glycero-3-phosphocholine + H2O = 1-octadecanoyl-sn-glycero-3-phosphate + choline + H(+)1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphocholine + H2O = 1-(9Z,12Z)-octadecadienoyl-sn-glycero-3-phosphate + choline + H(+)1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphocholine + H2O = 1-(5Z,8Z,11Z,14Z-eicosatetraenoyl)-sn-glycero-3-phosphate + choline + H(+)1-O-hexadecyl-sn-glycero-3-phosphocholine + H2O = 1-O-hexadecyl-sn-glycero-3-phosphate + choline + H(+)1-hexanoyl-sn-glycero-3-phosphocholine + H2O = 1-hexanoyl-sn-glycero-3-phosphate + choline + H(+)1,2-dioctanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-dioctanoyl-sn-glycero-3-phosphate + choline + H(+)1,2-didecanoyl-sn-glycero-3-phosphocholine + H2O = 1,2-didecanoyl-sn-glycero-3-phosphate + choline + H(+)1-O-(1Z-alkenyl)-sn-glycero-3-phosphocholine + H2O = 1-O-(1Z-alkenyl)-sn-glycero-3-phosphate + choline + H(+)1-(9Z-octadecenoyl)-sn-glycero-3-phosphoethanolamine + H2O = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + ethanolamine + H(+)1-(9Z-octadecenoyl)-sn-glycero-3-phospho-L-serine + H2O = 1-(9Z-octadecenoyl)-sn-glycero-3-phosphate + H(+) + L-serineZn(2+)Binds 2 Zn(2+) ions per subunit.Ca(2+)Binds 1 Ca(2+) ion per subunit.Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P). Inhibited by EDTA and EGTA (Probable).0.5 mM for 16:0-LPC (at pH 8.5)5.5 mM for pNP-TMP (at pH 8.5)11.3 mM for pNppp (isoform 1)5.7 mM for pNppp (isoform 2)19.8 mM for pNppp (isoform 3)96 uM for sn-1 lyso-PAF51 uM for sn-2 lyso-PAF0.1 mM for lysophosphatidylcholine0.23 mM for sphingosylphosphorylcholine1.9 nmol/min/ug enzyme with pNppp as substrate (isoform 1)0.67 nmol/min/ug enzyme with pNppp as substrate (isoform 2)1.6 nmol/min/ug enzyme with pNppp as substrate (isoform 3)0.11 umol/min/mg enzyme with sn-1 lyso-PAF as substrate0.025 umol/min/mg enzyme with sn-2 lyso-PAF as substrate11.8 nmol/min/ug enzyme with lysophosphatidylcholine as substrate6.1 nmol/min/ug enzyme with sphingosylphosphorylcholine as substrateOptimum pH is 9.0 (isoform 1), 8.0 (isoform 3). Isoform 1 is less sensitive to pH. Isoform 1, isoform 2 and isoform 3 all retain some activity at pH 9.5.Isoform 1 and isoform 3 are active from 45 to 60 degrees Celsius.SecretedQ13822-11ATXterBetaQ13822-22ATXmelAlphaQ13822-33GammaDetected in blood plasma (at protein level) (PubMed:12176993, PubMed:26371182). Predominantly expressed in brain, placenta, ovary, and small intestine. Expressed in a number of carcinomas such as hepatocellular and prostate carcinoma, neuroblastoma and non-small-cell lung cancer. Expressed in body fluids such as plasma, cerebral spinal fluid (CSF), saliva, follicular and amniotic fluids. Not detected in leukocytes. Isoform 1 is more highly expressed in peripheral tissues than in the central nervous system (CNS). Adipocytes only express isoform 1. Isoform 3 is more highly expressed in the brain than in peripheral tissues.Up-regulated in massively obese subjects with glucose intolerance, and during adipogenesis.N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity.The interdomain disulfide bond between Cys-414 and Cys-806 is essential for catalytic activity.Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.3D-structureAlternative splicingCalciumChemotaxisCleavage on pair of basic residuesDirect protein sequencingDisulfide bondGlycoproteinHydrolaseLipid degradationLipid metabolismMetal-bindingObesityReference proteomeRepeatSecretedSignalZincZn(2+)catalyticZn(2+)catalyticsubstratesubstratesubstratesubstrateZn(2+)catalyticZn(2+)catalyticZn(2+)catalyticZn(2+)catalyticZn(2+)catalyticCa(2+)Ca(2+)Ca(2+)Ca(2+)Ca(2+)EEESSYGSPFTPAKRPKRKVAPKRRQERPVAPPKKRRRKIHRMDHYAAETRQDKEEAETRKFRGSRNENKENINGNFEPRKSPNSSLSETAFYAVNAYQHQHQNSDHGAQRHRKPVSENPLPLSRVAYHNSQRHRSPFYSTPLMARRSSFQSCQIISLFTFAVGVNICLGFTAHRIKRAEGWEEGPPTVLSDSPWTNISGSCKGRCFELQEAGPPDCRCDNLCKSYTSCCHDFDELCLKTARGWECTKDRCGEVRNEENACHCSEDCLARGDCCTNYQVVCKGESHWVDDDCEEIKAAECPAGFVRPPLIIFSVDGFRASYMKKGSKVMPNIEKLRSCGTHSPYMRPVYPTKTFPNLYTLATGLYPESHGIVGNSMYDPVFDATFHLRGREKFNHRWWGGQPLWITATKQGVKAGTFFWSVVIPHERRILTILQWLTLPDHERPSVYAFYSEQPDFSGHKYGPFGPEMTNPLREIDKIVGQLMDGLKQLKLHRCVNVIFVGDHGMEDVTCDRTEFLSNYLTNVDDITLVPGTLGRIRSKFSNNAKYDPKAIIANLTCKKPDQHFKPYLKQHLPKRLHYANNRRIEDIHLLVERRWHVARKPLDVYKKPSGKCFFQGDHGFDNKVNSMQTVFVGYGSTFKYKTKVPPFENIELYNVMCDLLGLKPAPNNGTHGSLNHLLRTNTFRPTMPEEVTRPNYPGIMYLQSDFDLGCTCDDKVEPKNKLDELNKRLHTKGSTEERHLLYGRPAVLYRTRYDILYHTDFESGYSEIFLMPLWTSYTVSKQAEVSSVPDHLTSCVRPDVRVSPSFSQNCLAYKNDKQMSYGFLFPPYLSSSPEAKYDAFLVTNMVPMYPAFKRVWNYFQRVLVKKYASERNGVNVISGPIFDYDYDGLHDTEDKIKQYVEGSSIPVPTHYYSIITSCLDFTQPADKCDGPLSVSSFILPHRPDNEESCNSSEDESKWVEELMKMHTARVRDIEHLTSLDFFRKTSRSYPEILTLKTYLHTYESEI
Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms Distributed under the Creative Commons Attribution (CC BY 4.0) License