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Identification
HMDB Protein ID HMDBP00167
Secondary Accession Numbers
  • 5399
Name Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
Synonyms
  1. Autotaxin
  2. E-NPP 2
  3. Extracellular lysophospholipase D
  4. LysoPLD
Gene Name ENPP2
Protein Type Unknown
Biological Properties
General Function Involved in catalytic activity
Specific Function Hydrolyzes lysophospholipids to produce lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. 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. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development. Tumor cell motility-stimulating factor.
Pathways
  • Ether lipid metabolism
Reactions
1-alkyl-sn-glycero-3-phosphoethanolamine + Water → 1-alkyl-sn-glycerol 3-phosphate + Ethanolamine details
1-(1-Alkenyl)-sn-glycero-3-phosphoethanolamine + Water → 1-(1-Alkenyl)-sn-glycero-3-phosphate + Ethanolamine details
GO Classification
Biological Process
cellular component movement
chemotaxis
G-protein coupled receptor signaling pathway
phosphatidylcholine catabolic process
regulation of cell migration
immune response
Cellular Component
extracellular space
integral to plasma membrane
Function
ion binding
cation binding
metal ion binding
binding
catalytic activity
hydrolase activity
pattern binding
polysaccharide binding
receptor activity
transmembrane receptor activity
scavenger receptor activity
molecular transducer activity
signal transducer activity
nucleic acid binding
Molecular Function
nucleic acid binding
nucleotide diphosphatase activity
phosphodiesterase I activity
polysaccharide binding
scavenger receptor activity
alkylglycerophosphoethanolamine phosphodiesterase activity
lysophospholipase activity
transcription factor binding
zinc ion binding
calcium ion binding
Process
metabolic process
immune system process
immune response
Cellular Location
  1. Secreted
Gene Properties
Chromosome Location 8
Locus 8q24.1
SNPs ENPP2
Gene Sequence
>2592 bp
ATGGCAAGGAGGAGCTCGTTCCAGTCGTGTCAGATAATATCCCTGTTCACTTTTGCCGTT
GGAGTCAATATCTGCTTAGGATTCACTGCACATCGAATTAAGAGAGCAGAAGGATGGGAG
GAAGGTCCTCCTACAGTGCTATCAGACTCCCCCTGGACCAACATCTCCGGATCTTGCAAG
GGCAGGTGCTTTGAACTTCAAGAGGCTGGACCTCCTGATTGTCGCTGTGACAACTTGTGT
AAGAGCTATACCAGTTGCTGCCATGACTTTGATGAGCTGTGTTTGAAGACAGCCCGTGGC
TGGGAGTGTACTAAGGACAGATGTGGAGAAGTCAGAAATGAAGAAAATGCCTGTCACTGC
TCAGAGGACTGCTTGGCCAGGGGAGACTGCTGTACCAATTACCAAGTGGTTTGCAAAGGA
GAGTCGCATTGGGTTGATGATGACTGTGAGGAAATAAAGGCCGCAGAATGCCCTGCAGGG
TTTGTTCGCCCTCCATTAATCATCTTCTCCGTGGATGGCTTCCGTGCATCATACATGAAG
AAAGGCAGCAAAGTCATGCCTAATATTGAAAAACTAAGGTCTTGTGGCACACACTCTCCC
TACATGAGGCCGGTGTACCCAACTAAAACCTTTCCTAACTTATACACTTTGGCCACTGGG
CTATATCCAGAATCACATGGAATTGTTGGCAATTCAATGTATGATCCTGTATTTGATGCC
ACTTTTCATCTGCGAGGGCGAGAGAAATTTAATCATAGATGGTGGGGAGGTCAACCGCTA
TGGATTACAGCCACCAAGCAAGGGGTGAAAGCTGGAACATTCTTTTGGTCTGTTGTCATC
CCTCACGAGCGGAGAATATTAACCATATTGCAGTGGCTCACCCTGCCAGATCATGAGAGG
CCTTCGGTCTATGCCTTCTATTCTGAGCAACCTGATTTCTCTGGACACAAATATGGCCCT
TTCGGCCCTGAGATGACAAATCCTCTGAGGGAAATCGACAAAATTGTGGGGCAATTAATG
GATGGACTGAAACAACTAAAACTGCATCGGTGTGTCAACGTCATCTTTGTCGGAGACCAT
GGAATGGAAGATGTCACATGTGATAGAACTGAGTTCTTGAGTAATTACCTAACTAATGTG
GATGATATTACTTTAGTGCCTGGAACTCTAGGAAGAATTCGATCCAAATTTAGCAACAAT
GCTAAATATGACCCCAAAGCCATTATTGCCAATCTCACGTGTAAAAAACCAGATCAGCAC
TTTAAGCCTTACTTGAAACAGCACCTTCCCAAACGTTTGCACTATGCCAACAACAGAAGA
ATTGAGGATATCCATTTATTGGTGGAACGCAGATGGCATGTTGCAAGGAAACCTTTGGAT
GTTTATAAGAAACCATCAGGAAAATGCTTTTTCCAGGGAGACCACGGATTTGATAACAAG
GTCAACAGCATGCAGACTGTTTTTGTAGGTTATGGCTCAACATTTAAGTACAAGACTAAA
GTGCCTCCATTTGAAAACATTGAACTTTACAATGTTATGTGTGATCTCCTGGGATTGAAG
CCAGCTCCTAATAATGGGACCCATGGAAGTTTGAATCATCTCCTGCGCACTAATACCTTC
AGGCCAACCATGCCAGAGGAAGTTACCAGACCCAATTATCCAGGGATTATGTACCTTCAG
TCTGATTTTGACCTGGGCTGCACTTGTGATGATAAGGTAGAGCCAAAGAACAAGTTGGAT
GAACTCAACAAACGGCTTCATACAAAAGGGTCTACAGAAGAGAGACACCTCCTCTATGGG
CGACCTGCAGTGCTTTATCGGACTAGATATGATATCTTATATCACACTGACTTTGAAAGT
GGTTATAGTGAAATATTCCTAATGCCACTCTGGACATCATATACTGTTTCCAAACAGGCT
GAGGTTTCCAGCGTTCCTGACCATCTGACCAGTTGCGTCCGGCCTGATGTCCGTGTTTCT
CCGAGTTTCAGTCAGAACTGTTTGGCCTACAAAAATGATAAGCAGATGTCCTACGGATTC
CTCTTTCCTCCTTATCTGAGCTCTTCACCAGAGGCTAAATATGATGCATTCCTTGTAACC
AATATGGTTCCAATGTATCCTGCTTTCAAACGGGTCTGGAATTATTTCCAAAGGGTATTG
GTGAAGAAATATGCTTCGGAAAGAAATGGAGTTAACGTGATAAGTGGACCAATCTTCGAC
TATGACTATGATGGCTTACATGACACAGAAGACAAAATAAAACAGTACGTGGAAGGCAGT
TCCATTCCTGTTCCAACTCACTACTACAGCATCATCACCAGCTGTCTGGATTTCACTCAG
CCTGCCGACAAGTGTGACGGCCCTCTCTCTGTGTCCTCCTTCATCCTGCCTCACCGGCCT
GACAACGAGGAGAGCTGCAATAGCTCAGAGGACGAATCAAAATGGGTAGAAGAACTCATG
AAGATGCACACAGCTAGGGTGCGTGACATTGAACATCTCACCAGCCTGGACTTCTTCCGA
AAGACCAGCCGCAGCTACCCAGAAATCCTGACACTCAAGACATACCTGCATACATATGAG
AGCGAGATTTAA
Protein Properties
Number of Residues 863
Molecular Weight 98992.78
Theoretical pI 7.378
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
MARRSSFQSCQIISLFTFAVGVNICLGFTAHRIKRAEGWEEGPPTVLSDSPWTNISGSCK
GRCFELQEAGPPDCRCDNLCKSYTSCCHDFDELCLKTARGWECTKDRCGEVRNEENACHC
SEDCLARGDCCTNYQVVCKGESHWVDDDCEEIKAAECPAGFVRPPLIIFSVDGFRASYMK
KGSKVMPNIEKLRSCGTHSPYMRPVYPTKTFPNLYTLATGLYPESHGIVGNSMYDPVFDA
TFHLRGREKFNHRWWGGQPLWITATKQGVKAGTFFWSVVIPHERRILTILQWLTLPDHER
PSVYAFYSEQPDFSGHKYGPFGPEMTNPLREIDKIVGQLMDGLKQLKLHRCVNVIFVGDH
GMEDVTCDRTEFLSNYLTNVDDITLVPGTLGRIRSKFSNNAKYDPKAIIANLTCKKPDQH
FKPYLKQHLPKRLHYANNRRIEDIHLLVERRWHVARKPLDVYKKPSGKCFFQGDHGFDNK
VNSMQTVFVGYGSTFKYKTKVPPFENIELYNVMCDLLGLKPAPNNGTHGSLNHLLRTNTF
RPTMPEEVTRPNYPGIMYLQSDFDLGCTCDDKVEPKNKLDELNKRLHTKGSTEERHLLYG
RPAVLYRTRYDILYHTDFESGYSEIFLMPLWTSYTVSKQAEVSSVPDHLTSCVRPDVRVS
PSFSQNCLAYKNDKQMSYGFLFPPYLSSSPEAKYDAFLVTNMVPMYPAFKRVWNYFQRVL
VKKYASERNGVNVISGPIFDYDYDGLHDTEDKIKQYVEGSSIPVPTHYYSIITSCLDFTQ
PADKCDGPLSVSSFILPHRPDNEESCNSSEDESKWVEELMKMHTARVRDIEHLTSLDFFR
KTSRSYPEILTLKTYLHTYESEI
GenBank ID Protein 91823602
UniProtKB/Swiss-Prot ID Q13822
UniProtKB/Swiss-Prot Entry Name ENPP2_HUMAN
PDB IDs Not Available
GenBank Gene ID NM_001040092.1
GeneCard ID ENPP2
GenAtlas ID ENPP2
HGNC ID HGNC:3357
References
General References
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  2. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. [PubMed:16421571 ]
  3. Murata J, Lee HY, Clair T, Krutzsch HC, Arestad AA, Sobel ME, Liotta LA, Stracke ML: cDNA cloning of the human tumor motility-stimulating protein, autotaxin, reveals a homology with phosphodiesterases. J Biol Chem. 1994 Dec 2;269(48):30479-84. [PubMed:7982964 ]
  4. Kawagoe H, Soma O, Goji J, Nishimura N, Narita M, Inazawa J, Nakamura H, Sano K: Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2). Genomics. 1995 Nov 20;30(2):380-4. [PubMed:8586446 ]
  5. Lee HY, Murata J, Clair T, Polymeropoulos MH, Torres R, Manrow RE, Liotta LA, Stracke ML: Cloning, chromosomal localization, and tissue expression of autotaxin from human teratocarcinoma cells. Biochem Biophys Res Commun. 1996 Jan 26;218(3):714-9. [PubMed:8579579 ]
  6. van Meeteren LA, Ruurs P, Christodoulou E, Goding JW, Takakusa H, Kikuchi K, Perrakis A, Nagano T, Moolenaar WH: Inhibition of autotaxin by lysophosphatidic acid and sphingosine 1-phosphate. J Biol Chem. 2005 Jun 3;280(22):21155-61. Epub 2005 Mar 15. [PubMed:15769751 ]
  7. Giganti A, Rodriguez M, Fould B, Moulharat N, Coge F, Chomarat P, Galizzi JP, Valet P, Saulnier-Blache JS, Boutin JA, Ferry G: Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization. J Biol Chem. 2008 Mar 21;283(12):7776-89. doi: 10.1074/jbc.M708705200. Epub 2008 Jan 6. [PubMed:18175805 ]
  8. Tokumura A, Majima E, Kariya Y, Tominaga K, Kogure K, Yasuda K, Fukuzawa K: Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase. J Biol Chem. 2002 Oct 18;277(42):39436-42. Epub 2002 Aug 9. [PubMed:12176993 ]
  9. Stracke ML, Krutzsch HC, Unsworth EJ, Arestad A, Cioce V, Schiffmann E, Liotta LA: Identification, purification, and partial sequence analysis of autotaxin, a novel motility-stimulating protein. J Biol Chem. 1992 Feb 5;267(4):2524-9. [PubMed:1733949 ]
  10. Nam SW, Clair T, Kim YS, McMarlin A, Schiffmann E, Liotta LA, Stracke ML: Autotaxin (NPP-2), a metastasis-enhancing motogen, is an angiogenic factor. Cancer Res. 2001 Sep 15;61(18):6938-44. [PubMed:11559573 ]
  11. Boucher J, Quilliot D, Praderes JP, Simon MF, Gres S, Guigne C, Prevot D, Ferry G, Boutin JA, Carpene C, Valet P, Saulnier-Blache JS: Potential involvement of adipocyte insulin resistance in obesity-associated up-regulation of adipocyte lysophospholipase D/autotaxin expression. Diabetologia. 2005 Mar;48(3):569-77. Epub 2005 Feb 8. [PubMed:15700135 ]