Hmdb loader
Identification
HMDB Protein ID HMDBP12170
Secondary Accession Numbers None
Name Ectonucleotide pyrophosphatase/phosphodiesterase family member 2
Synonyms
  1. E-NPP 2
  2. Autotaxin
  3. Extracellular lysophospholipase D
  4. LysoPLD
Gene Name ENPP2
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids (PubMed:12633853, PubMed:29259743, PubMed:27660691, PubMed:27268273, PubMed:27075612, PubMed:12354767). Major substrate is lysophosphatidylcholine (PubMed:12119361, PubMed:27660691, PubMed:27268273, PubMed:27075612, PubMed:12176993). Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility (PubMed:12119361). Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP (PubMed:12633853, PubMed:27268273). 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 (By similarity). 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 (By similarity). Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF) (By similarity).
Pathways
  • Ether lipid metabolism
Reactions Not Available
GO Classification
Biological Process
regulation of angiogenesis
sphingolipid catabolic process
phospholipid metabolic process
negative regulation of cell-matrix adhesion
positive regulation of cell proliferation
cell chemotaxis
positive regulation of epithelial cell migration
phosphatidylcholine catabolic process
phospholipid catabolic process
cellular response to estradiol stimulus
positive regulation of peptidyl-tyrosine phosphorylation
regulation of cell migration
immune response
cellular response to cadmium ion
positive regulation of oligodendrocyte differentiation
estrous cycle
positive regulation of lamellipodium morphogenesis
positive regulation of substrate adhesion-dependent cell spreading
response to polycyclic arene
positive regulation of focal adhesion assembly
Cellular Component
cytoplasm
Golgi apparatus
extracellular space
Molecular Function
nucleic acid binding
nucleotide diphosphatase activity
phosphodiesterase I activity
polysaccharide binding
scavenger receptor activity
alkylglycerophosphoethanolamine phosphodiesterase activity
lysophospholipase activity
zinc ion binding
calcium ion binding
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 887
Molecular Weight 101575.51
Theoretical pI 7.513
Pfam Domain Function
Signals
  • 1-27;
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q64610
UniProtKB/Swiss-Prot Entry Name ENPP2_RAT
PDB IDs
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. 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 ]
  3. Narita M, Goji J, Nakamura H, Sano K: Molecular cloning, expression, and localization of a brain-specific phosphodiesterase I/nucleotide pyrophosphatase (PD-I alpha) from rat brain. J Biol Chem. 1994 Nov 11;269(45):28235-42. [PubMed:7961762 ]
  4. Koike S, Keino-Masu K, Ohto T, Masu M: The N-terminal hydrophobic sequence of autotaxin (ENPP2) functions as a signal peptide. Genes Cells. 2006 Feb;11(2):133-42. doi: 10.1111/j.1365-2443.2006.00924.x. [PubMed:16436050 ]
  5. Aoki J, Taira A, Takanezawa Y, Kishi Y, Hama K, Kishimoto T, Mizuno K, Saku K, Taguchi R, Arai H: Serum lysophosphatidic acid is produced through diverse phospholipase pathways. J Biol Chem. 2002 Dec 13;277(50):48737-44. doi: 10.1074/jbc.M206812200. Epub 2002 Sep 26. [PubMed:12354767 ]