Mouse Gene Enpp2 (ENSMUST00000171545.8) from GENCODE VM23 Comprehensive Transcript Set (only Basic displayed by default)
  Description: Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 2 (Enpp2), transcript variant 1, mRNA. (from RefSeq NM_001136077)
RefSeq Summary (NM_001136077): This gene encodes a member of the phosphodiesterase and nucleotide pyrophosphatase family of bifunctional enzymes that hydrolize phosphodiester bonds of various nucleotides. The encoded protein undergoes proteolytic processing to generate a mature protein with lysophospholipase D activity, catalyzing the cleavage of the choline group from lysophosphatidylcholine to produce lysophosphatidic acid. This gene is expressed in numerous tissues and participates in neural development, obesity, inflammation and oncogenesis. A complete lack of the encoded protein in mice results in aberrant vascular and neuronal development leading to embryonic lethality. Alternative splicing results in multiple transcript variants encoding different isoforms that may undergo similar processing to generate the mature protein. [provided by RefSeq, Sep 2015].
Gencode Transcript: ENSMUST00000171545.8
Gencode Gene: ENSMUSG00000022425.16
Transcript (Including UTRs)
   Position: mm10 chr15:54,839,366-54,919,961 Size: 80,596 Total Exon Count: 26 Strand: -
Coding Region
   Position: mm10 chr15:54,839,366-54,919,961 Size: 80,596 Coding Exon Count: 26 

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Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2019-09-19

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr15:54,839,366-54,919,961)mRNA (may differ from genome)Protein (914 aa)
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-  Comments and Description Text from UniProtKB
  ID: ENPP2_MOUSE
DESCRIPTION: RecName: Full=Ectonucleotide pyrophosphatase/phosphodiesterase family member 2; Short=E-NPP 2; EC=3.1.4.39; AltName: Full=Autotaxin; AltName: Full=Extracellular lysophospholipase D; Short=LysoPLD; Flags: Precursor;
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.
CATALYTIC ACTIVITY: 1-alkyl-sn-glycero-3-phosphoethanolamine + H(2)O = 1-alkyl-sn-glycerol 3-phosphate + ethanolamine.
COFACTOR: Binds 2 zinc ions per subunit.
COFACTOR: Binds 1 calcium ion per subunit.
ENZYME REGULATION: Inhibited by lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) (By similarity). Inhibited by EDTA and EGTA.
BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=12.9 mM for pNppp (isoform 1); KM=4.4 mM for pNppp (isoform 2); KM=11.8 mM for pNppp (isoform 3); Vmax=1.9 nmol/min/ug enzyme with pNppp as substrate (isoform 1); Vmax=0.35 nmol/min/ug enzyme with pNppp as substrate (isoform 2); Vmax=1.8 nmol/min/ug enzyme with pNppp as substrate (isoform 3); pH dependence: Optimum pH is 8.0 for isoforms 1, 2 and 3; Temperature dependence: Isoforms 1 and 3 have maximum activity from 45 to 55 degrees Celsius;
SUBCELLULAR LOCATION: Secreted. Note=Secreted by most body fluids including serum and CSF. Also by adipocytes and numerous cancer cells (By similarity).
TISSUE SPECIFICITY: Expressed in brain and adipose tissue.
INDUCTION: Up-regulated in adipocytes of obese-diabetic db/db mice.
PTM: N-glycosylation, but not furin-cleavage, plays a critical role on secretion and on lysoPLD activity. Secretion requires simultaneous glycosylation on Asn-53 and Asn-410, while probable glycosylation of Asn-410 has a preferential role on lysoPLD activity. Not O-glycosylated.
PTM: It has been suggested that the active SMB domain may be permitted considerable disulfide bond heterogeneity or variability, thus two alternate disulfide patterns based on 3D structures are described with 1 disulfide bond conserved in both. The interdomain disulfide bond between Cys-413 and Cys-805 is essential for catalytic activity.
DISEASE: Note=May contribute to obesity.
SIMILARITY: Belongs to the nucleotide pyrophosphatase/phosphodiesterase family.
SIMILARITY: Contains 2 SMB (somatomedin-B) domains.

-  Primer design for this transcript
 

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-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR017849 - Alkaline_Pase-like_a/b/a
IPR017850 - Alkaline_phosphatase_core
IPR001604 - DNA/RNA_non-sp_Endonuclease
IPR024873 - E-NPP
IPR020821 - Extracellular_endonuc_su_A
IPR002591 - Phosphodiest/P_Trfase
IPR020436 - Somatomedin_B_chordata
IPR001212 - Somatomedin_B_dom

Pfam Domains:
PF01033 - Somatomedin B domain
PF01223 - DNA/RNA non-specific endonuclease
PF01663 - Type I phosphodiesterase / nucleotide pyrophosphatase

SCOP Domains:
53649 - Alkaline phosphatase-like
54060 - His-Me finger endonucleases
90188 - Somatomedin B domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help
3NKM - X-ray 3NKN - X-ray 3NKO - X-ray 3NKP - X-ray 3NKQ - X-ray 3NKR - X-ray


ModBase Predicted Comparative 3D Structure on Q9R1E6
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-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
HumanRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene Details     
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Protein SequenceProtein Sequence    
AlignmentAlignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003676 nucleic acid binding
GO:0003824 catalytic activity
GO:0004528 phosphodiesterase I activity
GO:0004551 nucleotide diphosphatase activity
GO:0004622 lysophospholipase activity
GO:0005044 scavenger receptor activity
GO:0005509 calcium ion binding
GO:0008270 zinc ion binding
GO:0016787 hydrolase activity
GO:0030247 polysaccharide binding
GO:0046872 metal ion binding
GO:0047391 alkylglycerophosphoethanolamine phosphodiesterase activity

Biological Process:
GO:0001953 negative regulation of cell-matrix adhesion
GO:0006629 lipid metabolic process
GO:0006644 phospholipid metabolic process
GO:0006898 receptor-mediated endocytosis
GO:0006935 chemotaxis
GO:0006955 immune response
GO:0008152 metabolic process
GO:0008284 positive regulation of cell proliferation
GO:0009395 phospholipid catabolic process
GO:0010634 positive regulation of epithelial cell migration
GO:0016042 lipid catabolic process
GO:0030334 regulation of cell migration
GO:0034638 phosphatidylcholine catabolic process
GO:0045765 regulation of angiogenesis
GO:0048714 positive regulation of oligodendrocyte differentiation
GO:0050731 positive regulation of peptidyl-tyrosine phosphorylation
GO:0051894 positive regulation of focal adhesion assembly
GO:0060326 cell chemotaxis
GO:0090305 nucleic acid phosphodiester bond hydrolysis
GO:1900026 positive regulation of substrate adhesion-dependent cell spreading
GO:2000394 positive regulation of lamellipodium morphogenesis

Cellular Component:
GO:0005576 extracellular region
GO:0005615 extracellular space
GO:0005737 cytoplasm
GO:0005794 Golgi apparatus
GO:0005887 integral component of plasma membrane


-  Descriptions from all associated GenBank mRNAs
  BC003264 - Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 2, mRNA (cDNA clone MGC:6665 IMAGE:3499038), complete cds.
AF123542 - Mus musculus phosphodiesterase I/nucleotide pyrophosphatase (Npps2) mRNA, complete cds.
AK163881 - Mus musculus 0 day neonate cerebellum cDNA, RIKEN full-length enriched library, clone:C230007F18 product:ectonucleotide pyrophosphatase/phosphodiesterase 2, full insert sequence.
AK161144 - Mus musculus 10 days neonate skin cDNA, RIKEN full-length enriched library, clone:4732475I12 product:ectonucleotide pyrophosphatase/phosphodiesterase 2, full insert sequence.
BC058759 - Mus musculus ectonucleotide pyrophosphatase/phosphodiesterase 2, mRNA (cDNA clone MGC:68021 IMAGE:6491897), complete cds.
AK088491 - Mus musculus 2 days neonate thymus thymic cells cDNA, RIKEN full-length enriched library, clone:E430018O03 product:ectonucleotide pyrophosphatase/phosphodiesterase 2, full insert sequence.
EU131009 - Mus musculus autotaxin isoform alpha (Enpp2) mRNA, complete cds, alternatively spliced.
EU131010 - Mus musculus autotaxin isoform gamma (Enpp2) mRNA, complete cds, alternatively spliced.
AK038940 - Mus musculus adult male hypothalamus cDNA, RIKEN full-length enriched library, clone:A230077H09 product:ectonucleotide pyrophosphatase/phosphodiesterase 2, full insert sequence.
AK194880 - Mus musculus cDNA, clone:Y1G0116L09, strand:minus, reference:ENSEMBL:Mouse-Transcript-ENST:ENSMUST00000053359, based on BLAT search.
AK206102 - Mus musculus cDNA, clone:Y2G0103M01, strand:plus, reference:ENSEMBL:Mouse-Transcript-ENST:ENSMUST00000053359, based on BLAT search.
AK177529 - Mus musculus cDNA, clone:Y0G0103A19, strand:plus, reference:ENSEMBL:Mouse-Transcript-ENST:ENSMUST00000041591, based on BLAT search.
AK048453 - Mus musculus 16 days embryo head cDNA, RIKEN full-length enriched library, clone:C130061P16 product:unclassifiable, full insert sequence.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
mmu00565 - Ether lipid metabolism

-  Other Names for This Gene
  Alternate Gene Symbols: A8UH85, A8UH93, B2ZP54, ENPP2_MOUSE, NM_001136077, Npps2, Pdnp2, Q6PDE0, Q99LG9, Q9R1E6, uc011zsx.1, uc011zsx.2, uc011zsx.3, uc011zsx.4
UCSC ID: uc011zsx.4
RefSeq Accession: NM_001136077
Protein: Q9R1E6 (aka ENPP2_MOUSE or NPP2_MOUSE)
CCDS: CCDS49607.1, CCDS70629.1

-  Gene Model Information
  Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.