RGD Reference Report - An essential oligomannosidic glycan chain in the catalytic domain of autotaxin, a secreted lysophospholipase-D. - Rat Genome Database

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An essential oligomannosidic glycan chain in the catalytic domain of autotaxin, a secreted lysophospholipase-D.

Authors: Jansen, S  Callewaert, N  Dewerte, I  Andries, M  Ceulemans, H  Bollen, M 
Citation: Jansen S, etal., J Biol Chem. 2007 Apr 13;282(15):11084-91. Epub 2007 Feb 16.
RGD ID: 9685416
Pubmed: PMID:17307740   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M611503200   (Journal Full-text)

Autotaxin/NPP2, a secreted lysophospholipase-D, promotes cell proliferation, survival, and motility by generating the signaling molecule lysophosphatidic acid. Here we show that ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2) is N-glycosylated on Asn-53, Asn-410, and Asn-524. Mutagenesis and deglycosylation experiments revealed that only the glycosylation of Asn-524 is essential for the expression of the catalytic and motility-stimulating activities of NPP2. The N-glycan on Asn-524 was identified as Man8/9GlcNAc2, which is rarely present on mature eukaryotic glycoproteins. Additional studies show that this Asn-524-linked glycan is not accessible to alpha-1,2-mannosidase, suggesting that its non-reducing termini are buried inside the folded protein. Consistent with a structural role for the Asn-524-linked glycan, only the mutation of Asn-524 augmented the sensitivity of NPP2 to proteolysis and increased its mobility during Blue Native PAGE. Asn-524 is phylogenetically conserved and maps to the catalytic domain of NPP2, but a structural model of this domain suggests that Asn-524 is remote from the catalytic site. Our study defines an essential role for the Asn-524-linked glycan chain of NPP2.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell chemotaxis  IMP 9685416 RGD 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
phosphodiesterase I activity  IMP 9685416 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Enpp2  (ectonucleotide pyrophosphatase/phosphodiesterase 2)


Additional Information