Autotaxin

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Ectonucleotide pyrophosphatase/phosphodiesterase 2
3nkr.png
Mouse autotaxin in complex with lipid. PDB 3nkr
Identifiers
Symbols ENPP2 ; ATX; ATX-X; AUTOTAXIN; LysoPLD; NPP2; PD-IALPHA; PDNP2
External IDs OMIM601060 MGI1321390 HomoloGene4526 ChEMBL: 3691 GeneCards: ENPP2 Gene
EC number 3.1.4.39
RNA expression pattern
PBB GE ENPP2 209392 at tn.png
PBB GE ENPP2 210839 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 5168 18606
Ensembl ENSG00000136960 ENSMUSG00000022425
UniProt Q13822 Q9R1E6
RefSeq (mRNA) NM_001040092 NM_001136077
RefSeq (protein) NP_001035181 NP_001129549
Location (UCSC) Chr 8:
120.57 – 120.69 Mb
Chr 15:
54.84 – 54.92 Mb
PubMed search [1] [2]

Autotaxin also known as ectonucleotide pyrophosphatase/phosphodiesterase family member 2 (E-NPP 2) is an enzyme that in humans is encoded by the ENPP2 gene.[1][2]

Function[edit]

Autotaxin, also known as ectonucleotide pyrophosphatase/phosphodiesterase 2 (NPP2 or ENPP2), is a secreted enzyme important for generating the lipid signaling molecule lysophosphatidic acid (LPA). Autotaxin has lysophospholipase D activity that converts lysophosphatidylcholine into LPA.

Autotaxin was originally identified as a tumor cell-motility-stimulating factor; later it was shown to be LPA (which signals through Lysophospholipid receptors), the lipid product of the reaction catalyzed by autotaxin, which is responsible for its effects on cell-proliferation.

The protein encoded by this gene functions as both a phosphodiesterase, which cleaves phosphodiester bonds at the 5' end of oligonucleotides, and as a phospholipase, which catalyzes production of lysophosphatidic acid (LPA) in extracellular fluids. LPA evokes growth factor-like responses including stimulation of cell proliferation and chemotaxis. This gene product stimulates the motility of tumor cells, has angiogenic properties, and its expression is upregulated in several kinds of carcinomas. The gene product is secreted and further processed to make the biologically active form. Several alternatively spliced transcript variants have been identified, but the full-length nature of only two transcript variants has been determined.[2]

Structure[edit]

The crystal structures rat autotaxin[3] and mouse autotaxin[4] have been solved and deposited in the PDB. In each case, the apo structure have been solved along with product or inhibitor bound complexes. Both proteins consist of 4 domains, 2 N-terminal somatomedin-B-like (SMB) domains which may be involved in cell-surface localisation. The catalytic domain follows and contains a deep hydrophobic pocket in which the lipid substrate binds. At the C-terminus is the inactive nuclease domain which may function to aid protein stability.

For more information, see the QUIPS article at PDBe

See also[edit]

References[edit]

  1. ^ Kawagoe H, Soma O, Goji J, Nishimura N, Narita M, Inazawa J, Nakamura H, Sano K (Mar 1996). "Molecular cloning and chromosomal assignment of the human brain-type phosphodiesterase I/nucleotide pyrophosphatase gene (PDNP2)". Genomics 30 (2): 380–4. doi:10.1006/geno.1995.0036. PMID 8586446. 
  2. ^ a b "Entrez Gene: ENPP2 ectonucleotide pyrophosphatase/phosphodiesterase 2 (autotaxin)". 
  3. ^ NAT.STRUCT.MOL.BIOL. vol:18, pag:198 (2011)
  4. ^ Crystal structure of autotaxin and insight into GPCR activation by lipid mediators. NAT.STRUCT.MOL.BIOL.search (2011)

Further reading[edit]