The ENPP7 gene is 11.139 bp in length and is composed of 6 exons in the size of 1841 bp. The first 20 bp in exon 1, the last 17 bp in exon 5 and the exon 6 are not translated.

Besides the wild type transcript shown above, different transcripts have been identified. The first is the one with exon 4 deletion, which has been found in HepG2 liver cancer cells and some human colon and liver cancer tissues. The second one also deletes exon 4 but inserts 7 foreign amino acids due to the shift of the splice site. This transcript was identified in human HT29 colon cancer cells. The third one has a larger exon 1 than the wild type, which includes upstream another starting codon (219 bp upstream), and was identified in one liver tumor. Some factors such as ursodeoxycholic acid and psyllium have been found to stimulate the expression of ENPP7 whereas high fat diet decreases ENPP7 expression.

LOC401847

The wild type ENPP7 contains 458 amino acids, which shares 30-36% identity to other members of the NPP family. The protein has a signal peptide at the N-terminal, which is cleaved in the mature enzyme, and a transmembrane domain at the C-terminal, which anchors the enzyme on the plasma membrane. The rest part of the enzyme is located outside the cells. The enzyme has 5 N-glycosylation sites and glycosylation is important for both transport of the enzyme to the plasma membrane and for enzyme activity. Similar to other NPP members, ENPP7 has two metal binding sites formed by 6 amino acids. These sites are predicted to serve as substrate binding site.

The enzyme has so far been found to express in the intestinal mucosal cells of many species and additionally human liver cells. The expression in liver may be restricted to human, because no activity or mRNA of ENPP7 could be found in the bile or liver of many other species. The expression is associated with differentiation of both intestinal and hepatic cells. ENPP7 is developed early in the fetus and high activity has been found in the meconium of human fetus at the age of 23 week gestation.

The enzyme is localized at the apical part but not basolateral part of intestinal epithelial cells. The enzyme can be dissociated from the membrane by bile salt and by pancreatic trypsin and released into the lumen in fully active form. Along the intestinal tract, the activity is low in the duodenum, high in the jejunum, and rapidly decreasing in the distal part of ileum and colon. The enzyme is also found in human bile, which is expressed in the liver and released to the bile.

ENPP7 is a member of the ecto-nucleotide pyrophosphatase/ phosphodiesterase (NPP) family with specific activity against lipids with positively charged phosphocholine headgroup including sphingomyelin, lysophosphatidylcholine and platelet activating factor (PAF). It hydrolyzes sphingomyelin to generate ceramide, a potent antiproliferative and proapoptotic molecule. It hydrolyzes lysophosphatidylcholine to monoglyceride and therefore competes with lysophospholipase D to reduce the formation of lysophosphatidic acid, a potent factor for inflammation and angiogenesis. It hydrolyses PAF to 1-0-alkyl-2-acetyl-sn-glycerol and inhibits PAF-induced inflammatory responses. ENPP7 has been proposed as a tumor suppressor protein.
In addition, ENPP7 may influence cholesterol absorption by hydrolyzing sphingomyelin in the intestinal lumen and on the apical surface of microvilli, as the levels of sphingomyelin in the intestinal tract affect cholesterol absorption.

ENPP7 shares 30-35% homology with other members of ENPP family. Regard to ENPP7, human ENPP7 shares 85% identity with rat form (NP_001012484), 82% with the mouse form (NP_001025462.1), and 82% with fowl form (XP 423912.1). The N-glycosylation sites, the amino acids forming the metal coordinate sites and active core are all conserved in the forms mentioned above.