Cloning, chromosomal mapping, and expression of a novel human secretory phospholipase A(2)

Secretory phospholipases A(2) (sPLA(2)s) represent a rapidly expanding family of structurally related enzymes found in mammals as well as in insect and snake venoms. In this report, a cDNA coding for a novel sPLA(2) has been isolated from human fetal lung, and its gene has been mapped to chromosome 16p13.1-p12. The mature sPLA(2) protein has a molecular mass of 13.6 kDa, is acidic (pI 5.3), and made up of 123 amino acids. Key structural features of the sPLA(2) include: (i) a long prepropeptide ending with an arginine doublet, (ii) 16 cysteines located at positions that are characteristic of both group I and group II sPLA(2)s, (iii) a C-terminal extension typical of group II sPLA(2)s, (iv) and the absence of elapid and pancreatic loops that are characteristic of group I sPLA(2)s. Based on these structural properties, this sPLA(2) appears as a first member of a new group of sPLA(2)s, called group X. A 1.5-kilobase transcript coding for the human group X (hGX) sPLA(2) was found in spleen, thymus, and peripheral blood leukocytes, while a less abundant 0.8-kilobase transcript was detected in the pancreas, lung, and colon. When the hGX sPLA(2), cDNA was expressed in COS cells, sPLA(2), activity preferentially accumulated in the culture medium, indicating that hGX, sPLA(2) is an actively secreted enzyme. It is maximally active at physiological pH and with 10 mM Ca2+. hGX sPLA(2) prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine.