Cloning, chromosomal mapping, and expression of a novel human secretory phospholipase A2.
Secretory phospholipases A2 (sPLA2s) 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 sPLA2 has been isolated from human fetal lung, and its gene has been mapped to chromosome 16p13.1-p12. The mature sPLA2 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 sPLA2 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 sPLA2s, (iii) a C-terminal extension typical of group II sPLA2s, (iv) and the absence of elapid and pancreatic loops that are characteristic of group I sPLA2s. Based on these structural properties, this sPLA2 appears as a first member of a new group of sPLA2s, called group X. A 1.5-kilobase transcript coding for the human group X (hGX) sPLA2 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 sPLA2 cDNA was expressed in COS cells, sPLA2 activity preferentially accumulated in the culture medium, indicating that hGX sPLA2 is an actively secreted enzyme. It is maximally active at physiological pH and with 10 mM Ca2+. hGX sPLA2 prefers phosphatidylethanolamine and phosphatidylcholine liposomes to those of phosphatidylserine.
Cupillard
L
L
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS UPR 411, Sophia Antipolis, 660 route des Lucioles, 06560 Valbonne, France.
Koumanov
K
K
Mattéi
M G
MG
Lazdunski
M
M
Lambeau
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16; D003001:Cloning, Molecular; D019143:Evolution, Molecular; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics*; D054467:Phospholipases A2; D016415:Sequence Alignment; D013379:Substrate Specificity; D014158:Transcription, Genetic
D010741:Phospholipases A; D054467:Phospholipases A2