Alternative spliced variants in the pantetheinase family of genes expressed in human neutrophils.
Pantetheinase (EC 3.5.1.92) is an enzyme that hydrolyzes pantetheine, an intermediate metabolite of coenzyme A, into pantothenic acid (vitamin B(5)) and cysteamine, a potent antioxidant. The pantetheinase gene family consists of three independent genes, pantetheinase/vanin-1/VNN1, GPI-80/VNN2 and vanin-3/VNN3 that are each composed of seven exons. We herein report that human neutrophils express transcripts encoding at least nine splice variants of VNN3 and four splice variants of GPI-80/VNN2. Analysis of the DNA sequence of the human VNN3 gene demonstrated that the VNN3 locus in the human genome as well as the sequence of cDNA clones obtained in this study does not encode the complete VNN3 protein, as previously reported due to a frame shift caused by lack of one nucleotide. Moreover, the VNN3 locus indeed encodes smaller peptides compared to the proteins encoded by the mouse orthologous gene, vanin-3. The anti-GPI-80 monoclonal antibody 3H9 recognized amino acids 120-179 of the GPI-80/VNN2 protein as shown by the results of immunoblotting with recombinant GPI-80/VNN2 variant proteins. Immunoblotting with human neutrophil lysate suggests that the GPI-80/VNN2 variants exist in human neutrophils. The existence of splice variants in the pantetheinase gene family suggests the possibility of alternative roles in addition to canonical enzymatic activity in human neutrophils.
Nitto
Takeaki
T
Laboratory of Pharmacotherapy, Yokohama College of Pharmacy, Yokohama, Kanagawa 245-0066, Japan.
Inoue
Teruo
T
Node
Koichi
K
D017398:Alternative Splicing; D000581:Amidohydrolases / Q000235:genetics*; D000595:Amino Acid Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics; D058851:GPI-Linked Proteins; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006867:Hydrolases / Q000235:genetics; D008969:Molecular Sequence Data; D005810:Multigene Family; D009504:Neutrophils / Q000378:metabolism*
D000581:Amidohydrolases; D015815:Cell Adhesion Molecules; D058851:GPI-Linked Proteins; D006867:Hydrolases; C022314:pantetheinase; C121771:VNN2 protein, human; C121773:VNN3P protein, human