Characterization of the human gene (PTGS2) encoding prostaglandin-endoperoxide synthase 2.
The human gene (PTGS2) encoding an inducible isozyme of prostaglandin-endoperoxide synthase (prostaglandin-endoperoxide synthase 2) that is distinct from the well-characterized and constitutive isozyme (prostaglandin-endoperoxide synthase 1), was isolated using a polymerase-chain reaction-generated cDNA fragment probe for human prostaglandin-endoperoxide synthase 2. Nucleotide sequence analysis of the entire human prostaglandin-endoperoxide-synthase-2 gene demonstrated that it is more than 8.3 kb in size and consists of ten exons; this gene is very similar to the murine and chicken prostaglandin-endoperoxide-synthase-2 genes. The structures of exons in the human prostaglandin-endoperoxide-synthase-2 gene were also similar to those of the human prostaglandin-endoperoxide-synthase-1 gene (PTGS1). However, the sizes of introns in the human prostaglandin-endoperoxide-synthase-2 gene were generally smaller than those of the human prostaglandin-endoperoxide-synthase-1 gene. Primer-extension analysis indicated that the transcriptional-start site is 134 bases upstream of the translational-initiation site. The sequence of the 1.69-kb region of nucleotides preceding the transcriptional-start site and the first 0.8-kb intron contained a canonical TATA box and various transcriptional-regulatory elements (CArG box, NF-IL6, PEA-1, myb, GATA-1, xenobiotic-response element, cAMP-response element, NF-kappa B, PEA-3, Sp-1 and 12-O-tetradecanoyl-phorbol-13-acetate-response element). The nucleotide sequence of the 5'-flanking region (275 bp) of the human prostaglandin-endoperoxide-synthase-2 gene showed 63% similarity to the sequence of murine prostaglandin-endoperoxide-synthase-2/TIS10 gene, but essentially no homology to the chicken prostaglandin-endoperoxide-synthase-2 gene, and human and murine prostaglandin-endoperoxide-synthase-1 genes. A fluorescence in situ hybridization study showed that the human genes coding for prostaglandin-endoperoxide synthase 1 (PTGS1) and prostaglandin-endoperoxidase synthase 2 (PTGS2) were mapped to distinct chromosomes 9q32-q33.3 and 1q25.2-q25.3, respectively, indicating that these genes are not genetically linked.
Kosaka
T
T
Department of Pharmacology, National Cardiovascular Center Research Institute, Osaka, Japan.
Miyata
A
A
Ihara
H
H
Hara
S
S
Sugimoto
T
T
Takeda
O
O
Takahashi
E
E
Tanabe
T
T
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry; D004790:Enzyme Induction / Q000235:genetics*; D005091:Exons; D006801:Humans; D017403:In Situ Hybridization; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000737:chemistry / Q000235:genetics* / Q000302:isolation & purification; D012326:RNA Splicing; D012689:Sequence Homology, Nucleic Acid; D012984:Software; D016385:TATA Box; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D011451:Prostaglandin-Endoperoxide Synthases