Nonexpression of the human serum amyloid A three (SAA3) gene.
Serum amyloid A (SAA) is a major acute-phase plasma protein synthesized by the liver. In addition to the two major plasma isoforms described in humans (SAA1 and SAA2), a third form (SAA3) has been demonstrated in several other species and is distinguished by predominant extrahepatic expression. Two clones, Ch11g5-1-1 and HDg1-1, containing the human SAA3 gene are described in this report. The human SAA3 gene is comparable in organization to the SAA1 and SAA2 genes and shares with them 87% nucleotide identity in the region spanning exon 3 through exon 4. Sequences 5' to exon 3, however, are strikingly different from those in the SAA1 and SAA2 genes. For instance, the sequence deduced for amino acids 1-12 (exon 2) has only 25% identity with human SAA1 and SAA2; it most closely resembles that of rabbit SAA3 isolated from synovial fibroblast cultures (75% identity). Although rabbit SAA3 induces collagenase production in an autocrine fashion the human SAA3 gene is not expressed. This is shown by: (i) a single base insertion in the sequence corresponding to codon 31, (ii) the inability of a 918-bp fragment immediately upstream from SAA3 exon sequences to direct transcription of a chloramphenicol acetyltransferase reporter gene, and (iii) the absence of detectable human SAA3 in mRNA.
Kluve-Beckerman
B
B
Department of Medicine, Indiana University, Indianapolis.
Drumm
M L
ML
Benson
M D
MD
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D006224:Cricetinae; D005784:Gene Amplification; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D011817:Rabbits; D012689:Sequence Homology, Nucleic Acid; D000685:Serum Amyloid A Protein / Q000096:biosynthesis / Q000235:genetics*; D016385:TATA Box; D014162:Transfection
D015345:Oligonucleotide Probes; D000685:Serum Amyloid A Protein; D015500:Chloramphenicol O-Acetyltransferase