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Human serum amyloid A protein. The assignment of the six major isoforms to three published gene sequences and evidence for two genetic loci

Strachan, AF; Brandt, WF; Woo, P; van der Westhuyzen, DR; Coetzee, GA; De Beer, MC; ... de Beer, FC; + view all (1989) Human serum amyloid A protein. The assignment of the six major isoforms to three published gene sequences and evidence for two genetic loci. J.Biol.Chem. , 264 (31) 18368 - 18373.

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Abstract

Serum amyloid A protein (apo-SAA) is an acute-phase reactant and an apolipoprotein of high density lipoproteins (HDL). Six major isoforms of apo-SAA occur in humans (pI 6.0, 6.4, 7.0, 7.4, 7.5, 8.0). In this report we have rationalized the phenotypic expression of apo-SAA isoforms with published apo-SAA structures predicted from apo-SAA cDNA's pA1 and pSAA82 and the genomic DNA SAAg9. The six apo-SAA isoforms fall into three pairs, pI 6.0/6.4, 7.0/7.5, and 7.4/8.0, which are products of cDNA pA1, cDNA pSAA82, and genomic DNA SAAg9, respectively. The second of each isoform pair (i.e. pI 6.4, 7.5, and 8.0) is the "primary" product: a 104-residue peptide with the NH2-terminal sequence Arg-Ser-Phe-Phe. Each primary product is processed either to a major 103-residue peptide with the NH2-terminal sequence Ser-Phe-Phe or processed to a minor 102-residue product which results from the loss of both an Arg and a Ser residue from the NH2 termini. These "secondary" products have the lower pI values of 6.0, 7.0, and 7.4, respectively. The isoelectric points of the SAAg9 products were confirmed by expression of SAAg9 in transfected mouse L-cells. Both the pI 8.0 and 7.4 isoforms were present in cellular extracts, suggesting that post-translational modification of apo-SAA may occur intracellularly. However, the greater relative abundance of the pI 7.4 isoform extracellularly suggests that the major conversion may occur after secretion. Whereas the gene corresponding to the pA1 cDNA sequence does not show allelic variation, the segregation characteristics of the pI 7.0/7.5 and 7.4/8.0 isoform pairs amongst individuals suggests that these isoforms are the products of genes (with sequences corresponding to pSAA82 and SAAg9, respectively) which are allelic variants at a single locus distinct from that for the pI 6.0/6.4 isoform pair

Type:Article
Title:Human serum amyloid A protein. The assignment of the six major isoforms to three published gene sequences and evidence for two genetic loci
Additional information:DA - 19891128 IS - 0021-9258 LA - eng PT - Journal Article RN - 0 (Amino Acids) RN - 0 (Amyloid Protein SAA) RN - 9007-49-2 (DNA) SB - IM
Keywords:Amino Acid Sequence, Amino Acids, Amyloid, Amyloid Protein SAA, analysis, Animals, Dna, genetics, Human, Isoelectric Point, L Cells (Cell Line), Mice, Molecular Sequence Data, Protein Processing,Post-Translational, Support,Non-U.S.Gov't, Transfection
UCL classification:UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Infection and Immunity (Division of)

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