Identification of novel members of the serum amyloid A protein superfamily as constitutive apolipoproteins of high density lipoprotein

• Published in: The Journal of biological chemistry Vol. 267; no. 6; pp. 3862 - 3867
• Main Authors: WHITEHEAD, A. S, DE BEER, M. C, STEEL, D. M, RITS, M, LELIAS, J. M, LANE, W. S, DE BEER, F. C
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Biochemistry and Molecular Biology 25-02-1992
• Subjects: Amino Acid Sequence; Analytical, structural and metabolic biochemistry; apolipoproteins; Apolipoproteins - blood; Apolipoproteins - genetics; Base Sequence; Biological and medical sciences; DNA - genetics; Electrophoresis, Polyacrylamide Gel; Fundamental and applied biological sciences. Psychology; genes; Glycosylation; Humans; lipoprotein (high density); Lipoproteins, HDL - blood; Lipoproteins, HDL - genetics; Lipoproteins, myelin; Liver - metabolism; Molecular Sequence Data; Proteins; Serum Amyloid A Protein - analysis; Serum Amyloid A Protein - genetics; Human; Northern blotting; Serum amyloid protein SAA; Isoelectrical focusing; Primary structure; Apolipoproteins; Molecular cloning; Lipoprotein HDL
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/s0021-9258(19)50605-6

A novel serum amyloid A protein (SAA) has been identified as a normal apolipoprotein component of non-acute phase high density
lipoprotein. This novel SAA has been designated "constitutive" SAA (C-SAA) to distinguish it from "acute phase" SAA (A-SAA).
C-SAA was partially sequenced, and immunochemical analyses indicated that it constitutes a distinct subclass of apolipoproteins
within the SAA superfamily. A C-SAA cDNA clone was isolated from a human liver library and sequenced. The clone predicts a
pre-C-SAA molecule of 130 residues from which an 18-residue leader peptide is cleaved. The 112-residue mature molecule is
8 residues longer than human A-SAA; the size difference is due to the presence of an octapeptide between positions 70 and
77 that is not found in the corresponding region of human A-SAA. Paradoxically, octapeptides of similar composition are found
at similar positions in the A-SAAs of a number of other species. The C-SAA octapeptide specifies the first two residues of
a NSS tripeptide, the only potential N-linked glycosylation site in the molecule. Studies indicate that approximately 50%
of these sites are glycosylated, thereby giving rise to two size classes, 14 and 19 kDa, of C-SAA in vivo. Human acute phase
liver contains little C-SAA mRNA relative to the levels of A-SAA mRNA, and the treatment of PLC/PRF/5 hepatoma cells with
monocyte-conditioned medium does not induce C-SAA mRNA concentrations to detectable levels, in contrast to the massive induction
of A-SAA mRNA observed. C-SAA is therefore not a major acute phase reactant.