Identification of novel members of the serum amyloid A protein superfamily as constitutive apolipoproteins of high density lipoprotein.
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.
Whitehead
A S
AS
Department of Immunology, Children's Hospital, Boston, Massachusetts.
de Beer
M C
MC
Steel
D M
DM
Rits
M
M
Lelias
J M
JM
Lane
W S
WS
de Beer
F C
FC
D000595:Amino Acid Sequence; D001053:Apolipoproteins / Q000097:blood* / Q000235:genetics; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004591:Electrophoresis, Polyacrylamide Gel; D006031:Glycosylation; D006801:Humans; D008075:Lipoproteins, HDL / Q000097:blood* / Q000235:genetics; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D000685:Serum Amyloid A Protein / Q000032:analysis* / Q000235:genetics
D001053:Apolipoproteins; D008075:Lipoproteins, HDL; D000685:Serum Amyloid A Protein; D004247:DNA