Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen.
Apolipoprotein(a) [apo(a)] is a glycoprotein with Mr approximately equal to 280,000 that is disulfide linked to apolipoprotein B in lipoprotein(a) particles. Elevated plasma levels of lipoprotein(a) are correlated with atherosclerosis. Partial amino acid sequence of apo(a) shows that it has striking homology to plasminogen. Plasminogen is a plasma serine protease zymogen that consists of five homologous and tandemly repeated domains called kringles and a trypsin-like protease domain. The amino-terminal sequence obtained for apo(a) is homologous to the beginning of kringle 4 but not the amino terminus of plasminogen. Apo(a) was subjected to limited proteolysis by trypsin or V8 protease, and fragments generated were isolated and sequenced. Sequences obtained from several of these fragments are highly (77-100%) homologous to plasminogen residues 391-421, which reside within kringle 4. Analysis of these internal apo(a) sequences revealed that apo(a) may contain at least two kringle 4-like domains. A sequence obtained from another tryptic fragment also shows homology to the end of kringle 4 and the beginning of kringle 5. Sequence data obtained from two tryptic fragments show homology with the protease domain of plasminogen. One of these sequences is homologous to the sequences surrounding the activation site of plasminogen. Plasminogen is activated by the cleavage of a specific arginine residue by urokinase and tissue plasminogen activator; however, the corresponding site in apo(a) is a serine that would not be cleaved by tissue plasminogen activator or urokinase. Using a plasmin-specific assay, no proteolytic activity could be demonstrated for lipoprotein(a) particles. These results suggest that apo(a) contains kringle-like domains and an inactive protease domain.
Eaton
D L
DL
Fless
G M
GM
Kohr
W J
WJ
McLean
J W
JW
Xu
Q T
QT
Miller
C G
CG
Lawn
R M
RM
Scanu
A M
AM
D000595:Amino Acid Sequence; D001054:Apolipoproteins A / Q000097:blood* / Q000235:genetics / Q000302:isolation & purification; D001161:Arteriosclerosis / Q000097:blood; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis; D010958:Plasminogen / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid
D001054:Apolipoproteins A; D010446:Peptide Fragments; D010958:Plasminogen