apolipoprotein <a>

Function

• main constituent of lipoprotein<a>
• has serine proteinase activity
• capable of autoproteolysis
• inhibits tissue-type plasminogen activator 1
• may be a ligand for megalin/Gp 330
• binds to fibronectin & decorin

Structure

• found in lipoprotein<a> covalently linked to apo-B100 via a disulfide linkage
• homologous with plasminogen
• variable number of kringle domains (10-50)
• belongs to the peptidase S1 family, plasminogen subfamily
• contains 1 peptidase S1 domain
• N-glycosylated & O-glycosylated
• the N-glycans are complex biantennary structures present in either a mono- or disialylated state
• the O-glycans are mostly (80%) represented by monosialylated core type I structure, neuNAcalpha2-3galbeta1-3galNAc, with smaller amounts of disialylated & non-sialylated O-glycans

Pathology

• apo<a> fragments accumulate in atherosclerotic lesions, where they may promote thrombogenesis
• homology with plasminogen kringle domains IV & V is thought to underlie the atherogenicity of the protein, because the fragments are competing with plasminogen for fibrin/ fibrinogen binding

Polymorphism

• variable number of kringle domains (3-43)

Pharmacology

• olpasiran is a small interfering RNA that reduces apolipoprotein(a) synthesis in the liver

Notes

• known to be proteolytically cleaved, leading to the formation of the so-called mini-Lp<a>
• O-glycosylation may limit the extent of proteolytic fragmentation

More general terms

• apolipoprotein
• serine protease trypsin family
• glycoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=4018
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:4018
• OMIM: https://mirror.omim.org/entry/152200
• UniProt: http://www.uniprot.org/uniprot/P08519.html