GPIHBP1 binds HSPG:LPL dimer

Stable Identifier
Reaction [binding]
Homo sapiens
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Lipoprotein lipase (LPL) is mainly produced by adipocytes and myocytes but is also involved in hydrolysing triglyceride-rich lipoproteins in the lumen of capillaries of heart, adipose tissue, and skeletal muscle. Heparan sulfate proteoglycan (HSPG) serves as an membrane anchor for LPL dimer but for LPL to reach its site of action in capillaries, it binds to glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), an endothelial cell membrane-bound protein. Once bound, GPIHBP1 transports LPL from within interstitial spaces, across endothelial cells to the capillary lumen (Gin et al. 2007, Young et al. 2011, Adeyo et al. 2012). Defects in GPIHBP1 can cause mislocalisation of LPL leading to severe hypertriglyceridaemia and hyperlipoproteinemia type ID (MIM:615947) (Adeyo et al. 2012, Wang & Hegele 2007, Beigneux et al. 2009, Beigneux et al. 2015).
Literature References
PubMed ID Title Journal Year
17883852 Homozygous missense mutation (G56R) in glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPI-HBP1) in two siblings with fasting chylomicronemia (MIM 144650)

Wang, J, Hegele, RA

Lipids Health Dis 2007
19304573 Chylomicronemia with a mutant GPIHBP1 (Q115P) that cannot bind lipoprotein lipase

Kastelein, JJ, Walzem, RL, Melford, K, Dallinga-Thie, GM, Weinstein, MM, Beigneux, AP, Fong, LG, Peter, J, Kuivenhoven, JA, Franssen, R, Gin, P, Bensadoun, A, Davies, BS, Young, SG

Arterioscler. Thromb. Vasc. Biol. 2009
25387803 GPIHBP1 missense mutations often cause multimerization of GPIHBP1 and thereby prevent lipoprotein lipase binding

Ploug, M, Gårdsvoll, H, Beigneux, AP, Oberer, M, Bensadoun, A, Fong, LG, Davies, BS, Young, SG

Circ. Res. 2015
21844202 GPIHBP1, an endothelial cell transporter for lipoprotein lipase

Reue, K, Gin, P, Beigneux, AP, Weinstein, MM, Fong, LG, Bensadoun, A, Davies, BS, Tontonoz, P, Young, SG, Voss, CV

J. Lipid Res. 2011
23020258 Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 and the intravascular processing of triglyceride-rich lipoproteins

Adeyo, O, Goulbourne, CN, Fong, LG, Bensadoun, A, Young, SG, Beigneux, AP

J. Intern. Med. 2012
17997385 Normal binding of lipoprotein lipase, chylomicrons, and apo-AV to GPIHBP1 containing a G56R amino acid substitution

Young, MF, Davies, B, Gin, P, Ryan, RO, Beigneux, AP, Fong, LG, Bensadoun, A, Young, SG

Biochim. Biophys. Acta 2007
Orthologous Events
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