GPC5 (glypican 5)

Description	572 amino acids; 64 kDa protein (core protein). GPC5 is a heparan sulfate proteoglycan (HSPG), that is bound to the cell surface by a glycosyl-phosphatidylinositol (GPI) anchor.
Expression	GPC5 is expressed mainly in fetal tissues, including brain, lung and liver. In the adult, expression is primarily in brain tissue.
Localisation	Attached to the cell membrane by a GPI anchor.
	Schematic of glypican protein structure at the cell surface. The protein is held in the plasma membrane by a GPI anchor at the carboxyl terminus. Numerous glycosoaminoglycan (GAG) attachment sites close to the membrane surface allow heparin and chondroitin sulphate chains to be attached to the core protein (shown in green). The amino terminal end of the protein is a globular structure held together by a conserved set of cysteine residues forming disulphide bridges. (Picture reproduced from Filmus and Selleck, 2001).
Function	The precise functions of GPC5 have yet to be fully established. HSPGs are common constituents of cell surfaces and the extracellular matrix (ECM), with essential functions in cell growth and development (Burgess and Macaig, 1989; Andres et al., 1992). Glypicans appear to be expressed predominantly during development, with expression levels changing in a stage- and tissue-specific manner, suggesting their involvement in morphogenesis (Sing and Filmus, 2002). As they can bind numerous ligands and be associated with a variety of receptors, they act as co-receptors for a number of heparin-binding growth factors, modulating their activity. The heparan sulfate modifications of glypicans can mediate interactions with growth factors or ECM proteins, but ligands and ECM proteins can also bind through motifs in the core proteins (Mythreye and Blobe, 2009). Glypicans can be secreted from the cell surface, such soluble forms can also bind growth factors. Evidence to date suggests that glypicans can regulate Wnt, hedgehog, fibroblast growth factor and bone morphogenetic protein pathways. The effect on these pathways may be stimulatory or inhibitory depending on cellular context (Gallet et al., 2008; Capurro et al., 2008; Kreuger et al., 2004; Yan and Lin, 2007; Grisaru et al., 2001; Yan et al., 2010). GPC5 expression has been shown in the developing central nervous system, limbs and kidneys of mice, and its expression in mammalian fetal tissues suggests roles in growth and differentiation during development (Veugelers et al., 1997; Saunders et al., 1997; Luxardi et al., 2007). Its almost exclusive expression in adult brain tissue suggests a possible role in controlling neurotropic factors and maintaining neural function.
Homology	GPC5 is a member of the glypican family of HSPGs, of which six members (GPC1, GPC2, GPC3, GPC4, GPC5, GPC6) have been identified in mammals. GPC3 is the most homologous member to GPC5 in humans. There is approximately 20-60% sequence homology between family members, including conservation of a pattern of 14 cysteine residues. Homolog glypican-like genes are also present in Drosophila (dally and dally-like).

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