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Contactin-1 Contactin-1 Contactin-1 Transmembrane emp24 domain- containing protein 9 Transmembrane emp24 domain- containing protein 10 PGAP2 PGAP2 Contactin-1 Contactin-1 Transmembrane emp24 domain- containing protein 9 Transmembrane emp24 domain- containing protein 2 Transmembrane emp24 domain- containing protein 5 Transmembrane emp24 domain- containing protein 10 Contactin-1 Contactin-1 PGAP1 MPPE1 PGAP3 Contactin-1 H2O Hexadecanoic Acid H2O O- Phosphoethanolamine H2O Stearoyl-CoA CoA Ethanolamine phosphate– Manα1– 2(EtNP)Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– glycerophosphoinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– glycerophosphoinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– glycerophosphoinositol EtNP– Manα1– 2(EtNP)Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol (2-deacylated) EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4 N- acetylglucosamine– glycerophosphoinositol Unsaturated fatty acid glycosylphosphatidylinositol (GPI) biosynthesis Transmembrane emp24 domain- containing protein 2 Transmembrane emp24 domain- containing protein 5 Endoplasmic Reticulum Golgi Apparatus The cargo receptor for GPI-APs is composed of four p24 proteins that only recognize properly modeled GPI-APs The immature GPI-APs formed by GPI transamidase undergo more reactions to become mature GPI-APs Reacetylated GPI anchor core lacking lipid tail does not get created due to the mutation in the PGAP2 protein GPI glycan core lacking its hydrophobic membrane anchor becomes the final stage in the maturation process Extracellular Space Cytosol Mutation in the PGAP2 gene The GPI anchor is incomplete and therefore is unable to tether proteins to the cell surface. As a result it is released into the bloodstream. High concentrations of GPI anchored proteins in the bloodstream results in hgih levels of alkaline phosphatase in the blood which results in hyperphosphatasia. Nucleus
Endoplasmic Reticulum Golgi Apparatus Nucleus CNTN1 CNTN1 CNTN1 TMED9 TMED10 PGAP2 PGAP2 CNTN1 CNTN1 TMED9 TMED2 TMED5 TMED10 CNTN1 CNTN1 PGAP1 MPPE1 PGAP3 CNTN1 Water Hexadecanoic Acid Water O- Phosphoethanolamine Water Stearoyl-CoA Coenzyme A Ethanolamine phosphate– Manα1– 2(EtNP)Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– glycerophosphoinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– glycerophosphoinositol EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4GlcN– glycerophosphoinositol EtNP– Manα1– 2(EtNP)Manα1– 6(EtNP)Manα1– 4GlcN– phosphatidylinositol (2-deacylated) EtNP– Manα1– 2Manα1– 6(EtNP)Manα1– 4 N- acetylglucosamine– glycerophosphoinositol Unsaturated fatty acid glycosylphosphatidylinositol (GPI) biosynthesis TMED2 TMED5
CNTN1 CNTN1 CNTN1 TMED9 TMED10 PGAP2 PGAP2 CNTN1 CNTN1 TMED9 TMED2 TMED5 TMED10 CNTN1 CNTN1 PGAP1 MPPE1 PGAP3 CNTN1 H2O Hex Aci H2O Ethamp H2O COA18:0 CoA E p M 2 E M 2 6 E M 2 6 E M 2 6 E M 2 6 E M 2 6 E M 2 6 E M 2 6 UFA PW690996 TMED2 TMED5 Endoplasmic Reticulum Golgi Apparatus The cargo receptor for GPI-APs is composed of four p24 proteins that only recognize properly modeled GPI-APs The immature GPI-APs formed by GPI transamidase undergo more reactions to become mature GPI-APs Reacetylated GPI anchor core lacking lipid tail does not get created due to the mutation in the PGAP2 protein GPI glycan core lacking its hydrophobic membrane anchor becomes the final stage in the maturation process Extracellular Space Cytosol Mutation in the PGAP2 gene The GPI anchor is incomplete and therefore is unable to tether proteins to the cell surface. As a result it is released into the bloodstream. High concentrations of GPI anchored proteins in the bloodstream results in hgih levels of alkaline phosphatase in the blood which results in hyperphosphatasia. Nucleus
Endoplasmic Reticulum Golgi Apparatus Nucleus CNTN1 CNTN1 CNTN1 TMED9 TMED10 PGAP2 PGAP2 CNTN1 CNTN1 TMED9 TMED2 TMED5 TMED10 CNTN1 CNTN1 PGAP1 MPPE1 PGAP3 CNTN1 H2O Hex Aci H2O Ethamp H2O COA18:0 CoA E p M 2 E M 2 6 E M 2 6 E M 2 6 E M 2 6 E M 2 6 E M 2 6 E M 2 6 UFA PW690996 TMED2 TMED5