Receptor-associated protein (RAP); Receptor-associated protein, RAP, is an antagonist and a specialized chaperone in the endoplasmic reticulum that binds tightly to members of the low-density lipoprotein (LDL) receptor family and prevents them from associating with other ligands. RAP associates with (LDL) receptor-related protein (LRP) early in the secretory pathway, reducing its ligand binding capacity, and then dissociates from LRP in the low-pH environment of the Golgi; studies have shown that histidine residues in RAP D3 serve as a switch that facilitates its uncoupling from the receptor. RAP is a modular protein identified as having an internal triplication, with domains, D1, D2, and D3, each thought to have distinct functions; these domains are independent and do not interact. The carboxyl-terminal domain (D3) of RAP is required for folding and trafficking of LRP, while the amino-terminal tandem D1D2 domains of RAP are essential for blocking LRP from binding of certain ligands, such as activated forms of alpha2-macroglobulin.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|
gi 463882    1 ISPSDLSDIKGSVLHSRHTELKEKLRSINQGLDRLRRVSH 40
Cdd:cd14807 59 ISPSLEEDIKESVLHNKHTDLKERLRSINQGFERLRKVSH 98

Domain 2 of receptor-associated protein (RAP); This subfamily is the N-terminal domain (D2) of receptor-associated protein, RAP, an antagonist and a specialized chaperone in the endoplasmic reticulum that binds tightly to members of the low-density lipoprotein (LDL) receptor family and prevents them from associating with other ligands. D2, along with RAP domain 1 (D1), is essential for blocking low-density lipoprotein receptor-related protein (LRP) from binding of certain ligands, such as alpha2-macroglobulin; D1 and D2 each bind LRP weakly but the tandem D1D2 binds much more tightly to the second and the fourth ligand-binding clusters present on LRP, suggesting the avidity effects arising from amino acid residues contributed from each domain. Also, RAP has regions that interact weakly with heparin, one located in D2 and two located in D3. The double module of complement type repeats, CR56, of LRP binds many ligands including alpha2-macroglobulin, which promotes the catabolism of the Abeta-peptide implicated in Alzheimer's disease.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|
gi 463882    1 ISPSDLSDIKGSVLHSRHTELKEKLRSINQGLDRLRRVSH 40
Cdd:cd14807 59 ISPSLEEDIKESVLHNKHTDLKERLRSINQGFERLRKVSH 98

Domain 2 of receptor-associated protein (RAP); This subfamily is the N-terminal domain (D2) of receptor-associated protein, RAP, an antagonist and a specialized chaperone in the endoplasmic reticulum that binds tightly to members of the low-density lipoprotein (LDL) receptor family and prevents them from associating with other ligands. D2, along with RAP domain 1 (D1), is essential for blocking low-density lipoprotein receptor-related protein (LRP) from binding of certain ligands, such as alpha2-macroglobulin; D1 and D2 each bind LRP weakly but the tandem D1D2 binds much more tightly to the second and the fourth ligand-binding clusters present on LRP, suggesting the avidity effects arising from amino acid residues contributed from each domain. Also, RAP has regions that interact weakly with heparin, one located in D2 and two located in D3. The double module of complement type repeats, CR56, of LRP binds many ligands including alpha2-macroglobulin, which promotes the catabolism of the Abeta-peptide implicated in Alzheimer's disease.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|
gi 463882    1 ISPSDLSDIKGSVLHSRHTELKEKLRSINQGLDRLRRVSH 40
Cdd:cd14807 59 ISPSLEEDIKESVLHNKHTDLKERLRSINQGFERLRKVSH 98

Receptor-associated protein (RAP); Receptor-associated protein, RAP, is an antagonist and a specialized chaperone in the endoplasmic reticulum that binds tightly to members of the low-density lipoprotein (LDL) receptor family and prevents them from associating with other ligands. RAP associates with (LDL) receptor-related protein (LRP) early in the secretory pathway, reducing its ligand binding capacity, and then dissociates from LRP in the low-pH environment of the Golgi; studies have shown that histidine residues in RAP D3 serve as a switch that facilitates its uncoupling from the receptor. RAP is a modular protein identified as having an internal triplication, with domains, D1, D2, and D3, each thought to have distinct functions; these domains are independent and do not interact. The carboxyl-terminal domain (D3) of RAP is required for folding and trafficking of LRP, while the amino-terminal tandem D1D2 domains of RAP are essential for blocking LRP from binding of certain ligands, such as activated forms of alpha2-macroglobulin.

                       10        20        30        40
               ....*....|....*....|....*....|....*....|
gi 463882    1 ISPSDLSDIKGSVLHSRHTELKEKLRSINQGLDRLRRVSH 40
Cdd:cd14803 58 ESPGDLSDIKGEKHALGLDEDKEKEARLIRNLNVLLAKYG 97