LDL receptor-related protein 1 (LRP-1), also known as CD91 and the alpha 2-macroglobulin receptor, is a type I membrane protein in the LDL receptor superfamily. It is expressed on neurons, hepatocytes, adipocytes, vascular smooth muscle cells, fibroblasts, keratinocytes, macrophages, and megakaryocytes. LRP-1 is important for the clearance of a large number of circulating molecules involved in fatty acid metabolism and complexes of serine proteases with their inhibitors (1-4). LRP-1 also associates directly or through intracellular scaffold proteins with other membrane associated proteins on the same cell. This allows LRP-1 to modulate the activity or internalization of PDGF R beta , NMDA receptor subunits, TGF-beta receptors, Frizzled-1, various integrins, and the prion protein PrPc. Human LRP-1 is an N-glycosylated and sialylated molecule that is cleaved in the Golgi to produce an 85 kDa transmembrane beta chain and a 515 kDa alpha chain that associates noncovalently with the beta chain but does not itself cross the membrane (11, 12). The alpha chain of LRP-1 contains 31 LDLR class A repeats, 34 LDLR class B repeats, and 22 EGF-like repeats (13). The LDLR domains are clustered in four regions throughout the protein (13). Cluster IV (aa 3332-3779) contains eleven LDLR class A repeats (14). Within this region, human LRP-1 shares 99% aa sequence identity with mouse and rat LRP-1. A shed soluble form of LRP-1 circulates in the serum and retains ligand binding properties (15). Cluster IV contains binding sites for Apolipoprotein E, LPL, and LRPAP/RAP, alpha 2-macroglobulin, Coagulation Factor VIII light chain, Lactoferrin, PAI-1, tPA-PAI-1 complexes, Pro-uPA, and TFPI (14).
| Uniprot | Human |
| Product By Gene ID | 4035 |
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