LRP1

This gene encodes a member of the low-density lipoprotein receptor family of proteins. The encoded preproprotein is proteolytically processed by furin to generate 515 kDa and 85 kDa subunits that form the mature receptor (PMID: 8546712). This receptor is involved in several cellular processes, including intracellular signaling, lipid homeostasis, and clearance of apoptotic cells. In addition, the encoded protein is necessary for the alpha 2-macroglobulin-mediated clearance of secreted amyloid precursor protein and beta-amyloid, the main component of amyloid plaques found in Alzheimer patients. Expression of this gene decreases with age and has been found to be lower than controls in brain tissue from Alzheimer's disease patients.

LRP1

Endocytic receptor involved in endocytosis and in phagocytosis of apoptotic cells (PubMed:11907044, PubMed:12713657).
Required for early embryonic development (By similarity).
Involved in cellular lipid homeostasis. Involved in the plasma clearance of chylomicron remnants and activated LRPAP1 (alpha 2-macroglobulin), as well as the local metabolism of complexes between plasminogen activators and their endogenous inhibitors. Acts as an LRPAP1 alpha-2-macroglobulin receptor (PubMed:26142438, PubMed:1702392).
Acts as TAU/MAPT receptor and controls the endocytosis of TAU/MAPT as well as its subsequent spread (PubMed:32296178).
May modulate cellular events, such as APP metabolism, kinase-dependent intracellular signaling, neuronal calcium signaling as well as neurotransmission (PubMed:12888553).
(Microbial infection) Functions as a receptor for Pseudomonas aeruginosa exotoxin A.

Amyloid-beta clearanceManual Assertion Based On ExperimentTAS:BHF-UCL
Amyloid-beta clearance by cellular catabolic processManual Assertion Based On ExperimentIMP:ARUK-UCL
Amyloid-beta clearance by transcytosisManual Assertion Based On ExperimentIGI:ARUK-UCL
Aorta morphogenesisISS:BHF-UCL
Apoptotic cell clearanceISS:BHF-UCL
Astrocyte activation involved in immune responseISS:ARUK-UCL
Cellular response to amyloid-betaISS:ARUK-UCL
Enzyme linked receptor protein signaling pathwayBy SimilarityISS:BHF-UCL
Lipid metabolic processManual Assertion Based On ExperimentTAS:ARUK-UCL
Lipoprotein transport1 PublicationNAS:UniProtKB
Lysosomal transportISS:UniProtKB
Negative regulation of gene expressionBy SimilarityISS:BHF-UCL
Negative regulation of metallopeptidase activity1 PublicationIC:ARUK-UCL
Negative regulation of pathway-restricted SMAD protein phosphorylationBy SimilarityISS:BHF-UCL
Negative regulation of platelet-derived growth factor receptor-beta signaling pathwayISS:BHF-UCL
Negative regulation of SMAD protein signal transductionBy SimilarityISS:BHF-UCL
Negative regulation of smooth muscle cell migrationISS:BHF-UCL
Negative regulation of Wnt signaling pathwayISS:BHF-UCL
PhagocytosisManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of amyloid-beta clearanceISS:ARUK-UCL
Positive regulation of cell deathManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of cholesterol effluxISS:BHF-UCL
Positive regulation of endocytosisManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of lipid transportISS:BHF-UCL
Positive regulation of lysosomal protein catabolic processManual Assertion Based On ExperimentIMP:ARUK-UCL
Positive regulation of protein bindingManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of protein localization to plasma membraneManual Assertion Based On ExperimentIGI:ARUK-UCL
Positive regulation of transcytosisISS:ARUK-UCL
Receptor internalizationManual Assertion Based On ExperimentIDA:ComplexPortal
Receptor-mediated endocytosisManual Assertion Based On ExperimentIMP:ARUK-UCL
Regulation of actin cytoskeleton organizationISS:BHF-UCL
Regulation of cholesterol transportISS:BHF-UCL
Regulation of extracellular matrix disassemblyManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of phospholipase A2 activityISS:BHF-UCL
Retinoid metabolic processTAS:Reactome
TranscytosisManual Assertion Based On ExperimentTAS:ARUK-UCL
Transport across blood-brain barrierISS:ARUK-UCL

Low-density lipoprotein receptor-related protein 1 85 kDa subunit:
Cell membrane
Membrane, coated pit
Low-density lipoprotein receptor-related protein 1 515 kDa subunit:
Cell membrane ; Peripheral membrane protein
Membrane, coated pit
Low-density lipoprotein receptor-related protein 1 intracellular domain:
Cytoplasm
Nucleus
After cleavage, the intracellular domain (LRPICD) is detected both in the cytoplasm and in the nucleus.
Golgi outpost
Cytoplasm, cytoskeleton, microtubule organizing center
Localizes to the postsynaptic Golgi apparatus region, also named Golgi outpost, which shapes dendrite morphology by functioning as sites of acentrosomal microtubule nucleation.

Keratosis pilaris atrophicans (KPA):
A group of rare genodermatoses characterized by keratotic follicular papules, variable degrees of inflammation, and secondary atrophic scarring. Most cases are associated with an atopic diathesis and keratosis pilaris on the extensor extremities. KPA is comprised of three distinct clinical subtypes: keratosis pilaris atrophicans faciei, atrophoderma vermiculatum, and keratosis follicularis spinulosa decalvans. Affected individuals may present with features overlapping the 3 subtypes.

Extracellular: 20-4419
Helical: 4420-4444
Cytoplasmic: 4445-4544

Cleaved into a 85 kDa membrane-spanning subunit (LRP-85) and a 515 kDa large extracellular domain (LRP-515) that remains non-covalently associated. Gamma-secretase-dependent cleavage of LRP-85 releases the intracellular domain from the membrane.
The N-terminus is blocked.
Phosphorylated on serine and threonine residues.
Phosphorylated on tyrosine residues upon stimulation with PDGF. Tyrosine phosphorylation promotes interaction with SHC1.