Prolow-density lipoprotein receptor-related protein 1 (LRP1)
The protein contains 4544 amino acids for an estimated molecular weight of 504606 Da.
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. (updated: Aug. 12, 2020)
Protein identification was indicated in the following studies:
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.
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No binding partner found
Biological Process
Aging
Amyloid-beta clearance
Amyloid-beta clearance by cellular catabolic process
Amyloid-beta clearance by transcytosis
Aorta morphogenesis
Apoptotic cell clearance
Astrocyte activation involved in immune response
Cell population proliferation
Cellular lipid catabolic process
Cellular response to amyloid-beta
Cerebral cortex development
Chemoattraction of axon
Lipid metabolic process
Lipoprotein metabolic process
Lipoprotein transport
Lysosomal transport
Negative regulation of cytosolic calcium ion concentration
Negative regulation of focal adhesion assembly
Negative regulation of metallopeptidase activity
Negative regulation of neuron apoptotic process
Negative regulation of neuron projection development
Negative regulation of platelet-derived growth factor receptor-beta signaling pathway
Negative regulation of smooth muscle cell migration
Negative regulation of Wnt signaling pathway
Phagocytosis
Positive regulation of amyloid-beta clearance
Positive regulation of axon extension involved in regeneration
Positive regulation of cell death
Positive regulation of chemokine (C-C motif) ligand 2 secretion
Positive regulation of chemokine (C-X-C motif) ligand 2 production
Positive regulation of cholesterol efflux
Positive regulation of cholesterol import
Positive regulation of collateral sprouting of injured axon
Positive regulation of cytosolic calcium ion concentration
Positive regulation of endocytosis
Positive regulation of ERK1 and ERK2 cascade
Positive regulation of insulin secretion involved in cellular response to glucose stimulus
Positive regulation of lipid transport
Positive regulation of lysosomal protein catabolic process
Positive regulation of phagocytosis
Positive regulation of protein binding
Positive regulation of protein localization to plasma membrane
Positive regulation of Schwann cell migration
Positive regulation of transcytosis
Positive regulation of vascular associated smooth muscle cell migration
Protein kinase C-activating G protein-coupled receptor signaling pathway
Receptor internalization
Receptor-mediated endocytosis
Regulation of actin cytoskeleton organization
Regulation of cholesterol transport
Regulation of extracellular matrix disassembly
Regulation of phospholipase A2 activity
Retinoid metabolic process
Transcytosis
Transport across blood-brain barrier
Cellular Component
Apical part of cell
Axonal growth cone
Basolateral plasma membrane
Clathrin-coated pit
Clathrin-coated vesicle
Cytoskeleton
Dendrite
Early endosome
Endocytic vesicle membrane
Focal adhesion
Golgi apparatus
Insulin-responsive compartment
Integral component of plasma membrane
Lysosomal membrane
Membrane
Neuronal cell body
Nucleus
Obsolete cell
Plasma membrane
Plasma membrane protein complex
Postsynaptic Golgi apparatus
Receptor complex
Molecular Function
Alpha-2 macroglobulin receptor activity
Amyloid-beta binding
Apolipoprotein binding
Apolipoprotein receptor activity
Calcium ion binding
Cargo receptor activity
Clathrin heavy chain binding
Coreceptor activity
Heparan sulfate proteoglycan binding
Lipoprotein particle receptor binding
Low-density lipoprotein particle receptor activity
Protease binding
Protein-containing complex binding
RNA binding
Scavenger receptor activity
Signaling receptor activity
The reference OMIM entry for this protein is 107770
Low density lipoprotein receptor-related protein 1; lrp1
Lipoprotein receptor-related protein; lrp
Alpha-2-macroglobulin receptor; a2mr
Apolipoprotein receptor; apr
Apolipoprotein e receptor; apoer
Cd91
Ced1, c. elegans, homolog of
DESCRIPTION
LRP1 is synthesized as a 600-kD precursor transmembrane glycoprotein that is cleaved in trans-Golgi network by furin (136950) to generate a 515-kD alpha subunit and an 85-kD beta subunit. The alpha and beta subunits remain noncovalently associated during LRP1 transport to the cell membrane. LRP1 interacts with a broad range of secreted proteins and cell surface molecules and mediates their endocytosis and/or activates signaling pathways through multiple cytosolic adaptor and scaffold proteins. Phosphorylation of the LRP1 tail regulates ligand internalization and signal transduction (summary by Deane et al., 2004).CLONING
Herz et al. (1988) cloned a cDNA for the low density lipoprotein receptor-related protein (LRP) by virtue of its close homology to the LDL receptor (606945). The 4,544-amino acid protein contains a single transmembrane segment. Northern blot analysis detected LRP1 mRNA in liver, brain, and lung. Kristensen et al. (1990) and Strickland et al. (1990) demonstrated that LRP is identical to alpha-2-macroglobulin (A2M; 103950) receptor (A2MR). Like mannose-6-phosphate receptor (147280), the A2MR/LRP molecule is probably bifunctional. In the free-living nematode Caenorhabditis elegans, Yochem and Greenwald (1993) isolated and sequenced a gene more than 23 kb long that encodes a large integral membrane protein with a predicted structure similar to that of LRP of mammals. The 4,753-amino acid product predicted for the C. elegans gene shared a nearly identical number and arrangement of amino acid sequence motifs with human LRP, and several exons of the C. elegans LRP gene corresponded to exons of related parts of the human LRP gene. Ranganathan et al. (2011) stated that the heavy chain of LRP1 contains 4 clusters of ligand-binding repeats. The light chain includes the transmembrane domain and cytoplasmic domain, which contains 2 NPxY motifs and 2 dileucine repeats that contribute to LRP1 endocytosis. Ranganathan et al. (2011) also purified a soluble form of LRP1 from human plasma.MAPPING
Myklebost et al. (1989) mapped the gene for the LRP-related protein to 12q13-q14 by study of DNA from rodent-human cell hybrids and by in situ hybridization; the symbol APOER was used initially because of the putative APOE receptor function. By pulsed field gel analysis, Forus et al. (1991) found that the APR and GLI genes are closely situated; probes for either gene hybridized to DNA fragments of molecular weight 300-400 kb. More detailed restriction analysis showed that the intergenic region was between 200 and 300 kb (Forus and Myklebost, 1992). Hilliker et al. (1992) confirmed the assignment to 12q13-q14 using both nonisotopic and isotopic in situ hybridization. Also by in situ hybridization, they assigned the corresponding locus to mouse chromosome 15. Binder et al. (2000) pointed out that gp96 and CD91 both map to the long arm of chromosome 12.GENE FUNCTION
Herz et al. (1988) found that LRP showed strong calcium binding. Kounnas et al. (1995) showed that LRP mediates the endocytosis and degradation of secreted amyloid precursor protein (APP; 104760), suggesting that a single metabolic pathway links 2 molecules implicated in the pathophysiology of Alzheimer disease (AD; 104300). Narita et al. (1997) showed that A2M, via LRP, mediates the clearance and degradation of APP-generated beta-amyloid (A-beta), the major component of amyloid plaques in AD. Kang et al. (2000) demonstrated in v ... More on the omim web site
Aug. 24, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
June 30, 2020: Protein entry updated
Automatic update: OMIM entry 107770 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).