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FLASH GENE
Symbol LRP1 contributors: mct/pgu - updated : 14-03-2014
HGNC name low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor)
HGNC id 6692
Location 12q13.3      Physical location : 57.522.281 - 57.607.123
Synonym name
  • LDL receptor-related protein
  • alpha2-macroglobulin receptor
  • CD91 antigen
  • TbetaR-V/LRP-1/IGFBP-3 receptor
  • apolipoprotein E receptor
  • prolow-density lipoprotein receptor-related protein 1
  • Synonym symbol(s) A2MPR, A2MR, APR, LRP, CD91, APOER, IGFBP3R, LRP1A, TGFBR5
    EC.number 3.1.1.3
    DNA
    TYPE functioning gene
    STRUCTURE 84.86 kb     89 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    motif repetitive sequence   ALU
    text structure seven intronic Alu sequences
    MAPPING cloned Y linked N status confirmed
    Physical map
    PRIM1 12q13 primase, polypeptide 1, 49kDa NACA 12q23-q24.1 nascent-polypeptide-associated complex alpha polypeptide RODH 12q13 nascent-polypeptide-associated complex alpha polypeptide SDR-O 12q13.13 orphan short-chain dehydrogenase / reductase RODH-4 12q13.13-q13.2 microsomal NAD+-dependent retinol dehydrogenase 4 LOC390332 12 similar to sterol/retinol dehydrogenase ADMR 12q13.3-q14 adrenomedullin receptor KIAA0352 12q13.2-q15 adrenomedullin receptor TAC3 12q13-q21 tachykinin 3 (neuromedin K, neurokinin beta) MYO1A 12q13-q15 myosin IA KIAA0286 12q13.2 KIAA0286 protein NAB2 12q13.3-q14.1 NGFI-A binding protein 2 (EGR1 binding protein 2) STAT6 12q13.3-q14.1 signal transducer and activator of transcription 6, interleukin-4 induced LRP1 12q13.3 low density lipoprotein-related protein 1 (alpha-2-macroglobulin receptor) SHMT2 12q13.2 serine hydroxymethyltransferase 2 (mitochondrial) NXPH4 12q13.2 neurexophilin 4 LOC56901 12q13.2 NADH:ubiquinone oxidoreductase MLRQ subunit homolog MGC2793 12q13.2 hypothetical protein MGC2793 KIAA1002 12q13.2 Homo sapiens KIAA1002 protein (KIAA1002), mRNA. LOC338803 12q13.2 similar to RIKEN cDNA 1300003K24 INHBC 12q13.1 inhibin, beta C INHBE 12q13.2 inhibin, beta E GLI 12q13.3-q14.1 glioma-associated oncogene homolog (zinc finger protein) ARHGAP9 12q14 Rho GTPase activating protein 9 MARS 12q13.11-q14.3 methionine-tRNA synthetase DDIT3 12q13.1-q13.2 DNA-damage-inducible transcript 3 MBD6 12q13.2 methyl-CpG binding domain protein 6 DCTN2 12q13.2-q13.3 dynactin 2 (p50) KIF5A 12q13 kinesin family member 5A
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    89 - 14905 504.5 4544 - 1993 8506301
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   highly
    Nervousbrain   highly
    Reproductivefemale systemuterus   
    Respiratorylung   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier liningretinal pigment epithelium (RPE)  
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • thirty one copies of the ligand binding domain, equivalent to the classical LDL receptor motif, cysteine rich, arranged in four clusters
  • sixteen growth factor repeats
  • one EGF-like motif
  • a transmembrane segment (1TM)
  • a short cytoplasmic tail, with internalization signals, common 600 RD precursor of 500 and 85kD chains
  • two NPXY motifs in the intracellular domain (ICD) serve as docking sites for several cytoplasmic adaptor proteins, and interact with signaling proteins ,
  • FXNPXY63 motif not only governs cellular localization of the receptor but also exerts multiple functional effects on signalling pathways involved in cell growth regulation
  • isoforms Precursor
    HOMOLOGY
    intraspecies homolog to low-density lipoprotein receptor 1 (LDLR)
    Homologene
    FAMILY
  • LDLR superfamily
  • CATEGORY signaling , receptor
    SUBCELLULAR LOCALIZATION     plasma membrane
        intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endosome
    intracellular,cytoplasm,organelle,lysosome
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,nucleus
    basic FUNCTION
  • macroglobulin, alpha-2-receptor (proteinase complexes receptor)
  • multiligand receptor for beta lipoprotein, binding chylomicron remnants, beta VLDL, lipoprotein lipase, lactoferrin, proteinase inhibitors
  • fibronectin catabolic receptor involved in the phagocytosis of apoptotic cells in mammals
  • involved in the processes of cell migration and invasion, as well as in the regulation of growth factor homeostasis
  • may be involved in cell migration and invasion of the retinal pigment epithelial (RPE) cells
  • controls signaling pathways involved in cholesterol storage and fatty acid synthesis during adipocyte differentiation
  • required for lipolysis and stimulates fatty acid synthesis independently of the noradrenergic pathway, through inhibition of GSK3B and its previously unknown target acetyl-CoA carboxylase
  • essential for the maintenance of vascular wall integrity, particularly in the presence of high plasma lipid levels
  • integrator of adipogenic differentiation and fat storage signals
  • playing an unique role in endocytosis of a coagulation protein trafficked to alpha-granules and not destined for lysosomal degradation
  • may facilitate the development and growth of cancer metastases
  • controls both the surface, and biosynthetic, trafficking of PRNP in neurons
  • Glucocorticoids-stimulated macrophage uptake of apoptotic cells may involve an upregulation of macrophage LRP1 expression and enhanced LRP1-mediated phagocytosis
  • endocytic receptor involved in intracellular signal transduction
  • regulates human hepatic stellate cells (HHSCs) proliferation and migration through modulation of ERK1,2 phosphorylation and TGFB extracellular levels
  • is the master regulator of extracellular levels of TIMP3, and regulates ECM catabolism
  • LRP1-dependent cell signaling that includes NTRK3 activation promotes axonal growth in the CNS
  • LRP1-dependent cell signaling mechanism involved in CNS plasticity and regeneration
  • assembles unique co-receptor systems to initiate cell signaling in response to tissue-type plasminogen activator and myelin-associated glycoprotein
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS cell to cell transport
    PATHWAY
    metabolism
    signaling signal transduction
    a component
  • APP/APBB1/LRP1 complex is an important mediator of APP processing and affects beta-amyloid peptide production
  • INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • Ca2+
  • protein
  • binding lipoproteins
  • cellular uptake and degradationof beta amyloid peptide (APP)
  • FN1
  • stimulates a canonical WNT5A signaling pathway that prevents cholesterol accumulation
  • interacting with MAFB (ICD co-localizes with MAFB to the nucleus and negatively regulates its transcriptional activity, suggesting a possible role for LRP1 in brain development)
  • in Schwann cells, LRP1 activates PI3K/Akt-mediated cell survival signaling pathways and counteracts endoplasmic reticulum stress
  • SREBF1 play a role in transcriptional regulation of LRP1
  • LRP1 and THBS2 stimulate NOTCH activity by driving trans-endocytosis of the NOTCH ectodomain into the signal-sending cell
  • in addition to its role in APP trafficking--LRP1 affects APP processing by competing for cleavage by BACE1
  • mediates potentially the transcytosis of CTGF, which might be a crucial event that determines the distribution of CTGF in cartilage
  • LRP1-mediated internalization of CD44 appeared critical to define the adhesive properties of tumor cells
  • dictates physiological and pathological catabolism of aggrecan in cartilage as a key modulator of the extracellular activity of ADAMTS5
  • APBB1 might have signalling properties together with APP and LRP1, whereas GULP1 only mediates LRP1 transactivation
  • aggregated LDL (agLDL) prolongs the half life of LRP1 by preventing the receptor ubiquitinylation, at least in part, through CHFR targeting
  • PCSK9 is capable of inducing degradation of LRP1, the latter is not an essential factor for LDLR regulation, but the LDLR effectively competes with LRP1 for PCSK9 activity
  • cell & other
    REGULATION
    induced by dexamethasone induces increased macrophage expression of LRP1, which could be one mechanism behind the phagocytosis-stimulatory effect reported for glucocorticoid in terms of macrophage uptake of apoptotic cells
    Other regulated by phosphorylation
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --low  
    may be associated with abdominal aortic aneurysm progression
    Susceptibility
  • putative susceptibility factor for Alzheimer disease (see AD5), not confirmed
  • to abdominal aortic aneurysm
  • Variant & Polymorphism SNP
  • rs1466535, T allele which might disrupt a binding site for SREBF1, located within intron 1 of LRP1 significantly associated to abdominal aortic aneurysm
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    neurosensorial  
    target for therapeutic intervention in proliferative vitreoretinopathy
    obesity  
    pharmacological modulation of LRP1 activity might emerge as a novel rational approach for treating diabetes and obesity, as well as atherosclerosis
    diabete  
    pharmacological modulation of LRP1 activity might emerge as a novel rational approach for treating diabetes and obesity, as well as atherosclerosis
    neurologyacquired 
    LRP1 agonists promote regeneration after spinal cord injury
    ANIMAL & CELL MODELS
  • mice with conditional loss of LRP1 in post-mitotic neurons exhibit alterations in brain lipid metabolism, synapse loss, and neurodegeneration