LRP5: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor- ligand complexes into ribosome-sized signalsomes. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1 polymers to the plasma membrane which, in turn, recruits the AXIN1/GSK3B-complex to the cell surface promoting the formation of signalsomes and inhibiting AXIN1/GSK3- mediated phosphorylation and destruction of beta-catenin. Appears be required for postnatal control of vascular regression in the eye. Required for posterior patterning of the epiblast during gastrulation. Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling. Component of a Wnt-signaling complex that contains a WNT protein, a FZD protein and LRP5 or LRP6. Interacts with FZD8; the interaction is formed on WNT-binding and signaling. Interacts (via the phosphorylated PPPSP motif domains) with AXIN1; the interaction prevents inhibition of beta-catenin phosphorylation and signaling and is enhanced in the presence of GSK3B and WNT1 or WNT3A. Interacts (via beta-propeller regions 3 and 4) with DKK1; the interaction, enhanced by MESD and/or KREMEN, inhibits beta-catenin signaling by preventing GSK3-mediated phosphorylation of the PPPSP motifs and subsequent, AXIN1 binding. Interacts with MESD; the interaction prevents the formation of LRP5 aggregates, targets LRP5 to the plasma membrane and, when complexed with KREMEN2, increases DKK1 binding. Interacts with CSNK1E. Interacts with SOST; the interaction antagonizes canonical Wnt signaling. Interacts with APCDD1. Widely expressed, with the highest level of expression in the liver and in aorta. Belongs to the LDLR family.
Protein type: Membrane protein, integral; Receptor, misc.
Chromosomal Location of Human Ortholog: 11q13.4
Cellular Component: mitochondrion; endoplasmic reticulum; plasma membrane; integral to membrane; receptor complex
Molecular Function: Wnt-protein binding; protein binding; Wnt receptor activity; toxin transporter activity; coreceptor activity
Biological Process: response to peptide hormone stimulus; somatic stem cell maintenance; positive regulation of transcription, DNA-dependent; Wnt receptor signaling pathway through beta-catenin; bone remodeling; anatomical structure regression; regulation of apoptosis; anterior/posterior pattern formation; regulation of blood pressure; positive regulation of cell proliferation; positive regulation of mesenchymal cell proliferation; negative regulation of osteoblast differentiation; cell migration involved in gastrulation; embryonic limb morphogenesis; cholesterol metabolic process; Wnt receptor signaling pathway; positive regulation of mitosis; regulation of bone remodeling; endocytosis; gastrulation with mouth forming second; osteoblast development; bone marrow development; glucose catabolic process; cholesterol homeostasis; embryonic retina morphogenesis in camera-type eye; positive regulation of osteoblast proliferation; positive regulation of fat cell differentiation; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription factor activity; embryonic digit morphogenesis; embryonic camera-type eye morphogenesis; retina morphogenesis in camera-type eye
Disease: Osteoporosis-pseudoglioma Syndrome; Van Buchem Disease, Type 2; Exudative Vitreoretinopathy 1; Osteopetrosis, Autosomal Dominant 1; Exudative Vitreoretinopathy 4; Osteoporosis; Bone Mineral Density Quantitative Trait Locus 1; Endosteal Hyperostosis, Autosomal Dominant
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