LRP5 Human Recombinant Protein

This gene encodes a transmembrane low-density lipoprotein receptor that binds and internalizes ligands in the process of receptor-mediated endocytosis. This protein also acts as a co-receptor with Frizzled protein family members for transducing signals by Wnt proteins and was originally cloned on the basis of its association with type 1 diabetes mellitus in humans. This protein plays a key role in skeletal homeostasis and many bone density related diseases are caused by mutations in this gene. Mutations in this gene also cause familial exudative vitreoretinopathy. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

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