Low Density Lipoprotein Receptor Related Protein 5 (LRP5) Antibody – Rabbit Polyclonal

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: 11q13.2

Cellular Component: endoplasmic reticulum; integral component of membrane; mitochondrion; plasma membrane; receptor complex

Molecular Function: protein binding; toxin transporter activity; Wnt-activated receptor activity; Wnt-protein binding

Biological Process: anatomical structure regression; anterior/posterior pattern specification; bone marrow development; bone remodeling; cell migration involved in gastrulation; cholesterol homeostasis; cholesterol metabolic process; embryonic digit morphogenesis; endocytosis; gastrulation with mouth forming second; glucose catabolic process; negative regulation of osteoblast differentiation; osteoblast development; positive regulation of cell proliferation; positive regulation of fat cell differentiation; positive regulation of mesenchymal cell proliferation; positive regulation of mitotic nuclear division; positive regulation of osteoblast proliferation; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-templated; regulation of apoptosis; regulation of blood pressure; regulation of bone remodeling; response to peptide hormone; response to radiation; retina morphogenesis in camera-type eye; somatic stem cell maintenance; Wnt receptor signaling pathway through beta-catenin; Wnt signaling pathway

Disease: Bone Mineral Density Quantitative Trait Locus 1; Endosteal Hyperostosis, Autosomal Dominant; Exudative Vitreoretinopathy 1; Exudative Vitreoretinopathy 4; Osteopetrosis, Autosomal Dominant 1; Osteoporosis; Osteoporosis-pseudoglioma Syndrome; Van Buchem Disease, Type 2