LRP6: 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. Required for posterior patterning of the epiblast during gastrulation. Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling. Forms a WNT-signaling complex formed of a WNT protein, a FZD protein and LRP5 or LRP6. Interacts (via the extracellular domain) with WNT1; the interaction is enhanced by prior formation of the Wnt/Fzd complex. Interacts (via the beta-propeller regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a coreceptor complex for Wnt signaling and is inhibited by DKK1 and C1orf187. Interacts (via beta propeller region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2. Interacts with C1orf187/DRAXIN; the interaction inhibits Wnt signaling. Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface LRP6 signalsomes. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively regulating the Wnt signaling pathway. Interacts (via the extracellular domain) with RSPO1; the interaction activates Wnt/beta-catenin signaling. Interacts (via the extracellular domain) with RSPO3 (via the cysteine rich domain); the interaction activates Wnt/beta-catenin signaling. Interacts (via the beta- propeller regions 1 and 2) with SOST; the interaction competes with DKK1 for binding for inhibiting beta-catenin signaling. Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma membrane. Interacts (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin. Interacts with MACF1. Decreased levels on WNT3A stimulation. Widely co-expressed with LRP5 during embryogenesis and in adult tissues. Belongs to the LDLR family.
Protein type: Membrane protein, integral; Receptor, misc.
Chromosomal Location of Human Ortholog: 12p13.2
Cellular Component: caveola; cell soma; cell surface; cytoplasmic vesicle; early endosome; early endosome membrane; extracellular region; Golgi apparatus; plasma membrane; receptor complex; synapse
Molecular Function: apolipoprotein binding; frizzled binding; identical protein binding; kinase inhibitor activity; low-density lipoprotein receptor activity; protein binding; protein homodimerization activity; receptor binding; toxin transporter activity; Wnt receptor activity; Wnt-protein binding
Biological Process: cerebellum morphogenesis; cerebral cortex development; convergent extension; embryonic pattern specification; embryonic retina morphogenesis in camera-type eye; external genitalia morphogenesis; midbrain-hindbrain boundary development; negative regulation of protein amino acid phosphorylation; negative regulation of protein kinase activity; neural crest cell differentiation; neural crest formation; neural tube closure; odontogenesis of dentine-containing teeth; palate development; positive regulation of cell cycle; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; positive regulation of transcription, DNA-dependent; synaptic transmission; thalamus development; Wnt receptor signaling pathway; Wnt receptor signaling pathway through beta-catenin
Disease: Coronary Artery Disease, Autosomal Dominant 2; Tooth Agenesis, Selective, 7
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