LMPD Database

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LMP012345

UniProt Annotations

Entry Information
Gene Namelow density lipoprotein receptor-related protein 5
Protein Entry
UniProt IDO75197
SpeciesHuman
Comments
Comment typeDescription
DiseaseEndosteal hyperostosis, Worth type (WENHY) [MIM:144750]: An autosomal dominant sclerosing bone dysplasia clinically characterized by elongation of the mandible, increased gonial angle, flattened forehead, and the presence of a slowly enlarging osseous prominence of the hard palate (torus palatinus). Serum calcium, phosphorus and alkaline phosphatase levels are normal. Radiologically, it is characterized by early thickening of the endosteum of long bones, the skull and of the mandible. With advancing age, the trabeculae of the metaphysis become thickened. WENHY becomes clinically and radiologically evident by adolescence, does not cause deformity except in the skull and mandible, and is not associated with bone pain or fracture. Affected patients have normal height, proportion, intelligence and longevity Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseHigh bone mass trait (HBM) [MIM:601884]: Rare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings. {ECO:0000269|PubMed:11741193, ECO:0000269|PubMed:12015390, ECO:0000269|PubMed:15824861}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseOsteopetrosis, autosomal dominant 1 (OPTA1) [MIM:607634]: A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. OPTA1 is an autosomal dominant form characterized by generalized osteosclerosis most pronounced in the cranial vault. Patients are often asymptomatic, but some suffer from pain and hearing loss. It appears to be the only type of osteopetrosis not associated with an increased fracture rate Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseOsteoporosis (OSTEOP) [MIM:166710]: A systemic skeletal disorder characterized by decreased bone mass and deterioration of bone microarchitecture without alteration in the composition of bone. The result is fragile bones and an increased risk of fractures, even after minimal trauma. Osteoporosis is a chronic condition of multifactorial etiology and is usually clinically silent until a fracture occurs. {ECO:0000269|PubMed:14727154, ECO:0000269|PubMed:15824851, ECO:0000269|PubMed:16234968}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.
DiseaseOsteoporosis-pseudoglioma syndrome (OPPG) [MIM:259770]: A disease characterized by congenital or infancy-onset blindness and severe juvenile-onset osteoporosis and spontaneous fractures. Additional clinical manifestations may include microphthalmos, abnormalities of the iris, lens or vitreous, cataracts, short stature, microcephaly, ligamental laxity, mental retardation and hypotonia. {ECO:0000269|PubMed:11719191, ECO:0000269|PubMed:16252235, ECO:0000269|PubMed:16679074, ECO:0000269|PubMed:17437160, ECO:0000269|PubMed:18602879}. Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseVan Buchem disease 2 (VBCH2) [MIM:607636]: VBCH2 is an autosomal dominant sclerosing bone dysplasia characterized by cranial osteosclerosis, thickened calvaria and cortices of long bones, enlarged mandible and normal serum alkaline phosphatase levels Note=The disease is caused by mutations affecting the gene represented in this entry.
DiseaseVitreoretinopathy, exudative 4 (EVR4) [MIM:601813]: A disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:15024691, ECO:0000269|PubMed:15346351, ECO:0000269|PubMed:15981244, ECO:0000269|PubMed:16929062, ECO:0000269|PubMed:19324841, ECO:0000269|PubMed:20340138, ECO:0000269|PubMed:24715757}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionComponent 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. {ECO:0000269|PubMed:11336703, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:14727154, ECO:0000269|PubMed:14731402, ECO:0000269|PubMed:15778503}.
InteractionQ6IMN6:CAPRIN2; NbExp=3; IntAct=EBI-2466421, EBI-6918449;
PolymorphismGenetic variations in LRP5 define the bone mineral density quantitative trait locus 1 (BMND1) [MIM:601884]. Variance in bone mineral density influences bone mass and contributes to size determination in the general population.
PtmPhosphorylation of cytoplasmic PPPSP motifs regulates the signal transduction of the Wnt signaling pathway through acting as a docking site for AXIN1
SimilarityBelongs to the LDLR family
SimilarityContains 20 LDL-receptor class B repeats
SimilarityContains 3 LDL-receptor class A domains
SimilarityContains 4 EGF-like domains
Subcellular LocationMembrane; Single-pass type I membrane protein. Endoplasmic reticulum Note=Chaperoned to the plasma membrane by MESD
SubunitHomodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling (By similarity). 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. {ECO:0000250, ECO:0000269|PubMed:11336703, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:14731402, ECO:0000269|PubMed:15143163, ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:15908424, ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17488095, ECO:0000269|PubMed:19746449, ECO:0000269|PubMed:20393562}.
Tissue SpecificityWidely expressed, with the highest level of expression in the liver and in aorta
Web ResourceName=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/LRP5ID44282ch11q13.html";