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LRP5

LRP5 is 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.
Full Name
low density lipoprotein receptor-related protein 5
Function
Acts as a coreceptor with members of the frizzled family of seven-transmembrane spanning receptors to transduce signal by Wnt proteins (PubMed:11336703, PubMed:11448771, PubMed:15778503, PubMed:11719191, PubMed:15908424, PubMed:16252235).
Activates the canonical Wnt signaling pathway that controls cell fate determination and self-renewal during embryonic development and adult tissue regeneration (PubMed:11336703, PubMed:11719191).
In particular, may play an important role in the development of the posterior patterning of the epiblast during gastrulation (By similarity).
During bone development, regulates osteoblast proliferation and differentiation thus determining bone mass (PubMed:11719191).
Mechanistically, the formation of the signaling complex between Wnt ligand, frizzled receptor and LRP5 coreceptor promotes the recruitment of AXIN1 to LRP5, stabilizing beta-catenin/CTNNB1 and activating TCF/LEF-mediated transcriptional programs (PubMed:11336703, PubMed:25920554, PubMed:24706814, PubMed:14731402).
Acts as a coreceptor for non-Wnt proteins, such as norrin/NDP. Binding of norrin/NDP to frizzled 4/FZD4-LRP5 receptor complex triggers beta-catenin/CTNNB1-dependent signaling known to be required for retinal vascular development (PubMed:27228167, PubMed:16252235).
Plays a role in controlling postnatal vascular regression in retina via macrophage-induced endothelial cell apoptosis (By similarity).
Biological Process
Adipose tissue developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Anatomical structure regressionIEA:Ensembl
Anterior/posterior pattern specificationManual Assertion Based On ExperimentIBA:GO_Central
Apoptotic process involved in blood vessel morphogenesisIEA:Ensembl
Bone marrow developmentManual Assertion Based On ExperimentIMP:BHF-UCL
Bone morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Bone remodelingManual Assertion Based On ExperimentIBA:GO_Central
Branching involved in mammary gland duct morphogenesisManual Assertion Based On ExperimentIBA:GO_Central
Canonical Wnt signaling pathwayManual Assertion Based On ExperimentIDA:UniProtKB
Cell migration involved in gastrulationIEA:Ensembl
Cell-cell signaling involved in mammary gland developmentIEA:Ensembl
Cholesterol homeostasisManual Assertion Based On ExperimentIMP:BHF-UCL
Cholesterol metabolic processIEA:Ensembl
Embryonic digit morphogenesisIEA:Ensembl
EndocytosisIEA:UniProtKB-KW
Extracellular matrix-cell signalingIEA:Ensembl
Gastrulation with mouth forming secondManual Assertion Based On ExperimentIBA:GO_Central
Glucose catabolic processManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of osteoblast differentiationManual Assertion Based On ExperimentIMP:BHF-UCL
Negative regulation of protein serine/threonine kinase activityManual Assertion Based On ExperimentIMP:BHF-UCL
Norrin signaling pathwayManual Assertion Based On ExperimentIDA:BHF-UCL
Osteoblast developmentManual Assertion Based On ExperimentIBA:GO_Central
Positive regulation of cell population proliferationManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of DNA-binding transcription factor activityIEA:Ensembl
Positive regulation of fat cell differentiationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of mesenchymal cell proliferationManual Assertion Based On ExperimentIMP:BHF-UCL
Positive regulation of mitotic nuclear divisionManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of osteoblast differentiationISS:BHF-UCL
Positive regulation of osteoblast proliferationIEA:Ensembl
Positive regulation of transcription by RNA polymerase IIManual Assertion Based On ExperimentIDA:BHF-UCL
Positive regulation of transcription, DNA-templatedManual Assertion Based On ExperimentIDA:BHF-UCL
Regulation of apoptotic processIEA:Ensembl
Regulation of blood pressureManual Assertion Based On ExperimentIMP:BHF-UCL
Regulation of insulin secretion involved in cellular response to glucose stimulusManual Assertion Based On ExperimentIBA:GO_Central
Retina morphogenesis in camera-type eyeManual Assertion Based On ExperimentIMP:BHF-UCL
Retinal blood vessel morphogenesisManual Assertion Based On ExperimentIMP:BHF-UCL
Somatic stem cell population maintenanceIEA:Ensembl
Cellular Location
Membrane
Endoplasmic reticulum
Chaperoned to the plasma membrane by MESD.
Involvement in disease
Vitreoretinopathy, exudative 1 (EVR1):
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. In many ways the disease resembles retinopathy of prematurity but there is no evidence of prematurity or small birth weight in the patient history.
Vitreoretinopathy, exudative 4 (EVR4):
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.
Osteoporosis (OSTEOP):
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.
Osteoporosis-pseudoglioma syndrome (OPPG):
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.
High bone mass trait (HBM):
Rare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings.
Endosteal hyperostosis, Worth type (WENHY):
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.
Osteopetrosis, autosomal dominant 1 (OPTA1):
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.
Van Buchem disease 2 (VBCH2):
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.
Polycystic liver disease 4 with or without kidney cysts (PCLD4):
A form of polycystic liver disease, an autosomal dominant hepatobiliary disease characterized by overgrowth of biliary epithelium and supportive connective tissue, resulting in multiple liver cysts. PCLD4 patients may also develop kidney cysts that usually do not result in clinically significant renal disease.
Topology
Extracellular: 32-1384
Helical: 1385-1407
Cytoplasmic: 1408-1615
PTM
Phosphorylation of cytoplasmic PPPSP motifs regulates the signal transduction of the Wnt signaling pathway through acting as a docking site for AXIN1.

Anti-LRP5 antibodies

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Target: LRP5
Host: Mouse
Antibody Isotype: IgG
Specificity: Human
Clone: CBYJL-1976
Application*: E, WB
Target: LRP5
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human
Clone: CBYJL-1982
Application*: WB, IP
Target: LRP5
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey
Clone: CBYJL-1983
Application*: WB
Target: LRP5
Host: Mouse
Antibody Isotype: IgG1, κ
Specificity: Human
Clone: 1E9
Application*: WB, E
Target: LRP5
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat, Monkey
Clone: D5G4
Application*: WB
Target: LRP5
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: D80F2
Application*: WB, IP
Target: LRP5
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBYJL-1977
Application*: E, F, WB
Target: LRP5
Host: Mouse
Antibody Isotype: IgG1
Specificity: Human
Clone: CBYJL-1979
Application*: WB, F
Target: LRP5
Host: Mouse
Antibody Isotype: IgG2b
Specificity: Human
Clone: CBYJL-1980
Application*: WB
Target: LRP5
Host: Rabbit
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBYJL-1984
Application*: IP, WB
Target: LRP5
Host: Mouse
Antibody Isotype: IgG
Specificity: Human, Mouse, Rat
Clone: CBYJL-1985
Application*: WB, IP, IF, E
Target: Lrp5
Host: Rat
Antibody Isotype: IgG2b, κ
Specificity: Mouse
Clone: CBYJL-2408
Application*: FC
For Research Use Only. Not For Clinical Use.
(P): Predicted
* Abbreviations
IFImmunofluorescence
IHImmunohistochemistry
IPImmunoprecipitation
WBWestern Blot
EELISA
MMicroarray
CIChromatin Immunoprecipitation
FFlow Cytometry
FNFunction Assay
IDImmunodiffusion
RRadioimmunoassay
TCTissue Culture
GSGel Supershift
NNeutralization
BBlocking
AActivation
IInhibition
DDepletion
ESELISpot
DBDot Blot
MCMass Cytometry/CyTOF
CTCytotoxicity
SStimulation
AGAgonist
APApoptosis
IMImmunomicroscopy
BABioassay
CSCostimulation
EMElectron Microscopy
IEImmunoelectrophoresis
PAPeptide Array
ICImmunocytochemistry
PEPeptide ELISA
MDMeDIP
SHIn situ hybridization
IAEnzyme Immunoassay
SEsandwich ELISA
PLProximity Ligation Assay
ECELISA(Cap)
EDELISA(Det)
BIBioimaging
IOImmunoassay
LFLateral Flow Immunoassay
LALuminex Assay
CImmunohistochemistry-Frozen Sections
PImmunohistologyp-Paraffin Sections
ISIntracellular Staining for Flow Cytometry
MSElectrophoretic Mobility Shift Assay
RIRNA Binding Protein Immunoprecipitation (RIP)
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