InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: LRP5

Summary

InnateDB Protein

IDBP-61387.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

LRP5

Protein Name

low density lipoprotein receptor-related protein 5

Synonyms

BMND1; EVR1; EVR4; HBM; LR3; LRP-5; LRP7; OPPG; OPS; OPTA1; VBCH2;

Species

Homo sapiens

Ensembl Protein

ENSP00000294304

InnateDB Gene

IDBG-61383 (LRP5)

Protein Structure

UniProt Annotation

Function

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. {ECO:0000269PubMed:11336703, ECO:0000269PubMed:11448771, ECO:0000269PubMed:14727154, ECO:0000269PubMed:14731402, ECO:0000269PubMed:15778503}.

Subcellular Localization

Membrane; Single-pass type I membrane protein. Endoplasmic reticulum {ECO:0000250}. Note=Chaperoned to the plasma membrane by MESD. {ECO:0000250}.

Disease Associations

Vitreoretinopathy, 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:0000269PubMed:15024691, ECO:0000269PubMed:15346351, ECO:0000269PubMed:15981244, ECO:0000269PubMed:16929062, ECO:0000269PubMed:19324841, ECO:0000269PubMed:20340138, ECO:0000269PubMed:24715757}. Note=The disease is caused by mutations affecting the gene represented in this entry.Osteoporosis (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:0000269PubMed:14727154, ECO:0000269PubMed:15824851, ECO:0000269PubMed:16234968}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.Osteoporosis-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:0000269PubMed:11719191, ECO:0000269PubMed:16252235, ECO:0000269PubMed:16679074, ECO:0000269PubMed:17437160, ECO:0000269PubMed:18602879}. Note=The disease is caused by mutations affecting the gene represented in this entry.High 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:0000269PubMed:11741193, ECO:0000269PubMed:12015390, ECO:0000269PubMed:15824861}. Note=The disease is caused by mutations affecting the gene represented in this entry.Endosteal 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. {ECO:0000269PubMed:12579474}. Note=The disease is caused by mutations affecting the gene represented in this entry.Osteopetrosis, 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. {ECO:0000269PubMed:12579474}. Note=The disease is caused by mutations affecting the gene represented in this entry.Van 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. {ECO:0000269PubMed:12579474}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Widely expressed, with the highest level of expression in the liver and in aorta. {ECO:0000269PubMed:9790987}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 14 experimentally validated interaction(s) in this database.
They are also associated with 8 interaction(s) predicted by orthology.

Experimentally validated
Total	14 [view]
Protein-Protein	13 [view]
Protein-DNA	1 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	8 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0015026	coreceptor activity
GO:0017147	Wnt-protein binding
GO:0042813	Wnt-activated receptor activity

Biological Process

GO:0001702	gastrulation with mouth forming second
GO:0001944	vasculature development
GO:0002053	positive regulation of mesenchymal cell proliferation
GO:0002076	osteoblast development
GO:0006007	glucose catabolic process
GO:0006897	endocytosis
GO:0008203	cholesterol metabolic process
GO:0008217	regulation of blood pressure
GO:0008284	positive regulation of cell proliferation
GO:0009952	anterior/posterior pattern specification
GO:0016055	Wnt signaling pathway
GO:0030326	embryonic limb morphogenesis
GO:0033690	positive regulation of osteoblast proliferation
GO:0035019	somatic stem cell maintenance
GO:0035108	limb morphogenesis
GO:0035426	extracellular matrix-cell signaling
GO:0042074	cell migration involved in gastrulation
GO:0042632	cholesterol homeostasis
GO:0042733	embryonic digit morphogenesis
GO:0042981	regulation of apoptotic process
GO:0043434	response to peptide hormone
GO:0044332	Wnt signaling pathway involved in dorsal/ventral axis specification
GO:0045600	positive regulation of fat cell differentiation
GO:0045668	negative regulation of osteoblast differentiation
GO:0045840	positive regulation of mitosis
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046849	bone remodeling
GO:0046850	regulation of bone remodeling
GO:0048539	bone marrow development
GO:0048596	embryonic camera-type eye morphogenesis
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0060033	anatomical structure regression
GO:0060042	retina morphogenesis in camera-type eye
GO:0060059	embryonic retina morphogenesis in camera-type eye
GO:0060070	canonical Wnt signaling pathway
GO:0060348	bone development
GO:0060349	bone morphogenesis
GO:0060444	branching involved in mammary gland duct morphogenesis
GO:0060603	mammary gland duct morphogenesis
GO:0060612	adipose tissue development
GO:0060764	cell-cell signaling involved in mammary gland development
GO:0060828	regulation of canonical Wnt signaling pathway
GO:0061178	regulation of insulin secretion involved in cellular response to glucose stimulus
GO:0061299	retina vasculature morphogenesis in camera-type eye
GO:0061304	retinal blood vessel morphogenesis
GO:0071901	negative regulation of protein serine/threonine kinase activity
GO:1902262	apoptotic process involved in patterning of blood vessels

Cellular Component

GO:0005739	mitochondrion
GO:0005783	endoplasmic reticulum
GO:0005886	plasma membrane
GO:0016021	integral component of membrane
GO:0043235	receptor complex

Protein Structure and Domains

PDB ID

InterPro

IPR000033 LDLR class B repeat
IPR000742 Epidermal growth factor-like domain
IPR002172 Low-density lipoprotein (LDL) receptor class A repeat
IPR017049 Low density lipoprotein receptor-related protein, 5/6

PFAM

PF00058
PF00008
PF00057

PRINTS

PR00261

PIRSF

PIRSF036314

SMART

SM00135
SM00181
SM00192

TIGRFAMs

Post-translational Modifications

Modification

Cross-References