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Protein

Low-density lipoprotein receptor-related protein 5

Gene

LRP5

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Plays a role in norrin (NDP) signal transduction (PubMed:27228167). 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 (By similarity). Required for posterior patterning of the epiblast during gastrulation (By similarity).By similarity6 Publications

GO - Molecular functioni

  • coreceptor activity involved in canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • coreceptor activity involved in Wnt signaling pathway Source: ParkinsonsUK-UCL
  • Wnt-activated receptor activity Source: ParkinsonsUK-UCL
  • Wnt-protein binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • adipose tissue development Source: BHF-UCL
  • anatomical structure regression Source: Ensembl
  • anterior/posterior pattern specification Source: Ensembl
  • apoptotic process involved in patterning of blood vessels Source: Ensembl
  • beta-catenin destruction complex disassembly Source: Reactome
  • bone marrow development Source: BHF-UCL
  • bone morphogenesis Source: BHF-UCL
  • bone remodeling Source: Ensembl
  • branching involved in mammary gland duct morphogenesis Source: Ensembl
  • canonical Wnt signaling pathway Source: BHF-UCL
  • cell-cell signaling involved in mammary gland development Source: Ensembl
  • cell migration involved in gastrulation Source: Ensembl
  • cholesterol homeostasis Source: BHF-UCL
  • cholesterol metabolic process Source: Ensembl
  • embryonic digit morphogenesis Source: Ensembl
  • endocytosis Source: UniProtKB-KW
  • extracellular matrix-cell signaling Source: Ensembl
  • gastrulation with mouth forming second Source: Ensembl
  • glucose catabolic process Source: BHF-UCL
  • negative regulation of osteoblast differentiation Source: BHF-UCL
  • negative regulation of protein serine/threonine kinase activity Source: BHF-UCL
  • osteoblast development Source: GO_Central
  • positive regulation of cell proliferation Source: BHF-UCL
  • positive regulation of fat cell differentiation Source: BHF-UCL
  • positive regulation of mesenchymal cell proliferation Source: BHF-UCL
  • positive regulation of mitotic nuclear division Source: BHF-UCL
  • positive regulation of osteoblast proliferation Source: Ensembl
  • positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: BHF-UCL
  • positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • regulation of apoptotic process Source: Ensembl
  • regulation of blood pressure Source: BHF-UCL
  • regulation of bone remodeling Source: Ensembl
  • regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • regulation of insulin secretion involved in cellular response to glucose stimulus Source: GO_Central
  • response to peptide hormone Source: Ensembl
  • retinal blood vessel morphogenesis Source: BHF-UCL
  • retina morphogenesis in camera-type eye Source: BHF-UCL
  • somatic stem cell population maintenance Source: Ensembl
  • Wnt signaling pathway Source: BHF-UCL
  • Wnt signaling pathway involved in dorsal/ventral axis specification Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Endocytosis, Wnt signaling pathway

Enzyme and pathway databases

ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
R-HSA-4641263. Regulation of FZD by ubiquitination.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.
R-HSA-5340588. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinkiO75197.
SIGNORiO75197.

Names & Taxonomyi

Protein namesi
Recommended name:
Low-density lipoprotein receptor-related protein 5
Short name:
LRP-5
Gene namesi
Name:LRP5
Synonyms:LR3, LRP7
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:6697. LRP5.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini32 – 1384ExtracellularSequence analysisAdd BLAST1353
Transmembranei1385 – 1407HelicalSequence analysisAdd BLAST23
Topological domaini1408 – 1615CytoplasmicSequence analysisAdd BLAST208

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • mitochondrion Source: Ensembl
  • plasma membrane Source: BHF-UCL
  • receptor complex Source: BHF-UCL
  • Wnt-Frizzled-LRP5/6 complex Source: ParkinsonsUK-UCL
  • Wnt signalosome Source: ParkinsonsUK-UCL
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Vitreoretinopathy, exudative 1 (EVR1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:133780
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063948348R → W in OPPG and EVR1; reduces Norrin signal transduction. 2 Publications1
Natural variantiVAR_076548381D → N in EVR1; reduces Norrin signal transduction. 1 Publication1
Natural variantiVAR_063957444R → C in EVR4; associated in a EVR1 patient with mutation GLN-417 in FZD4. 1 PublicationCorresponds to variant rs80358308dbSNPEnsembl.1
Natural variantiVAR_076549624R → W in EVR1; reduces Norrin signal transduction. 1 Publication1
Natural variantiVAR_0765501517Y → C in EVR1; decreases protein abundance. 1 PublicationCorresponds to variant rs201030241dbSNPEnsembl.1
Vitreoretinopathy, exudative 4 (EVR4)7 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:601813
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063943145L → F in EVR4. 1 PublicationCorresponds to variant rs80358305dbSNPEnsembl.1
Natural variantiVAR_018465173T → M in EVR4; an individual with abnormal retinal vasculature and retinal folds. 2 PublicationsCorresponds to variant rs80358306dbSNPEnsembl.1
Natural variantiVAR_071012422A → T in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication1
Natural variantiVAR_063956441E → K in EVR4. 1 PublicationCorresponds to variant rs376152274dbSNPEnsembl.1
Natural variantiVAR_063957444R → C in EVR4; associated in a EVR1 patient with mutation GLN-417 in FZD4. 1 PublicationCorresponds to variant rs80358308dbSNPEnsembl.1
Natural variantiVAR_063962511D → A in EVR4. 1 Publication1
Natural variantiVAR_063964522A → T in EVR4. 1 PublicationCorresponds to variant rs80358309dbSNPEnsembl.1
Natural variantiVAR_063966535T → M in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs80358310dbSNPEnsembl.1
Natural variantiVAR_071013540L → P in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication1
Natural variantiVAR_063967550G → R in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs80358311dbSNPEnsembl.1
Natural variantiVAR_021222570R → Q in EVR4; autosomal recessive; has significantly reduced Wnt or Norrin signal transduction. 2 PublicationsCorresponds to variant rs80358312dbSNPEnsembl.1
Natural variantiVAR_063968610G → R in EVR4 and OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 60% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 2 PublicationsCorresponds to variant rs80358313dbSNPEnsembl.1
Natural variantiVAR_063969617F → C in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs80358314dbSNPEnsembl.1
Natural variantiVAR_021223752R → G in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs121908674dbSNPEnsembl.1
Natural variantiVAR_063972798T → A in EVR4. 1 PublicationCorresponds to variant rs80358316dbSNPEnsembl.1
Natural variantiVAR_063973805R → W in EVR4. 1 PublicationCorresponds to variant rs765952535dbSNPEnsembl.1
Natural variantiVAR_071015852T → M in EVR4; de novo mutation found in a patient also carrying mutation P-540; unknown pathological significance; the mutation results in significantly reduced Norrin signal transduction. 1 Publication1
Natural variantiVAR_0639771121N → D in EVR4. 1 PublicationCorresponds to variant rs80358317dbSNPEnsembl.1
Natural variantiVAR_0184661168Y → H in EVR4; an individual with total retinal detachment and retinoschisis; is unable to transduce Wnt or Norrin signal transduction. 2 PublicationsCorresponds to variant rs80358318dbSNPEnsembl.1
Natural variantiVAR_0639781253C → F in EVR4. 1 PublicationCorresponds to variant rs768615287dbSNPEnsembl.1
Natural variantiVAR_0184671361C → G in EVR4; autosomal dominant; has mildly reduced Wnt or Norrin signal transduction. 2 PublicationsCorresponds to variant rs80358320dbSNPEnsembl.1
Natural variantiVAR_0212241367E → K in EVR4; autosomal recessive. 2 PublicationsCorresponds to variant rs28939709dbSNPEnsembl.1
Osteoporosis (OSTEOP)3 Publications
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:166710
Osteoporosis-pseudoglioma syndrome (OPPG)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:259770
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063945203D → N in OPPG. 1 PublicationCorresponds to variant rs760548029dbSNPEnsembl.1
Natural variantiVAR_063946244T → M in OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 PublicationCorresponds to variant rs397514665dbSNPEnsembl.1
Natural variantiVAR_063947307S → F in OPPG. 1 Publication1
Natural variantiVAR_063948348R → W in OPPG and EVR1; reduces Norrin signal transduction. 2 Publications1
Natural variantiVAR_063949353R → Q in OPPG. 1 Publication1
Natural variantiVAR_063950356S → L in idiopathic osteoporosis and OPPG; appears to traffic comparably than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 2 Publications1
Natural variantiVAR_063951390T → K in OPPG; is unable to traffic normally; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication1
Natural variantiVAR_063952400A → E in OPPG. 1 Publication1
Natural variantiVAR_063953404G → R in OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 50% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 PublicationCorresponds to variant rs750791263dbSNPEnsembl.1
Natural variantiVAR_063954409T → A in OPPG. 1 Publication1
Natural variantiVAR_063955434D → N in OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 50% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 PublicationCorresponds to variant rs757888034dbSNPEnsembl.1
Natural variantiVAR_063959460E → K in OPPG. 1 Publication1
Natural variantiVAR_063960478W → R in OPPG. 1 Publication1
Natural variantiVAR_021814494R → Q in OPPG. 2 PublicationsCorresponds to variant rs121908664dbSNPEnsembl.1
Natural variantiVAR_063961504W → C in OPPG. 1 Publication1
Natural variantiVAR_063963520G → V in OPPG; appears to traffic comparably than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication1
Natural variantiVAR_063965531N → I in OPPG. 1 Publication1
Natural variantiVAR_021815570R → W in OPPG. 2 PublicationsCorresponds to variant rs121908665dbSNPEnsembl.1
Natural variantiVAR_063968610G → R in EVR4 and OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 60% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 2 PublicationsCorresponds to variant rs80358313dbSNPEnsembl.1
Natural variantiVAR_063970683D → N in OPPG. 1 Publication1
Natural variantiVAR_063971733Y → H in OPPG. 1 PublicationCorresponds to variant rs746701187dbSNPEnsembl.1
Natural variantiVAR_0639751099D → Y in OPPG. 1 Publication1
Natural variantiVAR_0639761113R → C in OPPG. 1 PublicationCorresponds to variant rs377258285dbSNPEnsembl.1
Natural variantiVAR_0639791401G → D in OPPG. 1 Publication1
High bone mass trait (HBM)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionRare phenotype characterized by exceptionally dense bones. HBM individuals show otherwise a completely normal skeletal structure and no other unusual clinical findings.
See also OMIM:601884
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063944154R → M in HBM. 1 Publication1
Natural variantiVAR_021809171G → V in HBM; also in HBM individuals with enlarged mandible and torus palatinus; abolishes interaction with MESD; impairs transport to cell surface; no enhancement of DKK1 binding by MESD resulting in impaired inhibition of Wnt signaling by DKK1. 4 PublicationsCorresponds to variant rs121908668dbSNPEnsembl.1
Natural variantiVAR_063412282M → V in HBM; unknown pathological significance; lowered LRP5-mediated Wnt signaling; no effect on DKK1 binding. 1 Publication1
Endosteal hyperostosis, Worth type (WENHY)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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.
See also OMIM:144750
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021810214A → T in WENHY. 1 PublicationCorresponds to variant rs121908671dbSNPEnsembl.1
Natural variantiVAR_021811214A → V in WENHY. 1 PublicationCorresponds to variant rs121908672dbSNPEnsembl.1
Natural variantiVAR_021812242A → T in OPTA1, VBCH2 and WENHY. 1 PublicationCorresponds to variant rs121908670dbSNPEnsembl.1
Osteopetrosis, autosomal dominant 1 (OPTA1)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA 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.
See also OMIM:607634
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021807111D → Y in OPTA1. 1 Publication1
Natural variantiVAR_021808171G → R in OPTA1. 1 PublicationCorresponds to variant rs121908669dbSNPEnsembl.1
Natural variantiVAR_021812242A → T in OPTA1, VBCH2 and WENHY. 1 PublicationCorresponds to variant rs121908670dbSNPEnsembl.1
Natural variantiVAR_021813253T → I in OPTA1. 1 PublicationCorresponds to variant rs121908673dbSNPEnsembl.1
Van Buchem disease 2 (VBCH2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionVBCH2 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.
See also OMIM:607636
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021812242A → T in OPTA1, VBCH2 and WENHY. 1 PublicationCorresponds to variant rs121908670dbSNPEnsembl.1

Keywords - Diseasei

Disease mutation, Osteogenesis imperfecta, Osteopetrosis

Organism-specific databases

DisGeNETi4041.
MalaCardsiLRP5.
MIMi133780. phenotype.
144750. phenotype.
166710. phenotype.
259770. phenotype.
601813. phenotype.
601884. phenotype.
607634. phenotype.
607636. phenotype.
OpenTargetsiENSG00000162337.
Orphaneti2783. Autosomal dominant osteopetrosis type 1.
2790. Autosomal dominant osteosclerosis, Worth type.
891. Familial exudative vitreoretinopathy.
3416. Hyperostosis corticalis generalisata.
85193. Idiopathic juvenile osteoporosis.
2924. Isolated polycystic liver disease.
2788. Osteoporosis - pseudoglioma.
178377. Osteosclerosis-developmental delay-craniosynostosis syndrome.
90050. Retinopathy of prematurity.
PharmGKBiPA30455.

Polymorphism and mutation databases

BioMutaiLRP5.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 31Sequence analysisAdd BLAST31
ChainiPRO_000001732832 – 1615Low-density lipoprotein receptor-related protein 5Add BLAST1584

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi93N-linked (GlcNAc...)Sequence analysis1
Glycosylationi138N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi299 ↔ 310PROSITE-ProRule annotation
Disulfide bondi306 ↔ 321PROSITE-ProRule annotation
Disulfide bondi323 ↔ 336PROSITE-ProRule annotation
Glycosylationi446N-linked (GlcNAc...)Sequence analysis1
Glycosylationi499N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi605 ↔ 616PROSITE-ProRule annotation
Disulfide bondi612 ↔ 625PROSITE-ProRule annotation
Disulfide bondi627 ↔ 640PROSITE-ProRule annotation
Glycosylationi705N-linked (GlcNAc...)Sequence analysis1
Glycosylationi878N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi906 ↔ 917PROSITE-ProRule annotation
Disulfide bondi913 ↔ 926PROSITE-ProRule annotation
Disulfide bondi928 ↔ 941PROSITE-ProRule annotation
Disulfide bondi1217 ↔ 1228PROSITE-ProRule annotation
Disulfide bondi1224 ↔ 1238PROSITE-ProRule annotation
Disulfide bondi1240 ↔ 1253PROSITE-ProRule annotation
Disulfide bondi1259 ↔ 1273PROSITE-ProRule annotation
Disulfide bondi1266 ↔ 1286PROSITE-ProRule annotation
Disulfide bondi1280 ↔ 1295PROSITE-ProRule annotation
Disulfide bondi1298 ↔ 1310PROSITE-ProRule annotation
Disulfide bondi1305 ↔ 1323PROSITE-ProRule annotation
Disulfide bondi1317 ↔ 1332PROSITE-ProRule annotation
Disulfide bondi1336 ↔ 1348PROSITE-ProRule annotation
Disulfide bondi1343 ↔ 1361PROSITE-ProRule annotation
Disulfide bondi1355 ↔ 1370PROSITE-ProRule annotation

Post-translational modificationi

Phosphorylation of cytoplasmic PPPSP motifs regulates the signal transduction of the Wnt signaling pathway through acting as a docking site for AXIN1.By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein

Proteomic databases

EPDiO75197.
PaxDbiO75197.
PeptideAtlasiO75197.
PRIDEiO75197.

PTM databases

iPTMnetiO75197.
PhosphoSitePlusiO75197.

Expressioni

Tissue specificityi

Widely expressed, with the highest level of expression in the liver and in aorta.1 Publication

Gene expression databases

BgeeiENSG00000162337.
CleanExiHS_LRP5.
ExpressionAtlasiO75197. baseline and differential.
GenevisibleiO75197. HS.

Organism-specific databases

HPAiCAB013001.
HPA030505.
HPA030506.

Interactioni

Subunit structurei

Homodimer; 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.By similarity10 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CAPRIN2Q6IMN63EBI-2466421,EBI-6918449
SOSTQ9BQB42EBI-2466421,EBI-5746563

GO - Molecular functioni

  • Wnt-protein binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi110220. 35 interactors.
DIPiDIP-47265N.
IntActiO75197. 9 interactors.
MINTiMINT-1189744.
STRINGi9606.ENSP00000294304.

Structurei

3D structure databases

ProteinModelPortaliO75197.
SMRiO75197.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati75 – 119LDL-receptor class B 1Add BLAST45
Repeati78 – 81YWTD 14
Repeati120 – 162LDL-receptor class B 2Add BLAST43
Repeati123 – 126YWTD 24
Repeati163 – 206LDL-receptor class B 3Add BLAST44
Repeati166 – 169YWTD 34
Repeati207 – 247LDL-receptor class B 4Add BLAST41
Repeati248 – 290LDL-receptor class B 5Add BLAST43
Repeati251 – 254YWTD 44
Domaini295 – 337EGF-like 1Add BLAST43
Repeati385 – 427LDL-receptor class B 6Add BLAST43
Repeati388 – 391YWTD 54
Repeati428 – 470LDL-receptor class B 7Add BLAST43
Repeati431 – 434YWTD 64
Repeati471 – 514LDL-receptor class B 8Add BLAST44
Repeati474 – 477YWTD 74
Repeati515 – 557LDL-receptor class B 9Add BLAST43
Repeati558 – 600LDL-receptor class B 10Add BLAST43
Repeati559 – 562YWTD 84
Domaini601 – 641EGF-like 2Add BLAST41
Repeati687 – 729LDL-receptor class B 11Add BLAST43
Repeati690 – 693YWTD 94
Repeati730 – 772LDL-receptor class B 12Add BLAST43
Repeati773 – 815LDL-receptor class B 13Add BLAST43
Repeati816 – 855LDL-receptor class B 14Add BLAST40
Repeati819 – 822YWTD 104
Repeati856 – 898LDL-receptor class B 15Add BLAST43
Repeati859 – 862YWTD 114
Domaini902 – 942EGF-like 3Add BLAST41
Repeati989 – 1035LDL-receptor class B 16Add BLAST47
Repeati1036 – 1078LDL-receptor class B 17Add BLAST43
Repeati1079 – 1123LDL-receptor class B 18Add BLAST45
Repeati1124 – 1164LDL-receptor class B 19Add BLAST41
Repeati1165 – 1207LDL-receptor class B 20Add BLAST43
Domaini1213 – 1254EGF-like 4Add BLAST42
Domaini1258 – 1296LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST39
Domaini1297 – 1333LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST37
Domaini1335 – 1371LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST37

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni32 – 288Beta-propeller 1Add BLAST257
Regioni341 – 602Beta-propeller 2Add BLAST262
Regioni644 – 903Beta-propeller 3Add BLAST260
Regioni945 – 1212Beta-propeller 4Add BLAST268

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi1500 – 1506PPPSP motif A7
Motifi1538 – 1545PPPSP motif B8
Motifi1574 – 1581PPPSP motif C8
Motifi1591 – 1596PPPSP motif D6
Motifi1605 – 1612PPPSP motif E8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi1495 – 1610Pro-richAdd BLAST116

Sequence similaritiesi

Belongs to the LDLR family.Curated
Contains 4 EGF-like domains.Curated
Contains 3 LDL-receptor class A domains.PROSITE-ProRule annotation
Contains 20 LDL-receptor class B repeats.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IPT4. Eukaryota.
ENOG410XSY5. LUCA.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000230697.
HOVERGENiHBG049167.
InParanoidiO75197.
KOiK03068.
OMAiLFWTCEA.
OrthoDBiEOG091G0178.
PhylomeDBiO75197.
TreeFamiTF315253.

Family and domain databases

Gene3Di2.120.10.30. 4 hits.
4.10.400.10. 3 hits.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR000742. EGF-like_dom.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR017049. LRP5/6.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 3 hits.
PF00058. Ldl_recept_b. 13 hits.
[Graphical view]
PIRSFiPIRSF036314. LDL_recpt-rel_p5/6. 1 hit.
PRINTSiPR00261. LDLRECEPTOR.
SMARTiSM00181. EGF. 4 hits.
SM00192. LDLa. 3 hits.
SM00135. LY. 20 hits.
[Graphical view]
SUPFAMiSSF57424. SSF57424. 3 hits.
PROSITEiPS01209. LDLRA_1. 3 hits.
PS50068. LDLRA_2. 3 hits.
PS51120. LDLRB. 20 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O75197-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEAAPPGPPW PLLLLLLLLL ALCGCPAPAA ASPLLLFANR RDVRLVDAGG
60 70 80 90 100
VKLESTIVVS GLEDAAAVDF QFSKGAVYWT DVSEEAIKQT YLNQTGAAVQ
110 120 130 140 150
NVVISGLVSP DGLACDWVGK KLYWTDSETN RIEVANLNGT SRKVLFWQDL
160 170 180 190 200
DQPRAIALDP AHGYMYWTDW GETPRIERAG MDGSTRKIIV DSDIYWPNGL
210 220 230 240 250
TIDLEEQKLY WADAKLSFIH RANLDGSFRQ KVVEGSLTHP FALTLSGDTL
260 270 280 290 300
YWTDWQTRSI HACNKRTGGK RKEILSALYS PMDIQVLSQE RQPFFHTRCE
310 320 330 340 350
EDNGGCSHLC LLSPSEPFYT CACPTGVQLQ DNGRTCKAGA EEVLLLARRT
360 370 380 390 400
DLRRISLDTP DFTDIVLQVD DIRHAIAIDY DPLEGYVYWT DDEVRAIRRA
410 420 430 440 450
YLDGSGAQTL VNTEINDPDG IAVDWVARNL YWTDTGTDRI EVTRLNGTSR
460 470 480 490 500
KILVSEDLDE PRAIALHPVM GLMYWTDWGE NPKIECANLD GQERRVLVNA
510 520 530 540 550
SLGWPNGLAL DLQEGKLYWG DAKTDKIEVI NVDGTKRRTL LEDKLPHIFG
560 570 580 590 600
FTLLGDFIYW TDWQRRSIER VHKVKASRDV IIDQLPDLMG LKAVNVAKVV
610 620 630 640 650
GTNPCADRNG GCSHLCFFTP HATRCGCPIG LELLSDMKTC IVPEAFLVFT
660 670 680 690 700
SRAAIHRISL ETNNNDVAIP LTGVKEASAL DFDVSNNHIY WTDVSLKTIS
710 720 730 740 750
RAFMNGSSVE HVVEFGLDYP EGMAVDWMGK NLYWADTGTN RIEVARLDGQ
760 770 780 790 800
FRQVLVWRDL DNPRSLALDP TKGYIYWTEW GGKPRIVRAF MDGTNCMTLV
810 820 830 840 850
DKVGRANDLT IDYADQRLYW TDLDTNMIES SNMLGQERVV IADDLPHPFG
860 870 880 890 900
LTQYSDYIYW TDWNLHSIER ADKTSGRNRT LIQGHLDFVM DILVFHSSRQ
910 920 930 940 950
DGLNDCMHNN GQCGQLCLAI PGGHRCGCAS HYTLDPSSRN CSPPTTFLLF
960 970 980 990 1000
SQKSAISRMI PDDQHSPDLI LPLHGLRNVK AIDYDPLDKF IYWVDGRQNI
1010 1020 1030 1040 1050
KRAKDDGTQP FVLTSLSQGQ NPDRQPHDLS IDIYSRTLFW TCEATNTINV
1060 1070 1080 1090 1100
HRLSGEAMGV VLRGDRDKPR AIVVNAERGY LYFTNMQDRA AKIERAALDG
1110 1120 1130 1140 1150
TEREVLFTTG LIRPVALVVD NTLGKLFWVD ADLKRIESCD LSGANRLTLE
1160 1170 1180 1190 1200
DANIVQPLGL TILGKHLYWI DRQQQMIERV EKTTGDKRTR IQGRVAHLTG
1210 1220 1230 1240 1250
IHAVEEVSLE EFSAHPCARD NGGCSHICIA KGDGTPRCSC PVHLVLLQNL
1260 1270 1280 1290 1300
LTCGEPPTCS PDQFACATGE IDCIPGAWRC DGFPECDDQS DEEGCPVCSA
1310 1320 1330 1340 1350
AQFPCARGQC VDLRLRCDGE ADCQDRSDEA DCDAICLPNQ FRCASGQCVL
1360 1370 1380 1390 1400
IKQQCDSFPD CIDGSDELMC EITKPPSDDS PAHSSAIGPV IGIILSLFVM
1410 1420 1430 1440 1450
GGVYFVCQRV VCQRYAGANG PFPHEYVSGT PHVPLNFIAP GGSQHGPFTG
1460 1470 1480 1490 1500
IACGKSMMSS VSLMGGRGGV PLYDRNHVTG ASSSSSSSTK ATLYPPILNP
1510 1520 1530 1540 1550
PPSPATDPSL YNMDMFYSSN IPATARPYRP YIIRGMAPPT TPCSTDVCDS
1560 1570 1580 1590 1600
DYSASRWKAS KYYLDLNSDS DPYPPPPTPH SQYLSAEDSC PPSPATERSY
1610
FHLFPPPPSP CTDSS
Length:1,615
Mass (Da):179,145
Last modified:April 12, 2005 - v2
Checksum:i8BA25D07F51E02CA
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1525 – 1528Missing in AAK52433 (PubMed:11401438).Curated4

Polymorphismi

Genetic variations in LRP5 define the bone mineral density quantitative trait locus 1 (BMND1) [MIMi:601884]. Variance in bone mineral density influences bone mass and contributes to size determination in the general population.1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05858215 – 20Missing Found in a family with osteoporosis pseudoglioma syndrome; impairs protein trafficking to the endoplasmic reticulum and cell membrane. 1 Publication6
Natural variantiVAR_02180418 – 20Missing .1 Publication3
Natural variantiVAR_02180520L → LL.1 Publication1
Natural variantiVAR_06394129A → T in primary osteoporosis. 1 Publication1
Natural variantiVAR_02180689Q → R.2 PublicationsCorresponds to variant rs41494349dbSNPEnsembl.1
Natural variantiVAR_06394297A → V.1 PublicationCorresponds to variant rs143433231dbSNPEnsembl.1
Natural variantiVAR_021807111D → Y in OPTA1. 1 Publication1
Natural variantiVAR_063943145L → F in EVR4. 1 PublicationCorresponds to variant rs80358305dbSNPEnsembl.1
Natural variantiVAR_063944154R → M in HBM. 1 Publication1
Natural variantiVAR_021808171G → R in OPTA1. 1 PublicationCorresponds to variant rs121908669dbSNPEnsembl.1
Natural variantiVAR_021809171G → V in HBM; also in HBM individuals with enlarged mandible and torus palatinus; abolishes interaction with MESD; impairs transport to cell surface; no enhancement of DKK1 binding by MESD resulting in impaired inhibition of Wnt signaling by DKK1. 4 PublicationsCorresponds to variant rs121908668dbSNPEnsembl.1
Natural variantiVAR_018465173T → M in EVR4; an individual with abnormal retinal vasculature and retinal folds. 2 PublicationsCorresponds to variant rs80358306dbSNPEnsembl.1
Natural variantiVAR_063945203D → N in OPPG. 1 PublicationCorresponds to variant rs760548029dbSNPEnsembl.1
Natural variantiVAR_021810214A → T in WENHY. 1 PublicationCorresponds to variant rs121908671dbSNPEnsembl.1
Natural variantiVAR_021811214A → V in WENHY. 1 PublicationCorresponds to variant rs121908672dbSNPEnsembl.1
Natural variantiVAR_021812242A → T in OPTA1, VBCH2 and WENHY. 1 PublicationCorresponds to variant rs121908670dbSNPEnsembl.1
Natural variantiVAR_063946244T → M in OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 PublicationCorresponds to variant rs397514665dbSNPEnsembl.1
Natural variantiVAR_021813253T → I in OPTA1. 1 PublicationCorresponds to variant rs121908673dbSNPEnsembl.1
Natural variantiVAR_063412282M → V in HBM; unknown pathological significance; lowered LRP5-mediated Wnt signaling; no effect on DKK1 binding. 1 Publication1
Natural variantiVAR_063947307S → F in OPPG. 1 Publication1
Natural variantiVAR_063948348R → W in OPPG and EVR1; reduces Norrin signal transduction. 2 Publications1
Natural variantiVAR_063949353R → Q in OPPG. 1 Publication1
Natural variantiVAR_063950356S → L in idiopathic osteoporosis and OPPG; appears to traffic comparably than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 2 Publications1
Natural variantiVAR_076548381D → N in EVR1; reduces Norrin signal transduction. 1 Publication1
Natural variantiVAR_063951390T → K in OPPG; is unable to traffic normally; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication1
Natural variantiVAR_063952400A → E in OPPG. 1 Publication1
Natural variantiVAR_063953404G → R in OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 50% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 PublicationCorresponds to variant rs750791263dbSNPEnsembl.1
Natural variantiVAR_063954409T → A in OPPG. 1 Publication1
Natural variantiVAR_071012422A → T in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication1
Natural variantiVAR_063955434D → N in OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 50% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 PublicationCorresponds to variant rs757888034dbSNPEnsembl.1
Natural variantiVAR_063956441E → K in EVR4. 1 PublicationCorresponds to variant rs376152274dbSNPEnsembl.1
Natural variantiVAR_063957444R → C in EVR4; associated in a EVR1 patient with mutation GLN-417 in FZD4. 1 PublicationCorresponds to variant rs80358308dbSNPEnsembl.1
Natural variantiVAR_063958455S → L in idiopathic osteoporosis; shows an inhibitory effect on Wnt signal transduction. 1 Publication1
Natural variantiVAR_063959460E → K in OPPG. 1 Publication1
Natural variantiVAR_063960478W → R in OPPG. 1 Publication1
Natural variantiVAR_021814494R → Q in OPPG. 2 PublicationsCorresponds to variant rs121908664dbSNPEnsembl.1
Natural variantiVAR_063961504W → C in OPPG. 1 Publication1
Natural variantiVAR_063962511D → A in EVR4. 1 Publication1
Natural variantiVAR_063963520G → V in OPPG; appears to traffic comparably than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication1
Natural variantiVAR_063964522A → T in EVR4. 1 PublicationCorresponds to variant rs80358309dbSNPEnsembl.1
Natural variantiVAR_063965531N → I in OPPG. 1 Publication1
Natural variantiVAR_063966535T → M in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs80358310dbSNPEnsembl.1
Natural variantiVAR_071013540L → P in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication1
Natural variantiVAR_063967550G → R in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs80358311dbSNPEnsembl.1
Natural variantiVAR_021222570R → Q in EVR4; autosomal recessive; has significantly reduced Wnt or Norrin signal transduction. 2 PublicationsCorresponds to variant rs80358312dbSNPEnsembl.1
Natural variantiVAR_021815570R → W in OPPG. 2 PublicationsCorresponds to variant rs121908665dbSNPEnsembl.1
Natural variantiVAR_063968610G → R in EVR4 and OPPG; appears to traffic less well than does the wild-type protein; appears to be post-translationally modified similar to wild-type protein; has 60% of wild-type activity to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 2 PublicationsCorresponds to variant rs80358313dbSNPEnsembl.1
Natural variantiVAR_063969617F → C in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs80358314dbSNPEnsembl.1
Natural variantiVAR_076549624R → W in EVR1; reduces Norrin signal transduction. 1 Publication1
Natural variantiVAR_021816667V → M.3 PublicationsCorresponds to variant rs4988321dbSNPEnsembl.1
Natural variantiVAR_063970683D → N in OPPG. 1 Publication1
Natural variantiVAR_063971733Y → H in OPPG. 1 PublicationCorresponds to variant rs746701187dbSNPEnsembl.1
Natural variantiVAR_021223752R → G in EVR4; autosomal recessive. 1 PublicationCorresponds to variant rs121908674dbSNPEnsembl.1
Natural variantiVAR_063972798T → A in EVR4. 1 PublicationCorresponds to variant rs80358316dbSNPEnsembl.1
Natural variantiVAR_063973805R → W in EVR4. 1 PublicationCorresponds to variant rs765952535dbSNPEnsembl.1
Natural variantiVAR_071014816Q → P Rare polymorphism; no effect on Norrin signal transduction. 1 Publication1
Natural variantiVAR_071015852T → M in EVR4; de novo mutation found in a patient also carrying mutation P-540; unknown pathological significance; the mutation results in significantly reduced Norrin signal transduction. 1 Publication1
Natural variantiVAR_0639741036R → Q in primary osteoporosis. 1 PublicationCorresponds to variant rs61889560dbSNPEnsembl.1
Natural variantiVAR_0639751099D → Y in OPPG. 1 Publication1
Natural variantiVAR_0639761113R → C in OPPG. 1 PublicationCorresponds to variant rs377258285dbSNPEnsembl.1
Natural variantiVAR_0639771121N → D in EVR4. 1 PublicationCorresponds to variant rs80358317dbSNPEnsembl.1
Natural variantiVAR_0184661168Y → H in EVR4; an individual with total retinal detachment and retinoschisis; is unable to transduce Wnt or Norrin signal transduction. 2 PublicationsCorresponds to variant rs80358318dbSNPEnsembl.1
Natural variantiVAR_0352081204V → L.Corresponds to variant rs11607268dbSNPEnsembl.1
Natural variantiVAR_0639781253C → F in EVR4. 1 PublicationCorresponds to variant rs768615287dbSNPEnsembl.1
Natural variantiVAR_0218171330A → V.4 PublicationsCorresponds to variant rs3736228dbSNPEnsembl.1
Natural variantiVAR_0184671361C → G in EVR4; autosomal dominant; has mildly reduced Wnt or Norrin signal transduction. 2 PublicationsCorresponds to variant rs80358320dbSNPEnsembl.1
Natural variantiVAR_0212241367E → K in EVR4; autosomal recessive. 2 PublicationsCorresponds to variant rs28939709dbSNPEnsembl.1
Natural variantiVAR_0639791401G → D in OPPG. 1 Publication1
Natural variantiVAR_0765501517Y → C in EVR1; decreases protein abundance. 1 PublicationCorresponds to variant rs201030241dbSNPEnsembl.1
Natural variantiVAR_0212251525A → V.2 PublicationsCorresponds to variant rs1127291dbSNPEnsembl.1
Natural variantiVAR_0639801537A → T Could be associated with idiopathic osteoporosis; does not result in a significant alteration of Wnt signal transduction. 1 PublicationCorresponds to variant rs144376510dbSNPEnsembl.1
Natural variantiVAR_0639811540T → M.1 PublicationCorresponds to variant rs141407040dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077820 mRNA. Translation: AAC72791.1.
AF064548 mRNA. Translation: AAC36467.1.
AF283321, AF283320 Genomic DNA. Translation: AAK52433.1.
AB017498 mRNA. Translation: BAA33051.1.
AP000807 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74705.1.
BC150595 mRNA. Translation: AAI50596.1.
CCDSiCCDS8181.1.
PIRiJE0372.
RefSeqiNP_001278831.1. NM_001291902.1.
NP_002326.2. NM_002335.3.
UniGeneiHs.6347.

Genome annotation databases

EnsembliENST00000294304; ENSP00000294304; ENSG00000162337.
GeneIDi4041.
KEGGihsa:4041.
UCSCiuc001ont.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF077820 mRNA. Translation: AAC72791.1.
AF064548 mRNA. Translation: AAC36467.1.
AF283321, AF283320 Genomic DNA. Translation: AAK52433.1.
AB017498 mRNA. Translation: BAA33051.1.
AP000807 Genomic DNA. No translation available.
CH471076 Genomic DNA. Translation: EAW74705.1.
BC150595 mRNA. Translation: AAI50596.1.
CCDSiCCDS8181.1.
PIRiJE0372.
RefSeqiNP_001278831.1. NM_001291902.1.
NP_002326.2. NM_002335.3.
UniGeneiHs.6347.

3D structure databases

ProteinModelPortaliO75197.
SMRiO75197.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110220. 35 interactors.
DIPiDIP-47265N.
IntActiO75197. 9 interactors.
MINTiMINT-1189744.
STRINGi9606.ENSP00000294304.

PTM databases

iPTMnetiO75197.
PhosphoSitePlusiO75197.

Polymorphism and mutation databases

BioMutaiLRP5.

Proteomic databases

EPDiO75197.
PaxDbiO75197.
PeptideAtlasiO75197.
PRIDEiO75197.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000294304; ENSP00000294304; ENSG00000162337.
GeneIDi4041.
KEGGihsa:4041.
UCSCiuc001ont.4. human.

Organism-specific databases

CTDi4041.
DisGeNETi4041.
GeneCardsiLRP5.
GeneReviewsiLRP5.
HGNCiHGNC:6697. LRP5.
HPAiCAB013001.
HPA030505.
HPA030506.
MalaCardsiLRP5.
MIMi133780. phenotype.
144750. phenotype.
166710. phenotype.
259770. phenotype.
601813. phenotype.
601884. phenotype.
603506. gene.
607634. phenotype.
607636. phenotype.
neXtProtiNX_O75197.
OpenTargetsiENSG00000162337.
Orphaneti2783. Autosomal dominant osteopetrosis type 1.
2790. Autosomal dominant osteosclerosis, Worth type.
891. Familial exudative vitreoretinopathy.
3416. Hyperostosis corticalis generalisata.
85193. Idiopathic juvenile osteoporosis.
2924. Isolated polycystic liver disease.
2788. Osteoporosis - pseudoglioma.
178377. Osteosclerosis-developmental delay-craniosynostosis syndrome.
90050. Retinopathy of prematurity.
PharmGKBiPA30455.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IPT4. Eukaryota.
ENOG410XSY5. LUCA.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000230697.
HOVERGENiHBG049167.
InParanoidiO75197.
KOiK03068.
OMAiLFWTCEA.
OrthoDBiEOG091G0178.
PhylomeDBiO75197.
TreeFamiTF315253.

Enzyme and pathway databases

ReactomeiR-HSA-201681. TCF dependent signaling in response to WNT.
R-HSA-3772470. Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
R-HSA-4641262. Disassembly of the destruction complex and recruitment of AXIN to the membrane.
R-HSA-4641263. Regulation of FZD by ubiquitination.
R-HSA-5339717. Misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.
R-HSA-5340588. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinkiO75197.
SIGNORiO75197.

Miscellaneous databases

ChiTaRSiLRP5. human.
GeneWikiiLRP5.
GenomeRNAii4041.
PROiO75197.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000162337.
CleanExiHS_LRP5.
ExpressionAtlasiO75197. baseline and differential.
GenevisibleiO75197. HS.

Family and domain databases

Gene3Di2.120.10.30. 4 hits.
4.10.400.10. 3 hits.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR000742. EGF-like_dom.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR017049. LRP5/6.
[Graphical view]
PfamiPF00057. Ldl_recept_a. 3 hits.
PF00058. Ldl_recept_b. 13 hits.
[Graphical view]
PIRSFiPIRSF036314. LDL_recpt-rel_p5/6. 1 hit.
PRINTSiPR00261. LDLRECEPTOR.
SMARTiSM00181. EGF. 4 hits.
SM00192. LDLa. 3 hits.
SM00135. LY. 20 hits.
[Graphical view]
SUPFAMiSSF57424. SSF57424. 3 hits.
PROSITEiPS01209. LDLRA_1. 3 hits.
PS50068. LDLRA_2. 3 hits.
PS51120. LDLRB. 20 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLRP5_HUMAN
AccessioniPrimary (citable) accession number: O75197
Secondary accession number(s): Q96TD6, Q9UES7, Q9UP66
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: April 12, 2005
Last modified: November 2, 2016
This is version 166 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.