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O75197

- LRP5_HUMAN

UniProt

O75197 - LRP5_HUMAN

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Protein

Low-density lipoprotein receptor-related protein 5

Gene

LRP5

Organism
Homo sapiens (Human)
Status
Reviewed - 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. 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.5 Publications

GO - Molecular functioni

  1. coreceptor activity Source: RefGenome
  2. Wnt-activated receptor activity Source: RefGenome
  3. Wnt-protein binding Source: RefGenome

GO - Biological processi

  1. adipose tissue development Source: BHF-UCL
  2. anatomical structure regression Source: Ensembl
  3. anterior/posterior pattern specification Source: RefGenome
  4. apoptotic process involved in patterning of blood vessels Source: Ensembl
  5. bone marrow development Source: BHF-UCL
  6. bone morphogenesis Source: BHF-UCL
  7. bone remodeling Source: RefGenome
  8. branching involved in mammary gland duct morphogenesis Source: RefGenome
  9. canonical Wnt signaling pathway Source: BHF-UCL
  10. cell-cell signaling involved in mammary gland development Source: Ensembl
  11. cell migration involved in gastrulation Source: Ensembl
  12. cholesterol homeostasis Source: BHF-UCL
  13. cholesterol metabolic process Source: Ensembl
  14. embryonic camera-type eye morphogenesis Source: RefGenome
  15. embryonic digit morphogenesis Source: Ensembl
  16. embryonic limb morphogenesis Source: RefGenome
  17. embryonic retina morphogenesis in camera-type eye Source: RefGenome
  18. endocytosis Source: UniProtKB-KW
  19. extracellular matrix-cell signaling Source: Ensembl
  20. gastrulation with mouth forming second Source: RefGenome
  21. glucose catabolic process Source: BHF-UCL
  22. negative regulation of osteoblast differentiation Source: BHF-UCL
  23. negative regulation of protein serine/threonine kinase activity Source: BHF-UCL
  24. osteoblast development Source: RefGenome
  25. positive regulation of cell proliferation Source: BHF-UCL
  26. positive regulation of fat cell differentiation Source: BHF-UCL
  27. positive regulation of mesenchymal cell proliferation Source: BHF-UCL
  28. positive regulation of mitosis Source: BHF-UCL
  29. positive regulation of osteoblast proliferation Source: Ensembl
  30. positive regulation of sequence-specific DNA binding transcription factor activity Source: Ensembl
  31. positive regulation of transcription, DNA-templated Source: BHF-UCL
  32. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  33. regulation of apoptotic process Source: Ensembl
  34. regulation of blood pressure Source: BHF-UCL
  35. regulation of bone remodeling Source: Ensembl
  36. regulation of canonical Wnt signaling pathway Source: BHF-UCL
  37. regulation of insulin secretion involved in cellular response to glucose stimulus Source: RefGenome
  38. response to peptide hormone Source: Ensembl
  39. retinal blood vessel morphogenesis Source: BHF-UCL
  40. retina morphogenesis in camera-type eye Source: BHF-UCL
  41. somatic stem cell maintenance Source: Ensembl
  42. Wnt signaling pathway Source: BHF-UCL
  43. 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

ReactomeiREACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200643. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
REACT_200716. regulation of FZD by ubiquitination.
REACT_200777. TCF dependent signaling in response to WNT.
REACT_228096. misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.
REACT_228188. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinkiO75197.

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
ProteomesiUP000005640: Chromosome 11

Organism-specific databases

HGNCiHGNC:6697. LRP5.

Subcellular locationi

Membrane; Single-pass type I membrane protein. Endoplasmic reticulum By similarity
Note: Chaperoned to the plasma membrane by MESD.By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini32 – 13841353ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1385 – 140723HelicalSequence AnalysisAdd
BLAST
Topological domaini1408 – 1615208CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endoplasmic reticulum Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. mitochondrion Source: Ensembl
  4. plasma membrane Source: BHF-UCL
  5. receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

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.7 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti145 – 1451L → F in EVR4. 1 Publication
VAR_063943
Natural varianti173 – 1731T → M in EVR4; an individual with abnormal retinal vasculature and retinal folds. 1 Publication
VAR_018465
Natural varianti422 – 4221A → T in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication
VAR_071012
Natural varianti441 – 4411E → K in EVR4. 1 Publication
VAR_063956
Natural varianti444 – 4441R → C in EVR4; associated in a EVR1 patient with mutation GLN-417 in FZD4. 1 Publication
VAR_063957
Natural varianti511 – 5111D → A in EVR4. 1 Publication
VAR_063962
Natural varianti522 – 5221A → T in EVR4. 1 Publication
VAR_063964
Natural varianti535 – 5351T → M in EVR4; autosomal recessive. 1 Publication
VAR_063966
Natural varianti540 – 5401L → P in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication
VAR_071013
Natural varianti550 – 5501G → R in EVR4; autosomal recessive. 1 Publication
VAR_063967
Natural varianti570 – 5701R → Q in EVR4; autosomal recessive; has significantly reduced Wnt or Norrin signal transduction. 1 Publication
VAR_021222
Natural varianti610 – 6101G → R in EVR4 and OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally 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 Publications
VAR_063968
Natural varianti617 – 6171F → C in EVR4; autosomal recessive. 1 Publication
VAR_063969
Natural varianti752 – 7521R → G in EVR4; autosomal recessive. 1 Publication
VAR_021223
Natural varianti798 – 7981T → A in EVR4. 1 Publication
VAR_063972
Natural varianti805 – 8051R → W in EVR4. 1 Publication
VAR_063973
Natural varianti852 – 8521T → 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 Publication
VAR_071015
Natural varianti1121 – 11211N → D in EVR4. 1 Publication
Corresponds to variant rs80358317 [ dbSNP | Ensembl ].
VAR_063977
Natural varianti1168 – 11681Y → H in EVR4; an individual with total retinal detachment and retinoschisis; is unable to transduce Wnt or Norrin signal transduction. 1 Publication
VAR_018466
Natural varianti1253 – 12531C → F in EVR4. 1 Publication
VAR_063978
Natural varianti1361 – 13611C → G in EVR4; autosomal dominant; has mildly reduced Wnt or Norrin signal transduction. 1 Publication
VAR_018467
Natural varianti1367 – 13671E → K in EVR4; autosomal recessive. 1 Publication
Corresponds to variant rs28939709 [ dbSNP | Ensembl ].
VAR_021224
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.3 Publications
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.5 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti203 – 2031D → N in OPPG. 1 Publication
VAR_063945
Natural varianti244 – 2441T → M in OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication
VAR_063946
Natural varianti307 – 3071S → F in OPPG. 1 Publication
VAR_063947
Natural varianti348 – 3481R → W in OPPG. 1 Publication
VAR_063948
Natural varianti353 – 3531R → Q in OPPG. 1 Publication
VAR_063949
Natural varianti356 – 3561S → L in idiopathic osteoporosis and OPPG; appears to traffic comparably than does the wild-type protein; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 2 Publications
VAR_063950
Natural varianti390 – 3901T → K in OPPG; is unable to traffic normally; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication
VAR_063951
Natural varianti400 – 4001A → E in OPPG. 1 Publication
VAR_063952
Natural varianti404 – 4041G → R in OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally 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 Publication
VAR_063953
Natural varianti409 – 4091T → A in OPPG. 1 Publication
VAR_063954
Natural varianti434 – 4341D → N in OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally 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 Publication
VAR_063955
Natural varianti460 – 4601E → K in OPPG. 1 Publication
VAR_063959
Natural varianti478 – 4781W → R in OPPG. 1 Publication
VAR_063960
Natural varianti494 – 4941R → Q in OPPG. 2 Publications
VAR_021814
Natural varianti504 – 5041W → C in OPPG. 1 Publication
VAR_063961
Natural varianti520 – 5201G → V in OPPG; appears to traffic comparably than does the wild-type protein; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication
VAR_063963
Natural varianti531 – 5311N → I in OPPG. 1 Publication
VAR_063965
Natural varianti570 – 5701R → W in OPPG. 2 Publications
VAR_021815
Natural varianti610 – 6101G → R in EVR4 and OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally 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 Publications
VAR_063968
Natural varianti683 – 6831D → N in OPPG. 1 Publication
VAR_063970
Natural varianti733 – 7331Y → H in OPPG. 1 Publication
VAR_063971
Natural varianti1099 – 10991D → Y in OPPG. 1 Publication
VAR_063975
Natural varianti1113 – 11131R → C in OPPG. 1 Publication
VAR_063976
Natural varianti1401 – 14011G → D in OPPG. 1 Publication
VAR_063979
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.3 Publications
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti154 – 1541R → M in HBM. 1 Publication
VAR_063944
Natural varianti171 – 1711G → 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. 2 Publications
VAR_021809
Natural varianti282 – 2821M → V in HBM; lowered LRP5-mediated Wnt signaling. No effect on DKK1 binding.
VAR_063412
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti214 – 2141A → T in WENHY. 1 Publication
VAR_021810
Natural varianti214 – 2141A → V in WENHY. 1 Publication
VAR_021811
Natural varianti242 – 2421A → T in OPTA1, VBCH2 and WENHY. 1 Publication
VAR_021812
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti111 – 1111D → Y in OPTA1. 1 Publication
VAR_021807
Natural varianti171 – 1711G → R in OPTA1. 1 Publication
VAR_021808
Natural varianti242 – 2421A → T in OPTA1, VBCH2 and WENHY. 1 Publication
VAR_021812
Natural varianti253 – 2531T → I in OPTA1. 1 Publication
VAR_021813
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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti242 – 2421A → T in OPTA1, VBCH2 and WENHY. 1 Publication
VAR_021812

Keywords - Diseasei

Disease mutation, Osteogenesis imperfecta, Osteopetrosis

Organism-specific databases

MIMi144750. phenotype.
166710. phenotype.
259770. phenotype.
601813. phenotype.
601884. phenotype.
607634. phenotype.
607636. phenotype.
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.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3131Sequence AnalysisAdd
BLAST
Chaini32 – 16151584Low-density lipoprotein receptor-related protein 5PRO_0000017328Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi93 – 931N-linked (GlcNAc...)Sequence Analysis
Glycosylationi138 – 1381N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi299 ↔ 310PROSITE-ProRule annotation
Disulfide bondi306 ↔ 321PROSITE-ProRule annotation
Disulfide bondi323 ↔ 336PROSITE-ProRule annotation
Glycosylationi446 – 4461N-linked (GlcNAc...)Sequence Analysis
Glycosylationi499 – 4991N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi605 ↔ 616PROSITE-ProRule annotation
Disulfide bondi612 ↔ 625PROSITE-ProRule annotation
Disulfide bondi627 ↔ 640PROSITE-ProRule annotation
Glycosylationi705 – 7051N-linked (GlcNAc...)Sequence Analysis
Glycosylationi878 – 8781N-linked (GlcNAc...)Sequence Analysis
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

MaxQBiO75197.
PaxDbiO75197.
PRIDEiO75197.

PTM databases

PhosphoSiteiO75197.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO75197.
CleanExiHS_LRP5.
ExpressionAtlasiO75197. baseline and differential.
GenevestigatoriO75197.

Organism-specific databases

HPAiCAB013001.

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

Protein-protein interaction databases

BioGridi110220. 17 interactions.
DIPiDIP-47265N.
IntActiO75197. 8 interactions.
MINTiMINT-1189744.
STRINGi9606.ENSP00000294304.

Structurei

3D structure databases

ProteinModelPortaliO75197.
SMRiO75197. Positions 32-1367.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati75 – 11945LDL-receptor class B 1Add
BLAST
Repeati78 – 814YWTD 1
Repeati120 – 16243LDL-receptor class B 2Add
BLAST
Repeati123 – 1264YWTD 2
Repeati163 – 20644LDL-receptor class B 3Add
BLAST
Repeati166 – 1694YWTD 3
Repeati207 – 24741LDL-receptor class B 4Add
BLAST
Repeati248 – 29043LDL-receptor class B 5Add
BLAST
Repeati251 – 2544YWTD 4
Domaini295 – 33743EGF-like 1Add
BLAST
Repeati385 – 42743LDL-receptor class B 6Add
BLAST
Repeati388 – 3914YWTD 5
Repeati428 – 47043LDL-receptor class B 7Add
BLAST
Repeati431 – 4344YWTD 6
Repeati471 – 51444LDL-receptor class B 8Add
BLAST
Repeati474 – 4774YWTD 7
Repeati515 – 55743LDL-receptor class B 9Add
BLAST
Repeati558 – 60043LDL-receptor class B 10Add
BLAST
Repeati559 – 5624YWTD 8
Domaini601 – 64141EGF-like 2Add
BLAST
Repeati687 – 72943LDL-receptor class B 11Add
BLAST
Repeati690 – 6934YWTD 9
Repeati730 – 77243LDL-receptor class B 12Add
BLAST
Repeati773 – 81543LDL-receptor class B 13Add
BLAST
Repeati816 – 85540LDL-receptor class B 14Add
BLAST
Repeati819 – 8224YWTD 10
Repeati856 – 89843LDL-receptor class B 15Add
BLAST
Repeati859 – 8624YWTD 11
Domaini902 – 94241EGF-like 3Add
BLAST
Repeati989 – 103547LDL-receptor class B 16Add
BLAST
Repeati1036 – 107843LDL-receptor class B 17Add
BLAST
Repeati1079 – 112345LDL-receptor class B 18Add
BLAST
Repeati1124 – 116441LDL-receptor class B 19Add
BLAST
Repeati1165 – 120743LDL-receptor class B 20Add
BLAST
Domaini1213 – 125442EGF-like 4Add
BLAST
Domaini1258 – 129639LDL-receptor class A 1PROSITE-ProRule annotationAdd
BLAST
Domaini1297 – 133337LDL-receptor class A 2PROSITE-ProRule annotationAdd
BLAST
Domaini1335 – 137137LDL-receptor class A 3PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni32 – 288257Beta-propeller 1Add
BLAST
Regioni341 – 602262Beta-propeller 2Add
BLAST
Regioni644 – 903260Beta-propeller 3Add
BLAST
Regioni945 – 1212268Beta-propeller 4Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi1500 – 15067PPPSP motif A
Motifi1538 – 15458PPPSP motif B
Motifi1574 – 15818PPPSP motif C
Motifi1591 – 15966PPPSP motif D
Motifi1605 – 16128PPPSP motif E

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi1495 – 1610116Pro-richAdd
BLAST

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

eggNOGiNOG121718.
GeneTreeiENSGT00760000118968.
HOGENOMiHOG000230697.
HOVERGENiHBG049167.
InParanoidiO75197.
KOiK03068.
OMAiLFWTCEA.
OrthoDBiEOG75XGK3.
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. EG-like_dom.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR017049. Low_density_Lipo_rcpt-rel_p5/6.
[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.

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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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1525 – 15284Missing in AAK52433. (PubMed:11401438)Curated

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti15 – 206Missing Found in a family with osteoporosis pseudoglioma syndrome; impairs protein trafficking to the endoplasmic reticulum and cell membrane. 1 Publication
VAR_058582
Natural varianti18 – 203Missing.1 Publication
VAR_021804
Natural varianti20 – 201L → LL.1 Publication
VAR_021805
Natural varianti29 – 291A → T in primary osteoporosis. 1 Publication
VAR_063941
Natural varianti89 – 891Q → R.2 Publications
Corresponds to variant rs41494349 [ dbSNP | Ensembl ].
VAR_021806
Natural varianti97 – 971A → V.1 Publication
Corresponds to variant rs143433231 [ dbSNP | Ensembl ].
VAR_063942
Natural varianti111 – 1111D → Y in OPTA1. 1 Publication
VAR_021807
Natural varianti145 – 1451L → F in EVR4. 1 Publication
VAR_063943
Natural varianti154 – 1541R → M in HBM. 1 Publication
VAR_063944
Natural varianti171 – 1711G → R in OPTA1. 1 Publication
VAR_021808
Natural varianti171 – 1711G → 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. 2 Publications
VAR_021809
Natural varianti173 – 1731T → M in EVR4; an individual with abnormal retinal vasculature and retinal folds. 1 Publication
VAR_018465
Natural varianti203 – 2031D → N in OPPG. 1 Publication
VAR_063945
Natural varianti214 – 2141A → T in WENHY. 1 Publication
VAR_021810
Natural varianti214 – 2141A → V in WENHY. 1 Publication
VAR_021811
Natural varianti242 – 2421A → T in OPTA1, VBCH2 and WENHY. 1 Publication
VAR_021812
Natural varianti244 – 2441T → M in OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication
VAR_063946
Natural varianti253 – 2531T → I in OPTA1. 1 Publication
VAR_021813
Natural varianti282 – 2821M → V in HBM; lowered LRP5-mediated Wnt signaling. No effect on DKK1 binding.
VAR_063412
Natural varianti307 – 3071S → F in OPPG. 1 Publication
VAR_063947
Natural varianti348 – 3481R → W in OPPG. 1 Publication
VAR_063948
Natural varianti353 – 3531R → Q in OPPG. 1 Publication
VAR_063949
Natural varianti356 – 3561S → L in idiopathic osteoporosis and OPPG; appears to traffic comparably than does the wild-type protein; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 2 Publications
VAR_063950
Natural varianti390 – 3901T → K in OPPG; is unable to traffic normally; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication
VAR_063951
Natural varianti400 – 4001A → E in OPPG. 1 Publication
VAR_063952
Natural varianti404 – 4041G → R in OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally 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 Publication
VAR_063953
Natural varianti409 – 4091T → A in OPPG. 1 Publication
VAR_063954
Natural varianti422 – 4221A → T in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication
VAR_071012
Natural varianti434 – 4341D → N in OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally 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 Publication
VAR_063955
Natural varianti441 – 4411E → K in EVR4. 1 Publication
VAR_063956
Natural varianti444 – 4441R → C in EVR4; associated in a EVR1 patient with mutation GLN-417 in FZD4. 1 Publication
VAR_063957
Natural varianti455 – 4551S → L in idiopathic osteoporosis; shows an inhibitory effect on Wnt signal transduction. 1 Publication
VAR_063958
Natural varianti460 – 4601E → K in OPPG. 1 Publication
VAR_063959
Natural varianti478 – 4781W → R in OPPG. 1 Publication
VAR_063960
Natural varianti494 – 4941R → Q in OPPG. 2 Publications
VAR_021814
Natural varianti504 – 5041W → C in OPPG. 1 Publication
VAR_063961
Natural varianti511 – 5111D → A in EVR4. 1 Publication
VAR_063962
Natural varianti520 – 5201G → V in OPPG; appears to traffic comparably than does the wild-type protein; appears to be postranslationally modified similar to wild-type protein; is unable to transduce Wnt signal; has a significantly reduced ability to transduce Norrin signal. 1 Publication
VAR_063963
Natural varianti522 – 5221A → T in EVR4. 1 Publication
VAR_063964
Natural varianti531 – 5311N → I in OPPG. 1 Publication
VAR_063965
Natural varianti535 – 5351T → M in EVR4; autosomal recessive. 1 Publication
VAR_063966
Natural varianti540 – 5401L → P in EVR4; the mutation results in significantly reduced Norrin signal transduction. 1 Publication
VAR_071013
Natural varianti550 – 5501G → R in EVR4; autosomal recessive. 1 Publication
VAR_063967
Natural varianti570 – 5701R → Q in EVR4; autosomal recessive; has significantly reduced Wnt or Norrin signal transduction. 1 Publication
VAR_021222
Natural varianti570 – 5701R → W in OPPG. 2 Publications
VAR_021815
Natural varianti610 – 6101G → R in EVR4 and OPPG; appears to traffic less well than does the wild-type protein; appears to be postranslationally 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 Publications
VAR_063968
Natural varianti617 – 6171F → C in EVR4; autosomal recessive. 1 Publication
VAR_063969
Natural varianti667 – 6671V → M.3 Publications
Corresponds to variant rs4988321 [ dbSNP | Ensembl ].
VAR_021816
Natural varianti683 – 6831D → N in OPPG. 1 Publication
VAR_063970
Natural varianti733 – 7331Y → H in OPPG. 1 Publication
VAR_063971
Natural varianti752 – 7521R → G in EVR4; autosomal recessive. 1 Publication
VAR_021223
Natural varianti798 – 7981T → A in EVR4. 1 Publication
VAR_063972
Natural varianti805 – 8051R → W in EVR4. 1 Publication
VAR_063973
Natural varianti816 – 8161Q → P Rare polymorphism with no effect on Norrin signal transduction. 1 Publication
VAR_071014
Natural varianti852 – 8521T → 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 Publication
VAR_071015
Natural varianti1036 – 10361R → Q in primary osteoporosis. 1 Publication
Corresponds to variant rs61889560 [ dbSNP | Ensembl ].
VAR_063974
Natural varianti1099 – 10991D → Y in OPPG. 1 Publication
VAR_063975
Natural varianti1113 – 11131R → C in OPPG. 1 Publication
VAR_063976
Natural varianti1121 – 11211N → D in EVR4. 1 Publication
Corresponds to variant rs80358317 [ dbSNP | Ensembl ].
VAR_063977
Natural varianti1168 – 11681Y → H in EVR4; an individual with total retinal detachment and retinoschisis; is unable to transduce Wnt or Norrin signal transduction. 1 Publication
VAR_018466
Natural varianti1204 – 12041V → L.
Corresponds to variant rs11607268 [ dbSNP | Ensembl ].
VAR_035208
Natural varianti1253 – 12531C → F in EVR4. 1 Publication
VAR_063978
Natural varianti1330 – 13301A → V.4 Publications
Corresponds to variant rs3736228 [ dbSNP | Ensembl ].
VAR_021817
Natural varianti1361 – 13611C → G in EVR4; autosomal dominant; has mildly reduced Wnt or Norrin signal transduction. 1 Publication
VAR_018467
Natural varianti1367 – 13671E → K in EVR4; autosomal recessive. 1 Publication
Corresponds to variant rs28939709 [ dbSNP | Ensembl ].
VAR_021224
Natural varianti1401 – 14011G → D in OPPG. 1 Publication
VAR_063979
Natural varianti1525 – 15251A → V.2 Publications
Corresponds to variant rs1127291 [ dbSNP | Ensembl ].
VAR_021225
Natural varianti1537 – 15371A → T Could be associated with idiopathic osteoporosis; does not result in a significant alteration of Wnt signal transduction. 1 Publication
VAR_063980
Natural varianti1540 – 15401T → M.1 Publication
Corresponds to variant rs141407040 [ dbSNP | Ensembl ].
VAR_063981

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.3. 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 .
CCDSi CCDS8181.1.
PIRi JE0372.
RefSeqi NP_001278831.1. NM_001291902.1.
NP_002326.2. NM_002335.3.
UniGenei Hs.6347.

3D structure databases

ProteinModelPortali O75197.
SMRi O75197. Positions 32-1367.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 110220. 17 interactions.
DIPi DIP-47265N.
IntActi O75197. 8 interactions.
MINTi MINT-1189744.
STRINGi 9606.ENSP00000294304.

PTM databases

PhosphoSitei O75197.

Proteomic databases

MaxQBi O75197.
PaxDbi O75197.
PRIDEi O75197.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000294304 ; ENSP00000294304 ; ENSG00000162337 .
GeneIDi 4041.
KEGGi hsa:4041.
UCSCi uc001ont.3. human.

Organism-specific databases

CTDi 4041.
GeneCardsi GC11P068080.
GeneReviewsi LRP5.
HGNCi HGNC:6697. LRP5.
HPAi CAB013001.
MIMi 144750. phenotype.
166710. phenotype.
259770. phenotype.
601813. phenotype.
601884. phenotype.
603506. gene.
607634. phenotype.
607636. phenotype.
neXtProti NX_O75197.
Orphaneti 2783. 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.
PharmGKBi PA30455.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG121718.
GeneTreei ENSGT00760000118968.
HOGENOMi HOG000230697.
HOVERGENi HBG049167.
InParanoidi O75197.
KOi K03068.
OMAi LFWTCEA.
OrthoDBi EOG75XGK3.
PhylomeDBi O75197.
TreeFami TF315253.

Enzyme and pathway databases

Reactomei REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200643. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
REACT_200716. regulation of FZD by ubiquitination.
REACT_200777. TCF dependent signaling in response to WNT.
REACT_228096. misspliced LRP5 mutants have enhanced beta-catenin-dependent signaling.
REACT_228188. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinki O75197.

Miscellaneous databases

ChiTaRSi LRP5. human.
GeneWikii LRP5.
GenomeRNAii 4041.
NextBioi 15826.
PROi O75197.
SOURCEi Search...

Gene expression databases

Bgeei O75197.
CleanExi HS_LRP5.
ExpressionAtlasi O75197. baseline and differential.
Genevestigatori O75197.

Family and domain databases

Gene3Di 2.120.10.30. 4 hits.
4.10.400.10. 3 hits.
InterProi IPR011042. 6-blade_b-propeller_TolB-like.
IPR000742. EG-like_dom.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR017049. Low_density_Lipo_rcpt-rel_p5/6.
[Graphical view ]
Pfami PF00057. Ldl_recept_a. 3 hits.
PF00058. Ldl_recept_b. 13 hits.
[Graphical view ]
PIRSFi PIRSF036314. LDL_recpt-rel_p5/6. 1 hit.
PRINTSi PR00261. LDLRECEPTOR.
SMARTi SM00181. EGF. 4 hits.
SM00192. LDLa. 3 hits.
SM00135. LY. 20 hits.
[Graphical view ]
SUPFAMi SSF57424. SSF57424. 3 hits.
PROSITEi PS01209. LDLRA_1. 3 hits.
PS50068. LDLRA_2. 3 hits.
PS51120. LDLRB. 20 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and characterization of LR3, a novel LDL receptor family protein with mitogenic activity."
    Dong Y., Lathrop W., Weaver D., Qiu Q., Cini J., Bertolini D., Chen D.
    Biochem. Biophys. Res. Commun. 251:784-790(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Tissue: Osteoblast.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-1525.
    Tissue: Osteoblast.
  3. "The sequence and gene characterization of a 400-kb candidate region for IDDM4 on chromosome 11q13."
    Twells R.C.J., Metzker M.L., Brown S.D., Cox R., Garey C., Hammond H., Hey P.J., Levy E., Nakagawa Y., Philips M.S., Todd J.A., Hess J.F.
    Genomics 72:231-242(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "Low-density lipoprotein receptor-related protein 5 (LRP5) is essential for normal cholesterol metabolism and glucose-induced insulin secretion."
    Fujino T., Asaba H., Kang M.J., Ikeda Y., Sone H., Takada S., Kim D.H., Ioka R.X., Ono M., Tomoyori H., Okubo M., Murase T., Kamataki A., Yamamoto J., Magoori K., Takahashi S., Miyamoto Y., Oishi H.
    , Nose M., Okazaki M., Usui S., Imaizumi K., Yanagisawa M., Sakai J., Yamamoto T.T.
    Proc. Natl. Acad. Sci. U.S.A. 100:229-234(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-1330.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  8. "Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6."
    Semenov M.V., Tamai K., Brott B.K., Kuhl M., Sokol S., He X.
    Curr. Biol. 11:951-961(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FZD8 IN WNT-FZD-LRP5-LRP6 COMPLEX, INTERACTION WITH DKK1, FUNCTION.
  9. "Low-density lipoprotein receptor-related protein-5 binds to Axin and regulates the canonical Wnt signaling pathway."
    Mao J., Wang J., Liu B., Pan W., Farr G.H. III, Flynn C., Yuan H., Takada S., Kimelman D., Li L., Wu D.
    Mol. Cell 7:801-809(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH AXIN1.
  10. Cited for: FUNCTION, PHOSPHORYLATION, INTERACTION WITH AXIN1.
  11. "The LRP5 high-bone-mass G171V mutation disrupts LRP5 interaction with Mesd."
    Zhang Y., Wang Y., Li X., Zhang J., Mao J., Li Z., Zheng J., Li L., Harris S., Wu D.
    Mol. Cell. Biol. 24:4677-4684(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MESD, CHARACTERIZATION OF VARIANT HBM VAL-171.
  12. "Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling."
    Li X., Zhang Y., Kang H., Liu W., Liu P., Zhang J., Harris S.E., Wu D.
    J. Biol. Chem. 280:19883-19887(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DKK1 AND SOST, FUNCTION.
  13. "SOST is a ligand for LRP5/LRP6 and a Wnt signaling inhibitor."
    Semenov M., Tamai K., He X.
    J. Biol. Chem. 280:26770-26775(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH WNT1 IN THE WNT-FZD-LRP5-LRP6 COMPLEX, INTERACTION WITH SOST.
  14. "Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation."
    Swiatek W., Kang H., Garcia B.A., Shabanowitz J., Coombs G.S., Hunt D.F., Virshup D.M.
    J. Biol. Chem. 281:12233-12241(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CSNK1E.
  15. "Requirement for natively unstructured regions of mesoderm development candidate 2 in promoting low-density lipoprotein receptor-related protein 6 maturation."
    Koduri V., Blacklow S.C.
    Biochemistry 46:6570-6577(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MESD.
  16. "A cell-based Dkk1 binding assay reveals roles for extracellular domains of LRP5 in Dkk1 interaction and highlights differences between wild-type and the high bone mass mutant LRP5(G171V)."
    Murrills R.J., Matteo J.J., Bhat B.M., Coleburn V.E., Allen K.M., Chen W., Damagnez V., Bhat R.A., Bex F.J., Bodine P.V.
    J. Cell. Biochem. 108:1066-1075(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DKK1 AND MESD, CHARACTERIZATION OF VARIANT VAL-171.
  17. Cited for: INTERACTION WITH APCDD1.
  18. "LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development."
    Gong Y., Slee R.B., Fukai N., Rawadi G., Roman-Roman S., Reginato A.M., Wang H., Cundy T., Glorieux F.H., Lev D., Zacharin M., Oexle K., Marcelino J., Suwairi W., Heeger S., Sabatakos G., Apte S., Adkins W.N.
    , Allgrove J., Arslan-Kirchner M., Batch J.A., Beighton P., Black G.C., Boles R.G., Boon L.M., Borrone C., Brunner H.G., Carle G.F., Dallapiccola B., De Paepe A., Floege B., Halfhide M.L., Hall B., Hennekam R.C.M., Hirose T., Jans A., Jueppner H., Kim C.A., Keppler-Noreuil K., Kohlschuetter A., LaCombe D., Lambert M., Lemyre E., Letteboer T., Peltonen L., Ramesar R.S., Romanengo M., Somer H., Steichen-Gersdorf E., Steinmann B., Sullivan B., Superti-Furga A., Swoboda W., van den Boogaard M.-J., Van Hul W., Vikkula M., Votruba M., Zabel B., Garcia T., Baron R., Olsen B.R., Warman M.L.
    Cell 107:513-523(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS OPPG GLN-494 AND TRP-570, VARIANT MET-667.
  19. Cited for: VARIANT HBM VAL-171.
  20. "High bone density due to a mutation in LDL-receptor-related protein 5."
    Boyden L.M., Mao J., Belsky J., Mitzner L., Farhi A., Mitnick M.A., Wu D., Insogna K., Lifton R.P.
    N. Engl. J. Med. 346:1513-1521(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT HBM VAL-171, CHARACTERIZATION OF VARIANT HBM VAL-171.
  21. "Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density."
    Van Wesenbeeck L., Cleiren E., Gram J., Beals R.K., Benichou O., Scopelliti D., Key L., Renton T., Bartels C., Gong Y., Warman M.L., de Vernejoul M.-C., Bollerslev J., Van Hul W.
    Am. J. Hum. Genet. 72:763-771(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS OPTA1 TYR-111; ARG-171; THR-242 AND ILE-253, VARIANTS WENHY THR-214; VAL-214 AND THR-242, VARIANT VBCH2 THR-242, VARIANTS 18-LEU--LEU-20 DEL; LEU-20 INS; ARG-89; MET-667 AND VAL-1330.
  22. Cited for: VARIANTS EVR4 MET-173; HIS-1168 AND GLY-1361, VARIANT VAL-1525.
  23. "Polymorphisms in the low-density lipoprotein receptor-related protein 5 (LRP5) gene are associated with variation in vertebral bone mass, vertebral bone size, and stature in whites."
    Ferrari S.L., Deutsch S., Choudhury U., Chevalley T., Bonjour J.-P., Dermitzakis E.T., Rizzoli R., Antonarakis S.E.
    Am. J. Hum. Genet. 74:866-875(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS MET-667 AND VAL-1330.
  24. "Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5."
    Jiao X., Ventruto V., Trese M.T., Shastry B.S., Hejtmancik J.F.
    Am. J. Hum. Genet. 75:878-884(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS EVR4 GLN-570; GLY-752 AND LYS-1367.
  25. "LRP5, low-density-lipoprotein-receptor-related protein 5, is a determinant for bone mineral density."
    Mizuguchi T., Furuta I., Watanabe Y., Tsukamoto K., Tomita H., Tsujihata M., Ohta T., Kishino T., Matsumoto N., Minakami H., Niikawa N., Yoshiura K.
    J. Hum. Genet. 49:80-86(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS ARG-89 AND VAL-1330, FUNCTION, INVOLVEMENT IN OSTEOPOROSIS.
  26. Cited for: VARIANTS OPPG ASN-203; MET-244; PHE-307; TRP-348; GLN-353; LEU-356; LYS-390; GLU-400; ARG-404; ASN-434; LYS-460; GLN-494; VAL-520; TRP-570; ARG-610; ASN-683; HIS-733; TYR-1099; CYS-1113 AND ASP-1401, CHARACTERIZATION OF VARIANTS OPPG MET-244; LEU-356; LYS-390; ARG-404; ASN-434; VAL-520 AND ARG-610, CHARACTERIZATION OF VARIANTS EVR4 MET-173; GLN-570; HIS-1168; GLY-1361 AND LYS-1367.
  27. "Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes."
    Qin M., Hayashi H., Oshima K., Tahira T., Hayashi K., Kondo H.
    Hum. Mutat. 26:104-112(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS EVR4 PHE-145; CYS-444; THR-522; MET-535; ARG-610; CYS-617; ALA-798 AND ASP-1121, VARIANTS VAL-97 AND MET-1540.
  28. "Heterozygous mutations in the LDL receptor-related protein 5 (LRP5) gene are associated with primary osteoporosis in children."
    Hartikka H., Makitie O., Mannikko M., Doria A.S., Daneman A., Cole W.G., Ala-Kokko L., Sochett E.B.
    J. Bone Miner. Res. 20:783-789(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS PRIMARY OSTEOPOROSIS THR-29 AND GLN-1036.
  29. "Oropharyngeal skeletal disease accompanying high bone mass and novel LRP5 mutation."
    Rickels M.R., Zhang X., Mumm S., Whyte M.P.
    J. Bone Miner. Res. 20:878-885(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT HBM MET-154.
  30. Cited for: VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356 AND LEU-455, VARIANT THR-1537, CHARACTERIZATION OF VARIANTS IDIOPATHIC OSTEOPOROSIS LEU-356 AND LEU-455, CHARACTERIZATION OF VARIANT THR-1537.
  31. "A family with osteoporosis pseudoglioma syndrome due to compound heterozygosity of two novel mutations in the LRP5 gene."
    Cheung W.M.W., Jin L.Y., Smith D.K., Cheung P.T., Kwan E.Y.W., Low L., Kung A.W.C.
    Bone 39:470-476(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS OPPG ARG-478 AND CYS-504.
  32. "Reduced bone mineral density and hyaloid vasculature remnants in a consanguineous recessive FEVR family with a mutation in LRP5."
    Downey L.M., Bottomley H.M., Sheridan E., Ahmed M., Gilmour D.F., Inglehearn C.F., Reddy A., Agrawal A., Bradbury J., Toomes C.
    Br. J. Ophthalmol. 90:1163-1167(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT EVR4 ARG-550.
  33. "A novel mutation in the LRP5 gene is associated with osteoporosis-pseudoglioma syndrome."
    Barros E.R., Dias da Silva M.R., Kunii I.S., Hauache O.M., Lazaretti-Castro M.
    Osteoporos. Int. 18:1017-1018(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT OPPG ILE-531.
  34. "Osteoporosis-pseudoglioma syndrome: description of 9 new cases and beneficial response to bisphosphonates."
    Streeten E.A., McBride D., Puffenberger E., Hoffman M.E., Pollin T.I., Donnelly P., Sack P., Morton H.
    Bone 43:584-590(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT OPPG ALA-409.
  35. "A mutation in the signal sequence of LRP5 in a family with an osteoporosis-pseudoglioma syndrome (OPPG)-like phenotype indicates a novel disease mechanism for trinucleotide repeats."
    Chung B.D., Kayserili H., Ai M., Freudenberg J., Uzumcu A., Uyguner O., Bartels C.F., Honing S., Ramirez A., Hanisch F.G., Nurnberg G., Nurnberg P., Warman M.L., Wollnik B., Kubisch C., Netzer C.
    Hum. Mutat. 30:641-648(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT 15-LEU--LEU-20 DEL.
  36. Cited for: VARIANTS EVR4 ALA-511 AND TRP-805.
  37. "Overview of the mutation spectrum in familial exudative vitreoretinopathy and Norrie disease with identification of 21 novel variants in FZD4, LRP5, and NDP."
    Nikopoulos K., Venselaar H., Collin R.W.J., Riveiro-Alvarez R., Boonstra F.N., Hooymans J.M., Mukhopadhyay A., Shears D., van Bers M., de Wijs I.J., van Essen A.J., Sijmons R.H., Tilanus M.A.D., van Nouhuys C.E., Ayuso C., Hoefsloot L.H., Cremers F.P.M.
    Hum. Mutat. 31:656-666(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS EVR4 LYS-441 AND PHE-1253.
  38. "Identification of two novel LRP5 mutations in families with familial exudative vitreoretinopathy."
    Fei P., Zhang Q., Huang L., Xu Y., Zhu X., Tai Z., Gong B., Ma S., Yao Q., Li J., Zhao P., Yang Z.
    Mol. Vis. 20:395-409(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT PRO-816, VARIANTS EVR4 THR-422; PRO-540 AND MET-852, CHARACTERIZATION OF VARIANTS EVR4 THR-422; PRO-540 AND MET-852, CHARACTERIZATION OF VARIANT PRO-816.

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 26, 2014
This is version 144 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

External Data

Dasty 3