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O75197

- LRP5_HUMAN

UniProt

O75197 - LRP5_HUMAN

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
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    • History
      Entry version 142 (01 Oct 2014)
      Sequence version 2 (12 Apr 2005)
      Previous versions | rss
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    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. protein binding Source: IntAct
    3. Wnt-activated receptor activity Source: RefGenome
    4. 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

    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.
    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

    GO - Cellular componenti

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

    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.
    2788. Osteoporosis - pseudoglioma.
    178377. Osteosclerosis - developmental delay - craniosynostosis.
    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

    ArrayExpressiO75197.
    BgeeiO75197.
    CleanExiHS_LRP5.
    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. 8 interactions.
    DIPiDIP-47265N.
    IntActiO75197. 8 interactions.
    MINTiMINT-1189744.
    STRINGi9606.ENSP00000294304.

    Structurei

    3D structure databases

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

    Topological domain

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

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1385 – 140723HelicalSequence AnalysisAdd
    BLAST

    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.
    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.

    O75197-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEAAPPGPPW PLLLLLLLLL ALCGCPAPAA ASPLLLFANR RDVRLVDAGG     50
    VKLESTIVVS GLEDAAAVDF QFSKGAVYWT DVSEEAIKQT YLNQTGAAVQ 100
    NVVISGLVSP DGLACDWVGK KLYWTDSETN RIEVANLNGT SRKVLFWQDL 150
    DQPRAIALDP AHGYMYWTDW GETPRIERAG MDGSTRKIIV DSDIYWPNGL 200
    TIDLEEQKLY WADAKLSFIH RANLDGSFRQ KVVEGSLTHP FALTLSGDTL 250
    YWTDWQTRSI HACNKRTGGK RKEILSALYS PMDIQVLSQE RQPFFHTRCE 300
    EDNGGCSHLC LLSPSEPFYT CACPTGVQLQ DNGRTCKAGA EEVLLLARRT 350
    DLRRISLDTP DFTDIVLQVD DIRHAIAIDY DPLEGYVYWT DDEVRAIRRA 400
    YLDGSGAQTL VNTEINDPDG IAVDWVARNL YWTDTGTDRI EVTRLNGTSR 450
    KILVSEDLDE PRAIALHPVM GLMYWTDWGE NPKIECANLD GQERRVLVNA 500
    SLGWPNGLAL DLQEGKLYWG DAKTDKIEVI NVDGTKRRTL LEDKLPHIFG 550
    FTLLGDFIYW TDWQRRSIER VHKVKASRDV IIDQLPDLMG LKAVNVAKVV 600
    GTNPCADRNG GCSHLCFFTP HATRCGCPIG LELLSDMKTC IVPEAFLVFT 650
    SRAAIHRISL ETNNNDVAIP LTGVKEASAL DFDVSNNHIY WTDVSLKTIS 700
    RAFMNGSSVE HVVEFGLDYP EGMAVDWMGK NLYWADTGTN RIEVARLDGQ 750
    FRQVLVWRDL DNPRSLALDP TKGYIYWTEW GGKPRIVRAF MDGTNCMTLV 800
    DKVGRANDLT IDYADQRLYW TDLDTNMIES SNMLGQERVV IADDLPHPFG 850
    LTQYSDYIYW TDWNLHSIER ADKTSGRNRT LIQGHLDFVM DILVFHSSRQ 900
    DGLNDCMHNN GQCGQLCLAI PGGHRCGCAS HYTLDPSSRN CSPPTTFLLF 950
    SQKSAISRMI PDDQHSPDLI LPLHGLRNVK AIDYDPLDKF IYWVDGRQNI 1000
    KRAKDDGTQP FVLTSLSQGQ NPDRQPHDLS IDIYSRTLFW TCEATNTINV 1050
    HRLSGEAMGV VLRGDRDKPR AIVVNAERGY LYFTNMQDRA AKIERAALDG 1100
    TEREVLFTTG LIRPVALVVD NTLGKLFWVD ADLKRIESCD LSGANRLTLE 1150
    DANIVQPLGL TILGKHLYWI DRQQQMIERV EKTTGDKRTR IQGRVAHLTG 1200
    IHAVEEVSLE EFSAHPCARD NGGCSHICIA KGDGTPRCSC PVHLVLLQNL 1250
    LTCGEPPTCS PDQFACATGE IDCIPGAWRC DGFPECDDQS DEEGCPVCSA 1300
    AQFPCARGQC VDLRLRCDGE ADCQDRSDEA DCDAICLPNQ FRCASGQCVL 1350
    IKQQCDSFPD CIDGSDELMC EITKPPSDDS PAHSSAIGPV IGIILSLFVM 1400
    GGVYFVCQRV VCQRYAGANG PFPHEYVSGT PHVPLNFIAP GGSQHGPFTG 1450
    IACGKSMMSS VSLMGGRGGV PLYDRNHVTG ASSSSSSSTK ATLYPPILNP 1500
    PPSPATDPSL YNMDMFYSSN IPATARPYRP YIIRGMAPPT TPCSTDVCDS 1550
    DYSASRWKAS KYYLDLNSDS DPYPPPPTPH SQYLSAEDSC PPSPATERSY 1600
    FHLFPPPPSP CTDSS 1615
    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.
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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. 8 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.
    2788. Osteoporosis - pseudoglioma.
    178377. Osteosclerosis - developmental delay - craniosynostosis.
    90050. Retinopathy of prematurity.
    PharmGKBi PA30455.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG121718.
    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.
    SignaLinki O75197.

    Miscellaneous databases

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

    Gene expression databases

    ArrayExpressi O75197.
    Bgeei O75197.
    CleanExi HS_LRP5.
    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

    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: October 1, 2014
    This is version 142 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