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O75581

- LRP6_HUMAN

UniProt

O75581 - LRP6_HUMAN

Protein

Low-density lipoprotein receptor-related protein 6

Gene

LRP6

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 2 (11 Jan 2011)
      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. Required for posterior patterning of the epiblast during gastrulation By similarity.By similarity

    GO - Molecular functioni

    1. apolipoprotein binding Source: RefGenome
    2. coreceptor activity involved in Wnt signaling pathway Source: BHF-UCL
    3. frizzled binding Source: BHF-UCL
    4. identical protein binding Source: IntAct
    5. kinase inhibitor activity Source: BHF-UCL
    6. low-density lipoprotein receptor activity Source: MGI
    7. protein binding Source: UniProtKB
    8. protein homodimerization activity Source: BHF-UCL
    9. receptor binding Source: BHF-UCL
    10. toxin transporter activity Source: BHF-UCL
    11. Wnt-activated receptor activity Source: RefGenome
    12. Wnt-protein binding Source: BHF-UCL

    GO - Biological processi

    1. anterior/posterior pattern specification Source: RefGenome
    2. axis elongation involved in somitogenesis Source: RefGenome
    3. bone morphogenesis Source: RefGenome
    4. bone remodeling Source: RefGenome
    5. branching involved in mammary gland duct morphogenesis Source: RefGenome
    6. canonical Wnt signaling pathway Source: UniProtKB
    7. canonical Wnt signaling pathway involved in cardiac neural crest cell differentiation involved in heart development Source: Ensembl
    8. canonical Wnt signaling pathway involved in neural crest cell differentiation Source: BHF-UCL
    9. canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation Source: Ensembl
    10. canonical Wnt signaling pathway involved in regulation of cell proliferation Source: BHF-UCL
    11. cell migration involved in gastrulation Source: Ensembl
    12. cellular response to cholesterol Source: BHF-UCL
    13. cerebellum morphogenesis Source: RefGenome
    14. cerebral cortex cell migration Source: Ensembl
    15. cerebral cortex development Source: RefGenome
    16. convergent extension Source: RefGenome
    17. dopaminergic neuron differentiation Source: Ensembl
    18. embryonic camera-type eye morphogenesis Source: RefGenome
    19. embryonic digit morphogenesis Source: Ensembl
    20. embryonic forelimb morphogenesis Source: Ensembl
    21. embryonic hindlimb morphogenesis Source: Ensembl
    22. embryonic limb morphogenesis Source: RefGenome
    23. embryonic pattern specification Source: RefGenome
    24. embryonic retina morphogenesis in camera-type eye Source: RefGenome
    25. external genitalia morphogenesis Source: RefGenome
    26. face morphogenesis Source: RefGenome
    27. forebrain radial glial cell differentiation Source: Ensembl
    28. formation of radial glial scaffolds Source: Ensembl
    29. gastrulation with mouth forming second Source: RefGenome
    30. heart looping Source: Ensembl
    31. mammary placode formation Source: Ensembl
    32. midbrain development Source: RefGenome
    33. midbrain-hindbrain boundary development Source: RefGenome
    34. negative regulation of epithelial cell proliferation Source: Ensembl
    35. negative regulation of fat cell differentiation Source: Ensembl
    36. negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis Source: Ensembl
    37. negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis Source: Ensembl
    38. negative regulation of planar cell polarity pathway involved in neural tube closure Source: Ensembl
    39. negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis Source: Ensembl
    40. negative regulation of planar cell polarity pathway involved in pericardium morphogenesis Source: Ensembl
    41. negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis Source: Ensembl
    42. negative regulation of protein kinase activity Source: BHF-UCL
    43. negative regulation of protein phosphorylation Source: BHF-UCL
    44. negative regulation of protein serine/threonine kinase activity Source: BHF-UCL
    45. negative regulation of smooth muscle cell apoptotic process Source: BHF-UCL
    46. neural crest cell differentiation Source: BHF-UCL
    47. neural crest formation Source: BHF-UCL
    48. neural tube closure Source: RefGenome
    49. odontogenesis of dentin-containing tooth Source: RefGenome
    50. palate development Source: RefGenome
    51. pericardium morphogenesis Source: RefGenome
    52. positive regulation of apoptotic process Source: Ensembl
    53. positive regulation of bone resorption Source: Ensembl
    54. positive regulation of canonical Wnt signaling pathway Source: BHF-UCL
    55. positive regulation of cell cycle Source: BHF-UCL
    56. positive regulation of cytosolic calcium ion concentration Source: Ensembl
    57. positive regulation of mesenchymal cell proliferation Source: Ensembl
    58. positive regulation of ossification Source: Ensembl
    59. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    60. positive regulation of transcription, DNA-templated Source: BHF-UCL
    61. positive regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
    62. positive regulation of Wnt signaling pathway involved in dorsal/ventral axis specification Source: BHF-UCL
    63. post-anal tail morphogenesis Source: Ensembl
    64. primitive streak formation Source: RefGenome
    65. receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport Source: RefGenome
    66. regulation of cell development Source: Ensembl
    67. regulation of fat cell differentiation Source: RefGenome
    68. regulation of ossification Source: RefGenome
    69. response to folic acid Source: Ensembl
    70. response to peptide hormone Source: Ensembl
    71. single organismal cell-cell adhesion Source: Ensembl
    72. synaptic transmission Source: RefGenome
    73. thalamus development Source: RefGenome
    74. toxin transport Source: GOC
    75. trachea cartilage morphogenesis Source: RefGenome
    76. Wnt signaling pathway Source: BHF-UCL
    77. Wnt signaling pathway involved in dorsal/ventral axis specification Source: BHF-UCL
    78. Wnt signaling pathway involved in forebrain neuroblast division Source: Ensembl
    79. Wnt signaling pathway involved in somitogenesis Source: RefGenome

    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.
    SignaLinkiO75581.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Low-density lipoprotein receptor-related protein 6
    Short name:
    LRP-6
    Gene namesi
    Name:LRP6
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:6698. LRP6.

    Subcellular locationi

    Membrane; Single-pass type I membrane protein. Endoplasmic reticulum
    Note: On Wnt signaling, undergoes a cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane location. Released from the endoplasmic reticulum on palmitoylation. Mono-ubiquitination retains it in the endoplasmic reticulum in the absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-signalsomes. Chaperoned to the plasma membrane by MESD By similarity.By similarity

    GO - Cellular componenti

    1. cell surface Source: BHF-UCL
    2. cytoplasmic vesicle Source: BHF-UCL
    3. early endosome Source: Ensembl
    4. endoplasmic reticulum Source: UniProtKB-SubCell
    5. integral component of membrane Source: UniProtKB-KW
    6. neuronal cell body Source: RefGenome
    7. plasma membrane Source: BHF-UCL
    8. receptor complex Source: RefGenome
    9. synapse Source: RefGenome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Coronary artery disease, autosomal dominant, 2 (ADCAD2) [MIM:610947]: A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti611 – 6111R → C in ADCAD2; impairs Wnt signaling in vitro. 1 Publication
    VAR_034701

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi1394 – 13941C → A: Some reduction of palmitoylation, little change in plasma membrane location in the presence of MESD nor in Wnt-signaling activity. Completely abolishes palmitoylation, no plasma membrane location, greatly reduced Wnt-signaling activity but no effect on ubiquitination; when associated with A-1399. Exhibits full Wnt-signaling activity and no change in plasma membrane location; when associated with A-1399 and R-1403. 1 Publication
    Mutagenesisi1399 – 13991C → A: Some reduction of palmitoylation, and little change in plasma membrane location in the presence of MESD nor in Wnt-signaling activity. Completely abolishes palmitoylation, no plasma membrane location, greatly reduced Wnt-signaling activity but no effect on ubiquitination; when associated with A-1394. Exhibits full Wnt-signaling activity and no change in plasma membrane location in the in presence of MESD; when associated with A-1394 and R-1403. 1 Publication
    Mutagenesisi1403 – 14031K → R: Abolishes ubiquitination, no change in plasma membrane location in the presence of MESD but greatly reduced Wnt-signaling activity. Exhibits full Wnt-signaling activity and no change in plasma membrane location; when associated with A-1394 and A-1399.
    Mutagenesisi1420 – 14201S → A: Enhanced AXIN1 binding and increased beta-catenin activity by 2.2-fold. Further enhanced AXIN1 binding and increases beta-catenin activity by 3.3-fold; when associated with A-1430. 1 Publication
    Mutagenesisi1430 – 14301S → A: Enhanced AXIN1 binding. Further enhanced AXIN1 binding and increases beta-catenin activity by 3.3-fold; when associated with A-1420. 1 Publication
    Mutagenesisi1485 – 14851L → A: No change in the phosphorylation state of PPPSP motif. Some reduction in Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1486 – 14861N → A: No change in the phosphorylation state of PPPSP motif. Increased Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1487 – 14871P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1487 – 14871P → C: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1488 – 14881P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1489 – 14891P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1490 – 14901S → A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1490 – 14901S → T: Some loss of phosphorylation of PPPSP motif A. Little reduction in Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1491 – 14911P → A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1492 – 14921A → G: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1493 – 14931T → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1494 – 14941E → A: No change in the phosphorylation state of PPPSP motif A. Little reduction of Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1495 – 14951R → A: No change in the phosphorylation state of PPPSP motif. No reduction of Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1529 – 15291T → A: No effect on the phosphorylation state of PPPSP motif B. 1 Publication
    Mutagenesisi1530 – 15301T → A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1531 – 15311P → A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1572 – 15721T → A: Abolishes Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1590 – 15901S → A: Abolishes Wnt/beta-catenin signaling. 1 Publication
    Mutagenesisi1607 – 16071S → A: Abolishes Wnt/beta-catenin signaling. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi610947. phenotype.
    Orphaneti94062. Coronary artery disease - hyperlipidemia - hypertension - diabetes - osteoporosis.
    PharmGKBiPA30456.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Sequence AnalysisAdd
    BLAST
    Chaini20 – 16131594Low-density lipoprotein receptor-related protein 6PRO_0000017330Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi81 – 811N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi281 – 2811N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi286 ↔ 297PROSITE-ProRule annotation
    Disulfide bondi293 ↔ 308PROSITE-ProRule annotation
    Disulfide bondi310 ↔ 323PROSITE-ProRule annotation
    Glycosylationi433 – 4331N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi486 – 4861N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi592 ↔ 603PROSITE-ProRule annotation
    Disulfide bondi599 ↔ 612PROSITE-ProRule annotation
    Disulfide bondi614 ↔ 627PROSITE-ProRule annotation
    Glycosylationi692 – 6921N-linked (GlcNAc...)2 Publications
    Glycosylationi859 – 8591N-linked (GlcNAc...)2 Publications
    Glycosylationi865 – 8651N-linked (GlcNAc...)2 Publications
    Disulfide bondi893 ↔ 9041 PublicationPROSITE-ProRule annotation
    Disulfide bondi900 ↔ 9141 PublicationPROSITE-ProRule annotation
    Disulfide bondi916 ↔ 9291 PublicationPROSITE-ProRule annotation
    Glycosylationi926 – 9261N-linked (GlcNAc...)2 Publications
    Glycosylationi1039 – 10391N-linked (GlcNAc...)2 Publications
    Disulfide bondi1207 ↔ 12181 PublicationPROSITE-ProRule annotation
    Disulfide bondi1214 ↔ 12281 PublicationPROSITE-ProRule annotation
    Disulfide bondi1230 ↔ 12431 PublicationPROSITE-ProRule annotation
    Disulfide bondi1249 ↔ 1263PROSITE-ProRule annotation
    Disulfide bondi1256 ↔ 1276PROSITE-ProRule annotation
    Disulfide bondi1270 ↔ 1285PROSITE-ProRule annotation
    Disulfide bondi1288 ↔ 1300PROSITE-ProRule annotation
    Disulfide bondi1295 ↔ 1313PROSITE-ProRule annotation
    Disulfide bondi1307 ↔ 1322PROSITE-ProRule annotation
    Disulfide bondi1326 ↔ 1338PROSITE-ProRule annotation
    Disulfide bondi1333 ↔ 1351PROSITE-ProRule annotation
    Disulfide bondi1345 ↔ 1360PROSITE-ProRule annotation
    Lipidationi1394 – 13941S-palmitoyl cysteine1 Publication
    Lipidationi1399 – 13991S-palmitoyl cysteine1 Publication
    Cross-linki1403 – 1403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Modified residuei1420 – 14201Phosphoserine; by CK11 Publication
    Modified residuei1430 – 14301Phosphoserine; by CK11 Publication
    Modified residuei1479 – 14791Phosphothreonine1 Publication
    Modified residuei1490 – 14901Phosphoserine; by CDK14, GRK5 and GRK64 Publications
    Modified residuei1493 – 14931Phosphothreonine; by CK11 Publication

    Post-translational modificationi

    Dual phosphorylation of cytoplasmic PPPSP motifs sequentially by GSK3 and CK1 is required for AXIN1-binding, and subsequent stabilization and activation of beta-catenin via preventing GSK3-mediated phosphorylation of beta-catenin. Phosphorylated, in vitro, by GRK5/6 within and outside the PPPSP motifs. Phosphorylation at Ser-1490 by CDK14 during G2/M phase leads to regulation of the Wnt signaling pathway during the cell cycle. Phosphorylation by GSK3B is induced by RPSO1 binding and inhibited by DKK1. Phosphorylated, in vitro, by casein kinase I on Thr-1479.10 Publications
    Undergoes gamma-secretase-dependent regulated intramembrane proteolysis (RIP). The extracellular domain is first released by shedding, and then, through the action of gamma-secretase, the intracellular domain (ICD) is released into the cytoplasm where it is free to bind to GSK3B and to activate canonical Wnt signaling.
    Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum.1 Publication
    Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.2 Publications
    N-glycosylation is required for cell surface location.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiO75581.
    PaxDbiO75581.
    PRIDEiO75581.

    PTM databases

    PhosphoSiteiO75581.

    Expressioni

    Tissue specificityi

    Widely coexpressed with LRP5 during embryogenesis and in adult tissues.

    Inductioni

    Decreased levels on WNT3A stimulation.1 Publication

    Gene expression databases

    ArrayExpressiO75581.
    BgeeiO75581.
    CleanExiHS_LRP6.
    GenevestigatoriO75581.

    Organism-specific databases

    HPAiCAB004490.
    HPA029925.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling. Forms a WNT-signaling complex formed of a WNT protein, a FZD protein and LRP5 or LRP6. Interacts (via the extracellular domain) with WNT1; the interaction is enhanced by prior formation of the Wnt/Fzd complex. Interacts (via the beta-propeller regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a coreceptor complex for Wnt signaling and is inhibited by DKK1 and DRAXIN. Interacts (via beta propeller region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2. Interacts with C1orf187/DRAXIN; the interaction inhibits Wnt signaling By similarity. Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface LRP6 signalsomes. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively regulating the Wnt signaling pathway By similarity. Interacts (via the extracellular domain) with RSPO1; the interaction activates Wnt/beta-catenin signaling. Interacts (via the extracellular domain) with RSPO3 (via the cysteine rich domain); the interaction activates Wnt/beta-catenin signaling. Interacts (via the beta-propeller regions 1 and 2) with SOST; the interaction competes with DKK1 for binding for inhibiting beta-catenin signaling. Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma membrane By similarity. Interacts (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin. Interacts with MACF1. Interacts with DAB2; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Interacts with TMEM198.By similarity15 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    itself2EBI-910915,EBI-910915
    AMMECR1Q9Y4X05EBI-910915,EBI-8583355
    ANTXR1Q9H6X23EBI-910915,EBI-905643
    Axin1O356252EBI-910915,EBI-2365912From a different organism.
    Axin1O7023912EBI-910915,EBI-6857773From a different organism.
    CAV1Q031353EBI-910915,EBI-603614
    DAB2P9808220EBI-910915,EBI-1171238
    DKK1O949073EBI-910915,EBI-742864
    Fzd8Q610914EBI-910915,EBI-6171689From a different organism.
    GSK3AP498402EBI-910915,EBI-1044067
    GSK3BP498414EBI-910915,EBI-373586
    LRRK2Q5S0073EBI-910915,EBI-5323863
    Mesdc1Q9ERE82EBI-910915,EBI-6985232From a different organism.
    Wnt1P044262EBI-910915,EBI-1570911From a different organism.

    Protein-protein interaction databases

    BioGridi110219. 21 interactions.
    DIPiDIP-29884N.
    IntActiO75581. 26 interactions.
    MINTiMINT-3369849.
    STRINGi9606.ENSP00000261349.

    Structurei

    Secondary structure

    1
    1613
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi22 – 265
    Beta strandi28 – 358
    Helixi36 – 383
    Beta strandi44 – 5916
    Helixi60 – 623
    Beta strandi64 – 696
    Turni70 – 734
    Beta strandi74 – 796
    Beta strandi82 – 843
    Beta strandi88 – 925
    Beta strandi99 – 1035
    Turni104 – 1074
    Beta strandi108 – 1136
    Turni114 – 1174
    Beta strandi118 – 1236
    Beta strandi130 – 1334
    Beta strandi138 – 1469
    Helixi147 – 1493
    Beta strandi151 – 1566
    Beta strandi158 – 1603
    Beta strandi162 – 1676
    Beta strandi174 – 1774
    Beta strandi184 – 1907
    Turni191 – 1944
    Beta strandi195 – 2006
    Turni201 – 2044
    Beta strandi205 – 2106
    Beta strandi217 – 2204
    Beta strandi227 – 2337
    Beta strandi236 – 2416
    Turni242 – 2454
    Beta strandi246 – 2516
    Turni252 – 2543
    Beta strandi259 – 2624
    Beta strandi271 – 2744
    Helixi276 – 2783
    Turni285 – 2895
    Helixi290 – 2923
    Beta strandi294 – 2996
    Beta strandi305 – 3095
    Beta strandi328 – 33710
    Beta strandi339 – 3468
    Beta strandi360 – 3689
    Turni369 – 3724
    Beta strandi373 – 3786
    Turni379 – 3824
    Beta strandi383 – 3886
    Beta strandi389 – 3913
    Beta strandi395 – 3984
    Beta strandi407 – 4115
    Turni412 – 4154
    Beta strandi416 – 4216
    Turni422 – 4254
    Beta strandi426 – 4316
    Beta strandi438 – 4414
    Beta strandi447 – 4548
    Turni455 – 4584
    Beta strandi459 – 4646
    Beta strandi466 – 4683
    Beta strandi470 – 4756
    Beta strandi482 – 4854
    Beta strandi492 – 4987
    Turni499 – 5024
    Beta strandi503 – 5086
    Turni509 – 5124
    Beta strandi513 – 5219
    Beta strandi525 – 5295
    Beta strandi538 – 5414
    Beta strandi544 – 5485
    Beta strandi555 – 5628
    Beta strandi565 – 5695
    Beta strandi575 – 58410
    Helixi591 – 5933
    Helixi595 – 5984
    Beta strandi600 – 6067
    Beta strandi609 – 6135
    Beta strandi633 – 6386
    Beta strandi641 – 6488
    Beta strandi653 – 6553
    Beta strandi664 – 6707
    Turni671 – 6744
    Beta strandi675 – 6806
    Turni681 – 6844
    Beta strandi685 – 6906
    Beta strandi697 – 7004
    Beta strandi709 – 7135
    Turni714 – 7174
    Beta strandi718 – 7236
    Turni724 – 7274
    Beta strandi728 – 7336
    Beta strandi740 – 7434
    Beta strandi750 – 7567
    Turni757 – 7604
    Beta strandi761 – 7666
    Beta strandi768 – 7703
    Beta strandi772 – 7776
    Beta strandi784 – 7874
    Beta strandi791 – 7999
    Turni800 – 8034
    Beta strandi804 – 8096
    Turni810 – 8134
    Beta strandi814 – 8196
    Beta strandi826 – 8305
    Beta strandi835 – 8417
    Beta strandi844 – 8496
    Turni850 – 8534
    Beta strandi854 – 8596
    Turni860 – 8623
    Beta strandi867 – 8704
    Beta strandi878 – 8825
    Helixi884 – 8863
    Turni892 – 8965
    Helixi897 – 8993
    Beta strandi901 – 9077
    Turni908 – 9103
    Beta strandi911 – 9155
    Beta strandi933 – 9408
    Beta strandi943 – 9475
    Beta strandi967 – 9737
    Turni974 – 9774
    Beta strandi978 – 9836
    Turni984 – 9874
    Beta strandi988 – 9936
    Beta strandi1000 – 10034
    Beta strandi1016 – 10227
    Turni1023 – 10264
    Beta strandi1027 – 10326
    Turni1033 – 10364
    Beta strandi1037 – 10426
    Beta strandi1047 – 10526
    Beta strandi1059 – 10657
    Turni1066 – 10694
    Beta strandi1070 – 10778
    Beta strandi1080 – 10878
    Beta strandi1094 – 10974
    Beta strandi1104 – 11107
    Turni1111 – 11144
    Beta strandi1115 – 11206
    Turni1121 – 11244
    Beta strandi1125 – 11306
    Beta strandi1137 – 11404
    Beta strandi1147 – 11537
    Beta strandi1156 – 11616
    Turni1162 – 11654
    Beta strandi1166 – 11716
    Beta strandi1174 – 11763
    Beta strandi1179 – 11824
    Beta strandi1188 – 11947
    Helixi1199 – 12046
    Turni1206 – 12094
    Helixi1210 – 12134
    Beta strandi1215 – 12206
    Turni1222 – 12243
    Beta strandi1226 – 12294
    Beta strandi1234 – 12363
    Beta strandi1238 – 12414

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    3S2KX-ray2.80A/B630-1246[»]
    3S8VX-ray3.10A/B629-1243[»]
    3S8ZX-ray2.80A629-1243[»]
    3S94X-ray2.80A/B20-630[»]
    3SOBX-ray1.90B20-335[»]
    3SOQX-ray1.90A20-326[»]
    3SOVX-ray1.27A20-326[»]
    4A0PX-ray1.90A629-1244[»]
    4DG6X-ray2.90A20-635[»]
    4NM5X-ray2.30C1568-1575[»]
    4NM7X-ray2.30C1603-1610[»]
    ProteinModelPortaliO75581.
    SMRiO75581. Positions 20-1246.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO75581.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini20 – 13701351ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1394 – 1613220CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1371 – 139323HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati63 – 10644LDL-receptor class B 1Add
    BLAST
    Repeati107 – 14943LDL-receptor class B 2Add
    BLAST
    Repeati150 – 19344LDL-receptor class B 3Add
    BLAST
    Repeati194 – 23643LDL-receptor class B 4Add
    BLAST
    Repeati237 – 27640LDL-receptor class B 5Add
    BLAST
    Domaini282 – 32443EGF-like 1Add
    BLAST
    Repeati372 – 41443LDL-receptor class B 6Add
    BLAST
    Repeati415 – 45743LDL-receptor class B 7Add
    BLAST
    Repeati458 – 50144LDL-receptor class B 8Add
    BLAST
    Repeati502 – 54241LDL-receptor class B 9Add
    BLAST
    Repeati543 – 58442LDL-receptor class B 10Add
    BLAST
    Domaini588 – 62841EGF-like 2Add
    BLAST
    Repeati674 – 71643LDL-receptor class B 11Add
    BLAST
    Repeati717 – 75943LDL-receptor class B 12Add
    BLAST
    Repeati760 – 80243LDL-receptor class B 13Add
    BLAST
    Repeati803 – 84240LDL-receptor class B 14Add
    BLAST
    Repeati843 – 88543LDL-receptor class B 15Add
    BLAST
    Domaini889 – 93042EGF-like 3Add
    BLAST
    Repeati977 – 102549LDL-receptor class B 16Add
    BLAST
    Repeati1026 – 106843LDL-receptor class B 17Add
    BLAST
    Repeati1069 – 111345LDL-receptor class B 18Add
    BLAST
    Repeati1114 – 115643LDL-receptor class B 19Add
    BLAST
    Repeati1157 – 119842LDL-receptor class B 20Add
    BLAST
    Domaini1203 – 124442EGF-like 4Add
    BLAST
    Domaini1248 – 128639LDL-receptor class A 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini1287 – 132337LDL-receptor class A 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini1325 – 136137LDL-receptor class A 3PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni20 – 275256Beta-propeller 1Add
    BLAST
    Regioni328 – 589262Beta-propeller 2Add
    BLAST
    Regioni631 – 890260Beta-propeller 3Add
    BLAST
    Regioni933 – 1202270Beta-propeller 4Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi1487 – 14937PPPSP motif A
    Motifi1527 – 15348PPPSP motif B
    Motifi1568 – 15758PPPSP motif C
    Motifi1588 – 15936PPPSP motif D
    Motifi1603 – 16108PPPSP motif E

    Domaini

    The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1.1 Publication
    The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway.1 Publication

    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.
    InParanoidiO75581.
    KOiK03068.
    OMAiLENGKTC.
    OrthoDBiEOG75XGK3.
    PhylomeDBiO75581.
    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. 12 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.
    PROSITEiPS01186. EGF_2. 1 hit.
    PS01209. LDLRA_1. 3 hits.
    PS50068. LDLRA_2. 3 hits.
    PS51120. LDLRB. 19 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

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

    O75581-1 [UniParc]FASTAAdd to Basket

    « Hide

    MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL     50
    EDAAAVDFVF SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL 100
    ACDWLGEKLY WTDSETNRIE VSNLDGSLRK VLFWQELDQP RAIALDPSSG 150
    FMYWTDWGEV PKIERAGMDG SSRFIIINSE IYWPNGLTLD YEEQKLYWAD 200
    AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT DWSTHSILAC 250
    NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 300
    PVKPFYQCAC PTGVKLLENG KTCKDGATEL LLLARRTDLR RISLDTPDFT 350
    DIVLQLEDIR HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA 400
    QIAHPDGIAV DWVARNLYWT DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA 450
    IVLDPMVGYM YWTDWGEIPK IERAALDGSD RVVLVNTSLG WPNGLALDYD 500
    EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL LGDYVYWTDW 550
    QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS 600
    HLCLYRPQGL RCACPIGFEL ISDMKTCIVP EAFLLFSRRA DIRRISLETN 650
    NNNVAIPLTG VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV 700
    EFGLDYPEGM AVDWLGKNLY WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP 750
    RALALDPAEG FMYWTEWGGK PKIDRAAMDG SERTTLVPNV GRANGLTIDY 800
    AKRRLYWTDL DTNLIESSNM LGLNREVIAD DLPHPFGLTQ YQDYIYWTDW 850
    SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQSGW NECASSNGHC 900
    SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APTTFLLFSQ KSAINRMVID 950
    EQQSPDIILP IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF 1000
    TVVVSSVPSQ NLEIQPYDLS IDIYSRYIYW TCEATNVINV TRLDGRSVGV 1050
    VLKGEQDRPR AVVVNPEKGY MYFTNLQERS PKIERAALDG TEREVLFFSG 1100
    LSKPIALALD SRLGKLFWAD SDLRRIESSD LSGANRIVLE DSNILQPVGL 1150
    TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ 1200
    EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS 1250
    PQQFTCFTGE IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC 1300
    IDGALRCNGD ANCQDKSDEK NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD 1350
    CSDKSDELDC YPTEEPAPQA TNTVGSVIGV IVTIFVSGTV YFICQRMLCP 1400
    RMKGDGETMT NDYVVHGPAS VPLGYVPHPS SLSGSLPGMS RGKSMISSLS 1450
    IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM 1500
    EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV 1550
    ATAKGYTSDL NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH 1600
    LYPPPPSPCT DSS 1613
    Length:1,613
    Mass (Da):180,429
    Last modified:January 11, 2011 - v2
    Checksum:i413D2CF70A5D8B5C
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti483 – 4831V → I.
    Corresponds to variant rs7975614 [ dbSNP | Ensembl ].
    VAR_030349
    Natural varianti611 – 6111R → C in ADCAD2; impairs Wnt signaling in vitro. 1 Publication
    VAR_034701
    Natural varianti817 – 8171S → C.
    Corresponds to variant rs2302686 [ dbSNP | Ensembl ].
    VAR_030350
    Natural varianti1062 – 10621V → I.1 Publication
    Corresponds to variant rs2302685 [ dbSNP | Ensembl ].
    VAR_024520
    Natural varianti1401 – 14011R → H.
    Corresponds to variant rs34815107 [ dbSNP | Ensembl ].
    VAR_034702

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF074264 mRNA. Translation: AAC33006.1.
    AC007537 Genomic DNA. No translation available.
    AC007621 Genomic DNA. No translation available.
    BC117136 mRNA. Translation: AAI17137.1.
    BC126405 mRNA. Translation: AAI26406.1.
    CCDSiCCDS8647.1.
    PIRiJE0272.
    RefSeqiNP_002327.2. NM_002336.2.
    XP_006719141.1. XM_006719078.1.
    UniGeneiHs.584775.
    Hs.658913.

    Genome annotation databases

    EnsembliENST00000261349; ENSP00000261349; ENSG00000070018.
    GeneIDi4040.
    KEGGihsa:4040.
    UCSCiuc001rah.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF074264 mRNA. Translation: AAC33006.1 .
    AC007537 Genomic DNA. No translation available.
    AC007621 Genomic DNA. No translation available.
    BC117136 mRNA. Translation: AAI17137.1 .
    BC126405 mRNA. Translation: AAI26406.1 .
    CCDSi CCDS8647.1.
    PIRi JE0272.
    RefSeqi NP_002327.2. NM_002336.2.
    XP_006719141.1. XM_006719078.1.
    UniGenei Hs.584775.
    Hs.658913.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    3S2K X-ray 2.80 A/B 630-1246 [» ]
    3S8V X-ray 3.10 A/B 629-1243 [» ]
    3S8Z X-ray 2.80 A 629-1243 [» ]
    3S94 X-ray 2.80 A/B 20-630 [» ]
    3SOB X-ray 1.90 B 20-335 [» ]
    3SOQ X-ray 1.90 A 20-326 [» ]
    3SOV X-ray 1.27 A 20-326 [» ]
    4A0P X-ray 1.90 A 629-1244 [» ]
    4DG6 X-ray 2.90 A 20-635 [» ]
    4NM5 X-ray 2.30 C 1568-1575 [» ]
    4NM7 X-ray 2.30 C 1603-1610 [» ]
    ProteinModelPortali O75581.
    SMRi O75581. Positions 20-1246.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110219. 21 interactions.
    DIPi DIP-29884N.
    IntActi O75581. 26 interactions.
    MINTi MINT-3369849.
    STRINGi 9606.ENSP00000261349.

    PTM databases

    PhosphoSitei O75581.

    Proteomic databases

    MaxQBi O75581.
    PaxDbi O75581.
    PRIDEi O75581.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000261349 ; ENSP00000261349 ; ENSG00000070018 .
    GeneIDi 4040.
    KEGGi hsa:4040.
    UCSCi uc001rah.4. human.

    Organism-specific databases

    CTDi 4040.
    GeneCardsi GC12M012173.
    H-InvDB HIX0036693.
    HGNCi HGNC:6698. LRP6.
    HPAi CAB004490.
    HPA029925.
    MIMi 603507. gene.
    610947. phenotype.
    neXtProti NX_O75581.
    Orphaneti 94062. Coronary artery disease - hyperlipidemia - hypertension - diabetes - osteoporosis.
    PharmGKBi PA30456.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG121718.
    HOGENOMi HOG000230697.
    HOVERGENi HBG049167.
    InParanoidi O75581.
    KOi K03068.
    OMAi LENGKTC.
    OrthoDBi EOG75XGK3.
    PhylomeDBi O75581.
    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 O75581.

    Miscellaneous databases

    EvolutionaryTracei O75581.
    GeneWikii LRP6.
    GenomeRNAii 4040.
    NextBioi 15822.
    PROi O75581.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O75581.
    Bgeei O75581.
    CleanExi HS_LRP6.
    Genevestigatori O75581.

    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. 12 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 PS01186. EGF_2. 1 hit.
    PS01209. LDLRA_1. 3 hits.
    PS50068. LDLRA_2. 3 hits.
    PS51120. LDLRB. 19 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family."
      Brown S.D., Twells R.C., Hey P.J., Cox R.D., Levy E.R., Soderman A.R., Metzker M.L., Caskey C.T., Todd J.A., Hess J.F.
      Biochem. Biophys. Res. Commun. 248:879-888(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-1062.
      Tissue: Kidney.
    2. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "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].
      Tissue: Cerebellum.
    4. "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 DKK1, FUNCTION.
    5. "LDL-receptor-related protein 6 is a receptor for Dickkopf proteins."
      Mao B., Wu W., Li Y., Hoppe D., Stannek P., Glinka A., Niehrs C.
      Nature 411:321-325(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH WNT1, FUNCTION.
    6. "Functional characterization of WNT7A signaling in PC12 cells: interaction with A FZD5 x LRP6 receptor complex and modulation by Dickkopf proteins."
      Caricasole A., Ferraro T., Iacovelli L., Barletta E., Caruso A., Melchiorri D., Terstappen G.C., Nicoletti F.
      J. Biol. Chem. 278:37024-37031(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FZD5; DKK1 AND DKK2.
    7. "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 SOST, FUNCTION.
    8. "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.
    9. "A dual-kinase mechanism for Wnt co-receptor phosphorylation and activation."
      Zeng X., Tamai K., Doble B., Li S., Huang H., Habas R., Okamura H., Woodgett J., He X.
      Nature 438:873-877(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION OF PPPSP MOTIFS, PHOSPHORYLATION AT SER-1490 AND THR-1493, FUNCTION.
    10. "The role of microtubule actin cross-linking factor 1 (MACF1) in the Wnt signaling pathway."
      Chen H.J., Lin C.M., Lin C.S., Perez-Olle R., Leung C.L., Liem R.K.
      Genes Dev. 20:1933-1945(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MACF1.
    11. "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: PHOSPHORYLATION AT SER-1420 AND SER-1430, FUNCTION, INTERACTION WITH CSNKIE AND AXIN1, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF SER-1420 AND SER-1430.
    12. "R-spondin1 is a high affinity ligand for LRP6 and induces LRP6 phosphorylation and beta-catenin signaling."
      Wei Q., Yokota C., Semenov M.V., Doble B., Woodgett J., He X.
      J. Biol. Chem. 282:15903-15911(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RSPO1, FUNCTION, PHOSPHORYLATION.
    13. "Regulated proteolytic processing of LRP6 results in release of its intracellular domain."
      Mi K., Johnson G.V.
      J. Neurochem. 101:517-529(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING, FUNCTION.
    14. "Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor."
      Khan Z., Vijayakumar S., de la Torre T.V., Rotolo S., Bafico A.
      Mol. Cell. Biol. 27:7291-7301(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION, PHOSPHORYLATION AT SER-1490, INTERACTION WITH AXIN1, HOMODIMERIZATION, INDUCTION, SUBCELLULAR LOCATION.
    15. "Wnt induces LRP6 signalosomes and promotes dishevelled-dependent LRP6 phosphorylation."
      Bilic J., Huang Y.L., Davidson G., Zimmermann T., Cruciat C.M., Bienz M., Niehrs C.
      Science 316:1619-1622(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT THR-1479, INTERACTION WITH AXIN1, SUBUNIT, SUBCELLULAR LOCATION.
    16. "Wnt signal amplification via activity, cooperativity, and regulation of multiple intracellular PPPSP motifs in the Wnt co-receptor LRP6."
      MacDonald B.T., Yokota C., Tamai K., Zeng X., He X.
      J. Biol. Chem. 283:16115-16123(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH AXIN1, PHOSPHORYLATION, MUTAGENESIS OF LEU-1485; ASN-1486; PRO-1487; PRO-1488; PRO-1489; SER-1490; PRO-1491; ALA-1492; THR-1493; GLU-1494; ARG-1495; THR-1529; THR-1530; PRO-1531; THR-1572; SER-1590 AND SER-1607.
    17. "Direct inhibition of GSK3beta by the phosphorylated cytoplasmic domain of LRP6 in Wnt/beta-catenin signaling."
      Piao S., Lee S.H., Kim H., Yum S., Stamos J.L., Xu Y., Lee S.J., Lee J., Oh S., Han J.K., Park B.J., Weis W.I., Ha N.C.
      PLoS ONE 3:E4046-E4046(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION ON PPPSP MOTIFS, FUNCTION.
    18. "Palmitoylation and ubiquitination regulate exit of the Wnt signaling protein LRP6 from the endoplasmic reticulum."
      Abrami L., Kunz B., Iacovache I., van der Goot F.G.
      Proc. Natl. Acad. Sci. U.S.A. 105:5384-5389(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PALMITOYLATION AT CYS-1394 AND CYS-1399, UBIQUITINATION AT LYS-1403, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-1394 AND CYS-1399.
    19. Cited for: DOMAIN PPPSP MOTIF, PHOSPHORYLATION AT SER-1490.
    20. "G Protein-coupled receptor kinases phosphorylate LRP6 in the Wnt pathway."
      Chen M., Philipp M., Wang J., Premont R.T., Garrison T.R., Caron M.G., Lefkowitz R.J., Chen W.
      J. Biol. Chem. 284:35040-35048(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION OF PPPSP MOTIFS, PHOSPHORYLATION AT SER-1490, FUNCTION.
    21. "Inhibition of GSK3 phosphorylation of beta-catenin via phosphorylated PPPSPXS motifs of Wnt coreceptor LRP6."
      Wu G., Huang H., Garcia Abreu J., He X.
      PLoS ONE 4:E4926-E4926(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION OF PPPSP MOTIFS, FUNCTION.
    22. "Reconstitution of a frizzled8.Wnt3a.LRP6 signaling complex reveals multiple Wnt and Dkk1 binding sites on LRP6."
      Bourhis E., Tam C., Franke Y., Bazan J.F., Ernst J., Hwang J., Costa M., Cochran A.G., Hannoush R.N.
      J. Biol. Chem. 285:9172-9179(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH WNT3A; WNT9B AND FZD8 IN THE WNT/FZD/LRP6 COMPLEX, INTERACTION WITH DKK1.
    23. "Transmembrane protein 198 promotes LRP6 phosphorylation and Wnt signaling activation."
      Liang J., Fu Y., Cruciat C.M., Jia S., Wang Y., Tong Z., Tao Q., Ingelfinger D., Boutros M., Meng A., Niehrs C., Wu W.
      Mol. Cell. Biol. 31:2577-2590(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TMEM198.
    24. "Disabled-2 (Dab2) inhibits Wnt/beta-catenin signalling by binding LRP6 and promoting its internalization through clathrin."
      Jiang Y., He X., Howe P.H.
      EMBO J. 31:2336-2349(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DAB2.
    25. Cited for: UBIQUITINATION BY ZNRF3.
    26. "Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6."
      Ahn V.E., Chu M.L., Choi H.J., Tran D., Abo A., Weis W.I.
      Dev. Cell 21:862-873(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 630-1246 IN COMPLEX WITH DKK1, SUBUNIT, DISULFIDE BONDS, GLYCOSYLATION AT ASN-692; ASN-859; ASN-865; ASN-926 AND ASN-1039.
    27. "LRP6 mutation in a family with early coronary disease and metabolic risk factors."
      Mani A., Radhakrishnan J., Wang H., Mani A., Mani M.-A., Nelson-Williams C., Carew K.S., Mane S., Najmabadi H., Wu D., Lifton R.P.
      Science 315:1278-1282(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT ADCAD2 CYS-611, CHARACTERIZATION OF VARIANT ADCAD2 CYS-611.

    Entry informationi

    Entry nameiLRP6_HUMAN
    AccessioniPrimary (citable) accession number: O75581
    Secondary accession number(s): Q17RZ2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 10, 2004
    Last sequence update: January 11, 2011
    Last modified: October 1, 2014
    This is version 124 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3