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O75581

- LRP6_HUMAN

UniProt

O75581 - LRP6_HUMAN

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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

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 homodimerization activity Source: BHF-UCL
  8. receptor binding Source: BHF-UCL
  9. toxin transporter activity Source: BHF-UCL
  10. Wnt-activated receptor activity Source: RefGenome
  11. 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
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, Receptor

Keywords - Biological processi

Endocytosis, Wnt signaling pathway

Enzyme and pathway databases

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 13701351ExtracellularSequence AnalysisAdd
BLAST
Transmembranei1371 – 139323HelicalSequence AnalysisAdd
BLAST
Topological domaini1394 – 1613220CytoplasmicSequence AnalysisAdd
BLAST

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-KW
  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
Complete GO annotation...

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...)1 Publication
Glycosylationi859 – 8591N-linked (GlcNAc...)1 Publication
Glycosylationi865 – 8651N-linked (GlcNAc...)1 Publication
Disulfide bondi893 ↔ 9041 PublicationPROSITE-ProRule annotation
Disulfide bondi900 ↔ 9141 PublicationPROSITE-ProRule annotation
Disulfide bondi916 ↔ 9291 PublicationPROSITE-ProRule annotation
Glycosylationi926 – 9261N-linked (GlcNAc...)1 Publication
Glycosylationi1039 – 10391N-linked (GlcNAc...)1 Publication
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)1 Publication
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

BgeeiO75581.
CleanExiHS_LRP6.
ExpressionAtlasiO75581. baseline and differential.
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. 28 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 – 265Combined sources
Beta strandi28 – 358Combined sources
Helixi36 – 383Combined sources
Beta strandi44 – 5916Combined sources
Helixi60 – 623Combined sources
Beta strandi64 – 696Combined sources
Turni70 – 734Combined sources
Beta strandi74 – 796Combined sources
Beta strandi82 – 843Combined sources
Beta strandi88 – 925Combined sources
Beta strandi99 – 1035Combined sources
Turni104 – 1074Combined sources
Beta strandi108 – 1136Combined sources
Turni114 – 1174Combined sources
Beta strandi118 – 1236Combined sources
Beta strandi130 – 1334Combined sources
Beta strandi138 – 1469Combined sources
Helixi147 – 1493Combined sources
Beta strandi151 – 1566Combined sources
Beta strandi158 – 1603Combined sources
Beta strandi162 – 1676Combined sources
Beta strandi174 – 1774Combined sources
Beta strandi184 – 1907Combined sources
Turni191 – 1944Combined sources
Beta strandi195 – 2006Combined sources
Turni201 – 2044Combined sources
Beta strandi205 – 2106Combined sources
Beta strandi217 – 2204Combined sources
Beta strandi227 – 2337Combined sources
Beta strandi236 – 2416Combined sources
Turni242 – 2454Combined sources
Beta strandi246 – 2516Combined sources
Turni252 – 2543Combined sources
Beta strandi259 – 2624Combined sources
Beta strandi271 – 2744Combined sources
Helixi276 – 2783Combined sources
Turni285 – 2895Combined sources
Helixi290 – 2923Combined sources
Beta strandi294 – 2996Combined sources
Beta strandi305 – 3095Combined sources
Beta strandi328 – 33710Combined sources
Beta strandi339 – 3468Combined sources
Beta strandi360 – 3689Combined sources
Turni369 – 3724Combined sources
Beta strandi373 – 3786Combined sources
Turni379 – 3824Combined sources
Beta strandi383 – 3886Combined sources
Beta strandi389 – 3913Combined sources
Beta strandi395 – 3984Combined sources
Beta strandi407 – 4115Combined sources
Turni412 – 4154Combined sources
Beta strandi416 – 4216Combined sources
Turni422 – 4254Combined sources
Beta strandi426 – 4316Combined sources
Beta strandi438 – 4414Combined sources
Beta strandi447 – 4548Combined sources
Turni455 – 4584Combined sources
Beta strandi459 – 4646Combined sources
Beta strandi466 – 4683Combined sources
Beta strandi470 – 4756Combined sources
Beta strandi482 – 4854Combined sources
Beta strandi492 – 4987Combined sources
Turni499 – 5024Combined sources
Beta strandi503 – 5086Combined sources
Turni509 – 5124Combined sources
Beta strandi513 – 5219Combined sources
Beta strandi525 – 5295Combined sources
Beta strandi538 – 5414Combined sources
Beta strandi544 – 5485Combined sources
Beta strandi555 – 5628Combined sources
Beta strandi565 – 5695Combined sources
Beta strandi575 – 58410Combined sources
Helixi591 – 5933Combined sources
Helixi595 – 5984Combined sources
Beta strandi600 – 6067Combined sources
Beta strandi609 – 6135Combined sources
Beta strandi633 – 6386Combined sources
Beta strandi641 – 6488Combined sources
Beta strandi653 – 6553Combined sources
Beta strandi664 – 6707Combined sources
Turni671 – 6744Combined sources
Beta strandi675 – 6806Combined sources
Turni681 – 6844Combined sources
Beta strandi685 – 6906Combined sources
Beta strandi697 – 7004Combined sources
Beta strandi709 – 7135Combined sources
Turni714 – 7174Combined sources
Beta strandi718 – 7236Combined sources
Turni724 – 7274Combined sources
Beta strandi728 – 7336Combined sources
Beta strandi740 – 7434Combined sources
Beta strandi750 – 7567Combined sources
Turni757 – 7604Combined sources
Beta strandi761 – 7666Combined sources
Beta strandi768 – 7703Combined sources
Beta strandi772 – 7776Combined sources
Beta strandi784 – 7874Combined sources
Beta strandi791 – 7999Combined sources
Turni800 – 8034Combined sources
Beta strandi804 – 8096Combined sources
Turni810 – 8134Combined sources
Beta strandi814 – 8196Combined sources
Beta strandi826 – 8305Combined sources
Beta strandi835 – 8417Combined sources
Beta strandi844 – 8496Combined sources
Turni850 – 8534Combined sources
Beta strandi854 – 8596Combined sources
Turni860 – 8623Combined sources
Beta strandi867 – 8704Combined sources
Beta strandi878 – 8825Combined sources
Helixi884 – 8863Combined sources
Turni892 – 8965Combined sources
Helixi897 – 8993Combined sources
Beta strandi901 – 9077Combined sources
Turni908 – 9103Combined sources
Beta strandi911 – 9155Combined sources
Beta strandi933 – 9408Combined sources
Beta strandi943 – 9475Combined sources
Beta strandi967 – 9737Combined sources
Turni974 – 9774Combined sources
Beta strandi978 – 9836Combined sources
Turni984 – 9874Combined sources
Beta strandi988 – 9936Combined sources
Beta strandi1000 – 10034Combined sources
Beta strandi1016 – 10227Combined sources
Turni1023 – 10264Combined sources
Beta strandi1027 – 10326Combined sources
Turni1033 – 10364Combined sources
Beta strandi1037 – 10426Combined sources
Beta strandi1047 – 10526Combined sources
Beta strandi1059 – 10657Combined sources
Turni1066 – 10694Combined sources
Beta strandi1070 – 10778Combined sources
Beta strandi1080 – 10878Combined sources
Beta strandi1094 – 10974Combined sources
Beta strandi1104 – 11107Combined sources
Turni1111 – 11144Combined sources
Beta strandi1115 – 11206Combined sources
Turni1121 – 11244Combined sources
Beta strandi1125 – 11306Combined sources
Beta strandi1137 – 11404Combined sources
Beta strandi1147 – 11537Combined sources
Beta strandi1156 – 11616Combined sources
Turni1162 – 11654Combined sources
Beta strandi1166 – 11716Combined sources
Beta strandi1174 – 11763Combined sources
Beta strandi1179 – 11824Combined sources
Beta strandi1188 – 11947Combined sources
Helixi1199 – 12046Combined sources
Turni1206 – 12094Combined sources
Helixi1210 – 12134Combined sources
Beta strandi1215 – 12206Combined sources
Turni1222 – 12243Combined sources
Beta strandi1226 – 12294Combined sources
Beta strandi1234 – 12363Combined sources
Beta strandi1238 – 12414Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
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.

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.
GeneTreeiENSGT00760000118968.
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

        10         20         30         40         50
MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL
60 70 80 90 100
EDAAAVDFVF SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL
110 120 130 140 150
ACDWLGEKLY WTDSETNRIE VSNLDGSLRK VLFWQELDQP RAIALDPSSG
160 170 180 190 200
FMYWTDWGEV PKIERAGMDG SSRFIIINSE IYWPNGLTLD YEEQKLYWAD
210 220 230 240 250
AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT DWSTHSILAC
260 270 280 290 300
NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS
310 320 330 340 350
PVKPFYQCAC PTGVKLLENG KTCKDGATEL LLLARRTDLR RISLDTPDFT
360 370 380 390 400
DIVLQLEDIR HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA
410 420 430 440 450
QIAHPDGIAV DWVARNLYWT DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA
460 470 480 490 500
IVLDPMVGYM YWTDWGEIPK IERAALDGSD RVVLVNTSLG WPNGLALDYD
510 520 530 540 550
EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL LGDYVYWTDW
560 570 580 590 600
QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS
610 620 630 640 650
HLCLYRPQGL RCACPIGFEL ISDMKTCIVP EAFLLFSRRA DIRRISLETN
660 670 680 690 700
NNNVAIPLTG VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV
710 720 730 740 750
EFGLDYPEGM AVDWLGKNLY WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP
760 770 780 790 800
RALALDPAEG FMYWTEWGGK PKIDRAAMDG SERTTLVPNV GRANGLTIDY
810 820 830 840 850
AKRRLYWTDL DTNLIESSNM LGLNREVIAD DLPHPFGLTQ YQDYIYWTDW
860 870 880 890 900
SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQSGW NECASSNGHC
910 920 930 940 950
SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APTTFLLFSQ KSAINRMVID
960 970 980 990 1000
EQQSPDIILP IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF
1010 1020 1030 1040 1050
TVVVSSVPSQ NLEIQPYDLS IDIYSRYIYW TCEATNVINV TRLDGRSVGV
1060 1070 1080 1090 1100
VLKGEQDRPR AVVVNPEKGY MYFTNLQERS PKIERAALDG TEREVLFFSG
1110 1120 1130 1140 1150
LSKPIALALD SRLGKLFWAD SDLRRIESSD LSGANRIVLE DSNILQPVGL
1160 1170 1180 1190 1200
TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ
1210 1220 1230 1240 1250
EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS
1260 1270 1280 1290 1300
PQQFTCFTGE IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC
1310 1320 1330 1340 1350
IDGALRCNGD ANCQDKSDEK NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD
1360 1370 1380 1390 1400
CSDKSDELDC YPTEEPAPQA TNTVGSVIGV IVTIFVSGTV YFICQRMLCP
1410 1420 1430 1440 1450
RMKGDGETMT NDYVVHGPAS VPLGYVPHPS SLSGSLPGMS RGKSMISSLS
1460 1470 1480 1490 1500
IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM
1510 1520 1530 1540 1550
EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV
1560 1570 1580 1590 1600
ATAKGYTSDL NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH
1610
LYPPPPSPCT DSS
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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:
PDBei
RCSB PDBi
PDBji
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. 28 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 GC12M012272.
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.
GeneTreei ENSGT00760000118968.
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.
REACT_228188. RNF mutants show enhanced WNT signaling and proliferation.
SignaLinki O75581.

Miscellaneous databases

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

Gene expression databases

Bgeei O75581.
CleanExi HS_LRP6.
ExpressionAtlasi O75581. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 126 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

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