UniProtKB - O75581 (LRP6_HUMAN)
Low-density lipoprotein receptor-related protein 6
LRP6
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 similarity10 PublicationsGO - Molecular functioni
- coreceptor activity involved in canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
- coreceptor activity involved in Wnt signaling pathway Source: BHF-UCL
- frizzled binding Source: BHF-UCL
- identical protein binding Source: IntAct
- kinase inhibitor activity Source: BHF-UCL
- low-density lipoprotein particle receptor activity Source: MGI
- protein homodimerization activity Source: BHF-UCL
- signaling receptor binding Source: BHF-UCL
- toxin transmembrane transporter activity Source: BHF-UCL
- Wnt-activated receptor activity Source: InterPro
- Wnt-protein binding Source: BHF-UCL
GO - Biological processi
- canonical Wnt signaling pathway Source: UniProtKB
- canonical Wnt signaling pathway involved in neural crest cell differentiation Source: BHF-UCL
- canonical Wnt signaling pathway involved in regulation of cell proliferation Source: BHF-UCL
- cell-cell adhesion Source: Ensembl
- cellular response to cholesterol Source: BHF-UCL
- chemical synaptic transmission Source: GO_Central
- dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
- midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
- negative regulation of protein kinase activity Source: BHF-UCL
- negative regulation of protein phosphorylation Source: BHF-UCL
- negative regulation of protein serine/threonine kinase activity Source: BHF-UCL
- negative regulation of smooth muscle cell apoptotic process Source: BHF-UCL
- neural crest cell differentiation Source: BHF-UCL
- neural crest formation Source: BHF-UCL
- positive regulation of cell cycle Source: BHF-UCL
- positive regulation of cytosolic calcium ion concentration Source: Ensembl
- positive regulation of DNA-binding transcription factor activity Source: BHF-UCL
- positive regulation of transcription, DNA-templated Source: BHF-UCL
- positive regulation of transcription by RNA polymerase II Source: BHF-UCL
- protein localization to plasma membrane Source: ParkinsonsUK-UCL
- receptor-mediated endocytosis involved in cholesterol transport Source: GO_Central
- response to peptide hormone Source: Ensembl
- Wnt signaling pathway Source: ParkinsonsUK-UCL
- Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation Source: ParkinsonsUK-UCL
- Wnt signaling pathway involved in somitogenesis Source: GO_Central
Keywordsi
Molecular function | Developmental protein, Receptor |
Biological process | Endocytosis, Wnt signaling pathway |
Enzyme and pathway databases
PathwayCommonsi | O75581 |
Reactomei | R-HSA-201681, TCF dependent signaling in response to WNT R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists R-HSA-4641262, Disassembly of the destruction complex and recruitment of AXIN to the membrane R-HSA-4641263, Regulation of FZD by ubiquitination R-HSA-5340588, Signaling by RNF43 mutants |
SignaLinki | O75581 |
SIGNORi | O75581 |
Names & Taxonomyi
Protein namesi | Recommended name: Low-density lipoprotein receptor-related protein 6Short name: LRP-6 |
Gene namesi | Name:LRP6 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:6698, LRP6 |
MIMi | 603507, gene |
neXtProti | NX_O75581 |
VEuPathDBi | HostDB:ENSG00000070018 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum 1 Publication
Plasma membrane
- Cell membrane 1 Publication; Single-pass type I membrane protein
Other locations
- Membrane raft 1 Publication
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
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB-SubCell
Endosome
- early endosome membrane Source: Reactome
Extracellular region or secreted
- extracellular region Source: Reactome
Plasma Membrane
- plasma membrane Source: BHF-UCL
- Wnt-Frizzled-LRP5/6 complex Source: ParkinsonsUK-UCL
Other locations
- cell surface Source: BHF-UCL
- cytoplasmic vesicle Source: UniProtKB
- integral component of membrane Source: UniProtKB-KW
- membrane raft Source: UniProtKB-SubCell
- neuronal cell body Source: Ensembl
- synapse Source: Ensembl
- Wnt signalosome Source: ParkinsonsUK-UCL
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 20 – 1370 | ExtracellularSequence analysisAdd BLAST | 1351 | |
Transmembranei | 1371 – 1393 | HelicalSequence analysisAdd BLAST | 23 | |
Topological domaini | 1394 – 1613 | CytoplasmicSequence analysisAdd BLAST | 220 |
Keywords - Cellular componenti
Cell membrane, Endoplasmic reticulum, MembranePathology & Biotechi
Involvement in diseasei
Coronary artery disease, autosomal dominant, 2 (ADCAD2)2 Publications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076208 | 360 | R → H in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs141212743EnsemblClinVar. | 1 | |
Natural variantiVAR_076209 | 433 | N → S in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs397515473EnsemblClinVar. | 1 | |
Natural variantiVAR_076210 | 473 | R → Q in ADCAD2; impairs Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397515474EnsemblClinVar. | 1 | |
Natural variantiVAR_034701 | 611 | R → C in ADCAD2; impairs Wnt signaling in vitro. 1 PublicationCorresponds to variant dbSNP:rs121918313EnsemblClinVar. | 1 |
Tooth agenesis, selective, 7 (STHAG7)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076207 | 19 | A → V in STHAG7; impairs Wnt signaling; prevents transport to plasma membrane location. 1 PublicationCorresponds to variant dbSNP:rs864309648EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 1394 | C → 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 | 1 | |
Mutagenesisi | 1399 | C → 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 | 1 | |
Mutagenesisi | 1403 | K → 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. | 1 | |
Mutagenesisi | 1420 | S → 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 | 1 | |
Mutagenesisi | 1430 | S → A: Enhanced AXIN1 binding. Further enhanced AXIN1 binding and increases beta-catenin activity by 3.3-fold; when associated with A-1420. 1 Publication | 1 | |
Mutagenesisi | 1485 | L → A: No change in the phosphorylation state of PPPSP motif. Some reduction in Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1486 | N → A: No change in the phosphorylation state of PPPSP motif. Increased Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1487 | P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1487 | P → C: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1488 | P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1489 | P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1490 | S → A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1490 | S → T: Some loss of phosphorylation of PPPSP motif A. Little reduction in Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1491 | P → A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1492 | A → G: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1493 | T → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1494 | E → A: No change in the phosphorylation state of PPPSP motif A. Little reduction of Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1495 | R → A: No change in the phosphorylation state of PPPSP motif. No reduction of Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1529 | T → A: No effect on the phosphorylation state of PPPSP motif B. 1 Publication | 1 | |
Mutagenesisi | 1530 | T → A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1531 | P → A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1572 | T → A: Abolishes Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1590 | S → A: Abolishes Wnt/beta-catenin signaling. 1 Publication | 1 | |
Mutagenesisi | 1607 | S → A: Abolishes Wnt/beta-catenin signaling. 1 Publication | 1 |
Keywords - Diseasei
Disease variantOrganism-specific databases
DisGeNETi | 4040 |
MalaCardsi | LRP6 |
MIMi | 610947, phenotype 616724, phenotype |
OpenTargetsi | ENSG00000070018 |
Orphaneti | 411969, NON RARE IN EUROPE: Metabolic syndrome 99798, Oligodontia |
PharmGKBi | PA30456 |
Miscellaneous databases
Pharosi | O75581, Tbio |
Chemistry databases
ChEMBLi | CHEMBL3745588 |
Genetic variation databases
BioMutai | LRP6 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 19 | Sequence analysisAdd BLAST | 19 | |
ChainiPRO_0000017330 | 20 – 1613 | Low-density lipoprotein receptor-related protein 6Add BLAST | 1594 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 42 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 81 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 281 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 286 ↔ 297 | PROSITE-ProRule annotation | ||
Disulfide bondi | 293 ↔ 308 | PROSITE-ProRule annotation | ||
Disulfide bondi | 310 ↔ 323 | PROSITE-ProRule annotation | ||
Glycosylationi | 433 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 486 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 592 ↔ 603 | PROSITE-ProRule annotation | ||
Disulfide bondi | 599 ↔ 612 | PROSITE-ProRule annotation | ||
Disulfide bondi | 614 ↔ 627 | PROSITE-ProRule annotation | ||
Glycosylationi | 692 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 859 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 865 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 893 ↔ 904 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 900 ↔ 914 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 916 ↔ 929 | PROSITE-ProRule annotation1 Publication | ||
Glycosylationi | 926 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 1039 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Disulfide bondi | 1207 ↔ 1218 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 1214 ↔ 1228 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 1230 ↔ 1243 | PROSITE-ProRule annotation1 Publication | ||
Disulfide bondi | 1249 ↔ 1263 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1256 ↔ 1276 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1270 ↔ 1285 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1288 ↔ 1300 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1295 ↔ 1313 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1307 ↔ 1322 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1326 ↔ 1338 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1333 ↔ 1351 | PROSITE-ProRule annotation | ||
Disulfide bondi | 1345 ↔ 1360 | PROSITE-ProRule annotation | ||
Lipidationi | 1394 | S-palmitoyl cysteine1 Publication | 1 | |
Lipidationi | 1399 | S-palmitoyl cysteine1 Publication | 1 | |
Cross-linki | 1403 | Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication | ||
Modified residuei | 1420 | Phosphoserine; by CK11 Publication | 1 | |
Modified residuei | 1430 | Phosphoserine; by CK11 Publication | 1 | |
Modified residuei | 1479 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 1490 | Phosphoserine; by CDK14, GRK5 and GRK6Combined sources7 Publications | 1 | |
Modified residuei | 1493 | Phosphothreonine; by CK11 Publication | 1 |
Post-translational modificationi
Keywords - PTMi
Disulfide bond, Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugationProteomic databases
EPDi | O75581 |
jPOSTi | O75581 |
MassIVEi | O75581 |
MaxQBi | O75581 |
PaxDbi | O75581 |
PeptideAtlasi | O75581 |
PRIDEi | O75581 |
ProteomicsDBi | 50097 |
PTM databases
GlyGeni | O75581, 12 sites |
iPTMneti | O75581 |
PhosphoSitePlusi | O75581 |
SwissPalmi | O75581 |
Expressioni
Tissue specificityi
Inductioni
Gene expression databases
Bgeei | ENSG00000070018, Expressed in metanephros and 246 other tissues |
ExpressionAtlasi | O75581, baseline and differential |
Genevisiblei | O75581, HS |
Organism-specific databases
HPAi | ENSG00000070018, Low tissue specificity |
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.
Interacts with CAPRIN2; the interaction promotes LRP6 phosphorylation at Ser-1490 (PubMed:18762581, PubMed:25331957).
Found in a complex with CAPRIN2, CCNY and CDK14 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus (PubMed:27821587).
Interacts with LYPD6 (PubMed:23987510).
Forms a ternary complex with DKK1 and KREM1 (PubMed:27524201).
Interacts with KREM1 in a DKK1-dependent manner (PubMed:17804805).
Interacts with MDK: this interaction is calcium dependent (By similarity).
Interacts with LMBR1L (PubMed:31073040).
By similarity1 Publication21 PublicationsBinary interactionsi
O75581
GO - Molecular functioni
- frizzled binding Source: BHF-UCL
- identical protein binding Source: IntAct
- protein homodimerization activity Source: BHF-UCL
- signaling receptor binding Source: BHF-UCL
- Wnt-protein binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 110219, 120 interactors |
CORUMi | O75581 |
DIPi | DIP-29884N |
IntActi | O75581, 60 interactors |
MINTi | O75581 |
STRINGi | 9606.ENSP00000261349 |
Chemistry databases
BindingDBi | O75581 |
Miscellaneous databases
RNActi | O75581, protein |
Structurei
Secondary structure
3D structure databases
SMRi | O75581 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O75581 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Repeati | 63 – 106 | LDL-receptor class B 1Add BLAST | 44 | |
Repeati | 107 – 149 | LDL-receptor class B 2Add BLAST | 43 | |
Repeati | 150 – 193 | LDL-receptor class B 3Add BLAST | 44 | |
Repeati | 194 – 236 | LDL-receptor class B 4Add BLAST | 43 | |
Repeati | 237 – 276 | LDL-receptor class B 5Add BLAST | 40 | |
Domaini | 282 – 324 | EGF-like 1Add BLAST | 43 | |
Repeati | 372 – 414 | LDL-receptor class B 6Add BLAST | 43 | |
Repeati | 415 – 457 | LDL-receptor class B 7Add BLAST | 43 | |
Repeati | 458 – 501 | LDL-receptor class B 8Add BLAST | 44 | |
Repeati | 502 – 542 | LDL-receptor class B 9Add BLAST | 41 | |
Repeati | 543 – 584 | LDL-receptor class B 10Add BLAST | 42 | |
Domaini | 588 – 628 | EGF-like 2Add BLAST | 41 | |
Repeati | 674 – 716 | LDL-receptor class B 11Add BLAST | 43 | |
Repeati | 717 – 759 | LDL-receptor class B 12Add BLAST | 43 | |
Repeati | 760 – 802 | LDL-receptor class B 13Add BLAST | 43 | |
Repeati | 803 – 842 | LDL-receptor class B 14Add BLAST | 40 | |
Repeati | 843 – 885 | LDL-receptor class B 15Add BLAST | 43 | |
Domaini | 889 – 930 | EGF-like 3Add BLAST | 42 | |
Repeati | 977 – 1025 | LDL-receptor class B 16Add BLAST | 49 | |
Repeati | 1026 – 1068 | LDL-receptor class B 17Add BLAST | 43 | |
Repeati | 1069 – 1113 | LDL-receptor class B 18Add BLAST | 45 | |
Repeati | 1114 – 1156 | LDL-receptor class B 19Add BLAST | 43 | |
Repeati | 1157 – 1198 | LDL-receptor class B 20Add BLAST | 42 | |
Domaini | 1203 – 1244 | EGF-like 4Add BLAST | 42 | |
Domaini | 1248 – 1286 | LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST | 39 | |
Domaini | 1287 – 1323 | LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST | 37 | |
Domaini | 1325 – 1361 | LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST | 37 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 20 – 275 | Beta-propeller 1Add BLAST | 256 | |
Regioni | 328 – 589 | Beta-propeller 2Add BLAST | 262 | |
Regioni | 631 – 890 | Beta-propeller 3Add BLAST | 260 | |
Regioni | 933 – 1202 | Beta-propeller 4Add BLAST | 270 | |
Regioni | 1556 – 1613 | DisorderedSequence analysisAdd BLAST | 58 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 1487 – 1493 | PPPSP motif A | 7 | |
Motifi | 1527 – 1534 | PPPSP motif B | 8 | |
Motifi | 1568 – 1575 | PPPSP motif C | 8 | |
Motifi | 1588 – 1593 | PPPSP motif D | 6 | |
Motifi | 1603 – 1610 | PPPSP motif E | 8 |
Domaini
Sequence similaritiesi
Keywords - Domaini
EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG1215, Eukaryota |
GeneTreei | ENSGT00940000158990 |
InParanoidi | O75581 |
OMAi | TGVNPCK |
OrthoDBi | 121310at2759 |
PhylomeDBi | O75581 |
TreeFami | TF315253 |
Family and domain databases
CDDi | cd00112, LDLa, 3 hits |
Gene3Di | 2.120.10.30, 4 hits 4.10.400.10, 3 hits |
IDEALi | IID00531 |
InterProi | View protein in InterPro IPR011042, 6-blade_b-propeller_TolB-like IPR000742, EGF-like_dom IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR000033, LDLR_classB_rpt IPR002172, LDrepeatLR_classA_rpt IPR017049, LRP5/6 |
Pfami | View protein in Pfam PF00057, Ldl_recept_a, 3 hits PF00058, Ldl_recept_b, 11 hits |
PIRSFi | PIRSF036314, LDL_recpt-rel_p5/6, 1 hit |
PRINTSi | PR00261, LDLRECEPTOR |
SMARTi | View protein in SMART SM00181, EGF, 4 hits SM00192, LDLa, 3 hits SM00135, LY, 20 hits |
SUPFAMi | SSF57424, SSF57424, 3 hits |
PROSITEi | View protein in PROSITE PS01186, EGF_2, 1 hit PS01209, LDLRA_1, 3 hits PS50068, LDLRA_2, 3 hits PS51120, LDLRB, 19 hits |
(1+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All
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
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF5H7J9 | F5H7J9_HUMAN | Low-density lipoprotein receptor-re... | LRP6 | 1,568 | Annotation score: | ||
H0YGW5 | H0YGW5_HUMAN | Low-density lipoprotein receptor-re... | LRP6 | 1,478 | Annotation score: | ||
H0YGH0 | H0YGH0_HUMAN | Low-density lipoprotein receptor-re... | LRP6 | 69 | Annotation score: | ||
F5H0Z3 | F5H0Z3_HUMAN | Low-density lipoprotein receptor-re... | LRP6 | 75 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_076207 | 19 | A → V in STHAG7; impairs Wnt signaling; prevents transport to plasma membrane location. 1 PublicationCorresponds to variant dbSNP:rs864309648EnsemblClinVar. | 1 | |
Natural variantiVAR_076208 | 360 | R → H in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs141212743EnsemblClinVar. | 1 | |
Natural variantiVAR_076209 | 433 | N → S in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs397515473EnsemblClinVar. | 1 | |
Natural variantiVAR_076210 | 473 | R → Q in ADCAD2; impairs Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397515474EnsemblClinVar. | 1 | |
Natural variantiVAR_030349 | 483 | V → I. Corresponds to variant dbSNP:rs7975614Ensembl. | 1 | |
Natural variantiVAR_034701 | 611 | R → C in ADCAD2; impairs Wnt signaling in vitro. 1 PublicationCorresponds to variant dbSNP:rs121918313EnsemblClinVar. | 1 | |
Natural variantiVAR_030350 | 817 | S → C. Corresponds to variant dbSNP:rs2302686Ensembl. | 1 | |
Natural variantiVAR_024520 | 1062 | V → I1 PublicationCorresponds to variant dbSNP:rs2302685Ensembl. | 1 | |
Natural variantiVAR_034702 | 1401 | R → H. Corresponds to variant dbSNP:rs34815107EnsemblClinVar. | 1 | |
Natural variantiVAR_083431 | 1415 | V → F Found in a patient with congenital hydrocephalus; unknown pathological significance. 1 Publication | 1 |
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_006719078.3 |
Genome annotation databases
Ensembli | ENST00000261349; ENSP00000261349; ENSG00000070018 ENST00000628182; ENSP00000486315; ENSG00000281324 |
GeneIDi | 4040 |
KEGGi | hsa:4040 |
MANE-Selecti | ENST00000261349.9; ENSP00000261349.4; NM_002336.3; NP_002327.2 |
UCSCi | uc001rah.6, human |
Similar proteinsi
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_006719078.3 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
5AIR | X-ray | 2.53 | A/B | 1565-1575 | [»] | |
5FWW | X-ray | 3.50 | A | 630-1246 | [»] | |
5GJE | electron microscopy | 21.00 | A | 20-630 | [»] | |
B | 631-1246 | [»] | ||||
6H15 | X-ray | 2.60 | A/B | 630-1244 | [»] | |
6H16 | X-ray | 2.90 | A | 630-1244 | [»] | |
6L6R | X-ray | 3.80 | A/B | 21-630 | [»] | |
SMRi | O75581 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 110219, 120 interactors |
CORUMi | O75581 |
DIPi | DIP-29884N |
IntActi | O75581, 60 interactors |
MINTi | O75581 |
STRINGi | 9606.ENSP00000261349 |
Chemistry databases
BindingDBi | O75581 |
ChEMBLi | CHEMBL3745588 |
PTM databases
GlyGeni | O75581, 12 sites |
iPTMneti | O75581 |
PhosphoSitePlusi | O75581 |
SwissPalmi | O75581 |
Genetic variation databases
BioMutai | LRP6 |
Proteomic databases
EPDi | O75581 |
jPOSTi | O75581 |
MassIVEi | O75581 |
MaxQBi | O75581 |
PaxDbi | O75581 |
PeptideAtlasi | O75581 |
PRIDEi | O75581 |
ProteomicsDBi | 50097 |
Protocols and materials databases
ABCDi | O75581, 6 sequenced antibodies |
Antibodypediai | 3851, 617 antibodies from 38 providers |
DNASUi | 4040 |
Genome annotation databases
Ensembli | ENST00000261349; ENSP00000261349; ENSG00000070018 ENST00000628182; ENSP00000486315; ENSG00000281324 |
GeneIDi | 4040 |
KEGGi | hsa:4040 |
MANE-Selecti | ENST00000261349.9; ENSP00000261349.4; NM_002336.3; NP_002327.2 |
UCSCi | uc001rah.6, human |
Organism-specific databases
CTDi | 4040 |
DisGeNETi | 4040 |
GeneCardsi | LRP6 |
HGNCi | HGNC:6698, LRP6 |
HPAi | ENSG00000070018, Low tissue specificity |
MalaCardsi | LRP6 |
MIMi | 603507, gene 610947, phenotype 616724, phenotype |
neXtProti | NX_O75581 |
OpenTargetsi | ENSG00000070018 |
Orphaneti | 411969, NON RARE IN EUROPE: Metabolic syndrome 99798, Oligodontia |
PharmGKBi | PA30456 |
VEuPathDBi | HostDB:ENSG00000070018 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1215, Eukaryota |
GeneTreei | ENSGT00940000158990 |
InParanoidi | O75581 |
OMAi | TGVNPCK |
OrthoDBi | 121310at2759 |
PhylomeDBi | O75581 |
TreeFami | TF315253 |
Enzyme and pathway databases
PathwayCommonsi | O75581 |
Reactomei | R-HSA-201681, TCF dependent signaling in response to WNT R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists R-HSA-4641262, Disassembly of the destruction complex and recruitment of AXIN to the membrane R-HSA-4641263, Regulation of FZD by ubiquitination R-HSA-5340588, Signaling by RNF43 mutants |
SignaLinki | O75581 |
SIGNORi | O75581 |
Miscellaneous databases
BioGRID-ORCSi | 4040, 9 hits in 1052 CRISPR screens |
ChiTaRSi | LRP6, human |
EvolutionaryTracei | O75581 |
GeneWikii | LRP6 |
GenomeRNAii | 4040 |
Pharosi | O75581, Tbio |
PROi | PR:O75581 |
RNActi | O75581, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000070018, Expressed in metanephros and 246 other tissues |
ExpressionAtlasi | O75581, baseline and differential |
Genevisiblei | O75581, HS |
Family and domain databases
CDDi | cd00112, LDLa, 3 hits |
Gene3Di | 2.120.10.30, 4 hits 4.10.400.10, 3 hits |
IDEALi | IID00531 |
InterProi | View protein in InterPro IPR011042, 6-blade_b-propeller_TolB-like IPR000742, EGF-like_dom IPR036055, LDL_receptor-like_sf IPR023415, LDLR_class-A_CS IPR000033, LDLR_classB_rpt IPR002172, LDrepeatLR_classA_rpt IPR017049, LRP5/6 |
Pfami | View protein in Pfam PF00057, Ldl_recept_a, 3 hits PF00058, Ldl_recept_b, 11 hits |
PIRSFi | PIRSF036314, LDL_recpt-rel_p5/6, 1 hit |
PRINTSi | PR00261, LDLRECEPTOR |
SMARTi | View protein in SMART SM00181, EGF, 4 hits SM00192, LDLa, 3 hits SM00135, LY, 20 hits |
SUPFAMi | SSF57424, SSF57424, 3 hits |
PROSITEi | View protein in PROSITE PS01186, EGF_2, 1 hit PS01209, LDLRA_1, 3 hits PS50068, LDLRA_2, 3 hits PS51120, LDLRB, 19 hits |
MobiDBi | Search... |
Entry informationi
Entry namei | LRP6_HUMAN | |
Accessioni | O75581Primary (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: | February 23, 2022 | |
This is version 191 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- Human chromosome 12
Human chromosome 12: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families