LRP6
entrez
4040
canonical
uniprot
O75581
canonical
ensembl
ENSG00000070018
resolver
ensembl
ENSG00000281324
resolver
ensp
ENSP00000261349
resolver
ensp
ENSP00000442472
resolver
ensp
ENSP00000486315
resolver
ensp
ENSP00000486524
resolver
ensp
ENSP00000534706
resolver
ensp
ENSP00000534708
resolver
ensp
ENSP00000610270
resolver
ensp
ENSP00000610271
resolver
enst
ENST00000261349
resolver
enst
ENST00000543091
resolver
enst
ENST00000626698
resolver
enst
ENST00000628182
resolver
enst
ENST00000940211
resolver
genesymbol
LRP6
resolver
hgnc
HGNC:6698
resolver
uniprot
F5H7J9
resolver
uniprot
Q17RZ2
resolver
uniprot_entry
F5H7J9_HUMAN
resolver
uniprot_entry
LRP6_HUMAN
resolver
uniprot_sec
Q17RZ2
resolver
amino_acid_sequence
MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGEIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDLNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS
uniprot
proteins
disease_involvement
DISEASE: 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. {ECO:0000269|PubMed:17332414, ECO:0000269|PubMed:23703864}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Tooth agenesis, selective, 7 (STHAG7) [MIM:616724]: An autosomal dominant form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth). {ECO:0000269|PubMed:26387593, ECO:0000269|PubMed:33164649}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Vitreoretinopathy, exudative 8 (EVR8) [MIM:621268]: An autosomal dominant form of exudative vitreoretinopathy, a disorder of the retinal vasculature characterized by an abrupt cessation of growth of peripheral capillaries, leading to an avascular peripheral retina. This may lead to compensatory retinal neovascularization, which is thought to be induced by hypoxia from the initial avascular insult. New vessels are prone to leakage and rupture causing exudates and bleeding, followed by scarring, retinal detachment and blindness. Clinical features can be highly variable, even within the same family. Patients with mild forms of the disease are asymptomatic, and their only disease related abnormality is an arc of avascular retina in the extreme temporal periphery. {ECO:0000269|PubMed:34896607}. Note=The disease may be caused by variants affecting the gene represented in this entry.; DISEASE: Osteopetrosis, autosomal dominant 4 (OPTA4) [MIM:621449]: An autosomal dominant disorder characterized by generalized osteosclerosis and endosteal hyperostosis, due to enhanced osteoblast-mediated bone formation. Affected individuals are taller than average, report a resistance to bone fractures, and present with missing teeth, torus palatinus, and intraoral exostoses. {ECO:0000269|PubMed:31085352, ECO:0000269|PubMed:32730923, ECO:0000269|PubMed:37065631, ECO:0000269|PubMed:38385987}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers beta-catenin signaling through inducing aggregation of receptor-ligand complexes into ribosome-sized signalosomes (PubMed:11357136, PubMed:11448771, PubMed:15778503, PubMed:16341017, PubMed:16513652, PubMed:17326769, PubMed:17400545, PubMed:19107203, PubMed:19293931, PubMed:19801552, PubMed:28341812, PubMed:34896607). Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in various processes including retinal angiogenesis and bone formation (PubMed:11357136, PubMed:11448771, PubMed:15778503, PubMed:16341017, PubMed:16513652, PubMed:17326769, PubMed:17400545, PubMed:19107203, PubMed:19293931, PubMed:19801552, PubMed:28341812, PubMed:34896607). 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 signalosomes and inhibiting AXIN1/GSK3-mediated phosphorylation and destruction of beta-catenin (PubMed:16513652). Required for posterior patterning of the epiblast during gastrulation (By similarity). {ECO:0000250|UniProtKB:O88572, ECO:0000269|PubMed:11357136, ECO:0000269|PubMed:11448771, ECO:0000269|PubMed:15778503, ECO:0000269|PubMed:16341017, ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17326769, ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:19107203, ECO:0000269|PubMed:19293931, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:28341812, ECO:0000269|PubMed:34896607}.
uniprot
proteins
mass_dalton
180429
uniprot
proteins
mutagenesis
MUTAGEN 1394; /note="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."; /evidence="ECO:0000269|PubMed:18378904"; MUTAGEN 1399; /note="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."; /evidence="ECO:0000269|PubMed:18378904"; MUTAGEN 1403; /note="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."; /evidence="ECO:0000269|PubMed:18378904"; MUTAGEN 1420; /note="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."; /evidence="ECO:0000269|PubMed:16513652"; MUTAGEN 1430; /note="S->A: Enhanced AXIN1 binding. Further enhanced AXIN1 binding and increases beta-catenin activity by 3.3-fold; when associated with A-1420."; /evidence="ECO:0000269|PubMed:16513652"; MUTAGEN 1485; /note="L->A: No change in the phosphorylation state of PPPSP motif. Some reduction in Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1486; /note="N->A: No change in the phosphorylation state of PPPSP motif. Increased Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1487; /note="P->A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1487; /note="P->C: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1488; /note="P->A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1489; /note="P->A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1490; /note="S->A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1490; /note="S->T: Some loss of phosphorylation of PPPSP motif A. Little reduction in Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1491; /note="P->A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1492; /note="A->G: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1493; /note="T->A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1494; /note="E->A: No change in the phosphorylation state of PPPSP motif A. Little reduction of Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1495; /note="R->A: No change in the phosphorylation state of PPPSP motif. No reduction of Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1529; /note="T->A: No effect on the phosphorylation state of PPPSP motif B."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1530; /note="T->A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1531; /note="P->A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1572; /note="T->A: Abolishes Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1590; /note="S->A: Abolishes Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152"; MUTAGEN 1607; /note="S->A: Abolishes Wnt/beta-catenin signaling."; /evidence="ECO:0000269|PubMed:18362152
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000269|PubMed:16341017, ECO:0000269|PubMed:16513652, ECO:0000269|PubMed:17400545, ECO:0000269|PubMed:17569865, ECO:0000269|PubMed:17698587, ECO:0000269|PubMed:18362152, ECO:0000269|PubMed:19107203, ECO:0000269|PubMed:19293931, ECO:0000269|PubMed:19801552, ECO:0000269|PubMed:20059949}.; PTM: 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.; PTM: Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum. {ECO:0000269|PubMed:18378904}.; PTM: Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome. {ECO:0000269|PubMed:18378904, ECO:0000269|PubMed:22575959}.; PTM: N-glycosylation is required for cell surface location. {ECO:0000269|PubMed:17698587, ECO:0000269|PubMed:21375506, ECO:0000269|PubMed:22000856}.
uniprot
proteins
protein_family
LDLR family
uniprot
proteins
pubmed
11357136
uniprot
proteins
pubmed
11448771
uniprot
proteins
pubmed
12857724
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15778503
uniprot
proteins
pubmed
15908424
uniprot
proteins
pubmed
16341017
uniprot
proteins
pubmed
16513652
uniprot
proteins
pubmed
16541075
uniprot
proteins
pubmed
16815997
uniprot
proteins
pubmed
17326769
uniprot
proteins
pubmed
17332414
uniprot
proteins
pubmed
17400545
uniprot
proteins
pubmed
17569865
uniprot
proteins
pubmed
17698587
uniprot
proteins
pubmed
17804805
uniprot
proteins
pubmed
18362152
uniprot
proteins
pubmed
18378904
uniprot
proteins
pubmed
18762581
uniprot
proteins
pubmed
19107203
uniprot
proteins
pubmed
19293931
uniprot
proteins
pubmed
19801552
uniprot
proteins
pubmed
20059949
uniprot
proteins
pubmed
20093360
uniprot
proteins
pubmed
21375506
uniprot
proteins
pubmed
21536646
uniprot
proteins
pubmed
22000856
uniprot
proteins
pubmed
22491013
uniprot
proteins
pubmed
22575959
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23572575
uniprot
proteins
pubmed
23703864
uniprot
proteins
pubmed
23987510
uniprot
proteins
pubmed
25331957
uniprot
proteins
pubmed
26387593
uniprot
proteins
pubmed
27524201
uniprot
proteins
pubmed
27821587
uniprot
proteins
pubmed
28341812
uniprot
proteins
pubmed
29983323
uniprot
proteins
pubmed
30069874
uniprot
proteins
pubmed
31073040
uniprot
proteins
pubmed
31085352
uniprot
proteins
pubmed
32730923
uniprot
proteins
pubmed
33164649
uniprot
proteins
pubmed
34896607
uniprot
proteins
pubmed
37065631
uniprot
proteins
pubmed
38385987
uniprot
proteins
pubmed
38696577
uniprot
proteins
pubmed
9704021
uniprot
proteins
sequence_length
1613
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21375506, ECO:0000269|PubMed:23572575, ECO:0000269|PubMed:26387593}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum {ECO:0000269|PubMed:26387593}. Membrane raft {ECO:0000269|PubMed:23987510}. 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-signalosomes (By similarity). Chaperoned to the plasma membrane by HSP90B1 and MESD (PubMed:23572575). {ECO:0000250|UniProtKB:O88572, ECO:0000269|PubMed:23572575}.
uniprot
proteins
transmembrane_region
TRANSMEM 1371..1393; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins