Lrp6
entrez
16974
canonical
uniprot
O88572
canonical
ensembl
ENSMUSG00000030201
resolver
ensp
ENSMUSP00000032322
resolver
enst
ENSMUST00000032322
resolver
genesymbol
Lrp6
resolver
uniprot
A0A0R4J0A9
resolver
uniprot_entry
A0A0R4J0A9_MOUSE
resolver
uniprot_entry
LRP6_MOUSE
resolver
amino_acid_sequence
MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFGHGLIYWSDVSEEAIKRTEFNKSESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFVIINTEIYWPNGLTLDYQERKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDTLYWTDWNTHSILACNKYTGEGLREIHSNIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLMENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGTIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATSVHRVIGSNPCAEDNGGCSHLCLYRPQGLRCACPIGFELIGDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSDMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQAGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPSTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNSIRKAHEDGGQGFNVVANSVANQNLEIQPYDLSIDIYSRYIYWTCEATNVIDVTRLDGRSVGVVLKGEQDRPRAIVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSKLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGDIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCVGKHKKCDHSVDCSDRSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTIYFICQRMLCPRMKGDGETMTNDYVVHSPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDVNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS
uniprot
proteins
disease_involvement
DISEASE: Note=Defects in Lrp6 are the cause of Ringelschwanz (rs) phenotype. Rs phenotype is a spontaneous mutation that is characterized by a combination of multiple Wnt-deficient phenotypes including dysmorphologies of the axial skeleton, digits and the neural tube. The establishment of the anteroposterior somite compartments, the epithelialization of nascent somites, and the formation of segment borders are disturbed in (rs) mutants. There is delayed ossification at birth and a low bone mass phenotype in adults. Functional analyses reveal impaired targeting to the plasma surface due to reduced interaction with MESD leading to inhibited Wnt/beta-catenin signaling. {ECO:0000269|PubMed:15469977, ECO:0000269|PubMed:18505367}.
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. Cell-surface coreceptor of Wnt/beta-catenin signaling, which plays a pivotal role in various processes including retinal angiogenesis and bone formation (By similarity). 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 (By similarity). Required for posterior patterning of the epiblast during gastrulation (PubMed:15142971). {ECO:0000250|UniProtKB:O75581, ECO:0000269|PubMed:15142971}.
uniprot
proteins
mass_dalton
180255
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 (By similarity). {ECO:0000250}.; 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 (By similarity). {ECO:0000250}.; PTM: Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum. {ECO:0000250}.; PTM: Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome (By similarity). {ECO:0000250}.; PTM: N-glycosylation is required for cell surface location. {ECO:0000250|UniProtKB:O75581}.
uniprot
proteins
protein_family
LDLR family
uniprot
proteins
pubmed
12573468
uniprot
proteins
pubmed
12581525
uniprot
proteins
pubmed
15142971
uniprot
proteins
pubmed
15469977
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16543246
uniprot
proteins
pubmed
17376403
uniprot
proteins
pubmed
17698587
uniprot
proteins
pubmed
18505367
uniprot
proteins
pubmed
19857465
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
31073040
uniprot
proteins
pubmed
9704021
uniprot
proteins
sequence_length
1613
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12581525}; Single-pass type I membrane protein {ECO:0000255}. Endoplasmic reticulum {ECO:0000269|PubMed:12581525}. Membrane raft {ECO:0000250|UniProtKB:O75581}. 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:12581525). {ECO:0000250|UniProtKB:O75581, ECO:0000269|PubMed:12581525}.
uniprot
proteins
transmembrane_region
TRANSMEM 1371..1393; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins