Protein name:
Low-density lipoprotein receptor-related protein 6(LRP-6);
Alternative:
Organism:
Human (Homo sapiens).
General Annotation
Sub Unit:
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 C1orf187. Interacts (via beta propeller regions 3 and 4) 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.
Function:
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.
Subcellular Location:
Membrane
Single-pass type I membrane protein
Endoplasmic reticulum
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.
Protein Attributes:
50:
MGAVLRSLLA | CSFCVLLRAA | PLLLYANRRD | LRLVDATNGK | ENATIVVGGL |
100:
EDAAAVDFVF | SHGLIYWSDV | SEEAIKRTEF | NKTESVQNVV | VSGLLSPDGL |
150:
ACDWLGEKLY | WTDSETNRIE | VSNLDGSLRK | VLFWQELDQP | RAIALDPSSG |
200:
FMYWTDWGEV | PKIERAGMDG | SSRFIIINSE | IYWPNGLTLD | YEEQKLYWAD |
250:
AKLNFIHKSN | LDGTNRQAVV | KGSLPHPFAL | TLFEDILYWT | DWSTHSILAC |
300:
NKYTGEGLRE | IHSDIFSPMD | IHAFSQQRQP | NATNPCGIDN | GGCSHLCLMS |
350:
PVKPFYQCAC | PTGVKLLENG | KTCKDGATEL | LLLARRTDLR | RISLDTPDFT |
400:
DIVLQLEDIR | HAIAIDYDPV | EGYIYWTDDE | VRAIRRSFID | GSGSQFVVTA |
450:
QIAHPDGIAV | DWVARNLYWT | DTGTDRIEVT | RLNGTMRKIL | ISEDLEEPRA |
500:
IVLDPMVGYM | YWTDWGEIPK | IERAALDGSD | RVVLVNTSLG | WPNGLALDYD |
550:
EGKIYWGDAK | TDKIEVMNTD | GTGRRVLVED | KIPHIFGFTL | LGDYVYWTDW |
600:
QRRSIERVHK | RSAEREVIID | QLPDLMGLKA | TNVHRVIGSN | PCAEENGGCS |
650:
HLCLYRPQGL | RCACPIGFEL | ISDMKTCIVP | EAFLLFSRRA | DIRRISLETN |
700:
NNNVAIPLTG | VKEASALDFD | VTDNRIYWTD | ISLKTISRAF | MNGSALEHVV |
750:
EFGLDYPEGM | AVDWLGKNLY | WADTGTNRIE | VSKLDGQHRQ | VLVWKDLDSP |
800:
RALALDPAEG | FMYWTEWGGK | PKIDRAAMDG | SERTTLVPNV | GRANGLTIDY |
850:
AKRRLYWTDL | DTNLIESSNM | LGLNREVIAD | DLPHPFGLTQ | YQDYIYWTDW |
900:
SRRSIERANK | TSGQNRTIIQ | GHLDYVMDIL | VFHSSRQSGW | NECASSNGHC |
950:
SHLCLAVPVG | GFVCGCPAHY | SLNADNRTCS | APTTFLLFSQ | KSAINRMVID |
1000:
EQQSPDIILP | IHSLRNVRAI | DYDPLDKQLY | WIDSRQNMIR | KAQEDGSQGF |
1050:
TVVVSSVPSQ | NLEIQPYDLS | IDIYSRYIYW | TCEATNVINV | TRLDGRSVGV |
1100:
VLKGEQDRPR | AVVVNPEKGY | MYFTNLQERS | PKIERAALDG | TEREVLFFSG |
1150:
LSKPIALALD | SRLGKLFWAD | SDLRRIESSD | LSGANRIVLE | DSNILQPVGL |
1200:
TVFENWLYWI | DKQQQMIEKI | DMTGREGRTK | VQARIAQLSD | IHAVKELNLQ |
1250:
EYRQHPCAQD | NGGCSHICLV | KGDGTTRCSC | PMHLVLLQDE | LSCGEPPTCS |
1300:
PQQFTCFTGE | IDCIPVAWRC | DGFTECEDHS | DELNCPVCSE | SQFQCASGQC |
1350:
IDGALRCNGD | ANCQDKSDEK | NCEVLCLIDQ | FRCANGQCIG | KHKKCDHNVD |
1400:
CSDKSDELDC | YPTEEPAPQA | TNTVGSVIGV | IVTIFVSGTV | YFICQRMLCP |
1450:
RMKGDGETMT | NDYVVHGPAS | VPLGYVPHPS | SLSGSLPGMS | RGKSMISSLS |
1500:
IMGGSSGPPY | DRAHVTGASS | SSSSSTKGTY | FPAILNPPPS | PATERSHYTM |
1550:
EFGYSSNSPS | THRSYSYRPY | SYRHFAPPTT | PCSTDVCDSD | YAPSRRMTSV |
1600:
ATAKGYTSDL | NYDSEPVPPP | PTPRSQYLSA | EENYESCPPS | PYTERSYSHH |
Vaild Sequence:
Related Databases
Uniprot: