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Protein Page:
LRP6 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitination
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
LRP6 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. 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 region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2. Interacts with C1orf187/DRAXIN; the interaction inhibits Wnt signaling. 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. 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. 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. Decreased levels on WNT3A stimulation. Widely co-expressed with LRP5 during embryogenesis and in adult tissues. Belongs to the LDLR family. Note: This description may include information from UniProtKB.
Protein type: Receptor, misc.; Membrane protein, integral
Cellular Component: Golgi apparatus; cell surface; cell soma; endoplasmic reticulum; early endosome; integral to membrane; plasma membrane; synapse; caveola; cytoplasmic vesicle; receptor complex
Molecular Function: low-density lipoprotein receptor activity; Wnt-protein binding; identical protein binding; protein binding; Wnt receptor activity; protein homodimerization activity; kinase inhibitor activity; frizzled binding; toxin transporter activity; apolipoprotein binding; receptor binding
Biological Process: radial glial cell differentiation in the forebrain; regulation of fat cell differentiation; positive regulation of apoptosis; positive regulation of transcription, DNA-dependent; cerebellum morphogenesis; Wnt receptor signaling pathway through beta-catenin; bone remodeling; embryonic pattern specification; Wnt receptor signaling pathway in forebrain neuroblast division; anterior/posterior pattern formation; cell-cell adhesion; elevation of cytosolic calcium ion concentration; convergent extension; response to folic acid; midbrain development; positive regulation of mesenchymal cell proliferation; embryonic limb morphogenesis; external genitalia morphogenesis; neural crest formation; positive regulation of cell cycle; negative regulation of fat cell differentiation; midbrain-hindbrain boundary development; negative regulation of protein kinase activity; positive regulation of transcription factor activity; positive regulation of transcription from RNA polymerase II promoter; cerebral cortex development; embryonic digit morphogenesis; regulation of ossification; embryonic forelimb morphogenesis; response to peptide hormone stimulus; palate development; thalamus development; embryonic hindlimb morphogenesis; synaptic transmission; negative regulation of protein amino acid phosphorylation; positive regulation of bone resorption; heart looping; neural crest cell differentiation; cell migration involved in gastrulation; negative regulation of epithelial cell proliferation; Wnt receptor signaling pathway; gastrulation with mouth forming second; positive regulation of ossification; odontogenesis of dentine-containing teeth; formation of radial glial scaffolds; cerebral cortex cell migration; embryonic retina morphogenesis in camera-type eye; neural tube closure; embryonic camera-type eye morphogenesis
Reference #:  O75581 (UniProtKB)
Alt. Names/Synonyms: ADCAD2; FLJ90062; FLJ90421; low density lipoprotein receptor-related protein 6; Low-density lipoprotein receptor-related protein 6; LRP-6; LRP6
Gene Symbols: LRP6
Molecular weight: 180,429 Da
Basal Isoelectric point: 5.12  Predict pI for various phosphorylation states
CST Pathways:  ESC Pluripotency and Differentiation  |  Microtubule Dynamics  |  mTOR Signaling  |  Translation: eIF4E and p70S6K  |  Wnt/├č-Catenin Signaling
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

LRP6

Protein Structure Not Found.


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Sites Implicated In
transcription, altered: S1490‑p
activity, induced: T1479‑p
intracellular localization: T1548‑p
molecular association, regulation: S1420‑p, S1431‑p, T1479‑p, S1490‑p, T1548‑p
phosphorylation: S1490‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 SS 

SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 MS 

MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

 
0 1 S171-p ERAGMDGssRFIIIN
0 1 S172-p RAGMDGssRFIIINS
0 1 S209-p KLNFIHKsNLDGtNR
0 1 T214-p HKsNLDGtNRQAVVK
0 1 T679 TDNRIYWTDISLKTI
0 1 K802-ac GLTIDYAkRRLYWTD
0 1 K977-ub IDYDPLDkQLYWIDS
0 1 T1001-p EDGSQGFtVVVSSVP
1 0 S1420-p YVVHGPAsVPLGYVP
1 0 S1431-p GYVPHPSsLSGSLPG
0 1 S1455-p SLSIMGGsSGPPYDR
0 1 S1474-p GASSSSSsstKGtyF
0 1 S1475-p ASSSSSsstKGtyFP
0 2 T1476-p SSSSSsstKGtyFPA
5 2 T1479-p SSsstKGtyFPAILN
0 1 Y1480-p SsstKGtyFPAILNP
13 58 S1490-p AILNPPPsPAtERsH
2 10 T1493-p NPPPsPAtERsHytM
0 1 S1496-p PsPAtERsHytMEFG
0 18 Y1498-p PAtERsHytMEFGyS
0 1 T1499-p AtERsHytMEFGySs
0 6 Y1504-p HytMEFGySsNsPsT
0 1 S1506-p tMEFGySsNsPsTHR
0 5 S1508-p EFGySsNsPsTHRSy
0 1 S1510-p GySsNsPsTHRSysy
0 1 Y1515-p sPsTHRSysyRPySy
0 2 S1516-p PsTHRSysyRPySyR
0 2 Y1517-p sTHRSysyRPySyRH
0 9 Y1520-p RSysyRPySyRHFAP
0 13 Y1522-p ysyRPySyRHFAPPT
0 56 Y1541-p TDVCDSDyAPsRRMt
1 1 S1544-p CDSDyAPsRRMtSVA
1 0 T1548-p yAPsRRMtSVATAkG
0 1 K1554-ub MtSVATAkGYTSDLN
0 8 Y1562-p GYTSDLNyDSEPVPP
3 2 T1572-p EPVPPPPtPRsQyLs
0 1 S1575-p PPPPtPRsQyLsAEE
0 3 Y1577-p PPtPRsQyLsAEENy
1 0 S1579-p tPRsQyLsAEENyES
0 12 Y1584-p yLsAEENyESCPPsP
0 2 S1590-p NyESCPPsPYTERSY
2 0 S1607-p HLYPPPPsPCTDss_
0 4 S1612-p PPsPCTDss______
0 2 S1613-p PsPCTDss_______
2568 : Phospho-LRP6 (Ser1490) Antibody
  mouse

 
S171 ERAGMDGSSRFVIIN
S172 RAGMDGSSRFVIINT
S209 KLNFIHKSNLDGTNR
T214 HKSNLDGTNRQAVVK
T679-p TDNRIYWtDISLKTI
K802 GLTIDYAKRRLYWTD
K977 IDYDPLDKQLYWIDS
N1001 EDGGQGFNVVANSVA
S1420 YVVHSPASVPLGYVP
S1431 GYVPHPSSLSGSLPG
S1455 SLSIMGGSSGPPYDR
S1474 GASSSSSSSTKGTYF
S1475 ASSSSSSSTKGTYFP
T1476 SSSSSSSTKGTYFPA
T1479 SSSSTKGTYFPAILN
Y1480 SSSTKGTYFPAILNP
S1490-p AILNPPPsPAtERSH
T1493-p NPPPsPAtERSHYTM
S1496 PsPAtERSHYTMEFG
Y1498 PAtERSHYTMEFGYS
T1499 AtERSHYTMEFGYSS
Y1504 HYTMEFGYSSNSPST
S1506 TMEFGYSSNSPSTHR
S1508 EFGYSSNSPSTHRSY
S1510 GYSSNSPSTHRSYSY
Y1515 SPSTHRSYSYRPYSY
S1516 PSTHRSYSYRPYSYR
Y1517 STHRSYSYRPYSYRH
Y1520 RSYSYRPYSYRHFAP
Y1522 YSYRPYSYRHFAPPT
Y1541-p TDVCDSDyAPSRRMT
S1544 CDSDyAPSRRMTSVA
T1548 yAPSRRMTSVATAKG
K1554 MTSVATAKGYTSDVN
Y1562 GYTSDVNYDSEPVPP
T1572-p EPVPPPPtPRSQYLs
S1575 PPPPtPRSQYLsAEE
Y1577 PPtPRSQYLsAEENY
S1579-p tPRSQYLsAEENYES
Y1584 YLsAEENYESCPPSP
S1590 NYESCPPSPYTERSY
S1607-p HLYPPPPsPCTDSS_
S1612 PPsPCTDSS______
S1613 PsPCTDSS_______
2568 : Phospho-LRP6 (Ser1490) Antibody
  rat

 
S20 ERAGMDGSSRFVIIN
S21 RAGMDGSSRFVIINT
S58 KLNFIHKSNLDGTNR
T63 HKSNLDGTNRQAVVK
T528 TDNRIYWTDISLKTI
K651 GLTIDYAKRRLYWTD
K826 IDYDPLDKQLYWIDS
T850 EDGGQGFTVVVSSVP
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