Names & Taxonomy
- Uniprot ID:
- O75581
- Entry Name:
- LRP6_HUMAN
- Status:
- reviewed
- Protein Names:
- Low-density lipoprotein receptor-related protein 6 (LRP-6)
- Gene Names:
- LRP6
- Gene Names Primary:
- LRP6
- Organism:
- Homo sapiens (Human)
Structure
- Length:
- 1613
- Sequence:
- MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGEIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDLNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS
- Proteomes:
- UP000005640
Subcellular location
- Subcellular Location:
- Membrane; Single-pass type I membrane protein. Endoplasmic reticulum. 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).
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 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).
- Gene Ontology Go:
- cell surface
cytoplasmic vesicle
cytosol
early endosome membrane
endoplasmic reticulum
extracellular region
integral component of membrane
neuronal cell body
plasma membrane
receptor complex
synapse
Wnt signalosome
Wnt-Frizzled-LRP5/6 complex
apolipoprotein binding
coreceptor activity involved in canonical Wnt signaling pathway
coreceptor activity involved in Wnt signaling pathway
frizzled binding
identical protein binding
kinase inhibitor activity
low-density lipoprotein receptor activity
protein homodimerization activity
receptor binding
toxin transporter activity
Wnt-activated receptor activity
Wnt-protein binding
axis elongation involved in somitogenesis
canonical Wnt signaling pathway
canonical Wnt signaling pathway involved in neural crest cell differentiation
canonical Wnt signaling pathway involved in regulation of cell proliferation
cellular response to cholesterol
cerebellum morphogenesis
cerebral cortex development
convergent extension
dopaminergic neuron differentiation
embryonic pattern specification
embryonic retina morphogenesis in camera-type eye
external genitalia morphogenesis
face morphogenesis
midbrain development
midbrain dopaminergic neuron differentiation
midbrain-hindbrain boundary development
negative regulation of canonical Wnt signaling pathway
negative regulation of protein kinase activity
negative regulation of protein phosphorylation
negative regulation of protein serine/threonine kinase activity
negative regulation of smooth muscle cell apoptotic process
neural crest cell differentiation
neural crest formation
neural tube closure
odontogenesis of dentin-containing tooth
palate development
pericardium morphogenesis
positive regulation of canonical Wnt signaling pathway
positive regulation of cell cycle
positive regulation of cytosolic calcium ion concentration
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of transcription from RNA polymerase II promoter
positive regulation of transcription, DNA-templated
positive regulation of Wnt signaling pathway involved in dorsal/ventral axis specification
primitive streak formation
protein localization to plasma membrane
receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport
response to peptide hormone
single organismal cell-cell adhesion
synaptic transmission
thalamus development
toxin transport
trachea cartilage morphogenesis
Wnt signaling pathway
Wnt signaling pathway involved in dorsal/ventral axis specification
Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation
Wnt signaling pathway involved in somitogenesis - Gene Ontology Biological Process:
- axis elongation involved in somitogenesis
canonical Wnt signaling pathway
canonical Wnt signaling pathway involved in neural crest cell differentiation
canonical Wnt signaling pathway involved in regulation of cell proliferation
cellular response to cholesterol
cerebellum morphogenesis
cerebral cortex development
convergent extension
dopaminergic neuron differentiation
embryonic pattern specification
embryonic retina morphogenesis in camera-type eye
external genitalia morphogenesis
face morphogenesis
midbrain development
midbrain dopaminergic neuron differentiation
midbrain-hindbrain boundary development
negative regulation of canonical Wnt signaling pathway
negative regulation of protein kinase activity
negative regulation of protein phosphorylation
negative regulation of protein serine/threonine kinase activity
negative regulation of smooth muscle cell apoptotic process
neural crest cell differentiation
neural crest formation
neural tube closure
odontogenesis of dentin-containing tooth
palate development
pericardium morphogenesis
positive regulation of canonical Wnt signaling pathway
positive regulation of cell cycle
positive regulation of cytosolic calcium ion concentration
positive regulation of sequence-specific DNA binding transcription factor activity
positive regulation of transcription, DNA-templated
positive regulation of transcription from RNA polymerase II promoter
positive regulation of Wnt signaling pathway involved in dorsal/ventral axis specification
primitive streak formation
protein localization to plasma membrane
receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport
response to peptide hormone
single organismal cell-cell adhesion
synaptic transmission
thalamus development
toxin transport
trachea cartilage morphogenesis
Wnt signaling pathway
Wnt signaling pathway involved in dorsal/ventral axis specification
Wnt signaling pathway involved in midbrain dopaminergic neuron differentiation
Wnt signaling pathway involved in somitogenesis - Gene Ontology Molecular Function:
- apolipoprotein binding
coreceptor activity involved in canonical Wnt signaling pathway
coreceptor activity involved in Wnt signaling pathway
frizzled binding
identical protein binding
kinase inhibitor activity
low-density lipoprotein receptor activity
protein homodimerization activity
receptor binding
toxin transporter activity
Wnt-activated receptor activity
Wnt-protein binding - Gene Ontology Cellular Component:
- cell surface
cytoplasmic vesicle
cytosol
early endosome membrane
endoplasmic reticulum
extracellular region
integral component of membrane
neuronal cell body
plasma membrane
receptor complex
synapse
Wnt-Frizzled-LRP5/6 complex
Wnt signalosome - Keywords:
- 3D-structure
Complete proteome
Developmental protein
Disease mutation
Disulfide bond
EGF-like domain
Endocytosis
Endoplasmic reticulum
Glycoprotein
Isopeptide bond
Lipoprotein
Membrane
Palmitate
Phosphoprotein
Polymorphism
Receptor
Reference proteome
Repeat
Signal
Transmembrane
Transmembrane helix
Ubl conjugation
Wnt signaling pathway - Interacts With:
- Itself; Q9Y4X0; Q9H6X2; O35625; O70239; Q03135; P98082; O94907; Q61091; P49840; P49841; Q5S007; Q9ERE8; Q9BQB4; P04426