InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Lrp6

Summary

InnateDB Protein

IDBP-194035.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Lrp6

Protein Name

low density lipoprotein receptor-related protein 6

Synonyms

C030016K15Rik; Cd; Gw; ska; ska26; skax26;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000032322

InnateDB Gene

IDBG-194033 (Lrp6)

Protein Structure

UniProt Annotation

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). {ECO:0000250}.

Subcellular Localization

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 (By similarity). Chaperoned to the plasma membrane by MESD. {ECO:0000250}.

Disease Associations

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 analyzes reveal impaired targeting to the plasma surface due to reduced interaction with MESD leading to inhibited Wnt/beta-catenin signaling.

Tissue Specificity

Expressed in early embryo. Broadly expressed throughout the embryonic ectoderm and in nascent mesoderm, and in endoderm emerging from the primitive streak. {ECO:0000269PubMed:15142971}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 19 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	19 [view]
Protein-Protein	16 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	3 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005041	low-density lipoprotein receptor activity
GO:0005102	receptor binding
GO:0005109	frizzled binding
GO:0005515	protein binding
GO:0015026	coreceptor activity
GO:0017147	Wnt-protein binding
GO:0019210	kinase inhibitor activity
GO:0019534	toxin transporter activity
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0042813	Wnt-activated receptor activity
GO:0071936	coreceptor activity involved in Wnt receptor signaling pathway

Biological Process

GO:0001702	gastrulation with mouth forming second
GO:0001756	somitogenesis
GO:0001843	neural tube closure
GO:0001933	negative regulation of protein phosphorylation
GO:0001947	heart looping
GO:0002053	positive regulation of mesenchymal cell proliferation
GO:0003344	pericardium morphogenesis
GO:0003401	axis elongation
GO:0006355	regulation of transcription, DNA-templated
GO:0006469	negative regulation of protein kinase activity
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0007268	synaptic transmission
GO:0009880	embryonic pattern specification
GO:0009950	dorsal/ventral axis specification
GO:0009952	anterior/posterior pattern specification
GO:0014029	neural crest formation
GO:0014033	neural crest cell differentiation
GO:0016055	Wnt signaling pathway
GO:0016337	single organismal cell-cell adhesion
GO:0021587	cerebellum morphogenesis
GO:0021794	thalamus development
GO:0021795	cerebral cortex cell migration
GO:0021861	forebrain radial glial cell differentiation
GO:0021872	forebrain generation of neurons
GO:0021874	Wnt receptor signaling pathway involved in forebrain neuroblast division
GO:0021915	neural tube development
GO:0021943	formation of radial glial scaffolds
GO:0021987	cerebral cortex development
GO:0030178	negative regulation of Wnt signaling pathway
GO:0030326	embryonic limb morphogenesis
GO:0030900	forebrain development
GO:0030901	midbrain development
GO:0030917	midbrain-hindbrain boundary development
GO:0034392	negative regulation of smooth muscle cell apoptotic process
GO:0035108	limb morphogenesis
GO:0035115	embryonic forelimb morphogenesis
GO:0035116	embryonic hindlimb morphogenesis
GO:0035261	external genitalia morphogenesis
GO:0036342	post-anal tail morphogenesis
GO:0042074	cell migration involved in gastrulation
GO:0042127	regulation of cell proliferation
GO:0042475	odontogenesis of dentin-containing tooth
GO:0042733	embryonic digit morphogenesis
GO:0043065	positive regulation of apoptotic process
GO:0043434	response to peptide hormone
GO:0044332	Wnt signaling pathway involved in dorsal/ventral axis specification
GO:0045599	negative regulation of fat cell differentiation
GO:0045778	positive regulation of ossification
GO:0045780	positive regulation of bone resorption
GO:0045787	positive regulation of cell cycle
GO:0045893	positive regulation of transcription, DNA-templated
GO:0045944	positive regulation of transcription from RNA polymerase II promoter
GO:0046849	bone remodeling
GO:0048596	embryonic camera-type eye morphogenesis
GO:0048699	generation of neurons
GO:0048705	skeletal system morphogenesis
GO:0050680	negative regulation of epithelial cell proliferation
GO:0051091	positive regulation of sequence-specific DNA binding transcription factor activity
GO:0051593	response to folic acid
GO:0060021	palate development
GO:0060026	convergent extension
GO:0060042	retina morphogenesis in camera-type eye
GO:0060059	embryonic retina morphogenesis in camera-type eye
GO:0060070	canonical Wnt signaling pathway
GO:0060284	regulation of cell development
GO:0060325	face morphogenesis
GO:0060444	branching involved in mammary gland duct morphogenesis
GO:0060535	trachea cartilage morphogenesis
GO:0060596	mammary placode formation
GO:0060603	mammary gland duct morphogenesis
GO:0061310	canonical Wnt receptor signaling pathway involved in cardiac neural crest cell differentiation involved in heart development
GO:0061324	canonical Wnt receptor signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation
GO:0071397	cellular response to cholesterol
GO:0071542	dopaminergic neuron differentiation
GO:0071901	negative regulation of protein serine/threonine kinase activity
GO:0090009	primitive streak formation
GO:0090118	receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport
GO:0090244	Wnt signaling pathway involved in somitogenesis
GO:0090245	axis elongation involved in somitogenesis
GO:0090263	positive regulation of canonical Wnt signaling pathway
GO:1901998	toxin transport
GO:2000051	negative regulation of non-canonical Wnt signaling pathway
GO:2000055	positive regulation of Wnt receptor signaling pathway involved in dorsal/ventral axis specification
GO:2000149	negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis
GO:2000151	negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis
GO:2000162	negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis
GO:2000164	negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis
GO:2000166	negative regulation of planar cell polarity pathway involved in pericardium morphogenesis
GO:2000168	negative regulation of planar cell polarity pathway involved in neural tube closure

Cellular Component

GO:0005769	early endosome
GO:0005783	endoplasmic reticulum
GO:0005794	Golgi apparatus
GO:0005886	plasma membrane
GO:0005901	caveola
GO:0009986	cell surface
GO:0016020	membrane
GO:0016021	integral component of membrane
GO:0031410	cytoplasmic vesicle
GO:0043025	neuronal cell body
GO:0043235	receptor complex
GO:0045202	synapse

Protein Structure and Domains

PDB ID

MGI:1298218

InterPro

IPR000033 LDLR class B repeat
IPR000742 Epidermal growth factor-like domain
IPR002172 Low-density lipoprotein (LDL) receptor class A repeat
IPR017049 Low density lipoprotein receptor-related protein, 5/6

PFAM

PF00058
PF00008
PF00057

PRINTS

PR00261

PIRSF

PIRSF036314

SMART

SM00135
SM00181
SM00192

TIGRFAMs

Post-translational Modifications

Modification

Cross-References