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Aliases for LRP6 Gene

Aliases for LRP6 Gene

  • Low Density Lipoprotein Receptor-Related Protein 6 2 3
  • ADCAD2 3 6
  • LRP-6 3 4
  • Low-Density Lipoprotein Receptor-Related Protein 6 3

External Ids for LRP6 Gene

Summaries for LRP6 Gene

Entrez Gene Summary for LRP6 Gene

  • This gene encodes a member of the low density lipoprotein (LDL) receptor gene family. LDL receptors are transmembrane cell surface proteins involved in receptor-mediated endocytosis of lipoprotein and protein ligands. The protein encoded by this gene functions as a receptor or, with Frizzled, a co-receptor for Wnt and thereby transmits the canonical Wnt/beta-catenin signaling cascade. Through its interaction with the Wnt/beta-catenin signaling cascade this gene plays a role in the regulation of cell differentiation, proliferation, and migration and the development of many cancer types. This protein undergoes gamma-secretase dependent RIP- (regulated intramembrane proteolysis) processing but the precise locations of the cleavage sites have not been determined.[provided by RefSeq, Dec 2009]

GeneCards Summary for LRP6 Gene

LRP6 (Low Density Lipoprotein Receptor-Related Protein 6) is a Protein Coding gene. Diseases associated with LRP6 include coronary artery disease, autosomal dominant, 2 and coronary artery disease - hyperlipidemia - hypertension - diabetes - osteoporosis. Among its related pathways are ERK Signaling and MicroRNAs in cardiomyocyte hypertrophy. GO annotations related to this gene include protein homodimerization activity and frizzled binding. An important paralog of this gene is LRP1B.

UniProtKB/Swiss-Prot for LRP6 Gene

  • 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 Wiki entry for LRP6 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for LRP6 Gene

Genomics for LRP6 Gene

Genomic Location for LRP6 Gene

Start:
12,116,025 bp from pter
End:
12,267,012 bp from pter
Size:
150,988 bases
Orientation:
Minus strand

Genomic View for LRP6 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for LRP6 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for LRP6 Gene

Regulatory Elements for LRP6 Gene

Proteins for LRP6 Gene

  • Protein details for LRP6 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O75581-LRP6_HUMAN
    Recommended name:
    Low-density lipoprotein receptor-related protein 6
    Protein Accession:
    O75581
    Secondary Accessions:
    • Q17RZ2

    Protein attributes for LRP6 Gene

    Size:
    1613 amino acids
    Molecular mass:
    180429 Da
    Quaternary structure:
    • 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 DRAXIN. 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 (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. Interacts with DAB2; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Interacts with TMEM198.

    Three dimensional structures from OCA and Proteopedia for LRP6 Gene

neXtProt entry for LRP6 Gene

Proteomics data for LRP6 Gene at MOPED

Post-translational modifications for LRP6 Gene

  • 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.
  • Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.
  • N-glycosylation is required for cell surface location.
  • Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum.
  • 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
  • Modification sites at PhosphoSitePlus
  • Ubiquitination at Lys1403
  • Glycosylation at Asn42, Asn81, Asn281, Asn433, Asn486, Asn692, Asn859, Asn865, Asn926, and Asn1039

Other Protein References for LRP6 Gene

ENSEMBL proteins:
Reactome Protein details:
REFSEQ proteins:

No data available for DME Specific Peptides for LRP6 Gene

Domains for LRP6 Gene

Gene Families for LRP6 Gene

HGNC:
  • LDLR :Low density lipoprotein receptors

Suggested Antigen Peptide Sequences for LRP6 Gene

Graphical View of Domain Structure for InterPro Entry

O75581

UniProtKB/Swiss-Prot:

LRP6_HUMAN
Domain:
  • The YWTD-EGF-like domains 1 and 2 are required for the interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and 4 are required for the interaction with DKK1.:
    • O75581
  • The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway.:
    • O75581
  • Contains 4 EGF-like domains.:
    • O75581
  • Contains 3 LDL-receptor class A domains.:
    • O75581
Family:
  • Belongs to the LDLR family.:
    • O75581
Similarity:
  • Contains 20 LDL-receptor class B repeats.:
    • O75581
genes like me logo Genes that share domains with LRP6: view

Function for LRP6 Gene

Molecular function for LRP6 Gene

GENATLAS Biochemistry: low-density lipoprotein receptor related protein 6,putative tumor suppressor of leukemia
UniProtKB/Swiss-Prot 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).
UniProtKB/Swiss-Prot Induction: Decreased levels on WNT3A stimulation.

Gene Ontology (GO) - Molecular Function for LRP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005041 low-density lipoprotein receptor activity IDA 16263759
GO:0005102 receptor binding IPI 14739301
GO:0005109 frizzled binding IPI 11029007
GO:0005515 protein binding IPI 11029007
GO:0017147 Wnt-protein binding IPI 11029007
genes like me logo Genes that share ontologies with LRP6: view
genes like me logo Genes that share phenotypes with LRP6: view

Animal Models for LRP6 Gene

MGI Knock Outs for LRP6:

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting and HOMER Transcription for LRP6 Gene

Localization for LRP6 Gene

Subcellular locations from UniProtKB/Swiss-Prot for LRP6 Gene

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). {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Jensen Localization Image for LRP6 Gene COMPARTMENTS Subcellular localization image for LRP6 gene
Compartment Confidence
endoplasmic reticulum 5
plasma membrane 4
endosome 2
extracellular 2
nucleus 2
lysosome 1

Gene Ontology (GO) - Cellular Components for LRP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region TAS --
GO:0005769 colocalizes_with early endosome IDA 16890161
GO:0005783 endoplasmic reticulum IEA --
GO:0005794 colocalizes_with Golgi apparatus IDA 16890161
GO:0005886 plasma membrane TAS --
genes like me logo Genes that share ontologies with LRP6: view

Pathways for LRP6 Gene

genes like me logo Genes that share pathways with LRP6: view

Pathways by source for LRP6 Gene

Gene Ontology (GO) - Biological Process for LRP6 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001702 gastrulation with mouth forming second IBA --
GO:0001756 somitogenesis --
GO:0001843 neural tube closure IBA --
GO:0001933 negative regulation of protein phosphorylation IMP 16365045
GO:0001947 heart looping IEA --
genes like me logo Genes that share ontologies with LRP6: view

Compounds for LRP6 Gene

(3) Novoseek inferred chemical compound relationships for LRP6 Gene

Compound -log(P) Hits PubMed IDs
glycogen 43.9 9
cysteine 3.93 1
tyrosine 0 2
genes like me logo Genes that share compounds with LRP6: view

Transcripts for LRP6 Gene

Unigene Clusters for LRP6 Gene

Low density lipoprotein receptor-related protein 6:
Representative Sequences:

Alternative Splicing Database (ASD) splice patterns (SP) for LRP6 Gene

No ASD Table

Relevant External Links for LRP6 Gene

GeneLoc Exon Structure for
LRP6
ECgene alternative splicing isoforms for
LRP6

Expression for LRP6 Gene

mRNA expression in normal human tissues for LRP6 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for LRP6 Gene

SOURCE GeneReport for Unigene cluster for LRP6 Gene Hs.584775

mRNA Expression by UniProt/SwissProt for LRP6 Gene

O75581-LRP6_HUMAN
Tissue specificity: Widely coexpressed with LRP5 during embryogenesis and in adult tissues
genes like me logo Genes that share expressions with LRP6: view

No data available for mRNA differential expression in normal tissues for LRP6 Gene

Orthologs for LRP6 Gene

This gene was present in the common ancestor of animals.

Orthologs for LRP6 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia LRP6 35
  • 99.67 (n)
  • 99.75 (a)
LRP6 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia LRP6 35
  • 93.99 (n)
  • 98.51 (a)
LRP6 36
  • 98 (a)
OneToOne
dog
(Canis familiaris)
Mammalia LRP6 35
  • 95.43 (n)
  • 99.07 (a)
LRP6 36
  • 99 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Lrp6 35
  • 90.91 (n)
  • 98.02 (a)
Lrp6 16
Lrp6 36
  • 98 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia LRP6 36
  • 97 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia LRP6 36
  • 95 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Lrp6 35
  • 90.3 (n)
  • 98.1 (a)
chicken
(Gallus gallus)
Aves LRP6 35
  • 82.17 (n)
  • 93.06 (a)
LRP6 36
  • 92 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia LRP6 36
  • 91 (a)
OneToOne
African clawed frog
(Xenopus laevis)
Amphibia lrp6-B 35
tropical clawed frog
(Silurana tropicalis)
Amphibia lrp6 35
  • 74.56 (n)
  • 86.88 (a)
Str.7507 35
zebrafish
(Danio rerio)
Actinopterygii lrp6 35
  • 69.39 (n)
  • 81.53 (a)
lrp6 36
  • 67 (a)
OneToOne
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP011770 35
  • 26.23 (n)
  • 8.3 (a)
fruit fly
(Drosophila melanogaster)
Insecta arr 35
  • 50.58 (n)
  • 45.65 (a)
arr 36
  • 42 (a)
OneToMany
arr 37
  • 42 (a)
sea squirt
(Ciona savignyi)
Ascidiacea -- 36
  • 58 (a)
OneToMany
Species with no ortholog for LRP6:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for LRP6 Gene

ENSEMBL:
Gene Tree for LRP6 (if available)
TreeFam:
Gene Tree for LRP6 (if available)

Paralogs for LRP6 Gene

Paralogs for LRP6 Gene

Selected SIMAP similar genes for LRP6 Gene using alignment to 6 proteins:

genes like me logo Genes that share paralogs with LRP6: view

Variants for LRP6 Gene

Sequence variations from dbSNP and Humsavar for LRP6 Gene

SNP ID Clin Chr 12 pos Sequence Context AA Info Type MAF
rs718403 -- 12,144,022(-) tttta(C/T)ggtta intron-variant
rs1012671 -- 12,132,418(-) GCTTA(A/G)AGCTA intron-variant
rs1012672 -- 12,131,981(-) CGGTG(C/T)GATGG reference, synonymous-codon, nc-transcript-variant
rs1015830 -- 12,133,860(-) cCTCC(C/T)CCCCC intron-variant
rs1015831 -- 12,133,846(-) CCCCC(A/C)AAAAA intron-variant

Structural Variations from Database of Genomic Variants (DGV) for LRP6 Gene

Variant ID Type Subtype PubMed ID
nsv529005 CNV Loss 19592680
nsv898806 CNV Gain 21882294
nsv832332 CNV Loss 17160897
esv2745567 CNV Deletion 23290073
esv2658217 CNV Deletion 23128226

Relevant External Links for LRP6 Gene

HapMap Linkage Disequilibrium report
LRP6
Human Gene Mutation Database (HGMD)
LRP6

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for LRP6 Gene

Disorders for LRP6 Gene

(1) OMIM Diseases for LRP6 Gene (603507)

UniProtKB/Swiss-Prot

LRP6_HUMAN
  • Coronary artery disease, autosomal dominant, 2 (ADCAD2) [MIM:610947]: A common heart disease characterized by reduced or absent blood flow in one or more of the arteries that encircle and supply the heart. Its most important complication is acute myocardial infarction. {ECO:0000269 PubMed:17332414}. Note=The disease is caused by mutations affecting the gene represented in this entry.

(2) University of Copenhagen DISEASES for LRP6 Gene

(7) Novoseek inferred disease relationships for LRP6 Gene

Disease -log(P) Hits PubMed IDs
high bone mass 61.1 1
anthrax 42.9 14
osteoporosis 42 3
cancer 13.8 6
colorectal cancer 10.5 1

Relevant External Links for LRP6

Genetic Association Database (GAD)
LRP6
Human Genome Epidemiology (HuGE) Navigator
LRP6
genes like me logo Genes that share disorders with LRP6: view

Publications for LRP6 Gene

  1. Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family. (PMID: 9704021) Brown S.D. … Hess J.F. (Biochem. Biophys. Res. Commun. 1998) 2 3 4 23
  2. Head inducer Dickkopf-1 is a ligand for Wnt coreceptor LRP6. (PMID: 11448771) Semenov M.V. … He X. (Curr. Biol. 2001) 3 4 23
  3. Common genetic variation of the low-density lipoprotein receptor-related protein 5 and 6 genes determines fracture risk in elderly white men. (PMID: 16355283) van Meurs J.B. … Uitterlinden A.G. (J. Bone Miner. Res. 2006) 3 23 48
  4. Functional candidate genes in age-related macular degeneration: significant association with VEGF, VLDLR, and LRP6. (PMID: 16384981) Haines J.L. … Pericak-Vance M.A. (Invest. Ophthalmol. Vis. Sci. 2006) 3 23 48
  5. Negative regulation of LRP6 function by casein kinase I epsilon phosphorylation. (PMID: 16513652) Swiatek W. … Virshup D.M. (J. Biol. Chem. 2006) 3 4 23

Products for LRP6 Gene

  • Addgene plasmids for LRP6

Sources for LRP6 Gene

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