LRP6 low density lipoprotein receptor-related protein 6 [Homo sapiens] - Gene

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Summary

Official Symbol: LRP6provided by HGNC
Official Full Name: low density lipoprotein receptor-related protein 6provided by HGNC
Primary source: HGNC:6698
See related: Ensembl:ENSG00000070018; HPRD:04617; MIM:603507; Vega:OTTHUMG00000168540
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: ADCAD2; FLJ90062; FLJ90421
Summary: 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]

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Genomic context

Location :: 12p13.2

Sequence :: Chromosome: 12; NC_000012.11 (12268959..12419811, complement)

See LRP6 in Epigenomics, MapViewer

Chromosome 12 - NC_000012.11 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

LRP6 protein regulates low density lipoprotein (LDL) receptor-mediated LDL uptake.
Title: LRP6 protein regulates low density lipoprotein (LDL) receptor-mediated LDL uptake.
The consensus E1 binding sequence motif is important for DKK1 and SOST binding to LRP6 and for inhibitory function.
Title: Wnt antagonists bind through a short peptide to the first β-propeller domain of LRP5/6.
The Wnts bound to either portion of the LRP6 ectodomain likely bear a similar spatial relationship to Frizzled coreceptors.
Title: Structural basis of Wnt signaling inhibition by Dickkopf binding to LRP5/6.
The LDL-receptor-related protein 6 (LRP6), alongside Frizzled receptors, transduces Wnt signaling across the plasma membrane.
Title: Structural and functional studies of LRP6 ectodomain reveal a platform for Wnt signaling.
These studies uncover a new and important molecular tuning mechanism for differential regulation of LRP5 and LRP6 phosphorylation and signaling activity.
Title: Dissecting molecular differences between Wnt coreceptors LRP5 and LRP6.
Results provide key insights for understanding LRP5/6 structure and the interaction of LRP5/6 with DKK1, as well as for drug discovery.
Title: Crystal structures of the extracellular domain of LRP6 and its complex with DKK1.
these results identified TMEM198 as a membrane scaffold protein that promotes LRP6 phosphorylation and Wnt signaling activation.
Title: Transmembrane protein 198 promotes LRP6 phosphorylation and Wnt signaling activation.
Two structural and functional domains of MESD required for proper folding and trafficking of LRP5/LRP6.
Title: Two structural and functional domains of MESD required for proper folding and trafficking of LRP5/6.
LRP6 variants with impaired Wnt/beta-catenin signaling appear to be involved in early coronary and carotid artery atherosclerosis, at least in hypertensive patients.
Title: Carotid artery atherosclerosis in hypertensive patients with a functional LDL receptor-related protein 6 gene variant.
findings implicate LRP6 as a critical modulator of PDGF-dependent regulation of cell cycle in smooth muscle and indicate that loss of this function contributes to development of early atherosclerosis in humans
Title: Wild-type LRP6 inhibits, whereas atherosclerosis-linked LRP6R611C increases PDGF-dependent vascular smooth muscle cell proliferation.

Submit: New GeneRIF Correction See all (70)

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Phenotypes

Review eQTL and phenotype association data in this region using PheGenI

Coronary artery disease, autosomal dominant, 2

MIM: 610947

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Products	Interactant	Other Gene	Source	Pubs	Description
O75581	Q9H6X2	ANTXR1	HPRD	PubMed
O75581	P58335	ANTXR2	HPRD	PubMed
O75581	O15169	AXIN1	HPRD	PubMed
O75581	O94907	DKK1	HPRD	PubMed
O75581	Q9UBU2	DKK2	HPRD	PubMed
O75581	Q13467	FZD5	HPRD	PubMed
O75581	Q9H461	FZD8	HPRD	PubMed
O75581	P49841	GSK3B	HPRD	PubMed
O75581	O75581	LRP6	HPRD	PubMed
O75581	Q9H1K6	MESDC1	HPRD	PubMed
O75581	P04628	WNT1	HPRD	PubMed
O75581	P56704	WNT3A	HPRD	PubMed
BioGRID:110219	BioGRID:106835	APOB	BioGRID	PubMed	Reconstituted Complex
BioGRID:110219	BioGRID:116599	DKK1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110219	BioGRID:113921	FZD8	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110219	BioGRID:116794	MESDC2	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110219	BioGRID:110925	NPC1	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110219	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS; Affinity Capture-Western
BioGRID:110219	BioGRID:113308	WNT1	BioGRID	PubMed	Affinity Capture-Western

Function	Evidence Code	Pubs
Wnt-activated receptor activity	IBA Inferred from Biological aspect of Ancestor more info
Wnt-protein binding	IPI Inferred from Physical Interaction more info	PubMed
apolipoprotein binding	IBA Inferred from Biological aspect of Ancestor more info
coreceptor activity involved in Wnt receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
frizzled binding	IPI Inferred from Physical Interaction more info	PubMed
kinase inhibitor activity	IMP Inferred from Mutant Phenotype more info	PubMed
low-density lipoprotein receptor activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein homodimerization activity	IPI Inferred from Physical Interaction more info	PubMed
receptor activity	IEA Inferred from Electronic Annotation more info
receptor binding	IPI Inferred from Physical Interaction more info	PubMed
toxin transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed
NOT toxin transporter activity	IMP Inferred from Mutant Phenotype more info	PubMed

Process	Evidence Code	Pubs
Wnt receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
Wnt receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
Wnt receptor signaling pathway involved in dorsal/ventral axis specification	IDA Inferred from Direct Assay more info	PubMed
Wnt receptor signaling pathway involved in forebrain neuroblast division	IEA Inferred from Electronic Annotation more info
Wnt receptor signaling pathway involved in somitogenesis	IBA Inferred from Biological aspect of Ancestor more info
anterior/posterior pattern specification	IBA Inferred from Biological aspect of Ancestor more info
axis elongation involved in somitogenesis	IBA Inferred from Biological aspect of Ancestor more info
bone morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
bone remodeling	IBA Inferred from Biological aspect of Ancestor more info
branching involved in mammary gland duct morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
canonical Wnt receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
canonical Wnt receptor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
canonical Wnt receptor signaling pathway involved in cardiac neural crest cell differentiation involved in heart development	IEA Inferred from Electronic Annotation more info
canonical Wnt receptor signaling pathway involved in neural crest cell differentiation	IC Inferred by Curator more info	PubMed
canonical Wnt receptor signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation	IEA Inferred from Electronic Annotation more info
canonical Wnt receptor signaling pathway involved in regulation of cell proliferation	IC Inferred by Curator more info	PubMed
cell migration involved in gastrulation	IEA Inferred from Electronic Annotation more info
cellular response to cholesterol	IMP Inferred from Mutant Phenotype more info	PubMed
cerebellum morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
cerebral cortex cell migration	IEA Inferred from Electronic Annotation more info
cerebral cortex development	IBA Inferred from Biological aspect of Ancestor more info
convergent extension	IBA Inferred from Biological aspect of Ancestor more info
dopaminergic neuron differentiation	IEA Inferred from Electronic Annotation more info
embryonic camera-type eye morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
embryonic digit morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic forelimb morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic hindlimb morphogenesis	IEA Inferred from Electronic Annotation more info
embryonic limb morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
embryonic pattern specification	IBA Inferred from Biological aspect of Ancestor more info
embryonic retina morphogenesis in camera-type eye	IBA Inferred from Biological aspect of Ancestor more info
endocytosis	IEA Inferred from Electronic Annotation more info
external genitalia morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
face morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
forebrain radial glial cell differentiation	IEA Inferred from Electronic Annotation more info
formation of radial glial scaffolds	IEA Inferred from Electronic Annotation more info
gastrulation with mouth forming second	IBA Inferred from Biological aspect of Ancestor more info
heart looping	IEA Inferred from Electronic Annotation more info
mammary placode formation	IEA Inferred from Electronic Annotation more info
midbrain development	IBA Inferred from Biological aspect of Ancestor more info
midbrain-hindbrain boundary development	IBA Inferred from Biological aspect of Ancestor more info
multicellular organismal development	IEA Inferred from Electronic Annotation more info
negative regulation of epithelial cell proliferation	IEA Inferred from Electronic Annotation more info
negative regulation of fat cell differentiation	IEA Inferred from Electronic Annotation more info
negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of planar cell polarity pathway involved in neural tube closure	IEA Inferred from Electronic Annotation more info
negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of planar cell polarity pathway involved in pericardium morphogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis	IEA Inferred from Electronic Annotation more info
negative regulation of protein kinase activity	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
negative regulation of protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
negative regulation of smooth muscle cell apoptosis	IMP Inferred from Mutant Phenotype more info	PubMed
neural crest cell differentiation	IDA Inferred from Direct Assay more info	PubMed
neural crest formation	IDA Inferred from Direct Assay more info	PubMed
neural tube closure	IBA Inferred from Biological aspect of Ancestor more info
neural tube development	IEA Inferred from Electronic Annotation more info
odontogenesis of dentin-containing tooth	IBA Inferred from Biological aspect of Ancestor more info
palate development	IBA Inferred from Biological aspect of Ancestor more info
pericardium morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
positive regulation of Wnt receptor signaling pathway involved in dorsal/ventral axis specification	IDA Inferred from Direct Assay more info	PubMed
positive regulation of apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of bone resorption	IEA Inferred from Electronic Annotation more info
positive regulation of canonical Wnt receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cell cycle	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of mesenchymal cell proliferation	IEA Inferred from Electronic Annotation more info
positive regulation of ossification	IEA Inferred from Electronic Annotation more info
positive regulation of sequence-specific DNA binding transcription factor activity	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription from RNA polymerase II promoter	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-dependent	IMP Inferred from Mutant Phenotype more info	PubMed
primitive streak formation	IBA Inferred from Biological aspect of Ancestor more info
receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport	IBA Inferred from Biological aspect of Ancestor more info
regulation of cell development	IEA Inferred from Electronic Annotation more info
regulation of fat cell differentiation	IBA Inferred from Biological aspect of Ancestor more info
regulation of ossification	IBA Inferred from Biological aspect of Ancestor more info
response to folic acid	IEA Inferred from Electronic Annotation more info
synaptic transmission	IBA Inferred from Biological aspect of Ancestor more info
tail morphogenesis	IBA Inferred from Biological aspect of Ancestor more info
thalamus development	IBA Inferred from Biological aspect of Ancestor more info
trachea cartilage morphogenesis	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
colocalizes_with caveola	IDA Inferred from Direct Assay more info	PubMed
cell surface	IDA Inferred from Direct Assay more info	PubMed
cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
early endosome	IEA Inferred from Electronic Annotation more info
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
integral to membrane	IEA Inferred from Electronic Annotation more info
membrane fraction	IEA Inferred from Electronic Annotation more info
neuronal cell body	IBA Inferred from Biological aspect of Ancestor more info
plasma membrane	IDA Inferred from Direct Assay more info	PubMed
receptor complex	IBA Inferred from Biological aspect of Ancestor more info
synapse	IBA Inferred from Biological aspect of Ancestor more info

General protein information

Preferred Names: low-density lipoprotein receptor-related protein 6

Names: low-density lipoprotein receptor-related protein 6; LRP-6

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_016168.1 RefSeqGene

Range

5001..155853

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_002336.2 → NP_002327.2 low-density lipoprotein receptor-related protein 6 precursor

Status: REVIEWED

Source sequence(s)

AA126261, AC007537, AF074264, BC126405, BP229563

Consensus CDS

CCDS8647.1

UniProtKB/Swiss-Prot

O75581

Related

ENSP00000261349, OTTHUMP00000238979, ENST00000261349, OTTHUMT00000400137

Conserved Domains (2) summary

cd00112
Location:1326 – 1360
Blast Score: 142

LDLa; Low Density Lipoprotein Receptor Class A domain, a cysteine-rich repeat that plays a central role in mammalian cholesterol metabolism; the receptor protein binds LDL and transports it into cells by endocytosis; 7 successive cysteine-rich repeats of about ...

cl10508
Location:483 – 524
Blast Score: 155

Ldl_recept_b; Low-density lipoprotein receptor repeat class B

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000012.11 Reference GRCh37.p5 Primary Assembly

Range

12268959..12419811, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000144.1 Alternate HuRef

Range

12034207..12184947, complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC007537.3 (85404..190857)	None
genomic	AC007621.34 (2004..47162)	None
genomic	AF090131.1	AAD21410.1
genomic	CH471094.1	EAW96253.1
genomic	JA738609.1	CCF76957.1
mRNA	AA126261.1	None
mRNA	AB209683.1	BAD92920.1
mRNA	AF074264.1	AAC33006.1
mRNA	AK074543.1	BAG51971.1
mRNA	AK074902.1	BAG52027.1
mRNA	AK094666.1	None
mRNA	AK124760.1	None
mRNA	BC029941.1	None
mRNA	BC117136.1	AAI17137.1
mRNA	BC126405.1	AAI26406.1
mRNA	BC143725.1	AAI43726.1
mRNA	BP229563.1	None

Protein Accession	Links
Protein Accession	GenPept Link	UniProtKB Link
O75581.2	GenPept	UniProtKB/Swiss-Prot:O75581
Q59EX8	GenPept	UniProtKB/TrEMBL:Q59EX8
Q9UQH4	GenPept	UniProtKB/TrEMBL:Q9UQH4