Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

UniProtKB - O75581 (LRP6_HUMAN)

Entry version 187 (10 Feb 2021)
Sequence version 2 (11 Jan 2011)
Previous versions | rss
Add a publicationFeedback
Protein

Low-density lipoprotein receptor-related protein 6

Gene

LRP6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

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).By similarity10 Publications

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processEndocytosis, Wnt signaling pathway

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		O75581

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-201681, TCF dependent signaling in response to WNT
R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-4641262, Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-4641263, Regulation of FZD by ubiquitination
R-HSA-5340588, RNF mutants show enhanced WNT signaling and proliferation

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		O75581

SIGNOR Signaling Network Open Resource

More...SIGNORi		O75581

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Low-density lipoprotein receptor-related protein 6
Short name:
LRP-6
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:LRP6
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 12

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:6698, LRP6

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		603507, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_O75581

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000070018.8

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte & Seán O’Donoghue; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the subcellular compartment where each non-membrane region of a membrane-spanning protein is found.<p><a href='/help/topo_dom' target='_top'>More...</a></p>Topological domaini20 – 1370ExtracellularSequence analysisAdd BLAST1351
<p>This subsection of the <a href="http://www.uniprot.org/help/subcellular%5Flocation%5Fsection">'Subcellular location'</a> section describes the extent of a membrane-spanning region of the protein. It denotes the presence of both alpha-helical transmembrane regions and the membrane spanning regions of beta-barrel transmembrane proteins.<p><a href='/help/transmem' target='_top'>More...</a></p>Transmembranei1371 – 1393HelicalSequence analysisAdd BLAST23
Topological domaini1394 – 1613CytoplasmicSequence analysisAdd BLAST220

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Coronary artery disease, autosomal dominant, 2 (ADCAD2)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_076208360R → H in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs141212743EnsemblClinVar.1
Natural variantiVAR_076209433N → S in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs397515473EnsemblClinVar.1
Natural variantiVAR_076210473R → Q in ADCAD2; impairs Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397515474EnsemblClinVar.1
Natural variantiVAR_034701611R → C in ADCAD2; impairs Wnt signaling in vitro. 1 PublicationCorresponds to variant dbSNP:rs121918313EnsemblClinVar.1
Tooth agenesis, selective, 7 (STHAG7)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant form of selective tooth agenesis, a common anomaly characterized by the congenital absence of one or more teeth. Selective tooth agenesis without associated systemic disorders has sometimes been divided into 2 types: oligodontia, defined as agenesis of 6 or more permanent teeth, and hypodontia, defined as agenesis of less than 6 teeth. The number in both cases does not include absence of third molars (wisdom teeth).
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07620719A → V in STHAG7; impairs Wnt signaling; prevents transport to plasma membrane location. 1 PublicationCorresponds to variant dbSNP:rs864309648EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi1394C → A: Some reduction of palmitoylation, little change in plasma membrane location in the presence of MESD nor in Wnt-signaling activity. Completely abolishes palmitoylation, no plasma membrane location, greatly reduced Wnt-signaling activity but no effect on ubiquitination; when associated with A-1399. Exhibits full Wnt-signaling activity and no change in plasma membrane location; when associated with A-1399 and R-1403. 1 Publication1
Mutagenesisi1399C → A: Some reduction of palmitoylation, and little change in plasma membrane location in the presence of MESD nor in Wnt-signaling activity. Completely abolishes palmitoylation, no plasma membrane location, greatly reduced Wnt-signaling activity but no effect on ubiquitination; when associated with A-1394. Exhibits full Wnt-signaling activity and no change in plasma membrane location in the in presence of MESD; when associated with A-1394 and R-1403. 1 Publication1
Mutagenesisi1403K → R: Abolishes ubiquitination, no change in plasma membrane location in the presence of MESD but greatly reduced Wnt-signaling activity. Exhibits full Wnt-signaling activity and no change in plasma membrane location; when associated with A-1394 and A-1399. 1
Mutagenesisi1420S → A: Enhanced AXIN1 binding and increased beta-catenin activity by 2.2-fold. Further enhanced AXIN1 binding and increases beta-catenin activity by 3.3-fold; when associated with A-1430. 1 Publication1
Mutagenesisi1430S → A: Enhanced AXIN1 binding. Further enhanced AXIN1 binding and increases beta-catenin activity by 3.3-fold; when associated with A-1420. 1 Publication1
Mutagenesisi1485L → A: No change in the phosphorylation state of PPPSP motif. Some reduction in Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1486N → A: No change in the phosphorylation state of PPPSP motif. Increased Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1487P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1487P → C: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1488P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1489P → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1490S → A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1490S → T: Some loss of phosphorylation of PPPSP motif A. Little reduction in Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1491P → A: Greatly reduced phosphorylation of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1492A → G: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1493T → A: No change in the phosphorylation state of PPPSP motif A. Greatly reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1494E → A: No change in the phosphorylation state of PPPSP motif A. Little reduction of Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1495R → A: No change in the phosphorylation state of PPPSP motif. No reduction of Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1529T → A: No effect on the phosphorylation state of PPPSP motif B. 1 Publication1
Mutagenesisi1530T → A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1531P → A: Abolishes phosphorylation of PPPSP motif B. Reduced Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1572T → A: Abolishes Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1590S → A: Abolishes Wnt/beta-catenin signaling. 1 Publication1
Mutagenesisi1607S → A: Abolishes Wnt/beta-catenin signaling. 1 Publication1

Keywords - Diseasei

Disease variant

Organism-specific databases

DisGeNET

More...DisGeNETi		4040

MalaCards human disease database

More...MalaCardsi		LRP6
MIMi610947, phenotype
616724, phenotype

Open Targets

More...OpenTargetsi		ENSG00000070018

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		411969, NON RARE IN EUROPE: Metabolic syndrome
99798, Oligodontia

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA30456

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		O75581, Tbio

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL3745588

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		LRP6

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section denotes the presence of an N-terminal signal peptide.<p><a href='/help/signal' target='_top'>More...</a></p>Signal peptidei1 – 19Sequence analysisAdd BLAST19
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_000001733020 – 1613Low-density lipoprotein receptor-related protein 6Add BLAST1594

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position and type of each covalently attached glycan group (mono-, di-, or polysaccharide).<p><a href='/help/carbohyd' target='_top'>More...</a></p>Glycosylationi42N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi81N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi281N-linked (GlcNAc...) asparagineSequence analysis1
<p>This subsection of the PTM / Processing":/help/ptm_processing_section section describes the positions of cysteine residues participating in disulfide bonds.<p><a href='/help/disulfid' target='_top'>More...</a></p>Disulfide bondi286 ↔ 297PROSITE-ProRule annotation
Disulfide bondi293 ↔ 308PROSITE-ProRule annotation
Disulfide bondi310 ↔ 323PROSITE-ProRule annotation
Glycosylationi433N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi486N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi592 ↔ 603PROSITE-ProRule annotation
Disulfide bondi599 ↔ 612PROSITE-ProRule annotation
Disulfide bondi614 ↔ 627PROSITE-ProRule annotation
Glycosylationi692N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi859N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi865N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi893 ↔ 904PROSITE-ProRule annotation1 Publication
Disulfide bondi900 ↔ 914PROSITE-ProRule annotation1 Publication
Disulfide bondi916 ↔ 929PROSITE-ProRule annotation1 Publication
Glycosylationi926N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi1039N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi1207 ↔ 1218PROSITE-ProRule annotation1 Publication
Disulfide bondi1214 ↔ 1228PROSITE-ProRule annotation1 Publication
Disulfide bondi1230 ↔ 1243PROSITE-ProRule annotation1 Publication
Disulfide bondi1249 ↔ 1263PROSITE-ProRule annotation
Disulfide bondi1256 ↔ 1276PROSITE-ProRule annotation
Disulfide bondi1270 ↔ 1285PROSITE-ProRule annotation
Disulfide bondi1288 ↔ 1300PROSITE-ProRule annotation
Disulfide bondi1295 ↔ 1313PROSITE-ProRule annotation
Disulfide bondi1307 ↔ 1322PROSITE-ProRule annotation
Disulfide bondi1326 ↔ 1338PROSITE-ProRule annotation
Disulfide bondi1333 ↔ 1351PROSITE-ProRule annotation
Disulfide bondi1345 ↔ 1360PROSITE-ProRule annotation
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section specifies the position(s) and the type of covalently attached lipid group(s).<p><a href='/help/lipid' target='_top'>More...</a></p>Lipidationi1394S-palmitoyl cysteine1 Publication1
Lipidationi1399S-palmitoyl cysteine1 Publication1
<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM / Processing</a> section describes <strong>covalent linkages</strong> of various types formed <strong>between two proteins (interchain cross-links)</strong> or <strong>between two parts of the same protein (intrachain cross-links)</strong>, except the disulfide bonds that are annotated in the <a href="http://www.uniprot.org/manual/disulfid">'Disulfide bond'</a> subsection.<p><a href='/help/crosslnk' target='_top'>More...</a></p>Cross-linki1403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei1420Phosphoserine; by CK11 Publication1
Modified residuei1430Phosphoserine; by CK11 Publication1
Modified residuei1479Phosphothreonine1 Publication1
Modified residuei1490Phosphoserine; by CDK14, GRK5 and GRK6Combined sources7 Publications1
Modified residuei1493Phosphothreonine; by CK11 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationi

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-1479.10 Publications
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.
Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum.1 Publication
Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.2 Publications
N-glycosylation is required for cell surface location.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		O75581

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		O75581

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		O75581

MaxQB - The MaxQuant DataBase

More...MaxQBi		O75581

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		O75581

PeptideAtlas

More...PeptideAtlasi		O75581

PRoteomics IDEntifications database

More...PRIDEi		O75581

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		50097

PTM databases

GlyGen: Computational and Informatics Resources for Glycoscience

More...GlyGeni		O75581, 12 sites

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		O75581

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		O75581

SwissPalm database of S-palmitoylation events

More...SwissPalmi		O75581

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityi

Widely coexpressed with LRP5 during embryogenesis and in adult tissues.

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductioni

Decreased levels on WNT3A stimulation.1 Publication

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000070018, Expressed in metanephros and 245 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		O75581, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		O75581, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000070018, Low tissue specificity

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

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.

Interacts with CAPRIN2; the interaction promotes LRP6 phosphorylation at Ser-1490 (PubMed:18762581, PubMed:25331957).

Found in a complex with CAPRIN2, CCNY and CDK14 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus (PubMed:27821587).

Interacts with LYPD6 (PubMed:23987510).

Forms a ternary complex with DKK1 and KREM1 (PubMed:27524201).

Interacts with KREM1 in a DKK1-dependent manner (PubMed:17804805).

Interacts with MDK: this interaction is calcium dependent (By similarity).

Interacts with LMBR1L (PubMed:31073040).

By similarity1 Publication21 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

Hide details

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		110219, 73 interactors

CORUM comprehensive resource of mammalian protein complexes

More...CORUMi		O75581

Database of interacting proteins

More...DIPi		DIP-29884N

Protein interaction database and analysis system

More...IntActi		O75581, 58 interactors

Molecular INTeraction database

More...MINTi		O75581

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000261349

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		O75581

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		O75581, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

11613
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		O75581

Database of comparative protein structure models

More...ModBasei		Search...

Protein Data Bank in Europe - Knowledge Base

More...PDBe-KBi		Search...

Miscellaneous databases

Relative evolutionary importance of amino acids within a protein sequence

More...EvolutionaryTracei		O75581

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section indicates the positions and types of repeated sequence motifs or repeated domains within the protein.<p><a href='/help/repeat' target='_top'>More...</a></p>Repeati63 – 106LDL-receptor class B 1Add BLAST44
Repeati107 – 149LDL-receptor class B 2Add BLAST43
Repeati150 – 193LDL-receptor class B 3Add BLAST44
Repeati194 – 236LDL-receptor class B 4Add BLAST43
Repeati237 – 276LDL-receptor class B 5Add BLAST40
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini282 – 324EGF-like 1Add BLAST43
Repeati372 – 414LDL-receptor class B 6Add BLAST43
Repeati415 – 457LDL-receptor class B 7Add BLAST43
Repeati458 – 501LDL-receptor class B 8Add BLAST44
Repeati502 – 542LDL-receptor class B 9Add BLAST41
Repeati543 – 584LDL-receptor class B 10Add BLAST42
Domaini588 – 628EGF-like 2Add BLAST41
Repeati674 – 716LDL-receptor class B 11Add BLAST43
Repeati717 – 759LDL-receptor class B 12Add BLAST43
Repeati760 – 802LDL-receptor class B 13Add BLAST43
Repeati803 – 842LDL-receptor class B 14Add BLAST40
Repeati843 – 885LDL-receptor class B 15Add BLAST43
Domaini889 – 930EGF-like 3Add BLAST42
Repeati977 – 1025LDL-receptor class B 16Add BLAST49
Repeati1026 – 1068LDL-receptor class B 17Add BLAST43
Repeati1069 – 1113LDL-receptor class B 18Add BLAST45
Repeati1114 – 1156LDL-receptor class B 19Add BLAST43
Repeati1157 – 1198LDL-receptor class B 20Add BLAST42
Domaini1203 – 1244EGF-like 4Add BLAST42
Domaini1248 – 1286LDL-receptor class A 1PROSITE-ProRule annotationAdd BLAST39
Domaini1287 – 1323LDL-receptor class A 2PROSITE-ProRule annotationAdd BLAST37
Domaini1325 – 1361LDL-receptor class A 3PROSITE-ProRule annotationAdd BLAST37

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni20 – 275Beta-propeller 1Add BLAST256
Regioni328 – 589Beta-propeller 2Add BLAST262
Regioni631 – 890Beta-propeller 3Add BLAST260
Regioni933 – 1202Beta-propeller 4Add BLAST270

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a short (usually not more than 20 amino acids) conserved sequence motif of biological significance.<p><a href='/help/motif' target='_top'>More...</a></p>Motifi1487 – 1493PPPSP motif A7
Motifi1527 – 1534PPPSP motif B8
Motifi1568 – 1575PPPSP motif C8
Motifi1588 – 1593PPPSP motif D6
Motifi1603 – 1610PPPSP motif E8

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

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 DKK1.1 Publication
The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the LDLR family.Curated

Keywords - Domaini

EGF-like domain, Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG1215, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000158990

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		O75581

Identification of Orthologs from Complete Genome Data

More...OMAi		TNCANGH

Database of Orthologous Groups

More...OrthoDBi		121310at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		O75581

TreeFam database of animal gene trees

More...TreeFami		TF315253

Family and domain databases

Conserved Domains Database

More...CDDi		cd00112, LDLa, 3 hits

Gene3D Structural and Functional Annotation of Protein Families

More...Gene3Di		2.120.10.30, 4 hits
4.10.400.10, 3 hits

Intrinsically Disordered proteins with Extensive Annotations and Literature

More...IDEALi		IID00531

Integrated resource of protein families, domains and functional sites

More...InterProi		View protein in InterPro
IPR011042, 6-blade_b-propeller_TolB-like
IPR000742, EGF-like_dom
IPR036055, LDL_receptor-like_sf
IPR023415, LDLR_class-A_CS
IPR000033, LDLR_classB_rpt
IPR002172, LDrepeatLR_classA_rpt
IPR017049, LRP5/6

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00057, Ldl_recept_a, 3 hits
PF00058, Ldl_recept_b, 11 hits

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF036314, LDL_recpt-rel_p5/6, 1 hit

Protein Motif fingerprint database; a protein domain database

More...PRINTSi		PR00261, LDLRECEPTOR

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00181, EGF, 4 hits
SM00192, LDLa, 3 hits
SM00135, LY, 20 hits

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF57424, SSF57424, 3 hits

PROSITE; a protein domain and family database

More...PROSITEi		View protein in PROSITE
PS01186, EGF_2, 1 hit
PS01209, LDLRA_1, 3 hits
PS50068, LDLRA_2, 3 hits
PS51120, LDLRB, 19 hits

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 4 potential isoforms that are computationally mapped.Show allAlign All

O75581-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL 
        60         70         80         90        100
EDAAAVDFVF SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL 
       110        120        130        140        150
ACDWLGEKLY WTDSETNRIE VSNLDGSLRK VLFWQELDQP RAIALDPSSG 
       160        170        180        190        200
FMYWTDWGEV PKIERAGMDG SSRFIIINSE IYWPNGLTLD YEEQKLYWAD 
       210        220        230        240        250
AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT DWSTHSILAC 
       260        270        280        290        300
NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 
       310        320        330        340        350
PVKPFYQCAC PTGVKLLENG KTCKDGATEL LLLARRTDLR RISLDTPDFT 
       360        370        380        390        400
DIVLQLEDIR HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA 
       410        420        430        440        450
QIAHPDGIAV DWVARNLYWT DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA 
       460        470        480        490        500
IVLDPMVGYM YWTDWGEIPK IERAALDGSD RVVLVNTSLG WPNGLALDYD 
       510        520        530        540        550
EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL LGDYVYWTDW 
       560        570        580        590        600
QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS 
       610        620        630        640        650
HLCLYRPQGL RCACPIGFEL ISDMKTCIVP EAFLLFSRRA DIRRISLETN 
       660        670        680        690        700
NNNVAIPLTG VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV 
       710        720        730        740        750
EFGLDYPEGM AVDWLGKNLY WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP 
       760        770        780        790        800
RALALDPAEG FMYWTEWGGK PKIDRAAMDG SERTTLVPNV GRANGLTIDY 
       810        820        830        840        850
AKRRLYWTDL DTNLIESSNM LGLNREVIAD DLPHPFGLTQ YQDYIYWTDW 
       860        870        880        890        900
SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQSGW NECASSNGHC 
       910        920        930        940        950
SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APTTFLLFSQ KSAINRMVID 
       960        970        980        990       1000
EQQSPDIILP IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF 
      1010       1020       1030       1040       1050
TVVVSSVPSQ NLEIQPYDLS IDIYSRYIYW TCEATNVINV TRLDGRSVGV 
      1060       1070       1080       1090       1100
VLKGEQDRPR AVVVNPEKGY MYFTNLQERS PKIERAALDG TEREVLFFSG 
      1110       1120       1130       1140       1150
LSKPIALALD SRLGKLFWAD SDLRRIESSD LSGANRIVLE DSNILQPVGL 
      1160       1170       1180       1190       1200
TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ 
      1210       1220       1230       1240       1250
EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS 
      1260       1270       1280       1290       1300
PQQFTCFTGE IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC 
      1310       1320       1330       1340       1350
IDGALRCNGD ANCQDKSDEK NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD 
      1360       1370       1380       1390       1400
CSDKSDELDC YPTEEPAPQA TNTVGSVIGV IVTIFVSGTV YFICQRMLCP 
      1410       1420       1430       1440       1450
RMKGDGETMT NDYVVHGPAS VPLGYVPHPS SLSGSLPGMS RGKSMISSLS 
      1460       1470       1480       1490       1500
IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM 
      1510       1520       1530       1540       1550
EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV 
      1560       1570       1580       1590       1600
ATAKGYTSDL NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH 
      1610 
LYPPPPSPCT DSS
Length:1,613
Mass (Da):180,429
Last modified:January 11, 2011 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:i413D2CF70A5D8B5C
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
F5H7J9F5H7J9_HUMAN
Low-density lipoprotein receptor-re...
LRP6
1,568Annotation score:

Annotation score:3 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YGW5H0YGW5_HUMAN
Low-density lipoprotein receptor-re...
LRP6
1,478Annotation score:

Annotation score:2 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
H0YGH0H0YGH0_HUMAN
Low-density lipoprotein receptor-re...
LRP6
69Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>
F5H0Z3F5H0Z3_HUMAN
Low-density lipoprotein receptor-re...
LRP6
75Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07620719A → V in STHAG7; impairs Wnt signaling; prevents transport to plasma membrane location. 1 PublicationCorresponds to variant dbSNP:rs864309648EnsemblClinVar.1
Natural variantiVAR_076208360R → H in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs141212743EnsemblClinVar.1
Natural variantiVAR_076209433N → S in ADCAD2. 1 PublicationCorresponds to variant dbSNP:rs397515473EnsemblClinVar.1
Natural variantiVAR_076210473R → Q in ADCAD2; impairs Wnt signaling. 1 PublicationCorresponds to variant dbSNP:rs397515474EnsemblClinVar.1
Natural variantiVAR_030349483V → I. Corresponds to variant dbSNP:rs7975614Ensembl.1
Natural variantiVAR_034701611R → C in ADCAD2; impairs Wnt signaling in vitro. 1 PublicationCorresponds to variant dbSNP:rs121918313EnsemblClinVar.1
Natural variantiVAR_030350817S → C. Corresponds to variant dbSNP:rs2302686Ensembl.1
Natural variantiVAR_0245201062V → I1 PublicationCorresponds to variant dbSNP:rs2302685Ensembl.1
Natural variantiVAR_0347021401R → H. Corresponds to variant dbSNP:rs34815107EnsemblClinVar.1
Natural variantiVAR_0834311415V → F Found in a patient with congenital hydrocephalus; unknown pathological significance. 1 Publication1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AF074264 mRNA Translation: AAC33006.1
AC007537 Genomic DNA No translation available.
AC007621 Genomic DNA No translation available.
BC117136 mRNA Translation: AAI17137.1
BC126405 mRNA Translation: AAI26406.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS8647.1

Protein sequence database of the Protein Information Resource

More...PIRi		JE0272

NCBI Reference Sequences

More...RefSeqi		NP_002327.2, NM_002336.2
XP_006719141.1, XM_006719078.3

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000261349; ENSP00000261349; ENSG00000070018
ENST00000628182; ENSP00000486315; ENSG00000281324

Database of genes from NCBI RefSeq genomes

More...GeneIDi		4040

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:4040

UCSC genome browser

More...UCSCi		uc001rah.6, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074264 mRNA Translation: AAC33006.1
AC007537 Genomic DNA No translation available.
AC007621 Genomic DNA No translation available.
BC117136 mRNA Translation: AAI17137.1
BC126405 mRNA Translation: AAI26406.1
CCDSiCCDS8647.1
PIRiJE0272
RefSeqiNP_002327.2, NM_002336.2
XP_006719141.1, XM_006719078.3

3D structure databases

Select the link destinations:

Protein Data Bank Europe

More...PDBei

Protein Data Bank RCSB

More...RCSB PDBi

Protein Data Bank Japan

More...PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3S2KX-ray2.80A/B630-1246[»]
3S8VX-ray3.10A/B629-1243[»]
3S8ZX-ray2.80A629-1243[»]
3S94X-ray2.80A/B20-630[»]
3SOBX-ray1.90B20-335[»]
3SOQX-ray1.90A20-326[»]
3SOVX-ray1.27A20-326[»]
4A0PX-ray1.90A629-1244[»]
4DG6X-ray2.90A20-635[»]
4NM5X-ray2.30C1568-1575[»]
4NM7X-ray2.30C1603-1610[»]
5AIRX-ray2.53A/B1565-1575[»]
5FWWX-ray3.50A630-1246[»]
5GJEelectron microscopy21.00A20-630[»]
B631-1246[»]
6H15X-ray2.60A/B630-1244[»]
6H16X-ray2.90A630-1244[»]
6L6RX-ray3.80A/B21-630[»]
SMRiO75581
ModBaseiSearch...
PDBe-KBiSearch...

Protein-protein interaction databases

BioGRIDi110219, 73 interactors
CORUMiO75581
DIPiDIP-29884N
IntActiO75581, 58 interactors
MINTiO75581
STRINGi9606.ENSP00000261349

Chemistry databases

BindingDBiO75581
ChEMBLiCHEMBL3745588

PTM databases

GlyGeniO75581, 12 sites
iPTMnetiO75581
PhosphoSitePlusiO75581
SwissPalmiO75581

Genetic variation databases

BioMutaiLRP6

Proteomic databases

EPDiO75581
jPOSTiO75581
MassIVEiO75581
MaxQBiO75581
PaxDbiO75581
PeptideAtlasiO75581
PRIDEiO75581
ProteomicsDBi50097

Protocols and materials databases

ABCD curated depository of sequenced antibodies

More...ABCDi		O75581, 4 sequenced antibodies

Antibodypedia a portal for validated antibodies

More...Antibodypediai		3851, 581 antibodies

Genome annotation databases

EnsembliENST00000261349; ENSP00000261349; ENSG00000070018
ENST00000628182; ENSP00000486315; ENSG00000281324
GeneIDi4040
KEGGihsa:4040
UCSCiuc001rah.6, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		4040
DisGeNETi4040

GeneCards: human genes, protein and diseases

More...GeneCardsi		LRP6
HGNCiHGNC:6698, LRP6
HPAiENSG00000070018, Low tissue specificity
MalaCardsiLRP6
MIMi603507, gene
610947, phenotype
616724, phenotype
neXtProtiNX_O75581
OpenTargetsiENSG00000070018
Orphaneti411969, NON RARE IN EUROPE: Metabolic syndrome
99798, Oligodontia
PharmGKBiPA30456
VEuPathDBiHostDB:ENSG00000070018.8

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG1215, Eukaryota
GeneTreeiENSGT00940000158990
InParanoidiO75581
OMAiTNCANGH
OrthoDBi121310at2759
PhylomeDBiO75581
TreeFamiTF315253

Enzyme and pathway databases

PathwayCommonsiO75581
ReactomeiR-HSA-201681, TCF dependent signaling in response to WNT
R-HSA-3772470, Negative regulation of TCF-dependent signaling by WNT ligand antagonists
R-HSA-4641262, Disassembly of the destruction complex and recruitment of AXIN to the membrane
R-HSA-4641263, Regulation of FZD by ubiquitination
R-HSA-5340588, RNF mutants show enhanced WNT signaling and proliferation
SignaLinkiO75581
SIGNORiO75581

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		4040, 9 hits in 880 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		LRP6, human
EvolutionaryTraceiO75581

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		LRP6

Database of phenotypes from RNA interference screens in Drosophila and Homo sapiens

More...GenomeRNAii		4040
PharosiO75581, Tbio

Protein Ontology

More...PROi		PR:O75581
RNActiO75581, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000070018, Expressed in metanephros and 245 other tissues
ExpressionAtlasiO75581, baseline and differential
GenevisibleiO75581, HS

Family and domain databases

CDDicd00112, LDLa, 3 hits
Gene3Di2.120.10.30, 4 hits
4.10.400.10, 3 hits
IDEALiIID00531
InterProiView protein in InterPro
IPR011042, 6-blade_b-propeller_TolB-like
IPR000742, EGF-like_dom
IPR036055, LDL_receptor-like_sf
IPR023415, LDLR_class-A_CS
IPR000033, LDLR_classB_rpt
IPR002172, LDrepeatLR_classA_rpt
IPR017049, LRP5/6
PfamiView protein in Pfam
PF00057, Ldl_recept_a, 3 hits
PF00058, Ldl_recept_b, 11 hits
PIRSFiPIRSF036314, LDL_recpt-rel_p5/6, 1 hit
PRINTSiPR00261, LDLRECEPTOR
SMARTiView protein in SMART
SM00181, EGF, 4 hits
SM00192, LDLa, 3 hits
SM00135, LY, 20 hits
SUPFAMiSSF57424, SSF57424, 3 hits
PROSITEiView protein in PROSITE
PS01186, EGF_2, 1 hit
PS01209, LDLRA_1, 3 hits
PS50068, LDLRA_2, 3 hits
PS51120, LDLRB, 19 hits

ProtoNet; Automatic hierarchical classification of proteins

More...ProtoNeti		Search...

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiLRP6_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: O75581
Secondary accession number(s): Q17RZ2
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: January 11, 2011
Last modified: February 10, 2021
This is version 187 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

3D-structure, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with genetic variants
    List of human entries with genetic variants
  3. Human variants curated from literature reports
    Index of human variants curated from literature reports
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again