LipidDB ID

LipidDB-9606-00456

Entry Name

UniProt Accession

O75581; Q17RZ2;

Theoretical PI

5.12

Molecular Weight

180429.34

Genbank Protein ID

AAC33006.1; AAI17137.1; AAI26406.1;

Genbank Nucleotide ID

AF074264; AC007537; AC007621; BC117136; BC126405;

Protein Name

Low-density lipoprotein receptor-related protein 6

Protein Synonyms/Alias

LRP-6;

Gene Name

LRP6

Gene Synonyms/Alias

Created Date

10-MAY-2004

Organism

Homo sapiens (Human)

NCBI Taxa ID

9606

Reference

[1] Abrami L, Kunz B, Iacovache I, van der Goot FG. Palmitoylation andubiquitination regulate exit of the Wnt signaling protein LRP6 from theendoplasmic reticulum. Proc Natl Acad Sci U S A. 2008 Apr 8;105(14):5384-9. doi: 10.1073/pnas.0710389105. Epub 2008 Mar 31.[PMID:18378904]

Functional Description

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).

Sequence Annotation

Topological domain: 20 1370 Extracellular.
Transmembrane: 1371 1393 Helical.
Topological domain: 1394 1613 Cytoplasmic.
Domain: 282 324 EGF-like 1.
Domain: 588 628 EGF-like 2.
Domain: 889 930 EGF-like 3.
Domain: 1203 1244 EGF-like 4.
Domain: 1248 1286 LDL-receptor class A 1.
Domain: 1287 1323 LDL-receptor class A 2.
Domain: 1325 1361 LDL-receptor class A 3.
Region: 20 275 Beta-propeller 1.
Region: 328 589 Beta-propeller 2.
Region: 631 890 Beta-propeller 3.
Region: 933 1202 Beta-propeller 4.
Motif: 1487 1493 PPPSP motif A.
Motif: 1527 1534 PPPSP motif B.
Motif: 1568 1575 PPPSP motif C.
Motif: 1588 1593 PPPSP motif D.
Motif: 1603 1610 PPPSP motif E.
Modified residue: 1420 1420 Phosphoserine; by CK1.
Modified residue: 1430 1430 Phosphoserine; by CK1.
Modified residue: 1479 1479 Phosphothreonine.
Modified residue: 1490 1490 Phosphoserine; by CDK14, GRK5 and GRK6.
Modified residue: 1493 1493 Phosphothreonine; by CK1.

Protein Length

1613 AA.

Protein Sequence
(Canonical)

FASTA
(Canonical)

Gene Ontology

GO:0009986; C:cell surface; IDA:BHF-UCL
GO:0031410; C:cytoplasmic vesicle; IDA:BHF-UCL
GO:0005769; C:early endosome; IEA:Ensembl
GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-KW
GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW
GO:0043025; C:neuronal cell body; IBA:RefGenome
GO:0005886; C:plasma membrane; IDA:BHF-UCL
GO:0043235; C:receptor complex; IBA:RefGenome
GO:0045202; C:synapse; IBA:RefGenome
GO:0034185; F:apolipoprotein binding; IBA:RefGenome
GO:0071936; F:coreceptor activity involved in Wnt signaling pathway; IDA:BHF-UCL
GO:0005109; F:frizzled binding; IPI:BHF-UCL
GO:0042802; F:identical protein binding; IPI:IntAct
GO:0019210; F:kinase inhibitor activity; IMP:BHF-UCL
GO:0005041; F:low-density lipoprotein receptor activity; IDA:MGI
GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL
GO:0005102; F:receptor binding; IPI:BHF-UCL
GO:0019534; F:toxin transporter activity; IMP:BHF-UCL
GO:0042813; F:Wnt-activated receptor activity; IBA:RefGenome
GO:0017147; F:Wnt-protein binding; IPI:BHF-UCL
GO:0009952; P:anterior/posterior pattern specification; IBA:RefGenome
GO:0090245; P:axis elongation involved in somitogenesis; IBA:RefGenome
GO:0060349; P:bone morphogenesis; IBA:RefGenome
GO:0046849; P:bone remodeling; IBA:RefGenome
GO:0060444; P:branching involved in mammary gland duct morphogenesis; IBA:RefGenome
GO:0060070; P:canonical Wnt signaling pathway; IDA:UniProtKB
GO:0061310; P:canonical Wnt signaling pathway involved in cardiac neural crest cell differentiation involved in heart development; IEA:Ensembl
GO:0044335; P:canonical Wnt signaling pathway involved in neural crest cell differentiation; IC:BHF-UCL
GO:0061324; P:canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation; IEA:Ensembl
GO:0044340; P:canonical Wnt signaling pathway involved in regulation of cell proliferation; IC:BHF-UCL
GO:0042074; P:cell migration involved in gastrulation; IEA:Ensembl
GO:0071397; P:cellular response to cholesterol; IMP:BHF-UCL
GO:0021587; P:cerebellum morphogenesis; IBA:RefGenome
GO:0021795; P:cerebral cortex cell migration; IEA:Ensembl
GO:0021987; P:cerebral cortex development; IBA:RefGenome
GO:0060026; P:convergent extension; IBA:RefGenome
GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl
GO:0048596; P:embryonic camera-type eye morphogenesis; IBA:RefGenome
GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl
GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl
GO:0035116; P:embryonic hindlimb morphogenesis; IEA:Ensembl
GO:0030326; P:embryonic limb morphogenesis; IBA:RefGenome
GO:0009880; P:embryonic pattern specification; IBA:RefGenome
GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IBA:RefGenome
GO:0035261; P:external genitalia morphogenesis; IBA:RefGenome
GO:0060325; P:face morphogenesis; IBA:RefGenome
GO:0021861; P:forebrain radial glial cell differentiation; IEA:Ensembl
GO:0021943; P:formation of radial glial scaffolds; IEA:Ensembl
GO:0001702; P:gastrulation with mouth forming second; IBA:RefGenome
GO:0001947; P:heart looping; IEA:Ensembl
GO:0060596; P:mammary placode formation; IEA:Ensembl
GO:0030901; P:midbrain development; IBA:RefGenome
GO:0030917; P:midbrain-hindbrain boundary development; IBA:RefGenome
GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl
GO:0045599; P:negative regulation of fat cell differentiation; IEA:Ensembl
GO:2000151; P:negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis; IEA:Ensembl
GO:2000162; P:negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis; IEA:Ensembl
GO:2000168; P:negative regulation of planar cell polarity pathway involved in neural tube closure; IEA:Ensembl
GO:2000164; P:negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis; IEA:Ensembl
GO:2000166; P:negative regulation of planar cell polarity pathway involved in pericardium morphogenesis; IEA:Ensembl
GO:2000149; P:negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis; IEA:Ensembl
GO:0006469; P:negative regulation of protein kinase activity; IMP:BHF-UCL
GO:0001933; P:negative regulation of protein phosphorylation; IMP:BHF-UCL
GO:0071901; P:negative regulation of protein serine/threonine kinase activity; IDA:BHF-UCL
GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; IMP:BHF-UCL
GO:0014033; P:neural crest cell differentiation; IDA:BHF-UCL
GO:0014029; P:neural crest formation; IDA:BHF-UCL
GO:0001843; P:neural tube closure; IBA:RefGenome
GO:0042475; P:odontogenesis of dentin-containing tooth; IBA:RefGenome
GO:0060021; P:palate development; IBA:RefGenome
GO:0003344; P:pericardium morphogenesis; IBA:RefGenome
GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl
GO:0045780; P:positive regulation of bone resorption; IEA:Ensembl
GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:BHF-UCL
GO:0045787; P:positive regulation of cell cycle; IMP:BHF-UCL
GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IEA:Ensembl
GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl
GO:0045778; P:positive regulation of ossification; IEA:Ensembl
GO:0051091; P:positive regulation of sequence-specific DNA binding transcription factor activity; IDA:BHF-UCL
GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IDA:BHF-UCL
GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:BHF-UCL
GO:2000055; P:positive regulation of Wnt signaling pathway involved in dorsal/ventral axis specification; IDA:BHF-UCL
GO:0036342; P:post-anal tail morphogenesis; IEA:Ensembl
GO:0090009; P:primitive streak formation; IBA:RefGenome
GO:0090118; P:receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport; IBA:RefGenome
GO:0060284; P:regulation of cell development; IEA:Ensembl
GO:0045598; P:regulation of fat cell differentiation; IBA:RefGenome
GO:0030278; P:regulation of ossification; IBA:RefGenome
GO:0051593; P:response to folic acid; IEA:Ensembl
GO:0043434; P:response to peptide hormone; IEA:Ensembl
GO:0016337; P:single organismal cell-cell adhesion; IEA:Ensembl
GO:0007268; P:synaptic transmission; IBA:RefGenome
GO:0021794; P:thalamus development; IBA:RefGenome
GO:1901998; P:toxin transport; IMP:GOC
GO:0060535; P:trachea cartilage morphogenesis; IBA:RefGenome
GO:0016055; P:Wnt signaling pathway; IMP:BHF-UCL
GO:0044332; P:Wnt signaling pathway involved in dorsal/ventral axis specification; IDA:BHF-UCL
GO:0021874; P:Wnt signaling pathway involved in forebrain neuroblast division; IEA:Ensembl
GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IBA:RefGenome

Interpro

InterPro; IPR011042; 6-blade_b-propeller_TolB-like
InterPro; IPR000742; EG-like_dom
InterPro; IPR023415; LDLR_class-A_CS
InterPro; IPR000033; LDLR_classB_rpt
InterPro; IPR002172; LDrepeatLR_classA_rpt
InterPro; IPR017049; Low_density_Lipo_rcpt-rel_p5/6

Pfam

Pfam; PF00057; Ldl_recept_a;
Pfam; PF00058; Ldl_recept_b;

SMART

SMART; SM00181; EGF;
SMART; SM00192; LDLa;
SMART; SM00135; LY;

PROSITE

PROSITE; PS01186; EGF_2;
PROSITE; PS01209; LDLRA_1;
PROSITE; PS50068; LDLRA_2;
PROSITE; PS51120; LDLRB;

PRINTS

PRINTS; PR00261; LDLRECEPTOR;