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O88572 (LRP6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Low-density lipoprotein receptor-related protein 6

Short name=LRP-6
Gene names
Name:Lrp6
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length1613 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.4

Subunit structure

Homodimer; disulfide-linked By similarity. Forms phosphorylated oligomer aggregates on Wnt-signaling By similarity. Component of the Wnt-Fzd-LRP5-LRP6 complex. 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 (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface LRP6 signalsomes. 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 (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin By similarity. Interacts with DRAXIN; the interaction inhibits Wnt signaling. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively regulating the Wnt signaling pathway. Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma membrane. Interacts with MACF1. Interacts with DAB2; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Interacts with TMEM198 By similarity. Ref.3 Ref.5 Ref.6 Ref.8 Ref.10

Subcellular location

Membrane; Single-pass type I membrane protein. Endoplasmic reticulum. Note: On Wnt signaling, undergoes a cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane location. Released from the endoplasmic reticulum on palmitoylation. Mono-ubiquitination retains it in the endoplasmic reticulum in the absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-signalsomes By similarity. Chaperoned to the plasma membrane by MESD. Ref.3 Ref.7 Ref.10

Tissue specificity

Expressed in early embryo. Broadly expressed throughout the embryonic ectoderm and in nascent mesoderm, and in endoderm emerging from the primitive streak. Ref.4

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 By similarity.

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

Post-translational modification

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 By similarity. Ref.7

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 By similarity.

Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum By similarity.

Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome By similarity.

N-glycosylation is required for cell surface location By similarity.

Involvement in disease

Defects in Lrp6 are the cause of Ringelschwanz (rs) phenotype. Rs phenotype is a spontaneous mutation that is characterized by a combination of multiple Wnt-deficient phenotypes including dysmorphologies of the axial skeleton, digits and the neural tube. The establishment of the anteroposterior somite compartments, the epithelialization of nascent somites, and the formation of segment borders are disturbed in (rs) mutants. There is delayed ossification at birth and a low bone mass phenotype in adults. Functional analyzes reveal impaired targeting to the plasma surface due to reduced interaction with MESD leading to inhibited Wnt/beta-catenin signaling.

Sequence similarities

Belongs to the LDLR family.

Contains 4 EGF-like domains.

Contains 3 LDL-receptor class A domains.

Contains 20 LDL-receptor class B repeats.

Ontologies

Keywords
   Biological processEndocytosis
Wnt signaling pathway
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainEGF-like domain
Repeat
Signal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
Receptor
   PTMDisulfide bond
Glycoprotein
Isopeptide bond
Lipoprotein
Palmitate
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from genetic interaction PubMed 11029008. Source: MGI

Wnt signaling pathway involved in dorsal/ventral axis specification

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt signaling pathway involved in forebrain neuroblast division

Inferred from mutant phenotype PubMed 16920270. Source: MGI

Wnt signaling pathway involved in somitogenesis

Inferred from mutant phenotype Ref.9. Source: MGI

anterior/posterior pattern specification

Inferred from mutant phenotype PubMed 16126904PubMed 19795512. Source: MGI

axis elongation

Inferred from mutant phenotype PubMed 19795512. Source: MGI

axis elongation involved in somitogenesis

Inferred from genetic interaction PubMed 11029008. Source: MGI

bone remodeling

Inferred from genetic interaction PubMed 15537447. Source: MGI

branching involved in mammary gland duct morphogenesis

Inferred from mutant phenotype PubMed 19503830. Source: MGI

canonical Wnt signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

canonical Wnt signaling pathway involved in cardiac neural crest cell differentiation involved in heart development

Inferred from mutant phenotype PubMed 19705442. Source: MGI

canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation

Inferred from mutant phenotype PubMed 19705442. Source: MGI

cell migration involved in gastrulation

Inferred from genetic interaction Ref.4. Source: MGI

cellular response to cholesterol

Inferred from electronic annotation. Source: Ensembl

cerebellum morphogenesis

Inferred from mutant phenotype PubMed 11029008. Source: MGI

cerebral cortex cell migration

Inferred from mutant phenotype PubMed 16920270. Source: MGI

cerebral cortex development

Inferred from mutant phenotype PubMed 16920270. Source: MGI

convergent extension

Inferred from genetic interaction PubMed 19795512. Source: MGI

dopaminergic neuron differentiation

Inferred from mutant phenotype PubMed 19795519. Source: MGI

dorsal/ventral axis specification

Inferred from mutant phenotype PubMed 18985738. Source: MGI

embryonic camera-type eye morphogenesis

Inferred from mutant phenotype PubMed 18985738PubMed 19653321. Source: MGI

embryonic digit morphogenesis

Inferred from mutant phenotype PubMed 19795512. Source: MGI

embryonic forelimb morphogenesis

Inferred from mutant phenotype PubMed 11029008PubMed 19653321. Source: MGI

embryonic hindlimb morphogenesis

Inferred from mutant phenotype PubMed 19653321. Source: MGI

embryonic limb morphogenesis

Inferred from genetic interaction PubMed 20359476. Source: MGI

embryonic pattern specification

Inferred from mutant phenotype PubMed 19653321. Source: MGI

embryonic retina morphogenesis in camera-type eye

Inferred from mutant phenotype PubMed 19653321. Source: MGI

external genitalia morphogenesis

Inferred from mutant phenotype PubMed 19653321. Source: MGI

face morphogenesis

Inferred from mutant phenotype PubMed 19653321PubMed 19700620. Source: MGI

forebrain development

Inferred from mutant phenotype PubMed 15384171. Source: MGI

forebrain generation of neurons

Inferred from mutant phenotype PubMed 14715945. Source: MGI

forebrain radial glial cell differentiation

Inferred from genetic interaction PubMed 14715945. Source: MGI

formation of radial glial scaffolds

Inferred from genetic interaction PubMed 14715945. Source: MGI

gastrulation with mouth forming second

Inferred from genetic interaction Ref.4. Source: MGI

generation of neurons

Inferred from mutant phenotype PubMed 15342729. Source: MGI

heart looping

Inferred from genetic interaction PubMed 19795512. Source: MGI

limb morphogenesis

Inferred from mutant phenotype Ref.9. Source: MGI

mammary gland duct morphogenesis

Inferred from genetic interaction PubMed 19503830. Source: MGI

mammary placode formation

Inferred from mutant phenotype PubMed 19503830. Source: MGI

midbrain development

Inferred from mutant phenotype PubMed 11029008. Source: MGI

midbrain-hindbrain boundary development

Inferred from mutant phenotype PubMed 11029008PubMed 19795512. Source: MGI

negative regulation of Wnt signaling pathway

Inferred from genetic interaction PubMed 16126904. Source: MGI

negative regulation of epithelial cell proliferation

Inferred from mutant phenotype PubMed 19700620. Source: MGI

negative regulation of fat cell differentiation

Inferred from mutant phenotype PubMed 17888405. Source: MGI

negative regulation of non-canonical Wnt signaling pathway

Inferred from genetic interaction PubMed 19056682. Source: MGI

negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis

Inferred from genetic interaction PubMed 19056682. Source: MGI

negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis

Inferred from genetic interaction PubMed 19056682. Source: MGI

negative regulation of planar cell polarity pathway involved in neural tube closure

Inferred from genetic interaction PubMed 19056682. Source: MGI

negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis

Inferred from genetic interaction PubMed 19056682. Source: MGI

negative regulation of planar cell polarity pathway involved in pericardium morphogenesis

Inferred from genetic interaction PubMed 19056682. Source: MGI

negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis

Inferred from genetic interaction PubMed 19056682. Source: MGI

negative regulation of protein serine/threonine kinase activity

Inferred from electronic annotation. Source: Ensembl

negative regulation of smooth muscle cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

neural crest formation

Inferred from Biological aspect of Ancestor. Source: RefGenome

neural tube closure

Inferred from mutant phenotype PubMed 10545599Ref.9PubMed 19653321. Source: MGI

neural tube development

Inferred from genetic interaction PubMed 19795512. Source: MGI

odontogenesis of dentin-containing tooth

Inferred from mutant phenotype PubMed 5893447PubMed 591875. Source: MGI

palate development

Inferred from mutant phenotype PubMed 19653321PubMed 19700620. Source: MGI

pericardium morphogenesis

Inferred from genetic interaction PubMed 19795512. Source: MGI

positive regulation of Wnt signaling pathway involved in dorsal/ventral axis specification

Inferred from electronic annotation. Source: Ensembl

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 19700620. Source: MGI

positive regulation of bone resorption

Inferred from mutant phenotype Ref.10. Source: MGI

positive regulation of canonical Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell cycle

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of mesenchymal cell proliferation

Inferred from mutant phenotype PubMed 19700620. Source: MGI

positive regulation of ossification

Inferred from mutant phenotype Ref.9. Source: MGI

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from mutant phenotype PubMed 15035989. Source: BHF-UCL

positive regulation of transcription from RNA polymerase II promoter

Inferred from Biological aspect of Ancestor. Source: RefGenome

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 15035989. Source: BHF-UCL

post-anal tail morphogenesis

Inferred from mutant phenotype PubMed 19653321PubMed 19795512. Source: MGI

primitive streak formation

Inferred from genetic interaction PubMed 19795512. Source: MGI

receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport

Inferred from mutant phenotype PubMed 18948618. Source: MGI

regulation of cell development

Inferred from mutant phenotype PubMed 19795519. Source: MGI

regulation of cell proliferation

Inferred from mutant phenotype PubMed 591875. Source: MGI

response to folic acid

Inferred from mutant phenotype PubMed 17050573. Source: MGI

response to peptide hormone

Inferred from electronic annotation. Source: Ensembl

retina morphogenesis in camera-type eye

Inferred from mutant phenotype PubMed 18985738. Source: MGI

single organismal cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

skeletal system morphogenesis

Inferred from mutant phenotype Ref.9. Source: MGI

somitogenesis

Inferred from genetic interaction PubMed 19795512. Source: MGI

synaptic transmission

Inferred from Biological aspect of Ancestor. Source: RefGenome

thalamus development

Inferred from mutant phenotype PubMed 15342729. Source: MGI

toxin transport

Inferred from mutant phenotype PubMed 16564009. Source: GOC

trachea cartilage morphogenesis

Inferred from genetic interaction PubMed 18256198. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

caveola

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell surface

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytoplasmic vesicle

Inferred from electronic annotation. Source: Ensembl

early endosome

Inferred from direct assay PubMed 18948618. Source: MGI

endoplasmic reticulum

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Inferred from direct assay PubMed 16126904. Source: MGI

neuronal cell body

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Inferred from direct assay PubMed 18948618. Source: MGI

receptor complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

synapse

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionWnt-activated receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-protein binding

Inferred from physical interaction PubMed 18606138. Source: MGI

coreceptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

coreceptor activity involved in Wnt signaling pathway

Inferred from electronic annotation. Source: Ensembl

kinase inhibitor activity

Inferred from electronic annotation. Source: Ensembl

low-density lipoprotein receptor activity

Inferred from sequence orthology PubMed 16263759. Source: MGI

protein binding

Inferred from physical interaction Ref.6Ref.8. Source: UniProtKB

toxin transporter activity

Inferred from mutant phenotype PubMed 16564009. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Potential
Chain20 – 16131594Low-density lipoprotein receptor-related protein 6
PRO_0000017331

Regions

Topological domain20 – 13701351Extracellular Potential
Transmembrane1371 – 139323Helical; Potential
Topological domain1394 – 1613220Cytoplasmic Potential
Repeat63 – 10644LDL-receptor class B 1
Repeat107 – 14943LDL-receptor class B 2
Repeat150 – 19344LDL-receptor class B 3
Repeat194 – 23542LDL-receptor class B 4
Repeat236 – 27742LDL-receptor class B 5
Domain282 – 32443EGF-like 1
Repeat372 – 41443LDL-receptor class B 6
Repeat415 – 45743LDL-receptor class B 7
Repeat458 – 50144LDL-receptor class B 8
Repeat502 – 54241LDL-receptor class B 9
Repeat543 – 58745LDL-receptor class B 10
Domain588 – 62841EGF-like 2
Repeat674 – 71643LDL-receptor class B 11
Repeat717 – 75943LDL-receptor class B 12
Repeat760 – 80243LDL-receptor class B 13
Repeat803 – 84240LDL-receptor class B 14
Repeat843 – 88543LDL-receptor class B 15
Domain889 – 93042EGF-like 3
Repeat977 – 102549LDL-receptor class B 16
Repeat1026 – 106843LDL-receptor class B 17
Repeat1069 – 111345LDL-receptor class B 18
Repeat1114 – 115643LDL-receptor class B 19
Repeat1157 – 119842LDL-receptor class B 20
Domain1203 – 124442EGF-like 4
Domain1248 – 128639LDL-receptor class A 1
Domain1287 – 132337LDL-receptor class A 2
Domain1325 – 136137LDL-receptor class A 3
Region20 – 275256Beta-propeller 1
Region328 – 589262Beta-propeller 2
Region631 – 890260Beta-propeller 3
Region933 – 1202270Beta-propeller 4
Motif1487 – 14937PPPSP motif A
Motif1527 – 15348PPPSP motif B
Motif1568 – 15758PPPSP motif C
Motif1588 – 15936PPPSP motif D
Motif1603 – 16108PPPSP motif E
Compositional bias1469 – 14757Poly-Ser
Compositional bias1566 – 15738Poly-Pro
Compositional bias1603 – 16086Poly-Pro

Amino acid modifications

Modified residue14201Phosphoserine; by CK1 By similarity
Modified residue14301Phosphoserine; by CK1 By similarity
Modified residue14791Phosphothreonine By similarity
Modified residue14901Phosphoserine; by CDK14, GRK5 and GRK6 By similarity
Modified residue14931Phosphothreonine; by CK1 By similarity
Lipidation13941S-palmitoyl cysteine By similarity
Lipidation13991S-palmitoyl cysteine By similarity
Glycosylation421N-linked (GlcNAc...) Potential
Glycosylation811N-linked (GlcNAc...) Potential
Glycosylation2811N-linked (GlcNAc...) Potential
Glycosylation4331N-linked (GlcNAc...) Potential
Glycosylation4861N-linked (GlcNAc...) Potential
Glycosylation6921N-linked (GlcNAc...) Potential
Glycosylation8591N-linked (GlcNAc...) Potential
Glycosylation8651N-linked (GlcNAc...) Potential
Glycosylation9261N-linked (GlcNAc...) Potential
Disulfide bond286 ↔ 297 By similarity
Disulfide bond293 ↔ 308 By similarity
Disulfide bond310 ↔ 323 By similarity
Disulfide bond592 ↔ 603 By similarity
Disulfide bond599 ↔ 612 By similarity
Disulfide bond614 ↔ 627 By similarity
Disulfide bond893 ↔ 904 By similarity
Disulfide bond900 ↔ 914 By similarity
Disulfide bond916 ↔ 929 By similarity
Disulfide bond1207 ↔ 1218 By similarity
Disulfide bond1214 ↔ 1228 By similarity
Disulfide bond1230 ↔ 1243 By similarity
Disulfide bond1249 ↔ 1263 By similarity
Disulfide bond1256 ↔ 1276 By similarity
Disulfide bond1270 ↔ 1285 By similarity
Disulfide bond1288 ↔ 1300 By similarity
Disulfide bond1295 ↔ 1313 By similarity
Disulfide bond1307 ↔ 1322 By similarity
Disulfide bond1326 ↔ 1338 By similarity
Disulfide bond1333 ↔ 1351 By similarity
Disulfide bond1345 ↔ 1360 By similarity
Cross-link1403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity

Natural variations

Natural variant8861R → W in rs. Ref.9 Ref.10

Experimental info

Sequence conflict831S → T in AAH60704. Ref.2
Sequence conflict3171M → L in AAH60704. Ref.2
Sequence conflict5861V → I in AAH60704. Ref.2
Sequence conflict6221G → S in AAH60704. Ref.2
Sequence conflict9331S → T in AAH60704. Ref.2

Sequences

Sequence LengthMass (Da)Tools
O88572 [UniParc].

Last modified November 1, 1998. Version 1.
Checksum: 3C2ABC8EEEB17622

FASTA1,613180,255
        10         20         30         40         50         60 
MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF 

        70         80         90        100        110        120 
GHGLIYWSDV SEEAIKRTEF NKSESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE 

       130        140        150        160        170        180 
VSNLDGSLRK VLFWQELDQP RAIALDPSSG FMYWTDWGEV PKIERAGMDG SSRFVIINTE 

       190        200        210        220        230        240 
IYWPNGLTLD YQERKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDTLYWT 

       250        260        270        280        290        300 
DWNTHSILAC NKYTGEGLRE IHSNIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 

       310        320        330        340        350        360 
PVKPFYQCAC PTGVKLMENG KTCKDGATEL LLLARRTDLR RISLDTPDFT DIVLQLEDIR 

       370        380        390        400        410        420 
HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA QIAHPDGIAV DWVARNLYWT 

       430        440        450        460        470        480 
DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA IVLDPMVGYM YWTDWGEIPK IERAALDGSD 

       490        500        510        520        530        540 
RVVLVNTSLG WPNGLALDYD EGTIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL 

       550        560        570        580        590        600 
LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TSVHRVIGSN PCAEDNGGCS 

       610        620        630        640        650        660 
HLCLYRPQGL RCACPIGFEL IGDMKTCIVP EAFLLFSRRA DIRRISLETN NNNVAIPLTG 

       670        680        690        700        710        720 
VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV EFGLDYPEGM AVDWLGKNLY 

       730        740        750        760        770        780 
WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP RALALDPAEG FMYWTEWGGK PKIDRAAMDG 

       790        800        810        820        830        840 
SERTTLVPNV GRANGLTIDY AKRRLYWTDL DTNLIESSDM LGLNREVIAD DLPHPFGLTQ 

       850        860        870        880        890        900 
YQDYIYWTDW SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQAGW NECASSNGHC 

       910        920        930        940        950        960 
SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APSTFLLFSQ KSAINRMVID EQQSPDIILP 

       970        980        990       1000       1010       1020 
IHSLRNVRAI DYDPLDKQLY WIDSRQNSIR KAHEDGGQGF NVVANSVANQ NLEIQPYDLS 

      1030       1040       1050       1060       1070       1080 
IDIYSRYIYW TCEATNVIDV TRLDGRSVGV VLKGEQDRPR AIVVNPEKGY MYFTNLQERS 

      1090       1100       1110       1120       1130       1140 
PKIERAALDG TEREVLFFSG LSKPIALALD SKLGKLFWAD SDLRRIESSD LSGANRIVLE 

      1150       1160       1170       1180       1190       1200 
DSNILQPVGL TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ 

      1210       1220       1230       1240       1250       1260 
EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS PQQFTCFTGD 

      1270       1280       1290       1300       1310       1320 
IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC IDGALRCNGD ANCQDKSDEK 

      1330       1340       1350       1360       1370       1380 
NCEVLCLIDQ FRCANGQCVG KHKKCDHSVD CSDRSDELDC YPTEEPAPQA TNTVGSVIGV 

      1390       1400       1410       1420       1430       1440 
IVTIFVSGTI YFICQRMLCP RMKGDGETMT NDYVVHSPAS VPLGYVPHPS SLSGSLPGMS 

      1450       1460       1470       1480       1490       1500 
RGKSMISSLS IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM 

      1510       1520       1530       1540       1550       1560 
EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV ATAKGYTSDV 

      1570       1580       1590       1600       1610 
NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS 

« Hide

References

« Hide 'large scale' references
[1]"Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family."
Brown S.D., Twells R.C., Hey P.J., Cox R.D., Levy E.R., Soderman A.R., Metzker M.L., Caskey C.T., Todd J.A., Hess J.F.
Biochem. Biophys. Res. Commun. 248:879-888(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: BALB/c.
Tissue: Liver.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain.
[3]"Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity."
Hsieh J.-C., Lee L., Zhang L., Wefer S., Brown K., DeRossi C., Wines M.E., Rosenquist T., Holdener B.C.
Cell 112:355-367(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MESD, SUBUNIT, SUBCELLULAR LOCATION.
[4]"The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice."
Kelly O.G., Pinson K.I., Skarnes W.C.
Development 131:2803-2815(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[5]"Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression."
Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.
J. Biol. Chem. 281:13247-13257(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RSPO1 AND RSPO3.
[6]"GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt signaling pathway."
Tezuka N., Brown A.M., Yanagawa S.
Biochem. Biophys. Res. Commun. 356:648-654(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GRB10.
[7]"Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor."
Khan Z., Vijayakumar S., de la Torre T.V., Rotolo S., Bafico A.
Mol. Cell. Biol. 27:7291-7301(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-1490, INDUCTION, SUBCELLULAR LOCATION.
[8]"Neucrin is a novel neural-specific secreted antagonist to canonical Wnt signaling."
Miyake A., Takahashi Y., Miwa H., Shimada A., Konishi M., Itoh N.
Biochem. Biophys. Res. Commun. 390:1051-1055(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DRAXIN.
[9]"Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis."
Kokubu C., Heinzmann U., Kokubu T., Sakai N., Kubota T., Kawai M., Wahl M.B., Galceran J., Grosschedl R., Ozono K., Imai K.
Development 131:5469-5480(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT RS TRP-886.
[10]"Lrp6 hypomorphic mutation affects bone mass through bone resorption in mice and impairs interaction with Mesd."
Kubota T., Michigami T., Sakaguchi N., Kokubu C., Suzuki A., Namba N., Sakai N., Nakajima S., Imai K., Ozono K.
J. Bone Miner. Res. 23:1661-1671(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT RINGELSCHWANZ PHENOTYPE TRP-886, SUBCELLULAR LOCATION, INTERACTION WITH DKK1; WNT1 AND MESD.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF074265 mRNA. Translation: AAC33007.1.
BC060704 mRNA. Translation: AAH60704.1.
CCDSCCDS39678.1.
PIRJE0273.
RefSeqNP_032540.2. NM_008514.4.
UniGeneMm.321990.

3D structure databases

ProteinModelPortalO88572.
SMRO88572. Positions 20-1360.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid201203. 8 interactions.
DIPDIP-46460N.
IntActO88572. 3 interactions.
STRING10090.ENSMUSP00000032322.

PTM databases

PhosphoSiteO88572.

Proteomic databases

PaxDbO88572.
PRIDEO88572.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000032322; ENSMUSP00000032322; ENSMUSG00000030201.
GeneID16974.
KEGGmmu:16974.
UCSCuc009ekl.2. mouse.

Organism-specific databases

CTD4040.
MGIMGI:1298218. Lrp6.

Phylogenomic databases

eggNOGNOG121718.
GeneTreeENSGT00750000117273.
HOGENOMHOG000230697.
HOVERGENHBG049167.
InParanoidO88572.
KOK03068.
OrthoDBEOG75XGK3.
PhylomeDBO88572.
TreeFamTF315253.

Gene expression databases

ArrayExpressO88572.
BgeeO88572.
GenevestigatorO88572.

Family and domain databases

Gene3D2.120.10.30. 4 hits.
4.10.400.10. 3 hits.
InterProIPR011042. 6-blade_b-propeller_TolB-like.
IPR000742. EG-like_dom.
IPR023415. LDLR_class-A_CS.
IPR000033. LDLR_classB_rpt.
IPR002172. LDrepeatLR_classA_rpt.
IPR017049. Low_density_Lipo_rcpt-rel_p5/6.
[Graphical view]
PfamPF00057. Ldl_recept_a. 3 hits.
PF00058. Ldl_recept_b. 13 hits.
[Graphical view]
PIRSFPIRSF036314. LDL_recpt-rel_p5/6. 1 hit.
PRINTSPR00261. LDLRECEPTOR.
SMARTSM00181. EGF. 4 hits.
SM00192. LDLa. 3 hits.
SM00135. LY. 20 hits.
[Graphical view]
SUPFAMSSF57424. SSF57424. 3 hits.
PROSITEPS01186. EGF_2. 1 hit.
PS01209. LDLRA_1. 3 hits.
PS50068. LDLRA_2. 3 hits.
PS51120. LDLRB. 20 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio291034.
PROO88572.
SOURCESearch...

Entry information

Entry nameLRP6_MOUSE
AccessionPrimary (citable) accession number: O88572
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: November 1, 1998
Last modified: July 9, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot