O88572 (LRP6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Low-density lipoprotein receptor-related protein 6
Short name=LRP-6

Gene names

Name:

Lrp6

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	1613 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Endocytosis Wnt signaling pathway
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	EGF-like domain Repeat Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein Receptor
PTM	Disulfide bond Glycoprotein Isopeptide bond Lipoprotein Palmitate Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway involved in dorsal/ventral axis specification Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt receptor signaling pathway involved in forebrain neuroblast division Inferred from mutant phenotype PubMed 16920270. Source: MGI Wnt receptor signaling pathway involved in somitogenesis Inferred from mutant phenotype Ref.9. 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 receptor signaling pathway involved in cardiac neural crest cell differentiation involved in heart development Inferred from mutant phenotype PubMed 19705442. Source: MGI canonical Wnt receptor 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: Compara cerebellum morphogenesis Inferred from mutant phenotype PubMed 11029008. Source: MGI cerebral cortex cell migration 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 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 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 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 heart looping Inferred from genetic interaction PubMed 19795512. 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 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 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: Compara negative regulation of smooth muscle cell apoptotic process Inferred from electronic annotation. Source: Compara neural crest formation Inferred from Biological aspect of Ancestor. Source: RefGenome neural tube closure Inferred from mutant phenotype PubMed 10545599Ref.9PubMed 19653321. 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 receptor signaling pathway involved in dorsal/ventral axis specification Inferred from electronic annotation. Source: Compara 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 receptor signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of cell cycle Inferred from electronic annotation. Source: Compara 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 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 response to folic acid Inferred from mutant phenotype PubMed 17050573. Source: MGI skeletal system morphogenesis Inferred from mutant phenotype Ref.9. Source: MGI synaptic transmission Inferred from Biological aspect of Ancestor. Source: RefGenome thalamus development Inferred from mutant phenotype PubMed 15342729. Source: MGI trachea cartilage morphogenesis Inferred from genetic interaction PubMed 18256198. Source: MGI
Cellular_component	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: Compara early endosome Inferred from direct assay PubMed 18948618. Source: MGI endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuronal cell body Inferred from Biological aspect of Ancestor. Source: RefGenome receptor complex Inferred from Biological aspect of Ancestor. Source: RefGenome synapse Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	Wnt-activated receptor activity Inferred from Biological aspect of Ancestor. Source: RefGenome coreceptor activity Inferred from Biological aspect of Ancestor. Source: RefGenome coreceptor activity involved in Wnt receptor signaling pathway Inferred from electronic annotation. Source: Compara kinase inhibitor activity Inferred from electronic annotation. Source: Compara low-density lipoprotein receptor activity Inferred from sequence orthology PubMed 16263759. Source: MGI toxin transporter activity Inferred from mutant phenotype PubMed 16564009. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 1613	1594	Low-density lipoprotein receptor-related protein 6		PRO_0000017331
Regions
	Topological domain	20 – 1370	1351	Extracellular Potential
	Transmembrane	1371 – 1393	23	Helical; Potential
	Topological domain	1394 – 1613	220	Cytoplasmic Potential
	Repeat	63 – 106	44	LDL-receptor class B 1
	Repeat	107 – 149	43	LDL-receptor class B 2
	Repeat	150 – 193	44	LDL-receptor class B 3
	Repeat	194 – 235	42	LDL-receptor class B 4
	Repeat	236 – 277	42	LDL-receptor class B 5
	Domain	282 – 324	43	EGF-like 1
	Repeat	372 – 414	43	LDL-receptor class B 6
	Repeat	415 – 457	43	LDL-receptor class B 7
	Repeat	458 – 501	44	LDL-receptor class B 8
	Repeat	502 – 542	41	LDL-receptor class B 9
	Repeat	543 – 587	45	LDL-receptor class B 10
	Domain	588 – 628	41	EGF-like 2
	Repeat	674 – 716	43	LDL-receptor class B 11
	Repeat	717 – 759	43	LDL-receptor class B 12
	Repeat	760 – 802	43	LDL-receptor class B 13
	Repeat	803 – 842	40	LDL-receptor class B 14
	Repeat	843 – 885	43	LDL-receptor class B 15
	Domain	889 – 930	42	EGF-like 3
	Repeat	977 – 1025	49	LDL-receptor class B 16
	Repeat	1026 – 1068	43	LDL-receptor class B 17
	Repeat	1069 – 1113	45	LDL-receptor class B 18
	Repeat	1114 – 1156	43	LDL-receptor class B 19
	Repeat	1157 – 1198	42	LDL-receptor class B 20
	Domain	1203 – 1244	42	EGF-like 4
	Domain	1248 – 1286	39	LDL-receptor class A 1
	Domain	1287 – 1323	37	LDL-receptor class A 2
	Domain	1325 – 1361	37	LDL-receptor class A 3
	Region	20 – 275	256	Beta-propeller 1
	Region	328 – 589	262	Beta-propeller 2
	Region	631 – 890	260	Beta-propeller 3
	Region	933 – 1202	270	Beta-propeller 4
	Motif	1487 – 1493	7	PPPSP motif A
	Motif	1527 – 1534	8	PPPSP motif B
	Motif	1568 – 1575	8	PPPSP motif C
	Motif	1588 – 1593	6	PPPSP motif D
	Motif	1603 – 1610	8	PPPSP motif E
	Compositional bias	1469 – 1475	7	Poly-Ser
	Compositional bias	1566 – 1573	8	Poly-Pro
	Compositional bias	1603 – 1608	6	Poly-Pro
Amino acid modifications
	Modified residue	1420	1	Phosphoserine; by CK1 By similarity
	Modified residue	1430	1	Phosphoserine; by CK1 By similarity
	Modified residue	1479	1	Phosphothreonine By similarity
	Modified residue	1490	1	Phosphoserine; by CDK14, GRK5 and GRK6 By similarity
	Modified residue	1493	1	Phosphothreonine; by CK1 By similarity
	Lipidation	1394	1	S-palmitoyl cysteine By similarity
	Lipidation	1399	1	S-palmitoyl cysteine By similarity
	Glycosylation	42	1	N-linked (GlcNAc...) Potential
	Glycosylation	81	1	N-linked (GlcNAc...) Potential
	Glycosylation	281	1	N-linked (GlcNAc...) Potential
	Glycosylation	433	1	N-linked (GlcNAc...) Potential
	Glycosylation	486	1	N-linked (GlcNAc...) Potential
	Glycosylation	692	1	N-linked (GlcNAc...) Potential
	Glycosylation	859	1	N-linked (GlcNAc...) Potential
	Glycosylation	865	1	N-linked (GlcNAc...) Potential
	Glycosylation	926	1	N-linked (GlcNAc...) Potential
	Disulfide bond	286 ↔ 297		By similarity
	Disulfide bond	293 ↔ 308		By similarity
	Disulfide bond	310 ↔ 323		By similarity
	Disulfide bond	592 ↔ 603		By similarity
	Disulfide bond	599 ↔ 612		By similarity
	Disulfide bond	614 ↔ 627		By similarity
	Disulfide bond	893 ↔ 904		By similarity
	Disulfide bond	900 ↔ 914		By similarity
	Disulfide bond	916 ↔ 929		By similarity
	Disulfide bond	1207 ↔ 1218		By similarity
	Disulfide bond	1214 ↔ 1228		By similarity
	Disulfide bond	1230 ↔ 1243		By similarity
	Disulfide bond	1249 ↔ 1263		By similarity
	Disulfide bond	1256 ↔ 1276		By similarity
	Disulfide bond	1270 ↔ 1285		By similarity
	Disulfide bond	1288 ↔ 1300		By similarity
	Disulfide bond	1295 ↔ 1313		By similarity
	Disulfide bond	1307 ↔ 1322		By similarity
	Disulfide bond	1326 ↔ 1338		By similarity
	Disulfide bond	1333 ↔ 1351		By similarity
	Disulfide bond	1345 ↔ 1360		By similarity
	Cross-link	1403		Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Natural variations
	Natural variant	886	1	R → W in rs. Ref.9 Ref.10
Experimental info
	Sequence conflict	83	1	S → T in AAH60704. Ref.2
	Sequence conflict	317	1	M → L in AAH60704. Ref.2
	Sequence conflict	586	1	V → I in AAH60704. Ref.2
	Sequence conflict	622	1	G → S in AAH60704. Ref.2
	Sequence conflict	933	1	S → T in AAH60704. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O88572 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 3C2ABC8EEEB17622	FASTA	1,613	180,255
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00271594.
PIR	JE0273.
RefSeq	NP_032540.2. NM_008514.4.
UniGene	Mm.321990.
3D structure databases
ProteinModelPortal	O88572.
SMR	O88572. Positions 20-1363.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-46460N.
IntAct	O88572. 1 interaction.
STRING	10090.ENSMUSP00000032322.
PTM databases
PhosphoSite	O88572.
Proteomic databases
PaxDb	O88572.
PRIDE	O88572.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000032322; ENSMUSP00000032322; ENSMUSG00000030201.
GeneID	16974.
KEGG	mmu:16974.
UCSC	uc009ekl.2. mouse.
Organism-specific databases
CTD	4040.
MGI	MGI:1298218. Lrp6.
Phylogenomic databases
eggNOG	NOG121718.
GeneTree	ENSGT00690000101695.
HOGENOM	HOG000230697.
HOVERGEN	HBG049167.
InParanoid	O88572.
KO	K03068.
OrthoDB	EOG4RNB7H.
Gene expression databases
ArrayExpress	O88572.
Bgee	O88572.
Genevestigator	O88572.
GermOnline	ENSMUSG00000030201. Mus musculus.
Family and domain databases
Gene3D	2.120.10.30. 4 hits. 4.10.400.10. 3 hits.
InterPro	IPR011042. 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]
Pfam	PF00057. Ldl_recept_a. 3 hits. PF00058. Ldl_recept_b. 13 hits. [Graphical view]
PIRSF	PIRSF036314. LDL_recpt-rel_p5/6. 1 hit.
SMART	SM00181. EGF. 4 hits. SM00192. LDLa. 3 hits. SM00135. LY. 20 hits. [Graphical view]
SUPFAM	SSF57424. LDL_rcpt_classA_cys-rich. 3 hits.
PROSITE	PS00022. EGF_1. False negative. PS01186. EGF_2. 1 hit. PS50026. EGF_3. False negative. PS01209. LDLRA_1. 3 hits. PS50068. LDLRA_2. 3 hits. PS51120. LDLRB. 20 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	291034.
SOURCE	Search...

Entry information

Entry name

LRP6_MOUSE

Accession

Primary (citable) accession number: O88572

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	November 1, 1998
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program