[1]	NUCLEOTIDE SEQUENCE [MRNA]. TISSUE=Kidney; DOI=10.1006/bbrc.1998.9061; PubMed=9704021 [NCBI, ExPASy, EBI, Israel, Japan] 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.; "Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family."; Biochem. Biophys. Res. Commun. 248:879-888(1998).
[2]	NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-1062. TISSUE=Cerebellum; DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team; "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."; Genome Res. 14:2121-2127(2004).
[3]	FUNCTION, AND DOMAINS REQUIRED FOR INTERACTION WITH DKK1 AND DKK2. DOI=10.1038/35077108; PubMed=11357136 [NCBI, ExPASy, EBI, Israel, Japan] Mao B., Wu W., Li Y., Hoppe D., Stannek P., Glinka A., Niehrs C.; "LDL-receptor-related protein 6 is a receptor for Dickkopf proteins."; Nature 411:321-325(2001).
[4]	INTERACTION WITH FZD5; DKK1 AND DKK2. DOI=10.1074/jbc.M300191200; PubMed=12857724 [NCBI, ExPASy, EBI, Israel, Japan] Caricasole A., Ferraro T., Iacovelli L., Barletta E., Caruso A., Melchiorri D., Terstappen G.C., Nicoletti F.; "Functional characterization of WNT7A signaling in PC12 cells: interaction with A FZD5 x LRP6 receptor complex and modulation by Dickkopf proteins."; J. Biol. Chem. 278:37024-37031(2003).
[5]	REVIEW. DOI=10.1242/dev.01117; PubMed=15084453 [NCBI, ExPASy, EBI, Israel, Japan] He X., Semenov M., Tamai K., Zeng X.; "LDL receptor-related proteins 5 and 6 in Wnt/beta-catenin signaling: arrows point the way."; Development 131:1663-1677(2004).
[6]	VARIANT ADCAD2 CYS-611, AND CHARACTERIZATION OF VARIANT ADCAD2 CYS-611. DOI=10.1126/science.1136370; PubMed=17332414 [NCBI, ExPASy, EBI, Israel, Japan] Mani A., Radhakrishnan J., Wang H., Mani A., Mani M.-A., Nelson-Williams C., Carew K.S., Mane S., Najmabadi H., Wu D., Lifton R.P.; "LRP6 mutation in a family with early coronary disease and metabolic risk factors."; Science 315:1278-1282(2007).

Comments

FUNCTION: Essential for the Wnt/beta catenin signaling pathway, probably by acting as a coreceptor together with Frizzled for Wnt. Specific high-affinity receptor for DKK1 and DKK2, but not DKK3. The interaction with DKK1 blocks LRP6-mediated Wnt/beta catenin signaling via LRP6 removal via Kremen proteins-mediated endocytosis.
SUBUNIT: Interacts with RSPO1 and RSPO3 (By similarity). Interacts with FZD5. Essential component of the Wnt7 receptor complex. Wnt7A interacts with the LRP6/FZD5 complex. This interaction is antagonized by DKK1 and DKK3.
INTERACTION:
Q9H6X2:ANTXR1; NbExp=1; IntAct=EBI-910915, EBI-905643;
P58335:ANTXR2; NbExp=1; IntAct=EBI-910915, EBI-456840;
SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein (Potential).
TISSUE SPECIFICITY: Widely co-expressed with LRP5 during embryogenesis and in adult tissues.
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.
DISEASE: Defects in LRP6 are the cause of autosomal dominant coronary artery disease type 2 (ADCAD2) [MIM:610947].
SIMILARITY: Belongs to the LDLR family.
SIMILARITY: Contains 4 EGF-like domains.
SIMILARITY: Contains 3 LDL-receptor class A domains.
SIMILARITY: Contains 20 LDL-receptor class B repeats.

Copyright

Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.

Cross-references

Sequence databases

EMBL

AF074264; AAC33006.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC117136; AAI17137.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]
BC126405; AAI26406.1; -; mRNA.	[EMBL / GenBank / DDBJ] [CoDingSequence]

IPI00000203; -.

JE0272; JE0272.

NP_002327.2; -.

3D structure databases

HSSP

P01130; 1AJJ. [HSSP ENTRY / SWISS-3DIMAGE / PDB]

ModBase

O75581.

Protein-protein interaction databases

IntAct

O75581; 2.

PTM databases

PhosphoSite

O75581; -.

Enzyme and pathway databases

Pathway_Interaction_DB

wnt_canonical_pathway; Canonical Wnt signaling pathway.
ps1pathway; Presenilin action in Notch and Wnt signaling.
wnt_signaling_pathway; Wnt signaling.

Organism-specific databases

GC12M012164; -.

HIX0036693; -.

HGNC:6698; LRP6.

CAB004490; -.

603507; gene. [NCBI / EBI]
610947; phenotype. [NCBI / EBI]

Orphanet

94062; Coronary artery disease - hyperlipidemia - hypertension - diabetes - osteoporosis.

PharmGKB

PA30456; -.

Gene expression databases

O75581; -.

O75581; -.

HS_LRP6; -.

ENSG00000070018; Homo sapiens.

Ontologies

GO:0016021;	Cellular component: integral to membrane (traceable author statement from ProtInc).
GO:0005886;	Cellular component: plasma membrane (inferred from direct assay from MGI).
GO:0005041;	Molecular function: low-density lipoprotein receptor activity (inferred from direct assay from MGI).
GO:0006897;	Biological process: endocytosis (inferred from electronic annotation from UniProtKB-KW).
GO:0007275;	Biological process: multicellular organismal development (inferred from electronic annotation from UniProtKB-KW).
GO:0016055;	Biological process: Wnt receptor signaling pathway (inferred from direct assay from MGI).
QuickGo view.

Family and domain databases

InterPro

IPR011042; 6-blade_b-propeller_TolB-like.
IPR006209; EGF.
IPR006210; EGF-like.
IPR013032; EGF-like_reg_CS.
IPR002172; LDL_rcpt_classA_cys-rich.
IPR000033; LDLR.
IPR017049; Low_density_Lipo_rcpt-rel_p5/6.
Graphical view of domain structure.

Gene3D

G3DSA:2.120.10.30; 6-blade_b-propeller_TolB-like; 4.
G3DSA:4.10.400.10; LDL_rcpt_classA_cys-rich; 3.

Pfam

PF00008; EGF; 4.
PF00057; Ldl_recept_a; 3.
PF00058; Ldl_recept_b; 20.
Pfam graphical view of domain structure.

PIRSF

PIRSF036314; LDL_recpt-rel_p5/6; 1.

PRINTS

PR00261; LDLRECEPTOR.

SMART

SM00181; EGF; 4.
SM00192; LDLa; 3.
SM00135; LY; 20.
SMART graphical view of domain structure.

PROSITE

PS00022; EGF_1; FALSE_NEG.
PS01186; EGF_2; 1.
PS50026; EGF_3; FALSE_NEG.
PS01209; LDLRA_1; 3.
PS50068; LDLRA_2; 3.
PS51120; LDLRB; 19.
PROSITE graphical view of domain structure (profiles).

Proteomic databases

PRIDE

O75581; -.

Genome annotation databases

Ensembl

ENSG00000070018; Homo sapiens. [Contig view]

GeneID

4040; -.

KEGG

hsa:4040; -.

Phylogenomic databases

HOGENOM

O75581; -.

HOVERGEN

O75581; -.

Other

15822; -.

LRP6; Homo sapiens.

View cluster of proteins with at least 50% / 90% / 100% identity.

Keywords

Developmental protein; Disease mutation; Disulfide bond; EGF-like domain; Endocytosis; Glycoprotein; Membrane; Polymorphism; Receptor; Repeat; Signal; Transmembrane; Wnt signaling pathway.

Features

Feature table viewer

Feature aligner

`Key`	`From To`	`Length`	`Description`	`FTId`
`SIGNAL`	`1 19`	`19`	`Potential.`
`CHAIN`	`20 1613`	`1594`	`Low-density lipoprotein receptor-related protein 6.`	`PRO_0000017330`
`TOPO_DOM`	`20 1370`	`1351`	`Extracellular (Potential).`
`TRANSMEM`	`1371 1393`	`23`	`Potential.`
`TOPO_DOM`	`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`	`194 236`	`43`	`LDL-receptor class B 4.`
`REPEAT`	`237 276`	`40`	`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`	`543 584`	`42`	`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.`
`MOTIF`	`1487 1491`	`5`	`PPPSP motif.`
`MOTIF`	`1604 1608`	`5`	`PPPSP motif.`
`CARBOHYD`	`42 42`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`81 81`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`281 281`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`433 433`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`486 486`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`692 692`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`859 859`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`865 865`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`926 926`		`N-linked (GlcNAc...) (Potential).`
`CARBOHYD`	`1039 1039`		`N-linked (GlcNAc...) (Potential).`
`DISULFID`	`286 297`		`By similarity.`
`DISULFID`	`293 308`		`By similarity.`
`DISULFID`	`310 323`		`By similarity.`
`DISULFID`	`592 603`		`By similarity.`
`DISULFID`	`599 612`		`By similarity.`
`DISULFID`	`614 627`		`By similarity.`
`DISULFID`	`893 904`		`By similarity.`
`DISULFID`	`900 914`		`By similarity.`
`DISULFID`	`916 929`		`By similarity.`
`DISULFID`	`1207 1218`		`By similarity.`
`DISULFID`	`1214 1228`		`By similarity.`
`DISULFID`	`1230 1243`		`By similarity.`
`DISULFID`	`1249 1263`		`By similarity.`
`DISULFID`	`1256 1276`		`By similarity.`
`DISULFID`	`1270 1285`		`By similarity.`
`DISULFID`	`1288 1300`		`By similarity.`
`DISULFID`	`1295 1313`		`By similarity.`
`DISULFID`	`1307 1322`		`By similarity.`
`DISULFID`	`1326 1338`		`By similarity.`
`DISULFID`	`1333 1351`		`By similarity.`
`DISULFID`	`1345 1360`		`By similarity.`
`VARIANT`	`483 483`	`1`	`V -> I (in dbSNP:rs7975614 [NCBI]).`	`VAR_030349`
`VARIANT`	`611 611`	`1`	`R -> C (in ADCAD2; impairs Wnt signaling in vitro).`	`VAR_034701`
`VARIANT`	`817 817`	`1`	`S -> C (in dbSNP:rs2302686 [NCBI]).`	`VAR_030350`
`VARIANT`	`1062 1062`	`1`	`I -> V (in dbSNP:rs2302685 [NCBI]).`	`VAR_024520`
`VARIANT`	`1401 1401`	`1`	`R -> H (in dbSNP:rs34815107 [NCBI]).`	`VAR_034702`

Sequence information

Length: 1613 AA [This is the length of the unprocessed precursor]

Molecular weight: 180443 Da [This is the MW of the unprocessed precursor]

CRC64: 4BC1141E395D8B5B [This is a checksum on the sequence]

        10         20         30         40         50         60 
MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF 

        70         80         90        100        110        120 
SHGLIYWSDV SEEAIKRTEF NKTESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE 

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

       190        200        210        220        230        240 
IYWPNGLTLD YEEQKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDILYWT 

       250        260        270        280        290        300 
DWSTHSILAC NKYTGEGLRE IHSDIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 

       310        320        330        340        350        360 
PVKPFYQCAC PTGVKLLENG 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 EGKIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL 

       550        560        570        580        590        600 
LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TNVHRVIGSN PCAEENGGCS 

       610        620        630        640        650        660 
HLCLYRPQGL RCACPIGFEL ISDMKTCIVP 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 DTNLIESSNM LGLNREVIAD DLPHPFGLTQ 

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

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

       970        980        990       1000       1010       1020 
IHSLRNVRAI DYDPLDKQLY WIDSRQNMIR KAQEDGSQGF TVVVSSVPSQ NLEIQPYDLS 

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

      1090       1100       1110       1120       1130       1140 
PKIERAALDG TEREVLFFSG LSKPIALALD SRLGKLFWAD 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 PQQFTCFTGE 

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

      1330       1340       1350       1360       1370       1380 
NCEVLCLIDQ FRCANGQCIG KHKKCDHNVD CSDKSDELDC YPTEEPAPQA TNTVGSVIGV 

      1390       1400       1410       1420       1430       1440 
IVTIFVSGTV YFICQRMLCP RMKGDGETMT NDYVVHGPAS 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 ATAKGYTSDL 

      1570       1580       1590       1600       1610 
NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS

O75581 in FASTA format

View entry in raw text format (no links)
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	BLAST submission on ExPASy/SIB or at NCBI (USA)		Sequence analysis tools: ProtParam, ProtScale, Compute pI/Mw, PeptideMass, PeptideCutter, Dotlet (Java)
	ScanProsite, MotifScan		Submit a homology modeling request to SWISS-MODEL
	NPSA Sequence analysis tools