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UniProtKB - O75581 (LRP6_HUMAN)

Protein

Low-density lipoprotein receptor-related protein 6

Gene

LRP6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

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

GO - Molecular functioni

  • apolipoprotein binding Source: GO_Central
  • coreceptor activity involved in canonical Wnt signaling pathway Source: ParkinsonsUK-UCL
  • coreceptor activity involved in Wnt signaling pathway Source: BHF-UCL
  • frizzled binding Source: BHF-UCL
  • identical protein binding Source: IntAct
  • kinase inhibitor activity Source: BHF-UCL
  • low-density lipoprotein particle receptor activity Source: MGI
  • protein homodimerization activity Source: BHF-UCL
  • signaling receptor binding Source: BHF-UCL
  • toxin transmembrane transporter activity Source: BHF-UCL
  • Wnt-activated receptor activity Source: InterPro
  • Wnt-protein binding Source: BHF-UCL
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein, Receptor
Biological processEndocytosis, Wnt signaling pathway

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
Low-density lipoprotein receptor-related protein 6
Short name:
LRP-6
Gene namesi
Name:LRP6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

EuPathDBiHostDB:ENSG00000070018.8
HGNCiHGNC:6698 LRP6
MIMi603507 gene
neXtProtiNX_O75581

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; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini20 – 1370ExtracellularSequence analysisAdd BLAST1351
Transmembranei1371 – 1393HelicalSequence analysisAdd BLAST23
Topological domaini1394 – 1613CytoplasmicSequence analysisAdd BLAST220

Keywords - Cellular componenti

Cell membrane, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Involvement in diseasei

Coronary artery disease, autosomal dominant, 2 (ADCAD2)2 Publications
The disease is caused by mutations 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.
See also OMIM:610947
Feature keyPosition(s)DescriptionActionsGraphical viewLength
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 mutations 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).
See also OMIM:616724
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
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 mutation

Organism-specific databases

DisGeNETi4040
MalaCardsiLRP6
MIMi610947 phenotype
616724 phenotype
OpenTargetsiENSG00000070018
Orphaneti411969 NON RARE IN EUROPE: Metabolic syndrome
99798 Oligodontia
PharmGKBiPA30456

Chemistry databases

ChEMBLiCHEMBL3745588

Polymorphism and mutation databases

BioMutaiLRP6

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 19Sequence analysisAdd BLAST19
ChainiPRO_000001733020 – 1613Low-density lipoprotein receptor-related protein 6Add BLAST1594

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi42N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi81N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi281N-linked (GlcNAc...) asparagineSequence analysis1
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
Lipidationi1394S-palmitoyl cysteine1 Publication1
Lipidationi1399S-palmitoyl cysteine1 Publication1
Cross-linki1403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)1 Publication
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

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

EPDiO75581
MaxQBiO75581
PaxDbiO75581
PeptideAtlasiO75581
PRIDEiO75581
ProteomicsDBi50097

PTM databases

GlyConnecti1469
iPTMnetiO75581
PhosphoSitePlusiO75581
SwissPalmiO75581

Expressioni

Tissue specificityi

Widely coexpressed with LRP5 during embryogenesis and in adult tissues.

Inductioni

Decreased levels on WNT3A stimulation.1 Publication

Gene expression databases

BgeeiENSG00000070018 Expressed in 234 organ(s), highest expression level in metanephros
CleanExiHS_LRP6
ExpressionAtlasiO75581 baseline and differential
GenevisibleiO75581 HS

Organism-specific databases

HPAiCAB004490
HPA029925

Interactioni

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).By similarity21 Publications

Binary interactionsi

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi110219, 51 interactors
DIPiDIP-29884N
IntActiO75581, 39 interactors
MINTiO75581
STRINGi9606.ENSP00000261349

Chemistry databases

BindingDBiO75581

Structurei

Secondary structure

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

3D structure databases

ProteinModelPortaliO75581
SMRiO75581
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO75581

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
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
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
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
Motifi1487 – 1493PPPSP motif A7
Motifi1527 – 1534PPPSP motif B8
Motifi1568 – 1575PPPSP motif C8
Motifi1588 – 1593PPPSP motif D6
Motifi1603 – 1610PPPSP motif E8

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

Sequence similaritiesi

Belongs to the LDLR family.Curated

Keywords - Domaini

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

Phylogenomic databases

eggNOGiENOG410IPT4 Eukaryota
ENOG410XSY5 LUCA
GeneTreeiENSGT00760000118968
HOGENOMiHOG000230697
HOVERGENiHBG049167
InParanoidiO75581
KOiK03068
OMAiWQELDQP
OrthoDBiEOG091G0178
PhylomeDBiO75581
TreeFamiTF315253

Family and domain databases

CDDicd00112 LDLa, 3 hits
Gene3Di2.120.10.30, 4 hits
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

Sequence (1+)i

Sequence statusi: Complete.

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
Checksum:i413D2CF70A5D8B5C
GO

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:
H0YGW5H0YGW5_HUMAN
Low-density lipoprotein receptor-re...
LRP6
1,478Annotation score:
F5H0Z3F5H0Z3_HUMAN
Low-density lipoprotein receptor-re...
LRP6
75Annotation score:
H0YGH0H0YGH0_HUMAN
Low-density lipoprotein receptor-re...
LRP6
69Annotation score:

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:rs34815107Ensembl.1

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
UniGeneiHs.584775
Hs.658913

Genome annotation databases

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

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

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
UniGeneiHs.584775
Hs.658913

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
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[»]
ProteinModelPortaliO75581
SMRiO75581
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110219, 51 interactors
DIPiDIP-29884N
IntActiO75581, 39 interactors
MINTiO75581
STRINGi9606.ENSP00000261349

Chemistry databases

BindingDBiO75581
ChEMBLiCHEMBL3745588

PTM databases

GlyConnecti1469
iPTMnetiO75581
PhosphoSitePlusiO75581
SwissPalmiO75581

Polymorphism and mutation databases

BioMutaiLRP6

Proteomic databases

EPDiO75581
MaxQBiO75581
PaxDbiO75581
PeptideAtlasiO75581
PRIDEiO75581
ProteomicsDBi50097

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4040
DisGeNETi4040
EuPathDBiHostDB:ENSG00000070018.8
GeneCardsiLRP6
H-InvDBiHIX0036693
HGNCiHGNC:6698 LRP6
HPAiCAB004490
HPA029925
MalaCardsiLRP6
MIMi603507 gene
610947 phenotype
616724 phenotype
neXtProtiNX_O75581
OpenTargetsiENSG00000070018
Orphaneti411969 NON RARE IN EUROPE: Metabolic syndrome
99798 Oligodontia
PharmGKBiPA30456
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IPT4 Eukaryota
ENOG410XSY5 LUCA
GeneTreeiENSGT00760000118968
HOGENOMiHOG000230697
HOVERGENiHBG049167
InParanoidiO75581
KOiK03068
OMAiWQELDQP
OrthoDBiEOG091G0178
PhylomeDBiO75581
TreeFamiTF315253

Enzyme and pathway databases

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

ChiTaRSiLRP6 human
EvolutionaryTraceiO75581
GeneWikiiLRP6
GenomeRNAii4040
PROiPR:O75581
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000070018 Expressed in 234 organ(s), highest expression level in metanephros
CleanExiHS_LRP6
ExpressionAtlasiO75581 baseline and differential
GenevisibleiO75581 HS

Family and domain databases

CDDicd00112 LDLa, 3 hits
Gene3Di2.120.10.30, 4 hits
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
ProtoNetiSearch...

Entry informationi

Entry nameiLRP6_HUMAN
AccessioniPrimary (citable) accession number: O75581
Secondary accession number(s): Q17RZ2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: January 11, 2011
Last modified: November 7, 2018
This is version 169 of the entry and version 2 of the sequence. See complete history.
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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  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. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
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