LRP6_MOUSE
ID LRP6_MOUSE Reviewed; 1613 AA.
AC O88572;
DT 10-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=Low-density lipoprotein receptor-related protein 6;
DE Short=LRP-6;
DE Flags: Precursor;
GN Name=Lrp6;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=9704021; DOI=10.1006/bbrc.1998.9061;
RA Brown S.D., Twells R.C., Hey P.J., Cox R.D., Levy E.R., Soderman A.R.,
RA Metzker M.L., Caskey C.T., Todd J.A., Hess J.F.;
RT "Isolation and characterization of LRP6, a novel member of the low density
RT lipoprotein receptor gene family.";
RL Biochem. Biophys. Res. Commun. 248:879-888(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP INTERACTION WITH MESD, SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=12581525; DOI=10.1016/s0092-8674(03)00045-x;
RA Hsieh J.-C., Lee L., Zhang L., Wefer S., Brown K., DeRossi C., Wines M.E.,
RA Rosenquist T., Holdener B.C.;
RT "Mesd encodes an LRP5/6 chaperone essential for specification of mouse
RT embryonic polarity.";
RL Cell 112:355-367(2003).
RN [4]
RP INTERACTION WITH MDK.
RX PubMed=12573468; DOI=10.1016/s0168-0102(02)00226-2;
RA Sakaguchi N., Muramatsu H., Ichihara-Tanaka K., Maeda N., Noda M.,
RA Yamamoto T., Michikawa M., Ikematsu S., Sakuma S., Muramatsu T.;
RT "Receptor-type protein tyrosine phosphatase zeta as a component of the
RT signaling receptor complex for midkine-dependent survival of embryonic
RT neurons.";
RL Neurosci. Res. 45:219-224(2003).
RN [5]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=15142971; DOI=10.1242/dev.01137;
RA Kelly O.G., Pinson K.I., Skarnes W.C.;
RT "The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in
RT mice.";
RL Development 131:2803-2815(2004).
RN [6]
RP INTERACTION WITH RSPO1 AND RSPO3.
RX PubMed=16543246; DOI=10.1074/jbc.m508324200;
RA Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.;
RT "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled
RT 8 and LRP6 receptors and activate beta-catenin-dependent gene expression.";
RL J. Biol. Chem. 281:13247-13257(2006).
RN [7]
RP INTERACTION WITH GRB10.
RX PubMed=17376403; DOI=10.1016/j.bbrc.2007.03.019;
RA Tezuka N., Brown A.M., Yanagawa S.;
RT "GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt
RT signaling pathway.";
RL Biochem. Biophys. Res. Commun. 356:648-654(2007).
RN [8]
RP PHOSPHORYLATION AT SER-1490, INDUCTION, AND SUBCELLULAR LOCATION.
RX PubMed=17698587; DOI=10.1128/mcb.00773-07;
RA Khan Z., Vijayakumar S., de la Torre T.V., Rotolo S., Bafico A.;
RT "Analysis of endogenous LRP6 function reveals a novel feedback mechanism by
RT which Wnt negatively regulates its receptor.";
RL Mol. Cell. Biol. 27:7291-7301(2007).
RN [9]
RP INTERACTION WITH DRAXIN.
RX PubMed=19857465; DOI=10.1016/j.bbrc.2009.10.113;
RA Miyake A., Takahashi Y., Miwa H., Shimada A., Konishi M., Itoh N.;
RT "Neucrin is a novel neural-specific secreted antagonist to canonical Wnt
RT signaling.";
RL Biochem. Biophys. Res. Commun. 390:1051-1055(2009).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [11]
RP INTERACTION WITH LMBR1L.
RX PubMed=31073040; DOI=10.1126/science.aau0812;
RA Choi J.H., Zhong X., McAlpine W., Liao T.C., Zhang D., Fang B., Russell J.,
RA Ludwig S., Nair-Gill E., Zhang Z., Wang K.W., Misawa T., Zhan X., Choi M.,
RA Wang T., Li X., Tang M., Sun Q., Yu L., Murray A.R., Moresco E.M.Y.,
RA Beutler B.;
RT "LMBR1L regulates lymphopoiesis through Wnt/beta-catenin signaling.";
RL Science 364:0-0(2019).
RN [12]
RP VARIANT RS TRP-886.
RX PubMed=15469977; DOI=10.1242/dev.01405;
RA Kokubu C., Heinzmann U., Kokubu T., Sakai N., Kubota T., Kawai M.,
RA Wahl M.B., Galceran J., Grosschedl R., Ozono K., Imai K.;
RT "Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required
RT for proper somitogenesis and osteogenesis.";
RL Development 131:5469-5480(2004).
RN [13]
RP CHARACTERIZATION OF VARIANT RS TRP-886, SUBCELLULAR LOCATION, AND
RP INTERACTION WITH DKK1; WNT1 AND MESD.
RX PubMed=18505367; DOI=10.1359/jbmr.080512;
RA Kubota T., Michigami T., Sakaguchi N., Kokubu C., Suzuki A., Namba N.,
RA Sakai N., Nakajima S., Imai K., Ozono K.;
RT "Lrp6 hypomorphic mutation affects bone mass through bone resorption in
RT mice and impairs interaction with Mesd.";
RL J. Bone Miner. Res. 23:1661-1671(2008).
CC -!- FUNCTION: Component of the Wnt-Fzd-LRP5-LRP6 complex that triggers
CC beta-catenin signaling through inducing aggregation of receptor-ligand
CC complexes into ribosome-sized signalsomes. Cell-surface coreceptor of
CC Wnt/beta-catenin signaling, which plays a pivotal role in bone
CC formation. The Wnt-induced Fzd/LRP6 coreceptor complex recruits DVL1
CC polymers to the plasma membrane which, in turn, recruits the
CC AXIN1/GSK3B-complex to the cell surface promoting the formation of
CC signalsomes and inhibiting AXIN1/GSK3-mediated phosphorylation and
CC destruction of beta-catenin. Required for posterior patterning of the
CC epiblast during gastrulation (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:15142971}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Forms
CC phosphorylated oligomer aggregates on Wnt-signaling (By similarity).
CC Component of the Wnt-Fzd-LRP5-LRP6 complex. Interacts (via the
CC extracellular domain) with WNT1; the interaction is enhanced by prior
CC formation of the Wnt/Fzd complex. Interacts (via the beta-propeller
CC regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions
CC 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a
CC coreceptor complex for Wnt signaling and is inhibited by DKK1 and
CC DRAXIN. Interacts (via beta propeller region) with DKK1; the
CC interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2.
CC Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the
CC interaction recruits the AXIN1/GSK3B complex to cell surface LRP6
CC signalsomes. Interacts (via the extracellular domain) with RSPO1; the
CC interaction activates Wnt/beta-catenin signaling. Interacts (via the
CC extracellular domain) with RSPO3 (via the cysteine rich domain); the
CC interaction activates Wnt/beta-catenin signaling. Interacts (via the
CC beta-propeller regions 1 and 2) with SOST; the interaction competes
CC with DKK1 for binding for inhibiting beta-catenin signaling. Interacts
CC (via the cytoplasmic domain) with CSNKIE; the interaction
CC phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated
CC phosphorylation of beta-catenin (By similarity). Interacts with DRAXIN;
CC the interaction inhibits Wnt signaling. Interacts with GRB10; the
CC interaction prevents AXIN1 binding, thus negatively regulating the Wnt
CC signaling pathway. Interacts with MESD; the interaction prevents the
CC formation of LRP6 aggregates and targets LRP6 to the plasma membrane.
CC Interacts with MACF1. Interacts with DAB2; the interaction involves
CC LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-
CC mediated endocytosis. Interacts with TMEM198 (By similarity). Interacts
CC with CAPRIN2; the interaction promotes LRP6 phosphorylation at Ser-1490
CC (By similarity). Found in a complex with CAPRIN2, CCNY and CDK14 during
CC G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding
CC to CCNY via its N terminus and to CDK14 via its C terminus. Interacts
CC with LYPD6. Forms a ternary complex with DKK1 and KREM1 (By
CC similarity). Interacts with KREM1 in a DKK1-dependent manner (By
CC similarity). Interacts with MDK: this interaction is calcium dependent
CC (PubMed:12573468). Interacts with LMBR1L (PubMed:31073040).
CC {ECO:0000250|UniProtKB:O75581, ECO:0000269|PubMed:12573468,
CC ECO:0000269|PubMed:12581525, ECO:0000269|PubMed:16543246,
CC ECO:0000269|PubMed:17376403, ECO:0000269|PubMed:18505367,
CC ECO:0000269|PubMed:19857465, ECO:0000269|PubMed:31073040}.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane
CC protein. Endoplasmic reticulum. Membrane raft
CC {ECO:0000250|UniProtKB:O75581}. Note=On Wnt signaling, undergoes a
CC cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane
CC location. Released from the endoplasmic reticulum on palmitoylation.
CC Mono-ubiquitination retains it in the endoplasmic reticulum in the
CC absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates
CC and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-
CC signalsomes (By similarity). Chaperoned to the plasma membrane by MESD.
CC {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in early embryo. Broadly expressed
CC throughout the embryonic ectoderm and in nascent mesoderm, and in
CC endoderm emerging from the primitive streak.
CC {ECO:0000269|PubMed:15142971}.
CC -!- DOMAIN: The YWTD-EGF-like domains 1 and 2 are required for the
CC interaction with Wnt-frizzled complex. The YWTD-EGF-like domains 3 and
CC 4 are required for the interaction with DKK1 (By similarity).
CC {ECO:0000250}.
CC -!- DOMAIN: The PPPSP motifs play a central role in signal transduction by
CC being phosphorylated, leading to activate the Wnt signaling pathway.
CC -!- PTM: Dual phosphorylation of cytoplasmic PPPSP motifs sequentially by
CC GSK3 and CK1 is required for AXIN1-binding, and subsequent
CC stabilization and activation of beta-catenin via preventing GSK3-
CC mediated phosphorylation of beta-catenin. Phosphorylated, in vitro, by
CC GRK5/6 within and outside the PPPSP motifs. Phosphorylation at Ser-1490
CC by CDK14 during G2/M phase leads to regulation of the Wnt signaling
CC pathway during the cell cycle. Phosphorylation by GSK3B is induced by
CC RPSO1 binding and inhibited by DKK1. Phosphorylated, in vitro, by
CC casein kinase I on Thr-1479 (By similarity). {ECO:0000250}.
CC -!- PTM: Undergoes gamma-secretase-dependent regulated intramembrane
CC proteolysis (RIP). The extracellular domain is first released by
CC shedding, and then, through the action of gamma-secretase, the
CC intracellular domain (ICD) is released into the cytoplasm where it is
CC free to bind to GSK3B and to activate canonical Wnt signaling (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Palmitoylation on the two sites near the transmembrane domain
CC leads to release of LRP6 from the endoplasmic reticulum. {ECO:0000250}.
CC -!- PTM: Mono-ubiquitinated which retains LRP6 in the endoplasmic
CC reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the
CC proteasome (By similarity). {ECO:0000250}.
CC -!- PTM: N-glycosylation is required for cell surface location.
CC {ECO:0000250}.
CC -!- DISEASE: Note=Defects in Lrp6 are the cause of Ringelschwanz (rs)
CC phenotype. Rs phenotype is a spontaneous mutation that is characterized
CC by a combination of multiple Wnt-deficient phenotypes including
CC dysmorphologies of the axial skeleton, digits and the neural tube. The
CC establishment of the anteroposterior somite compartments, the
CC epithelialization of nascent somites, and the formation of segment
CC borders are disturbed in (rs) mutants. There is delayed ossification at
CC birth and a low bone mass phenotype in adults. Functional analyses
CC reveal impaired targeting to the plasma surface due to reduced
CC interaction with MESD leading to inhibited Wnt/beta-catenin signaling.
CC {ECO:0000269|PubMed:15469977, ECO:0000269|PubMed:18505367}.
CC -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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DR EMBL; AF074265; AAC33007.1; -; mRNA.
DR EMBL; BC060704; AAH60704.1; -; mRNA.
DR CCDS; CCDS39678.1; -.
DR PIR; JE0273; JE0273.
DR RefSeq; NP_032540.2; NM_008514.4.
DR AlphaFoldDB; O88572; -.
DR SMR; O88572; -.
DR BioGRID; 201203; 12.
DR CORUM; O88572; -.
DR DIP; DIP-46460N; -.
DR IntAct; O88572; 7.
DR MINT; O88572; -.
DR STRING; 10090.ENSMUSP00000032322; -.
DR ChEMBL; CHEMBL4296099; -.
DR GlyGen; O88572; 9 sites.
DR iPTMnet; O88572; -.
DR PhosphoSitePlus; O88572; -.
DR MaxQB; O88572; -.
DR PaxDb; O88572; -.
DR PeptideAtlas; O88572; -.
DR PRIDE; O88572; -.
DR ProteomicsDB; 252525; -.
DR DNASU; 16974; -.
DR GeneID; 16974; -.
DR KEGG; mmu:16974; -.
DR UCSC; uc009ekl.2; mouse.
DR CTD; 4040; -.
DR MGI; MGI:1298218; Lrp6.
DR eggNOG; KOG1215; Eukaryota.
DR InParanoid; O88572; -.
DR OrthoDB; 121310at2759; -.
DR PhylomeDB; O88572; -.
DR TreeFam; TF315253; -.
DR Reactome; R-MMU-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR Reactome; R-MMU-4641262; Disassembly of the destruction complex and recruitment of AXIN to the membrane.
DR Reactome; R-MMU-4641263; Regulation of FZD by ubiquitination.
DR BioGRID-ORCS; 16974; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Lrp6; mouse.
DR PRO; PR:O88572; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; O88572; protein.
DR GO; GO:0005901; C:caveola; ISO:MGI.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0031410; C:cytoplasmic vesicle; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0043025; C:neuronal cell body; ISO:MGI.
DR GO; GO:0005886; C:plasma membrane; IDA:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:1990909; C:Wnt signalosome; ISO:MGI.
DR GO; GO:1990851; C:Wnt-Frizzled-LRP5/6 complex; ISO:MGI.
DR GO; GO:0034185; F:apolipoprotein binding; IPI:MGI.
DR GO; GO:0071936; F:coreceptor activity involved in Wnt signaling pathway; ISO:MGI.
DR GO; GO:0005109; F:frizzled binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0019210; F:kinase inhibitor activity; ISO:MGI.
DR GO; GO:0005041; F:low-density lipoprotein particle receptor activity; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0019534; F:toxin transmembrane transporter activity; IMP:BHF-UCL.
DR GO; GO:0042813; F:Wnt receptor activity; IEA:InterPro.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IMP:MGI.
DR GO; GO:0003401; P:axis elongation; IMP:MGI.
DR GO; GO:0090245; P:axis elongation involved in somitogenesis; IGI:MGI.
DR GO; GO:0046849; P:bone remodeling; IGI:MGI.
DR GO; GO:0060444; P:branching involved in mammary gland duct morphogenesis; IMP:MGI.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IMP:MGI.
DR GO; GO:0061310; P:canonical Wnt signaling pathway involved in cardiac neural crest cell differentiation involved in heart development; IMP:MGI.
DR GO; GO:0061324; P:canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation; IMP:MGI.
DR GO; GO:0042074; P:cell migration involved in gastrulation; IGI:MGI.
DR GO; GO:0098609; P:cell-cell adhesion; ISO:MGI.
DR GO; GO:0071397; P:cellular response to cholesterol; ISO:MGI.
DR GO; GO:0021587; P:cerebellum morphogenesis; IMP:MGI.
DR GO; GO:0021795; P:cerebral cortex cell migration; IMP:MGI.
DR GO; GO:0021987; P:cerebral cortex development; IMP:MGI.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:MGI.
DR GO; GO:0060026; P:convergent extension; IGI:MGI.
DR GO; GO:0071542; P:dopaminergic neuron differentiation; IMP:MGI.
DR GO; GO:0009950; P:dorsal/ventral axis specification; IMP:MGI.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IMP:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IMP:MGI.
DR GO; GO:0035116; P:embryonic hindlimb morphogenesis; IMP:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IGI:MGI.
DR GO; GO:0009880; P:embryonic pattern specification; IMP:MGI.
DR GO; GO:0060059; P:embryonic retina morphogenesis in camera-type eye; IMP:MGI.
DR GO; GO:0035261; P:external genitalia morphogenesis; IMP:MGI.
DR GO; GO:0060325; P:face morphogenesis; IMP:MGI.
DR GO; GO:0045444; P:fat cell differentiation; IMP:MGI.
DR GO; GO:0030900; P:forebrain development; IMP:MGI.
DR GO; GO:0021872; P:forebrain generation of neurons; IMP:MGI.
DR GO; GO:0021861; P:forebrain radial glial cell differentiation; IGI:MGI.
DR GO; GO:0021943; P:formation of radial glial scaffolds; IGI:MGI.
DR GO; GO:0001702; P:gastrulation with mouth forming second; IGI:MGI.
DR GO; GO:0048699; P:generation of neurons; IMP:MGI.
DR GO; GO:0001947; P:heart looping; IGI:MGI.
DR GO; GO:0035108; P:limb morphogenesis; IMP:MGI.
DR GO; GO:0060603; P:mammary gland duct morphogenesis; IGI:MGI.
DR GO; GO:0060596; P:mammary placode formation; IMP:MGI.
DR GO; GO:0010463; P:mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:0008078; P:mesodermal cell migration; IGI:MGI.
DR GO; GO:0030901; P:midbrain development; IMP:MGI.
DR GO; GO:0030917; P:midbrain-hindbrain boundary development; IMP:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IMP:MGI.
DR GO; GO:2000051; P:negative regulation of non-canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:2000151; P:negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis; IGI:MGI.
DR GO; GO:2000162; P:negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis; IGI:MGI.
DR GO; GO:2000168; P:negative regulation of planar cell polarity pathway involved in neural tube closure; IGI:MGI.
DR GO; GO:2000164; P:negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis; IGI:MGI.
DR GO; GO:2000166; P:negative regulation of planar cell polarity pathway involved in pericardium morphogenesis; IGI:MGI.
DR GO; GO:2000149; P:negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis; IGI:MGI.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISO:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISO:MGI.
DR GO; GO:0071901; P:negative regulation of protein serine/threonine kinase activity; ISO:MGI.
DR GO; GO:0034392; P:negative regulation of smooth muscle cell apoptotic process; ISO:MGI.
DR GO; GO:0014033; P:neural crest cell differentiation; ISO:MGI.
DR GO; GO:0014029; P:neural crest formation; ISO:MGI.
DR GO; GO:0001843; P:neural tube closure; IMP:MGI.
DR GO; GO:0021915; P:neural tube development; IGI:MGI.
DR GO; GO:0110135; P:Norrin signaling pathway; IDA:BHF-UCL.
DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI.
DR GO; GO:0003344; P:pericardium morphogenesis; IGI:MGI.
DR GO; GO:0061350; P:planar cell polarity pathway involved in cardiac muscle tissue morphogenesis; IGI:MGI.
DR GO; GO:0061349; P:planar cell polarity pathway involved in cardiac right atrium morphogenesis; IGI:MGI.
DR GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IGI:MGI.
DR GO; GO:0061347; P:planar cell polarity pathway involved in outflow tract morphogenesis; IGI:MGI.
DR GO; GO:0061354; P:planar cell polarity pathway involved in pericardium morphogenesis; IGI:MGI.
DR GO; GO:0061348; P:planar cell polarity pathway involved in ventricular septum morphogenesis; IGI:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR GO; GO:0045780; P:positive regulation of bone resorption; IMP:MGI.
DR GO; GO:0045787; P:positive regulation of cell cycle; ISO:MGI.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; ISO:MGI.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IMP:MGI.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IGI:ARUK-UCL.
DR GO; GO:0045778; P:positive regulation of ossification; IMP:MGI.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:BHF-UCL.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
DR GO; GO:0090009; P:primitive streak formation; IGI:MGI.
DR GO; GO:0072659; P:protein localization to plasma membrane; ISO:MGI.
DR GO; GO:0090118; P:receptor-mediated endocytosis involved in cholesterol transport; IMP:MGI.
DR GO; GO:0060284; P:regulation of cell development; IMP:MGI.
DR GO; GO:0050678; P:regulation of epithelial cell proliferation; IMP:MGI.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0051593; P:response to folic acid; IMP:MGI.
DR GO; GO:0060042; P:retina morphogenesis in camera-type eye; IMP:MGI.
DR GO; GO:0060021; P:roof of mouth development; IMP:MGI.
DR GO; GO:0048705; P:skeletal system morphogenesis; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IGI:MGI.
DR GO; GO:0072089; P:stem cell proliferation; IMP:MGI.
DR GO; GO:0021794; P:thalamus development; IMP:MGI.
DR GO; GO:0060535; P:trachea cartilage morphogenesis; IGI:MGI.
DR GO; GO:0016055; P:Wnt signaling pathway; ISO:MGI.
DR GO; GO:0021874; P:Wnt signaling pathway involved in forebrain neuroblast division; IMP:MGI.
DR GO; GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IMP:MGI.
DR CDD; cd00112; LDLa; 3.
DR Gene3D; 2.120.10.30; -; 4.
DR Gene3D; 4.10.400.10; -; 3.
DR InterPro; IPR011042; 6-blade_b-propeller_TolB-like.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR023415; LDLR_class-A_CS.
DR InterPro; IPR000033; LDLR_classB_rpt.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR017049; LRP5/6.
DR Pfam; PF00057; Ldl_recept_a; 3.
DR Pfam; PF00058; Ldl_recept_b; 11.
DR PIRSF; PIRSF036314; LDL_recpt-rel_p5/6; 1.
DR PRINTS; PR00261; LDLRECEPTOR.
DR SMART; SM00181; EGF; 4.
DR SMART; SM00192; LDLa; 3.
DR SMART; SM00135; LY; 20.
DR SUPFAM; SSF57424; SSF57424; 3.
DR PROSITE; PS01186; EGF_2; 1.
DR PROSITE; PS01209; LDLRA_1; 3.
DR PROSITE; PS50068; LDLRA_2; 3.
DR PROSITE; PS51120; LDLRB; 20.
PE 1: Evidence at protein level;
KW Cell membrane; Developmental protein; Disease variant; Disulfide bond;
KW EGF-like domain; Endocytosis; Endoplasmic reticulum; Glycoprotein;
KW Isopeptide bond; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Receptor; Reference proteome; Repeat; Signal; Transmembrane;
KW Transmembrane helix; Ubl conjugation; Wnt signaling pathway.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1613
FT /note="Low-density lipoprotein receptor-related protein 6"
FT /id="PRO_0000017331"
FT TOPO_DOM 20..1370
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1371..1393
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1394..1613
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT REPEAT 63..106
FT /note="LDL-receptor class B 1"
FT REPEAT 107..149
FT /note="LDL-receptor class B 2"
FT REPEAT 150..193
FT /note="LDL-receptor class B 3"
FT REPEAT 194..235
FT /note="LDL-receptor class B 4"
FT REPEAT 236..277
FT /note="LDL-receptor class B 5"
FT DOMAIN 282..324
FT /note="EGF-like 1"
FT REPEAT 372..414
FT /note="LDL-receptor class B 6"
FT REPEAT 415..457
FT /note="LDL-receptor class B 7"
FT REPEAT 458..501
FT /note="LDL-receptor class B 8"
FT REPEAT 502..542
FT /note="LDL-receptor class B 9"
FT REPEAT 543..587
FT /note="LDL-receptor class B 10"
FT DOMAIN 588..628
FT /note="EGF-like 2"
FT REPEAT 674..716
FT /note="LDL-receptor class B 11"
FT REPEAT 717..759
FT /note="LDL-receptor class B 12"
FT REPEAT 760..802
FT /note="LDL-receptor class B 13"
FT REPEAT 803..842
FT /note="LDL-receptor class B 14"
FT REPEAT 843..885
FT /note="LDL-receptor class B 15"
FT DOMAIN 889..930
FT /note="EGF-like 3"
FT REPEAT 977..1025
FT /note="LDL-receptor class B 16"
FT REPEAT 1026..1068
FT /note="LDL-receptor class B 17"
FT REPEAT 1069..1113
FT /note="LDL-receptor class B 18"
FT REPEAT 1114..1156
FT /note="LDL-receptor class B 19"
FT REPEAT 1157..1198
FT /note="LDL-receptor class B 20"
FT DOMAIN 1203..1244
FT /note="EGF-like 4"
FT DOMAIN 1248..1286
FT /note="LDL-receptor class A 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1287..1323
FT /note="LDL-receptor class A 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DOMAIN 1325..1361
FT /note="LDL-receptor class A 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT REGION 20..275
FT /note="Beta-propeller 1"
FT REGION 328..589
FT /note="Beta-propeller 2"
FT REGION 631..890
FT /note="Beta-propeller 3"
FT REGION 933..1202
FT /note="Beta-propeller 4"
FT REGION 1556..1613
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1487..1493
FT /note="PPPSP motif A"
FT MOTIF 1527..1534
FT /note="PPPSP motif B"
FT MOTIF 1568..1575
FT /note="PPPSP motif C"
FT MOTIF 1588..1593
FT /note="PPPSP motif D"
FT MOTIF 1603..1610
FT /note="PPPSP motif E"
FT MOD_RES 1420
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:O75581"
FT MOD_RES 1430
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:O75581"
FT MOD_RES 1479
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O75581"
FT MOD_RES 1490
FT /note="Phosphoserine; by CDK14, GRK5 and GRK6"
FT /evidence="ECO:0000250|UniProtKB:O75581"
FT MOD_RES 1493
FT /note="Phosphothreonine; by CK1"
FT /evidence="ECO:0000250|UniProtKB:O75581"
FT LIPID 1394
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT LIPID 1399
FT /note="S-palmitoyl cysteine"
FT /evidence="ECO:0000250"
FT CARBOHYD 42
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 81
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 281
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 433
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 486
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 692
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 859
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 865
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 926
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 286..297
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 293..308
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 310..323
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 592..603
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 599..612
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 614..627
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 893..904
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 900..914
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 916..929
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1207..1218
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1214..1228
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1230..1243
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1249..1263
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1256..1276
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1270..1285
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1288..1300
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1295..1313
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1307..1322
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1326..1338
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1333..1351
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT DISULFID 1345..1360
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00124"
FT CROSSLNK 1403
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:O75581"
FT VARIANT 886
FT /note="R -> W (in rs)"
FT /evidence="ECO:0000269|PubMed:15469977,
FT ECO:0000269|PubMed:18505367"
FT CONFLICT 83
FT /note="S -> T (in Ref. 2; AAH60704)"
FT /evidence="ECO:0000305"
FT CONFLICT 317
FT /note="M -> L (in Ref. 2; AAH60704)"
FT /evidence="ECO:0000305"
FT CONFLICT 586
FT /note="V -> I (in Ref. 2; AAH60704)"
FT /evidence="ECO:0000305"
FT CONFLICT 622
FT /note="G -> S (in Ref. 2; AAH60704)"
FT /evidence="ECO:0000305"
FT CONFLICT 933
FT /note="S -> T (in Ref. 2; AAH60704)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1613 AA; 180255 MW; 3C2ABC8EEEB17622 CRC64;
MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL EDAAAVDFVF
GHGLIYWSDV SEEAIKRTEF NKSESVQNVV VSGLLSPDGL ACDWLGEKLY WTDSETNRIE
VSNLDGSLRK VLFWQELDQP RAIALDPSSG FMYWTDWGEV PKIERAGMDG SSRFVIINTE
IYWPNGLTLD YQERKLYWAD AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDTLYWT
DWNTHSILAC NKYTGEGLRE IHSNIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS
PVKPFYQCAC PTGVKLMENG KTCKDGATEL LLLARRTDLR RISLDTPDFT DIVLQLEDIR
HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA QIAHPDGIAV DWVARNLYWT
DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA IVLDPMVGYM YWTDWGEIPK IERAALDGSD
RVVLVNTSLG WPNGLALDYD EGTIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL
LGDYVYWTDW QRRSIERVHK RSAEREVIID QLPDLMGLKA TSVHRVIGSN PCAEDNGGCS
HLCLYRPQGL RCACPIGFEL IGDMKTCIVP EAFLLFSRRA DIRRISLETN NNNVAIPLTG
VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV EFGLDYPEGM AVDWLGKNLY
WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP RALALDPAEG FMYWTEWGGK PKIDRAAMDG
SERTTLVPNV GRANGLTIDY AKRRLYWTDL DTNLIESSDM LGLNREVIAD DLPHPFGLTQ
YQDYIYWTDW SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQAGW NECASSNGHC
SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APSTFLLFSQ KSAINRMVID EQQSPDIILP
IHSLRNVRAI DYDPLDKQLY WIDSRQNSIR KAHEDGGQGF NVVANSVANQ NLEIQPYDLS
IDIYSRYIYW TCEATNVIDV TRLDGRSVGV VLKGEQDRPR AIVVNPEKGY MYFTNLQERS
PKIERAALDG TEREVLFFSG LSKPIALALD SKLGKLFWAD SDLRRIESSD LSGANRIVLE
DSNILQPVGL TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ
EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS PQQFTCFTGD
IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC IDGALRCNGD ANCQDKSDEK
NCEVLCLIDQ FRCANGQCVG KHKKCDHSVD CSDRSDELDC YPTEEPAPQA TNTVGSVIGV
IVTIFVSGTI YFICQRMLCP RMKGDGETMT NDYVVHSPAS VPLGYVPHPS SLSGSLPGMS
RGKSMISSLS IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM
EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV ATAKGYTSDV
NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH LYPPPPSPCT DSS
