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Database: UniProt
Entry: O88572
LinkDB: O88572
Original site: O88572 
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   13-FEB-2019, entry version 160.
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;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; 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
RT   density 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
RT   project: 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.,
RA   Wines M.E., 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   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   [5]
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
RT   Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene
RT   expression.";
RL   J. Biol. Chem. 281:13247-13257(2006).
RN   [6]
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   [7]
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
RT   mechanism by which Wnt negatively regulates its receptor.";
RL   Mol. Cell. Biol. 27:7291-7301(2007).
RN   [8]
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
RT   Wnt signaling.";
RL   Biochem. Biophys. Res. Commun. 390:1051-1055(2009).
RN   [9]
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
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [10]
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
RT   required for proper somitogenesis and osteogenesis.";
RL   Development 131:5469-5480(2004).
RN   [11]
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
RT   in 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-
CC       ligand complexes into ribosome-sized signalsomes. Cell-surface
CC       coreceptor of Wnt/beta-catenin signaling, which plays a pivotal
CC       role in bone formation. The Wnt-induced Fzd/LRP6 coreceptor
CC       complex recruits DVL1 polymers to the plasma membrane which, in
CC       turn, recruits the AXIN1/GSK3B-complex to the cell surface
CC       promoting the formation of signalsomes and inhibiting AXIN1/GSK3-
CC       mediated phosphorylation and destruction of beta-catenin. Required
CC       for posterior patterning of the epiblast during gastrulation (By
CC       similarity). {ECO:0000250, ECO:0000269|PubMed:15142971}.
CC   -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Forms
CC       phosphorylated oligomer aggregates on Wnt-signaling (By
CC       similarity). Component of the Wnt-Fzd-LRP5-LRP6 complex. Interacts
CC       (via the extracellular domain) with WNT1; the interaction is
CC       enhanced by prior formation of the Wnt/Fzd complex. Interacts (via
CC       the beta-propeller regions 3 and 4) with WNT3A. Interacts (via the
CC       beta-propeller regions 1 and 2) with WNT9B. Interacts with FZD5;
CC       the interaction forms a coreceptor complex for Wnt signaling and
CC       is inhibited by DKK1 and DRAXIN. Interacts (via beta propeller
CC       region) with DKK1; the interaction inhibits FZD5/LRP6 complex
CC       formation. Interacts with DKK2. Interacts (via the phosphorylated
CC       PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B
CC       complex to cell surface LRP6 signalsomes. Interacts (via the
CC       extracellular domain) with RSPO1; the interaction activates
CC       Wnt/beta-catenin signaling. Interacts (via the extracellular
CC       domain) with RSPO3 (via the cysteine rich domain); the interaction
CC       activates Wnt/beta-catenin signaling. Interacts (via the beta-
CC       propeller regions 1 and 2) with SOST; the interaction competes
CC       with DKK1 for binding for inhibiting beta-catenin signaling.
CC       Interacts (via the cytoplasmic domain) with CSNKIE; the
CC       interaction phosphorylates LRP6, binds AXIN1 and inhibits
CC       AXIN1/GSK3B-mediated phosphorylation of beta-catenin (By
CC       similarity). Interacts with DRAXIN; the interaction inhibits Wnt
CC       signaling. Interacts with GRB10; the interaction prevents AXIN1
CC       binding, thus negatively regulating the Wnt signaling pathway.
CC       Interacts with MESD; the interaction prevents the formation of
CC       LRP6 aggregates and targets LRP6 to the plasma membrane. Interacts
CC       with MACF1. Interacts with DAB2; the interaction involves LRP6
CC       phosphorylation by CK2 and sequesters LRP6 towards clathrin-
CC       mediated endocytosis. Interacts with TMEM198 (By similarity).
CC       Interacts with CAPRIN2; the interaction promotes LRP6
CC       phosphorylation at Ser-1490 (By similarity). Found in a complex
CC       with CAPRIN2, CCNY and CDK14 during G2/M stage; CAPRIN2 functions
CC       as a scaffold for the complex by binding to CCNY via its N
CC       terminus and to CDK14 via its C terminus. Interacts with LYPD6.
CC       Forms a ternary complex with DKK1 and KREM1 (By similarity).
CC       Interacts with KREM1 in a DKK1-dependent manner (By similarity).
CC       {ECO:0000250|UniProtKB:O75581, ECO:0000269|PubMed:12581525,
CC       ECO:0000269|PubMed:16543246, ECO:0000269|PubMed:17376403,
CC       ECO:0000269|PubMed:18505367, ECO:0000269|PubMed:19857465}.
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
CC       membrane location. Released from the endoplasmic reticulum on
CC       palmitoylation. Mono-ubiquitination retains it in the endoplasmic
CC       reticulum in the absence of palmitoylation. On Wnt signaling,
CC       phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at
CC       the plasma membrane in LRP6-signalsomes (By similarity).
CC       Chaperoned to the plasma membrane by MESD. {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
CC       and 4 are required for the interaction with DKK1 (By similarity).
CC       {ECO:0000250}.
CC   -!- DOMAIN: The PPPSP motifs play a central role in signal
CC       transduction by being phosphorylated, leading to activate the Wnt
CC       signaling pathway.
CC   -!- PTM: Dual phosphorylation of cytoplasmic PPPSP motifs sequentially
CC       by 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
CC       vitro, by GRK5/6 within and outside the PPPSP motifs.
CC       Phosphorylation at Ser-1490 by CDK14 during G2/M phase leads to
CC       regulation of the Wnt signaling pathway during the cell cycle.
CC       Phosphorylation by GSK3B is induced by RPSO1 binding and inhibited
CC       by DKK1. Phosphorylated, in vitro, by casein kinase I on Thr-1479
CC       (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
CC       is free to bind to GSK3B and to activate canonical Wnt signaling
CC       (By similarity). {ECO:0000250}.
CC   -!- PTM: Palmitoylation on the two sites near the transmembrane domain
CC       leads to release of LRP6 from the endoplasmic reticulum.
CC       {ECO:0000250}.
CC   -!- PTM: Mono-ubiquitinated which retains LRP6 in the endoplasmic
CC       reticulum. Ubiquitinated by ZNRF3, leading to its degradation by
CC       the 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
CC       characterized by a combination of multiple Wnt-deficient
CC       phenotypes including dysmorphologies of the axial skeleton, digits
CC       and the neural tube. The establishment of the anteroposterior
CC       somite compartments, the epithelialization of nascent somites, and
CC       the formation of segment borders are disturbed in (rs) mutants.
CC       There is delayed ossification at birth and a low bone mass
CC       phenotype in adults. Functional analyzes reveal impaired targeting
CC       to the plasma surface due to reduced interaction with MESD leading
CC       to inhibited Wnt/beta-catenin signaling.
CC       {ECO:0000269|PubMed:15469977, ECO:0000269|PubMed:18505367}.
CC   -!- SIMILARITY: Belongs to the LDLR family. {ECO:0000305}.
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   UniGene; Mm.321990; -.
DR   ProteinModelPortal; O88572; -.
DR   SMR; O88572; -.
DR   BioGrid; 201203; 9.
DR   CORUM; O88572; -.
DR   DIP; DIP-46460N; -.
DR   IntAct; O88572; 7.
DR   MINT; O88572; -.
DR   STRING; 10090.ENSMUSP00000032322; -.
DR   iPTMnet; O88572; -.
DR   PhosphoSitePlus; O88572; -.
DR   MaxQB; O88572; -.
DR   PaxDb; O88572; -.
DR   PeptideAtlas; O88572; -.
DR   PRIDE; O88572; -.
DR   GeneID; 16974; -.
DR   KEGG; mmu:16974; -.
DR   UCSC; uc009ekl.2; mouse.
DR   CTD; 4040; -.
DR   MGI; MGI:1298218; Lrp6.
DR   eggNOG; ENOG410IPT4; Eukaryota.
DR   eggNOG; ENOG410XSY5; LUCA.
DR   HOGENOM; HOG000230697; -.
DR   HOVERGEN; HBG049167; -.
DR   InParanoid; O88572; -.
DR   KO; K03068; -.
DR   OrthoDB; 121310at2759; -.
DR   PhylomeDB; O88572; -.
DR   TreeFam; TF315253; -.
DR   ChiTaRS; Lrp6; mouse.
DR   PRO; PR:O88572; -.
DR   Proteomes; UP000000589; Unplaced.
DR   GO; GO:0005901; C:caveola; IBA:GO_Central.
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: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; IBA:GO_Central.
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-activated 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:0060349; P:bone morphogenesis; IBA:GO_Central.
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: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: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:0042475; P:odontogenesis of dentin-containing tooth; IMP:MGI.
DR   GO; GO:0003344; P:pericardium 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: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:0042127; P:regulation of cell population 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: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   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; Complete proteome; Developmental protein;
KW   Disease mutation; Disulfide bond; EGF-like domain; Endocytosis;
KW   Endoplasmic reticulum; Glycoprotein; Isopeptide bond; Lipoprotein;
KW   Membrane; Palmitate; Phosphoprotein; Polymorphism; Receptor;
KW   Reference proteome; Repeat; Signal; Transmembrane;
KW   Transmembrane helix; Ubl conjugation; Wnt signaling pathway.
FT   SIGNAL        1     19       {ECO:0000255}.
FT   CHAIN        20   1613       Low-density lipoprotein receptor-related
FT                                protein 6.
FT                                /FTId=PRO_0000017331.
FT   TOPO_DOM     20   1370       Extracellular. {ECO:0000255}.
FT   TRANSMEM   1371   1393       Helical. {ECO:0000255}.
FT   TOPO_DOM   1394   1613       Cytoplasmic. {ECO:0000255}.
FT   REPEAT       63    106       LDL-receptor class B 1.
FT   REPEAT      107    149       LDL-receptor class B 2.
FT   REPEAT      150    193       LDL-receptor class B 3.
FT   REPEAT      194    235       LDL-receptor class B 4.
FT   REPEAT      236    277       LDL-receptor class B 5.
FT   DOMAIN      282    324       EGF-like 1.
FT   REPEAT      372    414       LDL-receptor class B 6.
FT   REPEAT      415    457       LDL-receptor class B 7.
FT   REPEAT      458    501       LDL-receptor class B 8.
FT   REPEAT      502    542       LDL-receptor class B 9.
FT   REPEAT      543    587       LDL-receptor class B 10.
FT   DOMAIN      588    628       EGF-like 2.
FT   REPEAT      674    716       LDL-receptor class B 11.
FT   REPEAT      717    759       LDL-receptor class B 12.
FT   REPEAT      760    802       LDL-receptor class B 13.
FT   REPEAT      803    842       LDL-receptor class B 14.
FT   REPEAT      843    885       LDL-receptor class B 15.
FT   DOMAIN      889    930       EGF-like 3.
FT   REPEAT      977   1025       LDL-receptor class B 16.
FT   REPEAT     1026   1068       LDL-receptor class B 17.
FT   REPEAT     1069   1113       LDL-receptor class B 18.
FT   REPEAT     1114   1156       LDL-receptor class B 19.
FT   REPEAT     1157   1198       LDL-receptor class B 20.
FT   DOMAIN     1203   1244       EGF-like 4.
FT   DOMAIN     1248   1286       LDL-receptor class A 1.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1287   1323       LDL-receptor class A 2.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DOMAIN     1325   1361       LDL-receptor class A 3.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   REGION       20    275       Beta-propeller 1.
FT   REGION      328    589       Beta-propeller 2.
FT   REGION      631    890       Beta-propeller 3.
FT   REGION      933   1202       Beta-propeller 4.
FT   MOTIF      1487   1493       PPPSP motif A.
FT   MOTIF      1527   1534       PPPSP motif B.
FT   MOTIF      1568   1575       PPPSP motif C.
FT   MOTIF      1588   1593       PPPSP motif D.
FT   MOTIF      1603   1610       PPPSP motif E.
FT   COMPBIAS   1469   1475       Poly-Ser.
FT   COMPBIAS   1566   1573       Poly-Pro.
FT   COMPBIAS   1603   1608       Poly-Pro.
FT   MOD_RES    1420   1420       Phosphoserine; by CK1.
FT                                {ECO:0000250|UniProtKB:O75581}.
FT   MOD_RES    1430   1430       Phosphoserine; by CK1.
FT                                {ECO:0000250|UniProtKB:O75581}.
FT   MOD_RES    1479   1479       Phosphothreonine.
FT                                {ECO:0000250|UniProtKB:O75581}.
FT   MOD_RES    1490   1490       Phosphoserine; by CDK14, GRK5 and GRK6.
FT                                {ECO:0000250|UniProtKB:O75581}.
FT   MOD_RES    1493   1493       Phosphothreonine; by CK1.
FT                                {ECO:0000250|UniProtKB:O75581}.
FT   LIPID      1394   1394       S-palmitoyl cysteine. {ECO:0000250}.
FT   LIPID      1399   1399       S-palmitoyl cysteine. {ECO:0000250}.
FT   CARBOHYD     42     42       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD     81     81       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    281    281       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    433    433       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    486    486       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    692    692       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    859    859       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    865    865       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    926    926       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    286    297       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    293    308       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    310    323       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    592    603       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    599    612       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    614    627       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    893    904       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    900    914       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID    916    929       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1207   1218       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1214   1228       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1230   1243       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1249   1263       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1256   1276       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1270   1285       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1288   1300       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1295   1313       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1307   1322       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1326   1338       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1333   1351       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   DISULFID   1345   1360       {ECO:0000255|PROSITE-ProRule:PRU00124}.
FT   CROSSLNK   1403   1403       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in ubiquitin).
FT                                {ECO:0000250|UniProtKB:O75581}.
FT   VARIANT     886    886       R -> W (in rs).
FT                                {ECO:0000269|PubMed:15469977,
FT                                ECO:0000269|PubMed:18505367}.
FT   CONFLICT     83     83       S -> T (in Ref. 2; AAH60704).
FT                                {ECO:0000305}.
FT   CONFLICT    317    317       M -> L (in Ref. 2; AAH60704).
FT                                {ECO:0000305}.
FT   CONFLICT    586    586       V -> I (in Ref. 2; AAH60704).
FT                                {ECO:0000305}.
FT   CONFLICT    622    622       G -> S (in Ref. 2; AAH60704).
FT                                {ECO:0000305}.
FT   CONFLICT    933    933       S -> T (in Ref. 2; AAH60704).
FT                                {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
//
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