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O88572

- LRP6_MOUSE

UniProt

O88572 - LRP6_MOUSE

Protein

Low-density lipoprotein receptor-related protein 6

Gene

Lrp6

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 119 (01 Oct 2014)
      Sequence version 1 (01 Nov 1998)
      Previous versions | rss
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    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 similarity

    GO - Molecular functioni

    1. coreceptor activity Source: RefGenome
    2. coreceptor activity involved in Wnt signaling pathway Source: Ensembl
    3. kinase inhibitor activity Source: Ensembl
    4. low-density lipoprotein receptor activity Source: MGI
    5. protein binding Source: UniProtKB
    6. toxin transporter activity Source: BHF-UCL
    7. Wnt-activated receptor activity Source: RefGenome
    8. Wnt-protein binding Source: MGI

    GO - Biological processi

    1. anterior/posterior pattern specification Source: MGI
    2. axis elongation Source: MGI
    3. axis elongation involved in somitogenesis Source: MGI
    4. bone remodeling Source: MGI
    5. branching involved in mammary gland duct morphogenesis Source: MGI
    6. canonical Wnt signaling pathway Source: UniProtKB
    7. canonical Wnt signaling pathway involved in cardiac neural crest cell differentiation involved in heart development Source: MGI
    8. canonical Wnt signaling pathway involved in positive regulation of cardiac outflow tract cell proliferation Source: MGI
    9. cell migration involved in gastrulation Source: MGI
    10. cellular response to cholesterol Source: Ensembl
    11. cerebellum morphogenesis Source: MGI
    12. cerebral cortex cell migration Source: MGI
    13. cerebral cortex development Source: MGI
    14. convergent extension Source: MGI
    15. dopaminergic neuron differentiation Source: MGI
    16. dorsal/ventral axis specification Source: MGI
    17. embryonic camera-type eye morphogenesis Source: MGI
    18. embryonic digit morphogenesis Source: MGI
    19. embryonic forelimb morphogenesis Source: MGI
    20. embryonic hindlimb morphogenesis Source: MGI
    21. embryonic limb morphogenesis Source: MGI
    22. embryonic pattern specification Source: MGI
    23. embryonic retina morphogenesis in camera-type eye Source: MGI
    24. external genitalia morphogenesis Source: MGI
    25. face morphogenesis Source: MGI
    26. forebrain development Source: MGI
    27. forebrain generation of neurons Source: MGI
    28. forebrain radial glial cell differentiation Source: MGI
    29. formation of radial glial scaffolds Source: MGI
    30. gastrulation with mouth forming second Source: MGI
    31. generation of neurons Source: MGI
    32. heart looping Source: MGI
    33. limb morphogenesis Source: MGI
    34. mammary gland duct morphogenesis Source: MGI
    35. mammary placode formation Source: MGI
    36. midbrain development Source: MGI
    37. midbrain-hindbrain boundary development Source: MGI
    38. negative regulation of epithelial cell proliferation Source: MGI
    39. negative regulation of fat cell differentiation Source: MGI
    40. negative regulation of non-canonical Wnt signaling pathway Source: MGI
    41. negative regulation of planar cell polarity pathway involved in cardiac muscle tissue morphogenesis Source: MGI
    42. negative regulation of planar cell polarity pathway involved in cardiac right atrium morphogenesis Source: MGI
    43. negative regulation of planar cell polarity pathway involved in neural tube closure Source: MGI
    44. negative regulation of planar cell polarity pathway involved in outflow tract morphogenesis Source: MGI
    45. negative regulation of planar cell polarity pathway involved in pericardium morphogenesis Source: MGI
    46. negative regulation of planar cell polarity pathway involved in ventricular septum morphogenesis Source: MGI
    47. negative regulation of protein serine/threonine kinase activity Source: Ensembl
    48. negative regulation of smooth muscle cell apoptotic process Source: Ensembl
    49. negative regulation of Wnt signaling pathway Source: MGI
    50. neural crest formation Source: RefGenome
    51. neural tube closure Source: MGI
    52. neural tube development Source: MGI
    53. odontogenesis of dentin-containing tooth Source: MGI
    54. palate development Source: MGI
    55. pericardium morphogenesis Source: MGI
    56. positive regulation of apoptotic process Source: MGI
    57. positive regulation of bone resorption Source: MGI
    58. positive regulation of canonical Wnt signaling pathway Source: Ensembl
    59. positive regulation of cell cycle Source: Ensembl
    60. positive regulation of cytosolic calcium ion concentration Source: Ensembl
    61. positive regulation of mesenchymal cell proliferation Source: MGI
    62. positive regulation of ossification Source: MGI
    63. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
    64. positive regulation of transcription, DNA-templated Source: BHF-UCL
    65. positive regulation of transcription from RNA polymerase II promoter Source: RefGenome
    66. positive regulation of Wnt signaling pathway involved in dorsal/ventral axis specification Source: Ensembl
    67. post-anal tail morphogenesis Source: MGI
    68. primitive streak formation Source: MGI
    69. receptor-mediated endocytosis of low-density lipoprotein particle involved in cholesterol transport Source: MGI
    70. regulation of cell development Source: MGI
    71. regulation of cell proliferation Source: MGI
    72. response to folic acid Source: MGI
    73. response to peptide hormone Source: Ensembl
    74. retina morphogenesis in camera-type eye Source: MGI
    75. single organismal cell-cell adhesion Source: Ensembl
    76. skeletal system morphogenesis Source: MGI
    77. somitogenesis Source: MGI
    78. synaptic transmission Source: RefGenome
    79. thalamus development Source: MGI
    80. toxin transport Source: GOC
    81. trachea cartilage morphogenesis Source: MGI
    82. Wnt signaling pathway Source: MGI
    83. Wnt signaling pathway involved in dorsal/ventral axis specification Source: RefGenome
    84. Wnt signaling pathway involved in forebrain neuroblast division Source: MGI
    85. Wnt signaling pathway involved in somitogenesis Source: MGI

    Keywords - Molecular functioni

    Developmental protein, Receptor

    Keywords - Biological processi

    Endocytosis, Wnt signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_207044. TCF dependent signaling in response to WNT.
    REACT_210612. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
    REACT_213035. regulation of FZD by ubiquitination.
    REACT_216784. disassembly of the destruction complex and recruitment of AXIN to the membrane.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Low-density lipoprotein receptor-related protein 6
    Short name:
    LRP-6
    Gene namesi
    Name:Lrp6
    OrganismiMus musculus (Mouse)
    Taxonomic identifieri10090 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
    ProteomesiUP000000589: Chromosome 6

    Organism-specific databases

    MGIiMGI:1298218. Lrp6.

    Subcellular locationi

    Membrane; Single-pass type I membrane protein. Endoplasmic reticulum
    Note: On Wnt signaling, undergoes a cycle of caveolin- or clathrin-mediated endocytosis and plasma membrane location. Released from the endoplasmic reticulum on palmitoylation. Mono-ubiquitination retains it in the endoplasmic reticulum in the absence of palmitoylation. On Wnt signaling, phosphorylated, aggregates and colocalizes with AXIN1 and GSK3B at the plasma membrane in LRP6-signalsomes By similarity. Chaperoned to the plasma membrane by MESD.By similarity

    GO - Cellular componenti

    1. caveola Source: RefGenome
    2. cell surface Source: RefGenome
    3. cytoplasmic vesicle Source: Ensembl
    4. early endosome Source: MGI
    5. endoplasmic reticulum Source: UniProtKB-SubCell
    6. Golgi apparatus Source: Ensembl
    7. integral component of membrane Source: UniProtKB-KW
    8. membrane Source: MGI
    9. neuronal cell body Source: RefGenome
    10. plasma membrane Source: MGI
    11. receptor complex Source: RefGenome
    12. synapse Source: RefGenome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Defects in Lrp6 are the cause of Ringelschwanz (rs) phenotype. Rs phenotype is a spontaneous mutation that is characterized by a combination of multiple Wnt-deficient phenotypes including dysmorphologies of the axial skeleton, digits and the neural tube. The establishment of the anteroposterior somite compartments, the epithelialization of nascent somites, and the formation of segment borders are disturbed in (rs) mutants. There is delayed ossification at birth and a low bone mass phenotype in adults. Functional analyzes reveal impaired targeting to the plasma surface due to reduced interaction with MESD leading to inhibited Wnt/beta-catenin signaling.

    Keywords - Diseasei

    Disease mutation

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Signal peptidei1 – 1919Sequence AnalysisAdd
    BLAST
    Chaini20 – 16131594Low-density lipoprotein receptor-related protein 6PRO_0000017331Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Glycosylationi42 – 421N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi81 – 811N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi281 – 2811N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi286 ↔ 297PROSITE-ProRule annotation
    Disulfide bondi293 ↔ 308PROSITE-ProRule annotation
    Disulfide bondi310 ↔ 323PROSITE-ProRule annotation
    Glycosylationi433 – 4331N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi486 – 4861N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi592 ↔ 603PROSITE-ProRule annotation
    Disulfide bondi599 ↔ 612PROSITE-ProRule annotation
    Disulfide bondi614 ↔ 627PROSITE-ProRule annotation
    Glycosylationi692 – 6921N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi859 – 8591N-linked (GlcNAc...)Sequence Analysis
    Glycosylationi865 – 8651N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi893 ↔ 904PROSITE-ProRule annotation
    Disulfide bondi900 ↔ 914PROSITE-ProRule annotation
    Disulfide bondi916 ↔ 929PROSITE-ProRule annotation
    Glycosylationi926 – 9261N-linked (GlcNAc...)Sequence Analysis
    Disulfide bondi1207 ↔ 1218PROSITE-ProRule annotation
    Disulfide bondi1214 ↔ 1228PROSITE-ProRule annotation
    Disulfide bondi1230 ↔ 1243PROSITE-ProRule annotation
    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
    Lipidationi1394 – 13941S-palmitoyl cysteineBy similarity
    Lipidationi1399 – 13991S-palmitoyl cysteineBy similarity
    Cross-linki1403 – 1403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)By similarity
    Modified residuei1420 – 14201Phosphoserine; by CK1By similarity
    Modified residuei1430 – 14301Phosphoserine; by CK1By similarity
    Modified residuei1479 – 14791PhosphothreonineBy similarity
    Modified residuei1490 – 14901Phosphoserine; by CDK14, GRK5 and GRK6By similarity
    Modified residuei1493 – 14931Phosphothreonine; by CK1By similarity

    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 By similarity.By similarity
    Undergoes gamma-secretase-dependent regulated intramembrane proteolysis (RIP). The extracellular domain is first released by shedding, and then, through the action of gamma-secretase, the intracellular domain (ICD) is released into the cytoplasm where it is free to bind to GSK3B and to activate canonical Wnt signaling By similarity.By similarity
    Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum.By similarity
    Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome By similarity.By similarity
    N-glycosylation is required for cell surface location.By similarity

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Isopeptide bond, Lipoprotein, Palmitate, Phosphoprotein, Ubl conjugation

    Proteomic databases

    PaxDbiO88572.
    PRIDEiO88572.

    PTM databases

    PhosphoSiteiO88572.

    Expressioni

    Tissue specificityi

    Expressed in early embryo. Broadly expressed throughout the embryonic ectoderm and in nascent mesoderm, and in endoderm emerging from the primitive streak.1 Publication

    Gene expression databases

    ArrayExpressiO88572.
    BgeeiO88572.
    GenevestigatoriO88572.

    Interactioni

    Subunit structurei

    Homodimer; disulfide-linked By similarity. Forms phosphorylated oligomer aggregates on Wnt-signaling By similarity. Component of the Wnt-Fzd-LRP5-LRP6 complex. Interacts (via the extracellular domain) with WNT1; the interaction is enhanced by prior formation of the Wnt/Fzd complex. Interacts (via the beta-propeller regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a coreceptor complex for Wnt signaling and is inhibited by DKK1 and DRAXIN. Interacts (via beta propeller region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2. Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface LRP6 signalsomes. Interacts (via the extracellular domain) with RSPO1; the interaction activates Wnt/beta-catenin signaling. Interacts (via the extracellular domain) with RSPO3 (via the cysteine rich domain); the interaction activates Wnt/beta-catenin signaling. Interacts (via the beta-propeller regions 1 and 2) with SOST; the interaction competes with DKK1 for binding for inhibiting beta-catenin signaling. Interacts (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin By similarity. Interacts with DRAXIN; the interaction inhibits Wnt signaling. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively regulating the Wnt signaling pathway. Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma membrane. Interacts with MACF1. Interacts with DAB2; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Interacts with TMEM198 By similarity.By similarity

    Protein-protein interaction databases

    BioGridi201203. 8 interactions.
    DIPiDIP-46460N.
    IntActiO88572. 4 interactions.
    STRINGi10090.ENSMUSP00000032322.

    Structurei

    3D structure databases

    ProteinModelPortaliO88572.
    SMRiO88572. Positions 20-1360.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini20 – 13701351ExtracellularSequence AnalysisAdd
    BLAST
    Topological domaini1394 – 1613220CytoplasmicSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei1371 – 139323HelicalSequence AnalysisAdd
    BLAST

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Repeati63 – 10644LDL-receptor class B 1Add
    BLAST
    Repeati107 – 14943LDL-receptor class B 2Add
    BLAST
    Repeati150 – 19344LDL-receptor class B 3Add
    BLAST
    Repeati194 – 23542LDL-receptor class B 4Add
    BLAST
    Repeati236 – 27742LDL-receptor class B 5Add
    BLAST
    Domaini282 – 32443EGF-like 1Add
    BLAST
    Repeati372 – 41443LDL-receptor class B 6Add
    BLAST
    Repeati415 – 45743LDL-receptor class B 7Add
    BLAST
    Repeati458 – 50144LDL-receptor class B 8Add
    BLAST
    Repeati502 – 54241LDL-receptor class B 9Add
    BLAST
    Repeati543 – 58745LDL-receptor class B 10Add
    BLAST
    Domaini588 – 62841EGF-like 2Add
    BLAST
    Repeati674 – 71643LDL-receptor class B 11Add
    BLAST
    Repeati717 – 75943LDL-receptor class B 12Add
    BLAST
    Repeati760 – 80243LDL-receptor class B 13Add
    BLAST
    Repeati803 – 84240LDL-receptor class B 14Add
    BLAST
    Repeati843 – 88543LDL-receptor class B 15Add
    BLAST
    Domaini889 – 93042EGF-like 3Add
    BLAST
    Repeati977 – 102549LDL-receptor class B 16Add
    BLAST
    Repeati1026 – 106843LDL-receptor class B 17Add
    BLAST
    Repeati1069 – 111345LDL-receptor class B 18Add
    BLAST
    Repeati1114 – 115643LDL-receptor class B 19Add
    BLAST
    Repeati1157 – 119842LDL-receptor class B 20Add
    BLAST
    Domaini1203 – 124442EGF-like 4Add
    BLAST
    Domaini1248 – 128639LDL-receptor class A 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini1287 – 132337LDL-receptor class A 2PROSITE-ProRule annotationAdd
    BLAST
    Domaini1325 – 136137LDL-receptor class A 3PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni20 – 275256Beta-propeller 1Add
    BLAST
    Regioni328 – 589262Beta-propeller 2Add
    BLAST
    Regioni631 – 890260Beta-propeller 3Add
    BLAST
    Regioni933 – 1202270Beta-propeller 4Add
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi1487 – 14937PPPSP motif A
    Motifi1527 – 15348PPPSP motif B
    Motifi1568 – 15758PPPSP motif C
    Motifi1588 – 15936PPPSP motif D
    Motifi1603 – 16108PPPSP motif E

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi1469 – 14757Poly-Ser
    Compositional biasi1566 – 15738Poly-Pro
    Compositional biasi1603 – 16086Poly-Pro

    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 By similarity.By similarity
    The PPPSP motifs play a central role in signal transduction by being phosphorylated, leading to activate the Wnt signaling pathway.

    Sequence similaritiesi

    Belongs to the LDLR family.Curated
    Contains 4 EGF-like domains.Curated
    Contains 3 LDL-receptor class A domains.PROSITE-ProRule annotation
    Contains 20 LDL-receptor class B repeats.PROSITE-ProRule annotation

    Keywords - Domaini

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

    Phylogenomic databases

    eggNOGiNOG121718.
    GeneTreeiENSGT00750000117273.
    HOGENOMiHOG000230697.
    HOVERGENiHBG049167.
    InParanoidiO88572.
    KOiK03068.
    OrthoDBiEOG75XGK3.
    PhylomeDBiO88572.
    TreeFamiTF315253.

    Family and domain databases

    Gene3Di2.120.10.30. 4 hits.
    4.10.400.10. 3 hits.
    InterProiIPR011042. 6-blade_b-propeller_TolB-like.
    IPR000742. EG-like_dom.
    IPR023415. LDLR_class-A_CS.
    IPR000033. LDLR_classB_rpt.
    IPR002172. LDrepeatLR_classA_rpt.
    IPR017049. Low_density_Lipo_rcpt-rel_p5/6.
    [Graphical view]
    PfamiPF00057. Ldl_recept_a. 3 hits.
    PF00058. Ldl_recept_b. 13 hits.
    [Graphical view]
    PIRSFiPIRSF036314. LDL_recpt-rel_p5/6. 1 hit.
    PRINTSiPR00261. LDLRECEPTOR.
    SMARTiSM00181. EGF. 4 hits.
    SM00192. LDLa. 3 hits.
    SM00135. LY. 20 hits.
    [Graphical view]
    SUPFAMiSSF57424. SSF57424. 3 hits.
    PROSITEiPS01186. EGF_2. 1 hit.
    PS01209. LDLRA_1. 3 hits.
    PS50068. LDLRA_2. 3 hits.
    PS51120. LDLRB. 20 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    O88572-1 [UniParc]FASTAAdd to Basket

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    MGAVLRSLLA CSFCVLLRAA PLLLYANRRD LRLVDATNGK ENATIVVGGL     50
    EDAAAVDFVF GHGLIYWSDV SEEAIKRTEF NKSESVQNVV VSGLLSPDGL 100
    ACDWLGEKLY WTDSETNRIE VSNLDGSLRK VLFWQELDQP RAIALDPSSG 150
    FMYWTDWGEV PKIERAGMDG SSRFVIINTE IYWPNGLTLD YQERKLYWAD 200
    AKLNFIHKSN LDGTNRQAVV KGSLPHPFAL TLFEDTLYWT DWNTHSILAC 250
    NKYTGEGLRE IHSNIFSPMD IHAFSQQRQP NATNPCGIDN GGCSHLCLMS 300
    PVKPFYQCAC PTGVKLMENG KTCKDGATEL LLLARRTDLR RISLDTPDFT 350
    DIVLQLEDIR HAIAIDYDPV EGYIYWTDDE VRAIRRSFID GSGSQFVVTA 400
    QIAHPDGIAV DWVARNLYWT DTGTDRIEVT RLNGTMRKIL ISEDLEEPRA 450
    IVLDPMVGYM YWTDWGEIPK IERAALDGSD RVVLVNTSLG WPNGLALDYD 500
    EGTIYWGDAK TDKIEVMNTD GTGRRVLVED KIPHIFGFTL LGDYVYWTDW 550
    QRRSIERVHK RSAEREVIID QLPDLMGLKA TSVHRVIGSN PCAEDNGGCS 600
    HLCLYRPQGL RCACPIGFEL IGDMKTCIVP EAFLLFSRRA DIRRISLETN 650
    NNNVAIPLTG VKEASALDFD VTDNRIYWTD ISLKTISRAF MNGSALEHVV 700
    EFGLDYPEGM AVDWLGKNLY WADTGTNRIE VSKLDGQHRQ VLVWKDLDSP 750
    RALALDPAEG FMYWTEWGGK PKIDRAAMDG SERTTLVPNV GRANGLTIDY 800
    AKRRLYWTDL DTNLIESSDM LGLNREVIAD DLPHPFGLTQ YQDYIYWTDW 850
    SRRSIERANK TSGQNRTIIQ GHLDYVMDIL VFHSSRQAGW NECASSNGHC 900
    SHLCLAVPVG GFVCGCPAHY SLNADNRTCS APSTFLLFSQ KSAINRMVID 950
    EQQSPDIILP IHSLRNVRAI DYDPLDKQLY WIDSRQNSIR KAHEDGGQGF 1000
    NVVANSVANQ NLEIQPYDLS IDIYSRYIYW TCEATNVIDV TRLDGRSVGV 1050
    VLKGEQDRPR AIVVNPEKGY MYFTNLQERS PKIERAALDG TEREVLFFSG 1100
    LSKPIALALD SKLGKLFWAD SDLRRIESSD LSGANRIVLE DSNILQPVGL 1150
    TVFENWLYWI DKQQQMIEKI DMTGREGRTK VQARIAQLSD IHAVKELNLQ 1200
    EYRQHPCAQD NGGCSHICLV KGDGTTRCSC PMHLVLLQDE LSCGEPPTCS 1250
    PQQFTCFTGD IDCIPVAWRC DGFTECEDHS DELNCPVCSE SQFQCASGQC 1300
    IDGALRCNGD ANCQDKSDEK NCEVLCLIDQ FRCANGQCVG KHKKCDHSVD 1350
    CSDRSDELDC YPTEEPAPQA TNTVGSVIGV IVTIFVSGTI YFICQRMLCP 1400
    RMKGDGETMT NDYVVHSPAS VPLGYVPHPS SLSGSLPGMS RGKSMISSLS 1450
    IMGGSSGPPY DRAHVTGASS SSSSSTKGTY FPAILNPPPS PATERSHYTM 1500
    EFGYSSNSPS THRSYSYRPY SYRHFAPPTT PCSTDVCDSD YAPSRRMTSV 1550
    ATAKGYTSDV NYDSEPVPPP PTPRSQYLSA EENYESCPPS PYTERSYSHH 1600
    LYPPPPSPCT DSS 1613
    Length:1,613
    Mass (Da):180,255
    Last modified:November 1, 1998 - v1
    Checksum:i3C2ABC8EEEB17622
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti83 – 831S → T in AAH60704. (PubMed:15489334)Curated
    Sequence conflicti317 – 3171M → L in AAH60704. (PubMed:15489334)Curated
    Sequence conflicti586 – 5861V → I in AAH60704. (PubMed:15489334)Curated
    Sequence conflicti622 – 6221G → S in AAH60704. (PubMed:15489334)Curated
    Sequence conflicti933 – 9331S → T in AAH60704. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti886 – 8861R → W in rs. 1 Publication

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF074265 mRNA. Translation: AAC33007.1.
    BC060704 mRNA. Translation: AAH60704.1.
    CCDSiCCDS39678.1.
    PIRiJE0273.
    RefSeqiNP_032540.2. NM_008514.4.
    UniGeneiMm.321990.

    Genome annotation databases

    EnsembliENSMUST00000032322; ENSMUSP00000032322; ENSMUSG00000030201.
    GeneIDi16974.
    KEGGimmu:16974.
    UCSCiuc009ekl.2. mouse.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF074265 mRNA. Translation: AAC33007.1 .
    BC060704 mRNA. Translation: AAH60704.1 .
    CCDSi CCDS39678.1.
    PIRi JE0273.
    RefSeqi NP_032540.2. NM_008514.4.
    UniGenei Mm.321990.

    3D structure databases

    ProteinModelPortali O88572.
    SMRi O88572. Positions 20-1360.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 201203. 8 interactions.
    DIPi DIP-46460N.
    IntActi O88572. 4 interactions.
    STRINGi 10090.ENSMUSP00000032322.

    PTM databases

    PhosphoSitei O88572.

    Proteomic databases

    PaxDbi O88572.
    PRIDEi O88572.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000032322 ; ENSMUSP00000032322 ; ENSMUSG00000030201 .
    GeneIDi 16974.
    KEGGi mmu:16974.
    UCSCi uc009ekl.2. mouse.

    Organism-specific databases

    CTDi 4040.
    MGIi MGI:1298218. Lrp6.

    Phylogenomic databases

    eggNOGi NOG121718.
    GeneTreei ENSGT00750000117273.
    HOGENOMi HOG000230697.
    HOVERGENi HBG049167.
    InParanoidi O88572.
    KOi K03068.
    OrthoDBi EOG75XGK3.
    PhylomeDBi O88572.
    TreeFami TF315253.

    Enzyme and pathway databases

    Reactomei REACT_207044. TCF dependent signaling in response to WNT.
    REACT_210612. negative regulation of TCF-dependent signaling by WNT ligand antagonists.
    REACT_213035. regulation of FZD by ubiquitination.
    REACT_216784. disassembly of the destruction complex and recruitment of AXIN to the membrane.

    Miscellaneous databases

    NextBioi 291034.
    PROi O88572.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi O88572.
    Bgeei O88572.
    Genevestigatori O88572.

    Family and domain databases

    Gene3Di 2.120.10.30. 4 hits.
    4.10.400.10. 3 hits.
    InterProi IPR011042. 6-blade_b-propeller_TolB-like.
    IPR000742. EG-like_dom.
    IPR023415. LDLR_class-A_CS.
    IPR000033. LDLR_classB_rpt.
    IPR002172. LDrepeatLR_classA_rpt.
    IPR017049. Low_density_Lipo_rcpt-rel_p5/6.
    [Graphical view ]
    Pfami PF00057. Ldl_recept_a. 3 hits.
    PF00058. Ldl_recept_b. 13 hits.
    [Graphical view ]
    PIRSFi PIRSF036314. LDL_recpt-rel_p5/6. 1 hit.
    PRINTSi PR00261. LDLRECEPTOR.
    SMARTi SM00181. EGF. 4 hits.
    SM00192. LDLa. 3 hits.
    SM00135. LY. 20 hits.
    [Graphical view ]
    SUPFAMi SSF57424. SSF57424. 3 hits.
    PROSITEi PS01186. EGF_2. 1 hit.
    PS01209. LDLRA_1. 3 hits.
    PS50068. LDLRA_2. 3 hits.
    PS51120. LDLRB. 20 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation and characterization of LRP6, a novel member of the low density lipoprotein receptor gene family."
      Brown S.D., Twells R.C., Hey P.J., Cox R.D., Levy E.R., Soderman A.R., Metzker M.L., Caskey C.T., Todd J.A., Hess J.F.
      Biochem. Biophys. Res. Commun. 248:879-888(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: BALB/c.
      Tissue: Liver.
    2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Strain: C57BL/6.
      Tissue: Brain.
    3. "Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity."
      Hsieh J.-C., Lee L., Zhang L., Wefer S., Brown K., DeRossi C., Wines M.E., Rosenquist T., Holdener B.C.
      Cell 112:355-367(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MESD, SUBUNIT, SUBCELLULAR LOCATION.
    4. "The Wnt co-receptors Lrp5 and Lrp6 are essential for gastrulation in mice."
      Kelly O.G., Pinson K.I., Skarnes W.C.
      Development 131:2803-2815(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    5. "Mouse cristin/R-spondin family proteins are novel ligands for the Frizzled 8 and LRP6 receptors and activate beta-catenin-dependent gene expression."
      Nam J.-S., Turcotte T.J., Smith P.F., Choi S., Yoon J.K.
      J. Biol. Chem. 281:13247-13257(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH RSPO1 AND RSPO3.
    6. "GRB10 binds to LRP6, the Wnt co-receptor and inhibits canonical Wnt signaling pathway."
      Tezuka N., Brown A.M., Yanagawa S.
      Biochem. Biophys. Res. Commun. 356:648-654(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH GRB10.
    7. "Analysis of endogenous LRP6 function reveals a novel feedback mechanism by which Wnt negatively regulates its receptor."
      Khan Z., Vijayakumar S., de la Torre T.V., Rotolo S., Bafico A.
      Mol. Cell. Biol. 27:7291-7301(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-1490, INDUCTION, SUBCELLULAR LOCATION.
    8. "Neucrin is a novel neural-specific secreted antagonist to canonical Wnt signaling."
      Miyake A., Takahashi Y., Miwa H., Shimada A., Konishi M., Itoh N.
      Biochem. Biophys. Res. Commun. 390:1051-1055(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DRAXIN.
    9. "Skeletal defects in ringelschwanz mutant mice reveal that Lrp6 is required for proper somitogenesis and osteogenesis."
      Kokubu C., Heinzmann U., Kokubu T., Sakai N., Kubota T., Kawai M., Wahl M.B., Galceran J., Grosschedl R., Ozono K., Imai K.
      Development 131:5469-5480(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT RS TRP-886.
    10. "Lrp6 hypomorphic mutation affects bone mass through bone resorption in mice and impairs interaction with Mesd."
      Kubota T., Michigami T., Sakaguchi N., Kokubu C., Suzuki A., Namba N., Sakai N., Nakajima S., Imai K., Ozono K.
      J. Bone Miner. Res. 23:1661-1671(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION OF VARIANT RINGELSCHWANZ PHENOTYPE TRP-886, SUBCELLULAR LOCATION, INTERACTION WITH DKK1; WNT1 AND MESD.

    Entry informationi

    Entry nameiLRP6_MOUSE
    AccessioniPrimary (citable) accession number: O88572
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: May 10, 2004
    Last sequence update: November 1, 1998
    Last modified: October 1, 2014
    This is version 119 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. MGD cross-references
      Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
    2. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3