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O88572

- LRP6_MOUSE

UniProt

O88572 - LRP6_MOUSE

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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

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.1 Publication

GO - Molecular functioni

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

GO - Biological processi

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

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.3 Publications

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini20 – 13701351Extracellular Reviewed prediction
Add
BLAST
Transmembranei1371 – 139323Helical; Reviewed prediction
Add
BLAST
Topological domaini1394 – 1613220Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. Golgi apparatus Source: Ensembl
  2. caveola Source: RefGenome
  3. cell surface Source: RefGenome
  4. cytoplasmic vesicle Source: Ensembl
  5. early endosome Source: MGI
  6. endoplasmic reticulum Source: UniProtKB-SubCell
  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
Complete GO annotation...

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 – 1919 Reviewed prediction
Add
BLAST
Chaini20 – 16131594Low-density lipoprotein receptor-related protein 6
PRO_0000017331Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi42 – 421N-linked (GlcNAc...) Reviewed prediction
Glycosylationi81 – 811N-linked (GlcNAc...) Reviewed prediction
Glycosylationi281 – 2811N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi286 ↔ 297 By similarity
Disulfide bondi293 ↔ 308 By similarity
Disulfide bondi310 ↔ 323 By similarity
Glycosylationi433 – 4331N-linked (GlcNAc...) Reviewed prediction
Glycosylationi486 – 4861N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi592 ↔ 603 By similarity
Disulfide bondi599 ↔ 612 By similarity
Disulfide bondi614 ↔ 627 By similarity
Glycosylationi692 – 6921N-linked (GlcNAc...) Reviewed prediction
Glycosylationi859 – 8591N-linked (GlcNAc...) Reviewed prediction
Glycosylationi865 – 8651N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi893 ↔ 904 By similarity
Disulfide bondi900 ↔ 914 By similarity
Disulfide bondi916 ↔ 929 By similarity
Glycosylationi926 – 9261N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1207 ↔ 1218 By similarity
Disulfide bondi1214 ↔ 1228 By similarity
Disulfide bondi1230 ↔ 1243 By similarity
Disulfide bondi1249 ↔ 1263 By similarity
Disulfide bondi1256 ↔ 1276 By similarity
Disulfide bondi1270 ↔ 1285 By similarity
Disulfide bondi1288 ↔ 1300 By similarity
Disulfide bondi1295 ↔ 1313 By similarity
Disulfide bondi1307 ↔ 1322 By similarity
Disulfide bondi1326 ↔ 1338 By similarity
Disulfide bondi1333 ↔ 1351 By similarity
Disulfide bondi1345 ↔ 1360 By similarity
Lipidationi1394 – 13941S-palmitoyl cysteine By similarity
Lipidationi1399 – 13991S-palmitoyl cysteine By similarity
Cross-linki1403 – 1403Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin) By similarity
Modified residuei1420 – 14201Phosphoserine; by CK1 By similarity
Modified residuei1430 – 14301Phosphoserine; by CK1 By similarity
Modified residuei1479 – 14791Phosphothreonine By similarity
Modified residuei1490 – 14901Phosphoserine; by CDK14, GRK5 and GRK6 By similarity
Modified residuei1493 – 14931Phosphothreonine; by CK1 By 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.1 Publication
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.
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.
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.5 Publications

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliO88572.
SMRiO88572. Positions 20-1360.

Family & Domainsi

Domains and Repeats

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

Region

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

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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti886 – 8861R → W in rs. 2 Publications

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti83 – 831S → T in AAH60704. 1 Publication
Sequence conflicti317 – 3171M → L in AAH60704. 1 Publication
Sequence conflicti586 – 5861V → I in AAH60704. 1 Publication
Sequence conflicti622 – 6221G → S in AAH60704. 1 Publication
Sequence conflicti933 – 9331S → T in AAH60704. 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 ]
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Publicationsi

« Hide 'large scale' publications
  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: September 3, 2014
This is version 118 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

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