Product: Phospho-LRP6 (Ser1490) Antibody
Catalog: DF2994
Description: Rabbit polyclonal antibody to Phospho-LRP6 (Ser1490)
Application: WB
Reactivity: Human, Mouse, Rat
Prediction: Pig, Bovine, Horse, Sheep, Rabbit, Dog, Chicken
Mol.Wt.: 180 KD; 180kD(Calculated).
Uniprot: O75581
RRID: AB_2840973

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 100ul $280 In stock
 200ul $350 In stock

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Product Info

Source:
Rabbit
Application:
WB 1:1000-3000
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Pig(100%), Bovine(100%), Horse(100%), Sheep(100%), Rabbit(100%), Dog(100%), Chicken(100%)
Clonality:
Polyclonal
Specificity:
Phospho-LRP6 (Ser1490) Antibody detects endogenous levels of LRP6 only when phosphorylated at Ser1490.
RRID:
AB_2840973
Cite Format: Affinity Biosciences Cat# DF2994, RRID:AB_2840973.
Conjugate:
Unconjugated.
Purification:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

ADCAD2; C030016K15Rik; Cd; FLJ90062; FLJ90421; Low density lipoprotein receptor related protein 6; Low-density lipoprotein receptor-related protein 6; LRP-6; LRP6; LRP6_HUMAN; OTTHUMP00000238979; OTTHUMP00000238980; OTTHUMP00000238982;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
O75581 LRP6_HUMAN:

Widely coexpressed with LRP5 during embryogenesis and in adult tissues.

Sequence:
MGAVLRSLLACSFCVLLRAAPLLLYANRRDLRLVDATNGKENATIVVGGLEDAAAVDFVFSHGLIYWSDVSEEAIKRTEFNKTESVQNVVVSGLLSPDGLACDWLGEKLYWTDSETNRIEVSNLDGSLRKVLFWQELDQPRAIALDPSSGFMYWTDWGEVPKIERAGMDGSSRFIIINSEIYWPNGLTLDYEEQKLYWADAKLNFIHKSNLDGTNRQAVVKGSLPHPFALTLFEDILYWTDWSTHSILACNKYTGEGLREIHSDIFSPMDIHAFSQQRQPNATNPCGIDNGGCSHLCLMSPVKPFYQCACPTGVKLLENGKTCKDGATELLLLARRTDLRRISLDTPDFTDIVLQLEDIRHAIAIDYDPVEGYIYWTDDEVRAIRRSFIDGSGSQFVVTAQIAHPDGIAVDWVARNLYWTDTGTDRIEVTRLNGTMRKILISEDLEEPRAIVLDPMVGYMYWTDWGEIPKIERAALDGSDRVVLVNTSLGWPNGLALDYDEGKIYWGDAKTDKIEVMNTDGTGRRVLVEDKIPHIFGFTLLGDYVYWTDWQRRSIERVHKRSAEREVIIDQLPDLMGLKATNVHRVIGSNPCAEENGGCSHLCLYRPQGLRCACPIGFELISDMKTCIVPEAFLLFSRRADIRRISLETNNNNVAIPLTGVKEASALDFDVTDNRIYWTDISLKTISRAFMNGSALEHVVEFGLDYPEGMAVDWLGKNLYWADTGTNRIEVSKLDGQHRQVLVWKDLDSPRALALDPAEGFMYWTEWGGKPKIDRAAMDGSERTTLVPNVGRANGLTIDYAKRRLYWTDLDTNLIESSNMLGLNREVIADDLPHPFGLTQYQDYIYWTDWSRRSIERANKTSGQNRTIIQGHLDYVMDILVFHSSRQSGWNECASSNGHCSHLCLAVPVGGFVCGCPAHYSLNADNRTCSAPTTFLLFSQKSAINRMVIDEQQSPDIILPIHSLRNVRAIDYDPLDKQLYWIDSRQNMIRKAQEDGSQGFTVVVSSVPSQNLEIQPYDLSIDIYSRYIYWTCEATNVINVTRLDGRSVGVVLKGEQDRPRAVVVNPEKGYMYFTNLQERSPKIERAALDGTEREVLFFSGLSKPIALALDSRLGKLFWADSDLRRIESSDLSGANRIVLEDSNILQPVGLTVFENWLYWIDKQQQMIEKIDMTGREGRTKVQARIAQLSDIHAVKELNLQEYRQHPCAQDNGGCSHICLVKGDGTTRCSCPMHLVLLQDELSCGEPPTCSPQQFTCFTGEIDCIPVAWRCDGFTECEDHSDELNCPVCSESQFQCASGQCIDGALRCNGDANCQDKSDEKNCEVLCLIDQFRCANGQCIGKHKKCDHNVDCSDKSDELDCYPTEEPAPQATNTVGSVIGVIVTIFVSGTVYFICQRMLCPRMKGDGETMTNDYVVHGPASVPLGYVPHPSSLSGSLPGMSRGKSMISSLSIMGGSSGPPYDRAHVTGASSSSSSSTKGTYFPAILNPPPSPATERSHYTMEFGYSSNSPSTHRSYSYRPYSYRHFAPPTTPCSTDVCDSDYAPSRRMTSVATAKGYTSDLNYDSEPVPPPPTPRSQYLSAEENYESCPPSPYTERSYSHHLYPPPPSPCTDSS

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
100
Horse
100
Bovine
100
Sheep
100
Dog
100
Chicken
100
Rabbit
100
Xenopus
0
Zebrafish
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - O75581 As Substrate

Site PTM Type Enzyme
K108 Ubiquitination
S122 Phosphorylation
S127 Phosphorylation
S171 Phosphorylation
S172 Phosphorylation
S209 Phosphorylation
T214 Phosphorylation
Y375 Phosphorylation
N692 N-Glycosylation
K733 Ubiquitination
K802 Acetylation
N859 N-Glycosylation
N865 N-Glycosylation
N926 N-Glycosylation
K941 Ubiquitination
K977 Ubiquitination
T1001 Phosphorylation
N1039 N-Glycosylation
K1195 Ubiquitination
K1403 Ubiquitination
S1420 Phosphorylation P49674 (CSNK1E)
S1430 Phosphorylation P49674 (CSNK1E)
S1431 Phosphorylation P49674 (CSNK1E)
K1443 Ubiquitination
S1444 Phosphorylation
S1448 Phosphorylation P34947 (GRK5) , P43250 (GRK6)
S1450 Phosphorylation P34947 (GRK5)
S1455 Phosphorylation
Y1460 Phosphorylation
S1474 Phosphorylation
S1475 Phosphorylation
T1476 Phosphorylation
T1479 Phosphorylation Q9HCP0 (CSNK1G1)
Y1480 Phosphorylation
S1490 Phosphorylation P28482 (MAPK1) , P34947 (GRK5) , P49841 (GSK3B) , P27361 (MAPK3) , O94921 (CDK14) , P43250 (GRK6)
T1493 Phosphorylation P48729 (CSNK1A1)
S1496 Phosphorylation
Y1498 Phosphorylation
T1499 Phosphorylation
Y1504 Phosphorylation
S1506 Phosphorylation
S1508 Phosphorylation P34947 (GRK5) , P43250 (GRK6)
S1510 Phosphorylation
Y1515 Phosphorylation
S1516 Phosphorylation
Y1517 Phosphorylation
R1518 Methylation
Y1520 Phosphorylation
S1521 Phosphorylation
Y1522 Phosphorylation
Y1541 Phosphorylation
S1544 Phosphorylation P49840 (GSK3A)
T1548 Phosphorylation P17612 (PRKACA)
K1554 Ubiquitination
Y1562 Phosphorylation
T1572 Phosphorylation P49841 (GSK3B) , P34947 (GRK5) , P43250 (GRK6) , P27361 (MAPK3) , P28482 (MAPK1)
S1575 Phosphorylation
Y1577 Phosphorylation
S1579 Phosphorylation
Y1584 Phosphorylation
S1590 Phosphorylation P34947 (GRK5) , P43250 (GRK6)
S1607 Phosphorylation P49841 (GSK3B) , P34947 (GRK5)
S1612 Phosphorylation
S1613 Phosphorylation

Research Backgrounds

Function:

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).

PTMs:

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.

Undergoes gamma-secretase-dependent regulated intramembrane proteolysis (RIP). The extracellular domain is first released by shedding, and then, through the action of gamma-secretase, the intracellular domain (ICD) is released into the cytoplasm where it is free to bind to GSK3B and to activate canonical Wnt signaling.

Palmitoylation on the two sites near the transmembrane domain leads to release of LRP6 from the endoplasmic reticulum.

Mono-ubiquitinated which retains LRP6 in the endoplasmic reticulum. Ubiquitinated by ZNRF3, leading to its degradation by the proteasome.

N-glycosylation is required for cell surface location.

Subcellular Location:

Cell membrane>Single-pass type I membrane protein. Endoplasmic reticulum. Membrane raft.
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. Chaperoned to the plasma membrane by MESD (By similarity).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Widely coexpressed with LRP5 during embryogenesis and in adult tissues.

Subunit Structure:

Homodimer; disulfide-linked. Forms phosphorylated oligomer aggregates on Wnt-signaling. Forms a WNT-signaling complex formed of a WNT protein, a FZD protein and LRP5 or LRP6. Interacts (via the extracellular domain) with WNT1; the interaction is enhanced by prior formation of the Wnt/Fzd complex. Interacts (via the beta-propeller regions 3 and 4) with WNT3A. Interacts (via the beta-propeller regions 1 and 2) with WNT9B. Interacts with FZD5; the interaction forms a coreceptor complex for Wnt signaling and is inhibited by DKK1 and DRAXIN. Interacts (via beta propeller region) with DKK1; the interaction inhibits FZD5/LRP6 complex formation. Interacts with DKK2. Interacts with C1orf187/DRAXIN; the interaction inhibits Wnt signaling (By similarity). Interacts (via the phosphorylated PPPSP motifs) with AXIN1; the interaction recruits the AXIN1/GSK3B complex to cell surface LRP6 signalsomes. Interacts with GRB10; the interaction prevents AXIN1 binding, thus negatively regulating the Wnt signaling pathway (By similarity). Interacts (via the extracellular domain) with RSPO1; the interaction activates Wnt/beta-catenin signaling. Interacts (via the extracellular domain) with RSPO3 (via the cysteine rich domain); the interaction activates Wnt/beta-catenin signaling. Interacts (via the beta-propeller regions 1 and 2) with SOST; the interaction competes with DKK1 for binding for inhibiting beta-catenin signaling. Interacts with MESD; the interaction prevents the formation of LRP6 aggregates and targets LRP6 to the plasma membrane (By similarity). Interacts (via the cytoplasmic domain) with CSNKIE; the interaction phosphorylates LRP6, binds AXIN1 and inhibits AXIN1/GSK3B-mediated phosphorylation of beta-catenin. Interacts with MACF1. Interacts with DAB2; the interaction involves LRP6 phosphorylation by CK2 and sequesters LRP6 towards clathrin-mediated endocytosis. Interacts with TMEM198. Interacts with CAPRIN2; the interaction promotes LRP6 phosphorylation at Ser-1490. Found in a complex with CAPRIN2, CCNY and CDK14 during G2/M stage; CAPRIN2 functions as a scaffold for the complex by binding to CCNY via its N terminus and to CDK14 via its C terminus. Interacts with LYPD6. Forms a ternary complex with DKK1 and KREM1. Interacts with KREM1 in a DKK1-dependent manner. Interacts with MDK: this interaction is calcium dependent (By similarity). Interacts with LMBR1L.

Family&Domains:

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.

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

Belongs to the LDLR family.

Research Fields

· Environmental Information Processing > Signal transduction > mTOR signaling pathway.   (View pathway)

· Environmental Information Processing > Signal transduction > Wnt signaling pathway.   (View pathway)

· Human Diseases > Cancers: Overview > Pathways in cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Breast cancer.   (View pathway)

· Human Diseases > Cancers: Specific types > Hepatocellular carcinoma.   (View pathway)

· Human Diseases > Cancers: Specific types > Gastric cancer.   (View pathway)

References

1). Huang X et al. Resveratrol ameliorates high-phosphate-induced VSMCs to osteoblast-like cells transdifferentiation and arterial medial calcification in CKD through regulating Wnt/β-catenin signaling. European Journal of Pharmacology 2022 Apr 25;174953. (PubMed: 35483665) [IF=5.0]

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