Recombinant Human Low-Density Lipoprotein Receptor-Related Protein 2 (LRP2) Protein (mFc)

Name: Recombinant Human Low-Density Lipoprotein Receptor-Related Protein 2 (LRP2) Protein (mFc)
Brand: Beta LifeScience
SKU: BLC-00862P
Price: 349.0 USD
Availability: InStock

Greater than 85% as determined by SDS-PAGE.

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Size

100ug

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Product Overview

Description	Recombinant Human Low-Density Lipoprotein Receptor-Related Protein 2 (LRP2) Protein (mFc) is produced by our Mammalian cell expression system. This is a protein fragment.
Purity	Greater than 85% as determined by SDS-PAGE.
Uniprotkb	P98164
Target Symbol	LRP2
Species	Homo sapiens (Human)
Expression System	Mammalian cell
Tag	C-mFc
Target Protein Sequence	NCTASQFKCASGDKCIGVTNRCDGVFDCSDNSDEAGCPTRPPGMCHSDEFQCQEDGICIPNFWECDGHPDCLYGSDEHNACVPKTCPSSYFHCDNGNCIHRAWLCDRDNDCGDMSDEKDCPTQPFRCPSWQWQCLGHNICVNLSVVCDGIFDCPNGTDESPLCNGNSCSDFNGGCTHECVQEPFGAKCLCPLGFLLANDSKTCE
Expression Range	1186-1389aa
Protein Length	Partial
Mol. Weight	50.8 kDa
Research Area	Immunology
Form	Liquid or Lyophilized powder
Buffer	Liquid form: default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol. Lyophilized powder form: the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose, pH 8.0.
Reconstitution	Briefly centrifuged the vial prior to opening to bring the contents to the bottom. Reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. It is recommended to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. The default final concentration of glycerol is 50%.
Storage	1. Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. 2. Avoid repeated freeze-thaw cycles. 3. Store working aliquots at 4°C for up to one week. 4. In general, protein in liquid form is stable for up to 6 months at -20°C/-80°C. Protein in lyophilized powder form is stable for up to 12 months at -20°C/-80°C.
Notes	Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Target Details

Target Function	Multiligand endocytic receptor. Acts together with CUBN to mediate endocytosis of high-density lipoproteins. Mediates receptor-mediated uptake of polybasic drugs such as aprotinin, aminoglycosides and polymyxin B. In the kidney, mediates the tubular uptake and clearance of leptin. Also mediates transport of leptin across the blood-brain barrier through endocytosis at the choroid plexus epithelium. Endocytosis of leptin in neuronal cells is required for hypothalamic leptin signaling and leptin-mediated regulation of feeding and body weight. Mediates endocytosis and subsequent lysosomal degradation of CST3 in kidney proximal tubule cells. Mediates renal uptake of 25-hydroxyvitamin D3 in complex with the vitamin D3 transporter GC/DBP. Mediates renal uptake of metallothionein-bound heavy metals. Together with CUBN, mediates renal reabsorption of myoglobin. Mediates renal uptake and subsequent lysosomal degradation of APOM. Plays a role in kidney selenium homeostasis by mediating renal endocytosis of selenoprotein SEPP1. Mediates renal uptake of the antiapoptotic protein BIRC5/survivin which may be important for functional integrity of the kidney. Mediates renal uptake of matrix metalloproteinase MMP2 in complex with metalloproteinase inhibitor TIMP1. Mediates endocytosis of Sonic hedgehog protein N-product (ShhN), the active product of SHH. Also mediates ShhN transcytosis. In the embryonic neuroepithelium, mediates endocytic uptake and degradation of BMP4, is required for correct SHH localization in the ventral neural tube and plays a role in patterning of the ventral telencephalon. Required at the onset of neurulation to sequester SHH on the apical surface of neuroepithelial cells of the rostral diencephalon ventral midline and to control PTCH1-dependent uptake and intracellular trafficking of SHH. During neurulation, required in neuroepithelial cells for uptake of folate bound to the folate receptor FOLR1 which is necessary for neural tube closure. In the adult brain, negatively regulates BMP signaling in the subependymal zone which enables neurogenesis to proceed. In astrocytes, mediates endocytosis of ALB which is required for the synthesis of the neurotrophic factor oleic acid. Involved in neurite branching. During optic nerve development, required for SHH-mediated migration and proliferation of oligodendrocyte precursor cells. Mediates endocytic uptake and clearance of SHH in the retinal margin which protects retinal progenitor cells from mitogenic stimuli and keeps them quiescent. Plays a role in reproductive organ development by mediating uptake in reproductive tissues of androgen and estrogen bound to the sex hormone binding protein SHBG. Mediates endocytosis of angiotensin-2. Also mediates endocytosis of angiotensis 1-7. Binds to the complex composed of beta-amyloid protein 40 and CLU/APOJ and mediates its endocytosis and lysosomal degradation. Required for embryonic heart development. Required for normal hearing, possibly through interaction with estrogen in the inner ear.
Subcellular Location	Apical cell membrane; Single-pass type I membrane protein. Endosome lumen. Membrane, coated pit. Cell projection, dendrite. Cell projection, axon.
Protein Families	LDLR family
Database References	HGNC: 6694 OMIM: 222448 KEGG: hsa:4036 STRING: 9606.ENSP00000263816 UniGene: Hs.657729
Associated Diseases	Donnai-Barrow syndrome (DBS)
Tissue Specificity	Expressed in first and third trimester cytotrophoblasts in the placenta (at protein level). Absorptive epithelia, including renal proximal tubules.

Gene Functions References

megalin is critical for mitochondrial biology; mitochondrial intracrine signaling is a continuum of the retrograde early endosome-to-Golgi-Rab32 pathway and defects in this pathway may underlie disease processes in many systems. PMID: 29916093
patients with OCRL-1 mutations or type 1 Dent disease showed abnormally low levels of urinary A-megalin PMID: 27766457
An Emerging Role for Megalin as a Regulator of Protein Leak in Acute Lung Injury. PMID: 29090957
Review of LRP2 function. LRP2 functions are crucial for developmental processes in a number of tissues, including the brain, the eye, and the heart, and defects in this receptor pathway are the cause of devastating congenital diseases in humans. PMID: 26872844
A novel LRP2 missense variant rs17848169 (N2632D) was found to be associated with lower risk for T2D-ESRD in this population. PMID: 27197912
we discovered one novel locus (LRP2; most significant single nucleotide polymorphism rs12988804) that reached genome-wide significance in predicting relapse risk (HR=2.18, p=3.30x10(-8)). PMID: 28739605
miR-148b directly down-regulates renal megalin expression. PMID: 28331063
Exocytosis-mediated urinary C-megalin excretion is associated with the development and progression of diabetic nephropathy in T2DM, particularly due to megalin-mediated lysosomal dysfunction in proximal tubules. PMID: 28289043
The studies suggest that impaired endocytosis of megalin/cubilin ligands, hemoglobin and albumin, rather than heme toxicity, may be the cause of tubular proteinuria in sickle cell disease patients. PMID: 28356267
VDR and MEGALIN gene variations can alter age-related cognitive trajectories differentially between men and women among African American urban adults, specifically in global mental status and domains of verbal fluency, visual/working memory, and executive function. PMID: 28446629
the main role for placental megalin is not to mediate uptake of nutrients from the maternal bloodstream; results point toward novel and complex functions for megalin in the cytotrophoblasts. PMID: 27798286
specific miRNA-146a regulation may contribute to Alzheimer's disease by downregulating the Lrp2/Akt pathway PMID: 27241555
abundances of megalin and Dab2 (p = 0.046) were reduced in infected placentas from women with LBW deliveries PMID: 27072056
homozygous Asp3779Asn and a hemizygous Ile262Met mutations in the LRP2 and TSPYL2 genes, respectively, in a Pakistani family with two boys affected with mild nonsyndromic intellectual disability PMID: 26529358
The megalin expression appears to vary inversely with gestational age with the greatest expression noted in the most premature samples. Age-dependent differences in placental megalin may therefore influence fetal exposure. PMID: 25304941
we are the first to identify the association between LRP2 and gout in a Chinese population and to confirm this association in Asians. PMID: 26147675
Two novel LRP2 mutations, a homozygous nonsense mutation and a missense mutation in two unrealted families with Donnai-Barrow syndrome. PMID: 25682901
Loss of LRP2 is associated with buphthalmos PMID: 26439398
melanoma cell expression of LRP2/megalin significantly decreases melanoma cell proliferation and survival rates. PMID: 25585665
levels of urinary C-megalin are associated with histological abnormalities in adult IgAN patients PMID: 25502002
A new mutation in LRP2 causes a predominantly ocular phenotype suggestive of Stickler syndrome. PMID: 23992033
LRP2 sequencing reveals multiple rare variants associated with urinary trefoil factor-3 PMID: 24876117
Serum uric acid-related gene LRP2 is not involved in gout susceptibility. PMID: 24366390
Transgenic/knock-out megalin-deficient mice develop anxiety behavior and impaired learning, as described in Alzheimer's disease. PMID: 24254699
Association of the T-allele of a single nucleotide polymorphism in LRP2 with gout risk in the Maori and Pacific subjects was consistent with this allele increasing serum urate in Japanese individuals PMID: 24286387
LOS treatment decreased microalbuminuria induced by Cd apparently through a cubilin receptor-dependent mechanism but independent of megalin. PMID: 24093454
Data suggest that endodermal layer of yolk sac and syncytiotrophoblast/cytotrophoblast cells of placental villi express megalin mRNA/protein; expression of megalin protein (but not mRNA) is up-regulated as gestation/placentation progresses. PMID: 23978537
This review explores current evidence linking megalin expression and function to the development, diagnosis, and progression of acute kidney injury --{REVIEW} PMID: 24197071
Megalin and Dab2 were expressed in prostate and colon epithelial cells, which was markedly enhanced following treatment with retinoic acid PMID: 23909735
The hypothalamic clusterin-low-density lipoprotein receptor-related protein-2 axis is a novel anorexigenic signalling pathway. PMID: 23673647
results suggested that GSTT1 wild genotype and C-allele of megalin gene rs2228171 SNPs might be risk factors for cisplatin-induced ototoxicity PMID: 23274376
Using NMR titration data in HADDOCK, we have generated a three-dimensional model describing the complex between megalin and gentamicin. PMID: 23275343
Expression of megalin and cubilin is decreased during experimental endotoxemia, which may contribute to an increase in urine levels of albumin during acute renal failure. PMID: 22437417
analysis of rare disease variants in LRP2, a gene linked and associated with autism spectrum disorders PMID: 22578327
This study confirmed that LRP2 rs2544390 C/T at intron 1 was associated with serum uric acid levels among Japanese males with SLC22A12 258WW, SLC2A9 rs11722228C allele, ABCG2 126QQ and 141Q allele. PMID: 22565184
A total of 330 Chinese female-offspring nuclear families with 1088 individuals and 400 Chinese male-offspring nuclear families with 1215 individuals were genotyped at six tag single nucleotide polymorphisms of the LRP2 gene. PMID: 22174918
Sex-specific VDR and Megalin gene variations can modify age-related cognitive decline among US adults. PMID: 22170372
megalin and cubilin are involved in the metabolism of vitamin D by reabsorbing vitamin D binding protein; dysfunction of these receptors is likely to be associated with the development of vitamin D deficiency in patients with chronic kidney disease PMID: 21595846
allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to Alzheimer's disease risk in the Chinese Han Population PMID: 20971101
in anagen VI hair follicles megalin was found in all keratinocytes of the distal region PMID: 21104416
Data show that MT-I + II and megalin are significantly altered in CNS lymphoma relative to controls. PMID: 20038220
No defect in the trafficking or function of megalin upon OCRL1 knockdown. PMID: 19940034
Megalin and cubilin: multifunctional endocytic receptors. A review. PMID: 11994745
This study reveals that LRP2 is a major autoantigen in rheumatoid arthritis and probably drives the production of anti-LRP2 autoantibodies, which may play pathological roles by inhibiting the reabsorbing function of LRP2. PMID: 12723989
megalin has a role in thyroid homeostasis with possible implications in thyroid diseases PMID: 14657389
a binding affinity of disabled homolog 2 mitogen-responsive phosphoprotein interaction domain for megalin CT of K(D) = 2.6 x 10(-7) +/- 5.3 x 10(-8) PMID: 15134832
megalin endocytosed NGAL by a mechanism completely blocked by an antibody against megalin PMID: 15670845
Further studies on the intracellular molecular signalling associated with megalin-mediated metabolic pathways may lead to the development of novel strategies for the treatment of nephropathies related to diabetes and metabolic syndrome. (Review) PMID: 16174284
This review focuses on the involvement of megalin during embryonic development and its interactions with the developmental morphogen sonic hedgehog. PMID: 16828734
Results show that the PPPSP motif and GSK3 activity are critical to allow megalin phosphorylation and also negatively regulate the receptor's recycling. PMID: 17555532

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Proteins are sensitive to heat, and freeze-drying can preserve the activity of the majority of proteins. It improves protein stability, extends storage time, and reduces shipping costs. However, freeze-drying can also lead to the loss of the active portion of the protein and cause aggregation and denaturation issues. Nonetheless, these adverse effects can be minimized by incorporating protective agents such as stabilizers, additives, and excipients, and by carefully controlling various lyophilization conditions.

Commonly used protectant include saccharides, polyols, polymers, surfactants, some proteins and amino acids etc. We usually add 8% (mass ratio by volume) of trehalose and mannitol as lyoprotectant. Trehalose can significantly prevent the alter of the protein secondary structure, the extension and aggregation of proteins during freeze-drying process; mannitol is also a universal applied protectant and fillers, which can reduce the aggregation of certain proteins after lyophilization.

Our protein products do not contain carrier protein or other additives (such as bovine serum albumin (BSA), human serum albumin (HSA) and sucrose, etc., and when lyophilized with the solution with the lowest salt content, they often cannot form A white grid structure, but a small amount of protein is deposited in the tube during the freeze-drying process, forming a thin or invisible transparent protein layer.

Reminder: Before opening the tube cap, we recommend that you quickly centrifuge for 20-30 seconds in a small centrifuge, so that the protein attached to the tube cap or the tube wall can be aggregated at the bottom of the tube. Our quality control procedures ensure that each tube contains the correct amount of protein, and although sometimes you can't see the protein powder, the amount of protein in the tube is still very precise.

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