Product Details

Purity

Greater than 90% as determined by SDS-PAGE.

Target Names

MYLIP

Uniprot No.

Q8WY64

Research Area

Epigenetics and Nuclear Signaling

Alternative Names

BM-023; BZF1; E3 ubiquitin protein ligase MYLIP; E3 ubiquitin-protein ligase MYLIP; Idol; Inducible degrader of the LDL-receptor; Lipoprotein receptor; MIR; MYLIP; MYLIP_HUMAN; Myosin regulatory light chain interacting protein; PP5242

Species

Homo sapiens (Human)

Source

Yeast

Expression Region

1-445aa

Target Protein Sequence

MLCYVTRPDAVLMEVEVEAKANGEDCLNQVCRRLGIIEVDYFGLQFTGSKGESLWLNLRNRISQQMDGLAPYRLKLRVKFFVEPHLILQEQTRHIFFLHIKEALLAGHLLCSPEQAVELSALLAQTKFGDYNQNTAKYNYEELCAKELSSATLNSIVAKHKELEGTSQASAEYQVLQIVSAMENYGIEWHSVRDSEGQKLLIGVGPEGISICKDDFSPINRIAYPVVQMATQSGKNVYLTVTKESGNSIVLLFKMISTRAASGLYRAITETHAFYRCDTVTSAVMMQYSRDLKGHLASLFLNENINLGKKYVFDIKRTSKEVYDHARRALYNAGVVDLVSRNNQSPSHSPLKSSESSMNCSSCEGLSCQQTRVLQEKLRKLKEAMLCMVCCEEEINSTFCPCGHTVCCESCAAQLQSCPVCRSRVEHVQHVYLPTHTSLLNLTVI
Note: The complete sequence may include tag sequence, target protein sequence, linker sequence and extra sequence that is translated with the protein sequence for the purpose(s) of secretion, stability, solubility, etc.
If the exact amino acid sequence of this recombinant protein is critical to your application, please explicitly request the full and complete sequence of this protein before ordering.

Mol. Weight

51.9kDa

Protein Length

Full Length

Tag Info

N-terminal 6xHis-tagged

Form

Liquid or Lyophilized powder
Note: We will preferentially ship the format that we have in stock, however, if you have any special requirement for the format, please remark your requirement when placing the order, we will prepare according to your demand.

Buffer

If the delivery form is liquid, the default storage buffer is Tris/PBS-based buffer, 5%-50% glycerol.
Note: If you have any special requirement for the glycerol content, please remark when you place the order.
If the delivery form is lyophilized powder, the buffer before lyophilization is Tris/PBS-based buffer, 6% Trehalose.

Reconstitution

We recommend that this vial be briefly centrifuged prior to opening to bring the contents to the bottom. Please reconstitute protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL.We recommend to add 5-50% of glycerol (final concentration) and aliquot for long-term storage at -20°C/-80°C. Our default final concentration of glycerol is 50%. Customers could use it as reference.

Troubleshooting and FAQs

Protein FAQs

Storage Condition

Store at -20°C/-80°C upon receipt, aliquoting is necessary for mutiple use. Avoid repeated freeze-thaw cycles.

Shelf Life

The shelf life is related to many factors, storage state, buffer ingredients, storage temperature and the stability of the protein itself.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. The shelf life of lyophilized form is 12 months at -20°C/-80°C.

Lead Time

Delivery time may differ from different purchasing way or location, please kindly consult your local distributors for specific delivery time.

Notes

Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.

Datasheet & COA

Please contact us to get it.

Description

The production of recombinant human E3 ubiquitin-protein ligase MYLIP in yeast involves co-cloning the gene of interest (1-445aa of human MYLIP) into an expression vector with an N-terminal 6xHis-tag gene and transforming it into yeast cells. These cells are cultured to induce protein expression. After sufficient growth is achieved, the cells are lysed to release the recombinant MYLIP protein. The harvested recombinant MYLIP protein is purified from the cell lysate through affinity chromatography. The purity of the MYLIP protein is assessed using SDS-PAGE, greater than 90%.

Human MYLIP, also known as IDOL (Inducible Degrader of the LDL Receptor), plays a crucial role in cholesterol regulation by regulating the LDL receptor (LDLR) pathway [1]. MYLIP is abundantly expressed in almost all human tissues, suggesting additional functions and targets for this protein [2]. The N342S MYLIP polymorphism has been associated with high total cholesterol levels and increased LDL receptor degradation in humans [1]. MYLIP is also involved in the degradation of Very Low-Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2), indicating its broad role in lipid metabolism and nervous system physiology [3].

References:
[1] D. Weissglas‐Volkov, A. Calkin, T. Tusié-Luna, J. Sinsheimer, N. Zelcer, L. Ribaet al., The n342s mylip polymorphism is associated with high total cholesterol and increased ldl receptor degradation in humans, Journal of Clinical Investigation, vol. 121, no. 8, p. 3062-3071, 2011. https://doi.org/10.1172/jci45504
[2] D. Lindholm, B. Bornhäuser, & L. Korhonen, Mylip makes an idol turn into regulation of ldl receptor, Cellular and Molecular Life Sciences, vol. 66, no. 21, p. 3399-3402, 2009. https://doi.org/10.1007/s00018-009-0127-y
[3] K. Hatta, J. Guo, S. Dhingra, K. Singh, M. Huang, R. Weiselet al., Expression of cnpy2 in mouse tissues: quantification and localization, Plos One, vol. 9, no. 11, p. e111370, 2014. https://doi.org/10.1371/journal.pone.0111370

Target Background

Function

E3 ubiquitin-protein ligase that mediates ubiquitination and subsequent proteasomal degradation of myosin regulatory light chain (MRLC), LDLR, VLDLR and LRP8. Activity depends on E2 enzymes of the UBE2D family. Proteasomal degradation of MRLC leads to inhibit neurite outgrowth in presence of NGF by counteracting the stabilization of MRLC by saposin-like protein (CNPY2/MSAP) and reducing CNPY2-stimulated neurite outgrowth. Acts as a sterol-dependent inhibitor of cellular cholesterol uptake by mediating ubiquitination and subsequent degradation of LDLR.

Gene References into Functions

the effects caused by human inducible degrader of the low-density lipoprotein expression are LDLR- dependent given the unchanged plasma lipids in LAhB mice lacking low-density lipoprotein receptor PMID: 26786161
The long noncoding RNA RP1-13D10.2 may contribute to LDL cholesterol levels in response to statins. PMID: 27071970
Specifically, loss of IDOL increases LDLR distribution in the hepatic cell, and subsequently reduces serum LDL-C levels in dyslipidemic patients PMID: 26601593
Data suggest inducible expression of IDOL is subject to robust, rapid regulation by process that is sensitive to deubiquitinase inhibition in human/mouse cell lines and primary human cells; transcriptional induction of IDOL leads to degradation of LDLR. PMID: 26719329
Identify USP2 as a novel regulator of lipoprotein clearance owing to its ability to control ubiquitylation-dependent degradation of the LDLR by IDOL. PMID: 26666640
The study identified MARCH6 as a negative regulator of SREBP2-mediated transcription and described an unexpected E3 circuit functionally linking MARCH6 and IDOL to limit uptake of low-density lipoprotein via the LDLR pathway. PMID: 26527619
IDOL N342S Variant, Atherosclerosis Progression and Cardiovascular Disorders in the Italian General Population. PMID: 25927920
Several lipid-related gene polymorphisms interact with overweight/obesity to modulate blood pressure levels. PMID: 23109900
study indicates that MYLIP p.N342S might be a pharmacogenetic marker for lipid-lowering therapy in patients with FH. PMID: 25171759
Liver-specific expression of dominant-active IDOL is associated with hypercholesterolemia and a marked elevation in atherosclerotic lesions in transgenic mice. PMID: 24935961
Results show that IDOL contributes to variation in circulating levels of LDL-C. PMID: 23324548
IDOL is recruited to plasma membrane by low-density lipoprotein receptor (LDLR), promotes LDLR internalization in the absence of clathrin or caveolae, and facilitates LDLR degradation by shuttling it into the multivesicular body protein-sorting pathway PMID: 23382078
MYLIP rs3757354 SNP is associated with serum TC, HDL-C and ApoAI levels in the Bai Ku Yao and Han populations. But the association is different between the two ethnic groups. PMID: 23107276
No association of the MYLIP rs9370867 genotypes with lipid profile, hemodynamic data, and coronary angiographic data was in a Brazilian population. PMID: 22741812
FGF21 also enhanced expression of Canopy2 (Cnpy2)/MIR-interacting Saposin-like protein (Msap) that is known to interact with Mylip/Idol. PMID: 22378787
expression levels rise with increasing age in hearts of men PMID: 22261164
both the FERM and RING domains are required for promoting lysosomal degradation of the LDLR by IDOL. PMID: 21734303
N342S MYLIP polymorphism is associated with high total cholesterol and increased LDL receptor degradation in humans PMID: 21765216
identify the IDOL-UBE2D complex as an important determinant of LDLR activity, and provide insight into molecular mechanisms underlying the regulation of cholesterol uptake PMID: 21685362
Data report that statins exert opposite effects on PCSK9 and Idol gene expression in human hepatoma-derived cell lines and primary hepatocytes isolated from hamsters and rats. PMID: 21069265
MSAP interacts with this protein that enhances neurite outgrowth and increases myosin regulatory light chain in fetal and adult brain. PMID: 12826659
c-MIR is the first example of an E3 ubiquitin ligase that is capable of inhibiting major histocompatibility (MHC) class II expression in antigen-presenting cells; c-MIR might potently regulate immune responses in vivo. PMID: 16785530
study shows the LXR-Idol(Mylip)-LDLR axis defines a complementary pathway to sterol response element-binding proteins for sterol regulation of cholesterol uptake PMID: 19520913
Novel insights into the physiology of this receptor come from studies on the ubiquitination and degradation of LDL receptor by the ubiquitin ligase Mylip/Idol that is induced in cells by the nuclear receptor, LXR. PMID: 19688294

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Subcellular Location

Cytoplasm. Cell membrane; Peripheral membrane protein.

Tissue Specificity

Ubiquitously expressed.

Database Links

HGNC: 21155

OMIM: 610082

KEGG: hsa:29116

STRING: 9606.ENSP00000349298

UniGene: Hs.484738

Code	CSB-YP855506HU
Abbreviation	Recombinant Human MYLIP protein
MSDS	MSDS Datasheet
Size	$250
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Image	(Tris-Glycine gel) Discontinuous SDS-PAGE (reduced) with 5% enrichment gel and 15% separation gel.
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Recombinant Human E3 ubiquitin-protein ligase MYLIP (MYLIP)

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Target Background

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