Product: HMGCR Antibody
Catalog: DF6518
Description: Rabbit polyclonal antibody to HMGCR
Application: WB IHC IF/ICC
Reactivity: Human, Mouse, Rat
Prediction: Pig, Bovine, Horse, Sheep, Rabbit, Dog, Xenopus
Mol.Wt.: 95kDa; 97kD(Calculated).
Uniprot: P04035
RRID: AB_2838480

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

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Product Info

Source:
Rabbit
Application:
WB 1:500-1:2000, IHC 1:50-1:200, IF/ICC 1:100-1:500
*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(88%), Bovine(100%), Horse(100%), Sheep(88%), Rabbit(88%), Dog(88%), Xenopus(88%)
Clonality:
Polyclonal
Specificity:
HMGCR Antibody detects endogenous levels of total HMGCR.
RRID:
AB_2838480
Cite Format: Affinity Biosciences Cat# DF6518, RRID:AB_2838480.
Conjugate:
Unconjugated.
Purification:
The antiserum was purified by peptide affinity chromatography using SulfoLink™ Coupling Resin (Thermo Fisher Scientific).
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

3 hydroxy 3 methylglutaryl CoA reductase; 3 hydroxy 3 methylglutaryl Coenzyme A reductase; 3 hydroxymethylglutaryl CoA reductase; 3-hydroxy-3-methylglutaryl CoA reductase (NADPH); 3-hydroxy-3-methylglutaryl-coenzyme A reductase; 3H3M; HMDH_HUMAN; HMG CoA reductase; HMG CoAR; HMG-CoA reductase; Hmgcr; Hydroxymethylglutaryl CoA reductase; LDLCQ3; MGC103269; Red;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Description:
HMG-CoA reductase is the rate-limiting enzyme for cholesterol synthesis and is regulated via a negative feedback mechanism mediated by sterols and non-sterol metabolites derived from mevalonate, the product of the reaction catalyzed by reductase. Normally in mammalian cells this enzyme is suppressed by cholesterol derived from the internalization and degradation of low density lipoprotein (LDL) via the LDL receptor. Competitive inhibitors of the reductase induce the expression of LDL receptors in the liver, which in turn increases the catabolism of plasma LDL and lowers the plasma concentration of cholesterol, an important determinant of atherosclerosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
Sequence:
MLSRLFRMHGLFVASHPWEVIVGTVTLTICMMSMNMFTGNNKICGWNYECPKFEEDVLSSDIIILTITRCIAILYIYFQFQNLRQLGSKYILGIAGLFTIFSSFVFSTVVIHFLDKELTGLNEALPFFLLLIDLSRASTLAKFALSSNSQDEVRENIARGMAILGPTFTLDALVECLVIGVGTMSGVRQLEIMCCFGCMSVLANYFVFMTFFPACVSLVLELSRESREGRPIWQLSHFARVLEEEENKPNPVTQRVKMIMSLGLVLVHAHSRWIADPSPQNSTADTSKVSLGLDENVSKRIEPSVSLWQFYLSKMISMDIEQVITLSLALLLAVKYIFFEQTETESTLSLKNPITSPVVTQKKVPDNCCRREPMLVRNNQKCDSVEEETGINRERKVEVIKPLVAETDTPNRATFVVGNSSLLDTSSVLVTQEPEIELPREPRPNEECLQILGNAEKGAKFLSDAEIIQLVNAKHIPAYKLETLMETHERGVSIRRQLLSKKLSEPSSLQYLPYRDYNYSLVMGACCENVIGYMPIPVGVAGPLCLDEKEFQVPMATTEGCLVASTNRGCRAIGLGGGASSRVLADGMTRGPVVRLPRACDSAEVKAWLETSEGFAVIKEAFDSTSRFARLQKLHTSIAGRNLYIRFQSRSGDAMGMNMISKGTEKALSKLHEYFPEMQILAVSGNYCTDKKPAAINWIEGRGKSVVCEAVIPAKVVREVLKTTTEAMIEVNINKNLVGSAMAGSIGGYNAHAANIVTAIYIACGQDAAQNVGSSNCITLMEASGPTNEDLYISCTMPSIEIGTVGGGTNLLPQQACLQMLGVQGACKDNPGENARQLARIVCGTVMAGELSLMAALAAGHLVKSHMIHNRSKINLQDLQGACTKKTA

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
Horse
100
Bovine
100
Pig
88
Sheep
88
Dog
88
Xenopus
88
Rabbit
88
Zebrafish
0
Chicken
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P04035 As Substrate

Site PTM Type Enzyme
K89 Ubiquitination
K142 Ubiquitination
K248 Ubiquitination
S261 Phosphorylation
S278 Phosphorylation
T286 Phosphorylation
K288 Ubiquitination
K299 Ubiquitination
K351 Ubiquitination
S356 Phosphorylation
K362 Ubiquitination
K363 Ubiquitination
K381 Ubiquitination
T389 Phosphorylation
K396 Ubiquitination
K401 Ubiquitination
T409 Phosphorylation
S420 Phosphorylation
T425 Phosphorylation
S427 Phosphorylation
T431 Phosphorylation
K457 Ubiquitination
K460 Ubiquitination
S463 Phosphorylation
K474 Ubiquitination
K480 Ubiquitination
K502 Ubiquitination
S504 Phosphorylation
S602 Phosphorylation
K606 Ubiquitination
K619 Ubiquitination
K633 Ubiquitination
S637 Phosphorylation
Y644 Phosphorylation
K662 Ubiquitination
K666 Ubiquitination
K670 Ubiquitination
K692 Sumoylation
K692 Ubiquitination
K704 Ubiquitination
K715 Ubiquitination
K864 Ubiquitination
S872 Phosphorylation
K873 Ubiquitination
T884 Phosphorylation
K885 Ubiquitination

Research Backgrounds

Function:

Transmembrane glycoprotein that is the rate-limiting enzyme in cholesterol biosynthesis as well as in the biosynthesis of nonsterol isoprenoids that are essential for normal cell function including ubiquinone and geranylgeranyl proteins.

PTMs:

N-glycosylated. Deglycosylated by NGLY1 on release from the endoplasmic reticulum (ER) in a sterol-mediated manner.

Undergoes sterol-mediated ubiquitination and ER-associated degradation (ERAD). Accumulation of sterols in the endoplasmic reticulum (ER) membrane, triggers binding of the reductase to the ER membrane protein INSIG1. This INSIG1 binding leads to the recruitment of the ubiquitin ligase, AMFR/gp78 or RNF145, initiating ubiquitination of the reductase. The ubiquitinated reductase is then extracted from the ER membrane and delivered to cytosolic 26S proteosomes by a mechanism probably mediated by the ATPase Valosin-containing protein VCP/p97. Lys-248 is the main site of ubiquitination. Ubiquitination is enhanced by the presence of a geranylgeranylated protein.

Subcellular Location:

Endoplasmic reticulum membrane>Multi-pass membrane protein.

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

Homodimer. Interacts (via its SSD) with INSIG1; the interaction, accelerated by sterols, leads to the recruitment of HMGCR to AMFR/gp78 for its ubiquitination by the sterol-mediated ERAD pathway. Interacts with UBIAD1.

Family&Domains:

Belongs to the HMG-CoA reductase family.

Research Fields

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

· Metabolism > Metabolism of terpenoids and polyketides > Terpenoid backbone biosynthesis.

· Metabolism > Global and overview maps > Metabolic pathways.

References

1). β-patchoulene improves lipid metabolism to alleviate non-alcoholic fatty liver disease via activating AMPK signaling pathway. BIOMEDICINE & PHARMACOTHERAPY, 2021 (PubMed: 33341045) [IF=7.5]

Application: WB    Species: Human    Sample: L02 cell

Fig. 4. β-PAE inhibits the expression of hepatic lipid synthesis-related proteins and genes in HFD-fed rats. (A–F) Western blot analysis on the expression of proteins referred to hepatic lipid synthesis including SREBP-1c, ACC1, p-ACC1, FASN, SCD1 and HMG-CR; (G–H) The mRNA expression of SREBP-1c and HMG-CR. Data are presented as the mean ± SD (n = 6~8). ##p < 0.01 vs. NC group; *p < 0.05, **p < 0.01 vs. Model group.

2). The role of AMPKα2 in the HFD-induced nonalcoholic steatohepatitis. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 2020 (PubMed: 32502647) [IF=6.2]

3). NPY stimulates cholesterol synthesis acutely by activating the SREBP2-HMGCR pathway through the Y1 and Y5 receptors in murine hepatocytes. LIFE SCIENCES, 2020 (PubMed: 32976883) [IF=6.1]

Application: WB    Species: rat    Sample: liver

Fig. 2. |NPY promotes HMGCR protein expression both in vivo and in vitro.(A) Hepatic portal vein injection of NPY (100 μg/kg) significantly increased HMGCR expression after 1 h in rats.

4). Augmentation of 3β-hydroxysteroid-Δ24 Reductase (DHCR24) Expression Induced by Bovine Viral Diarrhea Virus Infection Facilitates Viral Replication via Promoting Cholesterol Synthesis. Journal of Virology, 2022 (PubMed: 36468862) [IF=5.4]

Application: WB    Species: bovine    Sample: bovine cells

FIG 1 (A) Cholesterol synthesis pathway. (B) Heat map of the key genes (transcriptomic data) and corresponding proteins (proteomic data) involved in lipid metabolism in bovine viral diarrhea virus (BVDV)-infected bovine cells. (C, D) Identification of differentially expressed genes by quantitative reverse transcription-PCR (qRT-PCR) (C) and corresponding proteins by Western blotting (D). HMGCS1, 3- hydroxy-3-methylglutaryl-coenzyme A synthase 1; HMGCR, 3-hydroxy-3-methylglutaryl-coenzyme A reductase; MVK, mevalonate kinase; PMVK, phosphomevalonate kinase; MVD, diphosphomevalonate decarboxylase; FDPS, farnesyl diphosphate synthase; FDFT1, farnesyl diphosphate farnesyltransferase 1; SQLE, squalene epoxidase; GGPS, geranylgeranyl pyrophosphate synthase; LSS, lanosterol synthase; D8D7I, 3β-hydroxysterol-Δ8,7-isomerase; C5SD, 3β-hydroxysterol-C5 desaturase; DHCR7, 7-dehydrocholesterol reductase; DHCR24, 3β-hydroxysteroid-Δ24 reductase; SCD1, stearoyl-CoA desaturase; FASN, fatty acid synthase; ACACA, acetyl coenzyme A carboxylase alpha.

5). Qinlian hongqu decoction ameliorates hyperlipidemia via the IRE1-α/IKKB-β/NF-κb signaling pathway: Network pharmacology and experimental validation. Journal of Ethnopharmacology, 2024 (PubMed: 37406747) [IF=5.4]

6). Sleeve Gastrectomy Suppresses Hepatic De Novo Cholesterogenesis and Improves Hepatic Cholesterol Accumulation in Obese Rats with Type 2 Diabetes Mellitus. NUTRITION, 2022 (PubMed: 34952362) [IF=4.4]

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