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Mouse Anti-HMGCR Recombinant Antibody (A246) (CBMAB-AP9800LY)

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Datasheet
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Basic Information

Host Animal
Mouse
Clone
A246
Application
IF, IHC, IP, WB
Immunogen
Recombinant protein of human HMGCR
Specificity
Human, Mouse
Antibody Isotype
IgG
Clonality
Monoclonal
Application Notes
The COA includes recommended starting dilutions, optimal dilutions should be determined by the end user.

Formulations & Storage [For reference only, actual COA shall prevail!]

Format
Liquid
Purity
Affinity purity
Storage
Store at +4°C short term (1-2 weeks). Aliquot and store at -20°C long term. Avoid repeated freezethaw cycles.
More Infomation

Target

Full Name
3-Hydroxy-3-Methylglutaryl-CoA Reductase
Introduction
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]
Entrez Gene ID
Human3156
Mouse15357
UniProt ID
HumanP04035
MouseQ01237
Alternative Names
3-Hydroxy-3-Methylglutaryl-CoA Reductase; 3-Hydroxy-3-Methylglutaryl CoA Reductase (NADPH); 3-Hydroxy-3-Methylglutaryl-Coenzyme A Reductase; Hydroxymethylglutaryl-CoA Reductase; HMG-CoA Reductase; EC 1.1.1.34; EC 1.1.1; LDLCQ3;
Function
A10891
Biological Process
Cholesterol biosynthetic process Source: CACAO
Coenzyme A metabolic process Source: InterPro
Isoprenoid biosynthetic process Source: GO_Central
Negative regulation of amyloid-beta clearance Source: ARUK-UCL
Negative regulation of MAP kinase activity Source: Ensembl
Negative regulation of protein catabolic process Source: ARUK-UCL
Negative regulation of protein secretion Source: ARUK-UCL
Sterol biosynthetic process Source: GO_Central
Visual learning Source: Ensembl
Cellular Location
Peroxisome membrane; Endoplasmic reticulum membrane
Topology
Cytoplasmic: 1-9
Helical: 10-39
Lumenal: 40-56
Helical: 57-78
Cytoplasmic: 79-89
Helical: 90-114
Lumenal: 115-123
Helical: 124-149
Cytoplasmic: 150-159
Helical: 160-187
Lumenal: 188-191
Helical: 192-220
Cytoplasmic: 221-248
Helical: 249-275
Lumenal: 276-314
Helical: 315-339
Cytoplasmic: 340-888
PTM
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) (PubMed:12535518, PubMed:19458199, PubMed:21778231). Accumulation of sterols in the endoplasmic reticulum (ER) membrane, triggers binding of the reductase to the ER membrane protein INSIG1 or INSIG2 (PubMed:12535518, PubMed:19458199, PubMed:21778231, PubMed:22143767). The INSIG1 binding leads to the recruitment of the ubiquitin ligase, AMFR/gp78, RNF139 or RNF145, initiating ubiquitination of the reductase (PubMed:12535518, PubMed:19458199, PubMed:21778231). 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 (PubMed:12535518, PubMed:19458199, PubMed:21778231). The INSIG2-binding leads to the recruitment of the ubiquitin ligase RNF139, initiating ubiquitination of the reductase (PubMed:22143767). Lys-248 is the main site of ubiquitination (PubMed:19458199). Ubiquitination is enhanced by the presence of a geranylgeranylated protein (PubMed:21778231).
Phosphorylated. Phosphorylation at Ser-872 reduces the catalytic activity.

Kurashige, T. (2021). Anti-HMGCR myopathy: clinical and histopathological features, and prognosis. Current Opinion in Rheumatology, 33(6), 554-562.

Huang, J., Zhao, X., Li, X., Peng, J., Yang, W., & Mi, S. (2021). HMGCR inhibition stabilizes the glycolytic enzyme PKM2 to support the growth of renal cell carcinoma. PLoS biology, 19(4), e3001197.

Lu, X. Y., Shi, X. J., Hu, A., Wang, J. Q., Ding, Y., Jiang, W., ... & Song, B. L. (2020). Feeding induces cholesterol biosynthesis via the mTORC1–USP20–HMGCR axis. Nature, 588(7838), 479-484.

Meyer, A., Troyanov, Y., Drouin, J., Oligny-Longpré, G., Landon-Cardinal, O., Hoa, S., ... & Senécal, J. L. (2020). Statin-induced anti-HMGCR myopathy: successful therapeutic strategies for corticosteroid-free remission in 55 patients. Arthritis research & therapy, 22(1), 1-10.

Ma, S., Sun, W., Gao, L., & Liu, S. (2019). Therapeutic targets of hypercholesterolemia: HMGCR and LDLR. Diabetes, metabolic syndrome and obesity: targets and therapy, 1543-1553.

Mohassel, P., Landon-Cardinal, O., Foley, A. R., Donkervoort, S., Pak, K. S., Wahl, C., ... & Bönnemann, C. G. (2019). Anti-HMGCR myopathy may resemble limb-girdle muscular dystrophy. Neurology-Neuroimmunology Neuroinflammation, 6(1).

Bergua, C., Chiavelli, H., Allenbach, Y., Arouche-Delaperche, L., Arnoult, C., Bourdenet, G., ... & Boyer, O. (2019). In vivo pathogenicity of IgG from patients with anti-SRP or anti-HMGCR autoantibodies in immune-mediated necrotising myopathy. Annals of the rheumatic diseases, 78(1), 131-139.

Chen, L., Ma, M. Y., Sun, M., Jiang, L. Y., Zhao, X. T., Fang, X. X., ... & Song, B. L. (2019). Endogenous sterol intermediates of the mevalonate pathway regulate HMGCR degradation and SREBP-2 processing [S]. Journal of lipid research, 60(10), 1765-1775.

Landon-Cardinal, O., Allenbach, Y., Soulages, A., Rigolet, A., Hervier, B., Champtiaux, N., ... & Benveniste, O. (2019). Rituximab in the treatment of refractory anti-HMGCR immune-mediated necrotizing myopathy. The Journal of Rheumatology, 46(6), 623-627.

Mohassel, P., & Mammen, A. L. (2018). Anti-HMGCR myopathy. Journal of neuromuscular diseases, 5(1), 11-20.

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Please try the standard protocols which include: protocols, troubleshooting and guide.

Enzyme-linked Immunosorbent Assay (ELISA)
Flow Cytometry
Immunofluorescence (IF)
Immunohistochemistry (IHC)
Immunoprecipitation (IP)
Western Blot (WB)
Enzyme-Linked Immunospot (ELISpot)
Proteogenomics
Other Protocols

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