Human Recombinant HMGCR protein, His Tag (V2LY-0526-LY4563)

Name: Human Recombinant HMGCR protein, His Tag
SKU: V2LY-0526-LY4563
Rating: 5 (1 reviews)

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Datasheet

SDS

Request for COA

Datasheet Target References Q & As Review & reward Protocols Associated Products

Basic Information

Expressed Host

E. coli

Protein Species

Human

Tag

His Tag

Protein Construction

This product is Human Recombinant HMGCR protein, His Tag consist of Amino Acid: 426-888 and predicts a molecular mass of 50.6 kDa.

Molecule Mass

50.6 kDa

Sequence

Amino Acid: 426-888

Species

Human

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

Purity

≥90% as determined by SDS-PAGE.

Endotoxin

Please contact us for more information.

Format

Lyophilized

Reconstitution

Allow the vial and reconstitution buffer to equilibrate to room temperature. Briefly centrifuge or tap down the vial to ensure that all lyophilized powder is collected at the bottom of the vial. For the reconstitution of this product, we recommend adding PBS or sterile water to achieve a final antibody concentration of 1 mg/mL. Allow the vial to reconstitute for 10-15 minutes at room temperature with gentle agitation. Avoid vigorous shaking that can cause foaming and antibody denaturation. Aliquot into volumes based on your experiment and store liquid protein at -20°C or -80°C for long time.

Buffer

Lyophilized from sterile Please contact us for any concerns or special requirements.

Please refer to the specific buffer information in the hardcopy of datasheet or the lot-specific COA.

Preservative

None

Storage

Samples are stable for up to twelve months from date of receipt at -20°C to -80°C. Store it under sterile conditions at -20°C to -80°C. It is recommended that the protein be aliquoted for optimal storage. Avoid repeated freeze-thaw cycles.

More Infomation

Target

Full Name

3-Hydroxy-3-Methylglutaryl-CoA Reductase

Function

Catalyzes the conversion of (3S)-hydroxy-3-methylglutaryl-CoA (HMG-CoA) to mevalonic acid, the rate-limiting step in the synthesis of cholesterol and other isoprenoids, thus plays a critical role in cellular cholesterol homeostasis (PubMed:2991281, PubMed:21357570, PubMed:6995544).

HMGCR is the main target of statins, a class of cholesterol-lowering drugs (PubMed:11349148, PubMed:18540668).

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)
Proteogenomic
Other Protocols

Alternative Versions

Human HMGCR ELISA Kit (CAT#: V2LY-0626-LY1294)

Rat Hmgcr ELISA Kit (CAT#: V2LY-0626-LY2020)

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Mouse Anti-HMGCR Recombinant Antibody (CBFYH-1547) (CAT#: CBMAB-H2522-FY)

Human HMGCR ELISA Kit (CAT#: V2LY-0626-LY1294)

Isotype control

For research use only. Not intended for any clinical use.

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