HMGCR Antibodies

Background

HMGCR (3-hydroxy-3-methylglutaryl-coenzyme A reductase) is a transmembrane protein located on the endoplasmic reticulum membrane. As a rate-limiting enzyme in the cholesterol synthesis pathway, it regulates cholesterol homeostasis in the body by catalyzing the conversion of HMG-CoA to mevalonic acid. The activity of this enzyme directly affects the rate of cholesterol synthesis in the liver, thus becoming a specific target for statin lipid-lowering drugs. Since its function was clarified in the 1970s, the structural analysis of HMGCR has not only revealed the enzymatic catalytic mechanism and feedback inhibition principle, but also promoted major breakthroughs in the field of cardiovascular disease treatment. Continuous research on HMGCR has deepened people's understanding of the metabolic regulatory network and provided a key molecular basis for the development of new cholesterol-lowering drugs.

Structure Function Application Advantage Our Products

Structure of HMGCR

HMGCR is a transmembrane protein with a molecular weight of approximately 97-100 kDa. The molecular weight of this protein varies among different species, mainly due to the difference in the number of its transmembrane domains.

Species	Human	Rat	Hamster	Yeast
Molecular Weight (kDa)	97.3	97.5	99.8	90.0
Primary Structural Differences	Containing eight transmembrane domain structure, N end with C end are on the cytoplasmic side	High homology with human and highly conserved catalytic domain	The transmembrane regions are slightly different, affecting the anchoring of the endoplasmic reticulum	The structure is simpler and it is an early research model

The HMGCR protein contains approximately 888 amino acids, and its spatial structure is composed of an N-terminal transmembrane domain and a C-terminal catalytic domain. The catalytic domain contains a highly conserved HMG-CoA binding site and a NADPH binding site, which complete substrate reduction through synergistic action. The activity of this enzyme is regulated by the allosteric modification of sterol molecules. Its N-terminal domain acts as a "receptor" to sense the sterol level within the cell, thereby regulating the stability and degradation of proteins.

Fig. 1 Structure of the tetramer and respective dimer of the human HMGCR.¹

Key structural properties of HMGCR:

Endoplasmic reticulum membrane anchoring domains
Conservative catalytic active center
Sterol sensing unit

Functions of HMGCR

The core function of HMGCR is to catalyze the rate-limiting step in cholesterol biosynthesis. However, it is also involved in a variety of physiological and pathological processes, including cell proliferation, metabolic homeostasis and inflammatory responses.

Function	Description
Cholesterol synthesis	Catalyze the reduction of HMG-CoA to mevalonic acid, which is an irreversible rate-limiting step in the de novo cholesterol synthesis pathway in the body.
Regulation of metabolic homeostasis	The enzyme activity, directly controls the whole armour hydroxyl pentanoic acid pathway, affect the coenzyme Q10, isoamyl alkene and other important metabolite levels.
Cell proliferation support	Provide the required cholesterol for the formation of the cell membrane, and through the downstream products of isoamyl alkylene modify the key to regulating the cell cycle related protein.
Drug target action	As a direct target of statins, its activity, once inhibited, can effectively lower plasma cholesterol levels and prevent cardiovascular diseases.
Stress and inflammation regulation	Under cellular stress conditions, its expression and activity can change and affect the transduction of inflammatory signaling pathways through cholesterol levels.

The kinetic curve of this enzyme shows typical Mie model characteristics. Binding with statins will cause a change in its conformation, thereby achieving efficient and reversible inhibition of enzyme activity.

Applications of HMGCR and HMGCR Antibody in Literature

1. Wang, Haiyan, et al. "BRCC36 deubiquitinates HMGCR to regulate the interplay between ferroptosis and pyroptosis." Advanced Science 11.11 (2024): 2304263. https://doi.org/10.1002/advs.202304263

This study reveals that HMGCR has an antagonistic effect between ferroptosis and pyroptosis, and its location changes with the mode of death induction. Deubiquitinating enzyme BRCC36 inhibits ferroptosis and promotes pyroptosis by regulating HMGCR, thereby driving the progression of liver cancer. Targeting BRCC36 can effectively inhibit the growth of liver cancer and provide a new treatment strategy.

2. Pokhrel, Ram Hari, et al. "AMPK promotes antitumor immunity by downregulating PD-1 in regulatory T cells via the HMGCR/p38 signaling pathway." Molecular cancer 20.1 (2021): 133. https://doi.org/10.1186/s12943-021-01420-9

This study reveals that in regulatory T cells, AMPK deficiency up-regulates HMGCR and promotes glycolysis, thereby increasing PD-1 expression through the p38 MAPK/GSK3β signaling pathway and accelerating tumor growth. Targeting the AMPK-HMGCR axis can produce a synergistic anti-tumor effect in combination with immune checkpoint therapy.

3. Abida, Houssem, et al. "Anti-HMGCR myopathy: a first case report from North Africa and literature insights." Frontiers in Immunology 16 (2025): 1590913. https://doi.org/10.3389/fimmu.2025.1590913

This report presents the first case of anti-HMGCR myopathy in a patient from Tunisia and North Africa, characterized by severe muscle weakness and a significant increase in creatine kinase. This case is dependent on glucocorticoids and relapsed after dose reduction, and has an incomplete response to other immunosuppressant treatments, revealing the challenges in the diagnosis and treatment of such myopathy.

4. Zhang, Zhirong, et al. "Inhibiting HMGCR represses stemness and metastasis of hepatocellular carcinoma via Hedgehog signaling." Genes & Diseases 11.5 (2024): 101285. https://doi.org/10.1016/j.gendis.2024.101285

This study reveals that HMGCR is highly expressed in liver cancer stem cells and promotes tumor stemness and metastasis by activating the Hedgehog signaling pathway. The lipid-lowering drug simvastatin can effectively inhibit the above process by targeting HMGCR, providing a new strategy for the clinical treatment of liver cancer.

5. Baucells, Andrés, et al. "Anti‐HMGCR Specificity of HALIP: A Confirmatory Study." Journal of Immunology Research 2020.1 (2020): 6292631. https://doi.org/10.1155/2020/6292631

This study confirmed that the novel fluorescence mode of HALIP observed in liver tissue was specifically caused by anti-HMgCr autoantibodies. Through the purification of patient antibodies and animal tissue experiments, it was clearly shown that this fluorescence pattern was consistent with the localization of HMGCR, providing a reliable identifier for the detection of anti-HMGCR antibodies.

Creative Biolabs: HMGCR Antibodies for Research

Creative Biolabs specializes in the production of high-quality HMGCR antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom HMGCR Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our HMGCR antibodies, custom preparations, or technical support, contact us at email.

Reference

Gesto, Diana S., et al. "An atomic-level perspective of HMG-CoA-reductase: the target enzyme to treat hypercholesterolemia." Molecules 25.17 (2020): 3891. https://doi.org/10.3390/molecules25173891