NOTUM Antibodies

Background

The NOTUM gene encodes a secretory carbonase, which is mainly expressed in developing and adult tissues such as the liver, bones and intestines. This protein regulates the Wnt signaling pathway through hydrolyzed glycosylphosphatidylinositol anchoring modification, thereby influencing cell proliferation, differentiation and tissue homeostasis. Studies have shown that NOTUM plays a significant role in bone formation, metabolic regulation and cancer progression. Abnormal activity of Notum is associated with various diseases such as osteoporosis and fat metabolism disorders. Since its first identification in 2002, NOTUM has become a key target in developmental biology and disease mechanism research. The study of its structure and function has provided a new molecular basis for the development of drugs for WNT-related diseases.

Structure Function Application Advantage Our Products

Structure of NOTUM

NOTUM is a secretory carbonase with a molecular weight of approximately 35-40 kDa. The specific value may fluctuate slightly among different species due to differences in post-translational modifications.

Species	Human	Mouse	Zebrafish
Molecular Weight (kDa)	About 40	About 39	About 38
Primary Structural Differences	Complete with catalytic triplets and substrate combine domain	High homology with human and conserved core domain	Orthologous genes with similar functional domains were present

This protein is composed of approximately 450 amino acids, and its three-dimensional structure exhibits a typical α/β hydrolase folding. Its active center is composed of a catalytic triad of serine, aspartic acid and histidine, which is responsible for the hydrolysis of the glycosylphosphatidylinositol anchor. Specific hydrophobic pockets form on the surface of proteins for recognizing and binding to Wnt proteins. NOTUM is secreted outside the cell through its N-terminal signaling peptide, and its function depends on the conformation of the active site stabilized by this folding structure.

Fig. 1 Cartoon presentation of the Notum-ghrelin complex structure.¹

Key structural properties of NOTUM:

Typical α/β hydrolase folding structure
Conserved serine - aspartic acid - histidine catalyzes triplets
Specific hydrophobic pockets are used to identify lipid modifications of Wnt proteins

Functions of NOTUM

The main function of NOTUM is to act as a secretory hydrolase to negatively regulate the Wnt signaling pathway. In addition, it is also involved in a variety of physiological and pathological processes such as tissue homeostasis, metabolic regulation and cancer development.

Function	Description
Wnt signal suppression	By hydrolyzing the glycosylphosphatidylinositol anchor of Wnt protein to inactivate it, the activity of the classical Wnt signaling pathway is precisely inhibited.
Maintenance of tissue homeostasis	In the gut, liver and bone, expressed in multiple tissues by regulating stem cell proliferation and differentiation of balance to maintain the steady and regeneration.
Regulation of bone metabolism	In key inhibit the excessive activation of osteoblasts in bone development, its dysfunction is closely related to osteoporosis and other bone diseases.
The influence of fat metabolism	By regulating Wnt signaling, it participates in adipocyte differentiation and lipid storage, and affects energy metabolism and obesity.
Participation in cancer progression	The abnormal expression of Wnt in colorectal cancer and other tumors affects tumor growth and metastasis by changing WNT signaling in the tumor microenvironment.

The regulation of Wnt signaling by NOTUM shows a high degree of substrate specificity, and its activity is not directly regulated by common intracellular feedback loops, which makes it a key microenvironment regulator in development and disease.

Applications of NOTUM and NOTUM Antibody in Literature

Zhao, Yuguang, et al. "Small-molecule inhibitors of carboxylesterase Notum." Future medicinal chemistry 13.11 (2021): 1001-1015. https://doi.org/10.4155/fmc-2021-0036

The article indicates that NOTUM negatively regulates the Wnt pathway through depalmitylation, and the development of its inhibitors has become a new strategy for treating cancer, osteoporosis and neurodegenerative diseases. The discovery of multiple screening methods and lead compounds such as LP-922056 is promoting the translational research of this target.

Zhao, Yuguang, et al. "Notum deacylates octanoylated ghrelin." Molecular Metabolism 49 (2021): 101201. https://doi.org/10.1016/j.molmet.2021.101201

Research has found that NOTUM is not only a Wnt signal inhibitor but also can act as a ghrelin deacylase. Experiments have confirmed that it can regulate the level of acylated ghrelin in the circulation under high-fat diet conditions, revealing a new function of NOTUM in metabolic regulation.

Adasooriya, Dinuka, et al. "Notum regulates the cusp and root patterns in mouse molar." Scientific reports 14.1 (2024): 13633. https://doi.org/10.1038/s41598-024-64340-w

This study reveals that Notum is expressed in enamel nodules and dental papillae. Its absence leads to secondary enlargement of enamel nodules, which in turn causes changes in the shape of the tooth apex, reduction in the depression of the tooth crown contour, and root fusion. It indicates that the Wnt/Notum negative feedback loop affects the morphology of the crown and root by regulating the size of the enamel.

Zhao, Yuguang, et al. "Structural insights into notum covalent inhibition." Journal of Medicinal Chemistry 64.15 (2021): 11354-11363. https://doi.org/10.1021/acs.jmedchem.1c00701

Research has found that the novel covalent inhibitor forms a stable adduct with butyrate through serine-232, blocking the inactivation effect of NOTUM on the Wnt signaling pathway. Its mechanism of action lies in inhibiting the hydrolysis process of active sites, providing a new strategy for the development of targeted drugs for the treatment of osteoporosis and Alzheimer's disease.

Guo, Fangfei, et al. "NOTUM promotes thermogenic capacity and protects against diet-induced obesity in male mice." Scientific Reports 11.1 (2021): 16409. https://doi.org/10.1038/s41598-021-95720-1

Studies have confirmed that overexpression of NOTUM in the liver, by inhibiting the Wnt signaling pathway, not only promotes the Browning of white fat, enhances thermogenesis and lipolysis capacity, but also reduces adipose tissue fibrosis and inflammation, thereby significantly improving obesity and glucose homeostasis in mice on a high-fat diet.

Creative Biolabs: NOTUM Antibodies for Research

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

Custom NOTUM 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 NOTUM antibodies, custom preparations, or technical support, contact us at email.

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