Galectin 9 Recombinant Rabbit Monoclonal Antibody [PSH02-44]

Function

The protein has N- and C- terminal carbohydrate-binding domains connected by a link peptide. Multiple alternatively spliced transcript variants have been found for this gene. Galectin-9 is one of the most studied ligands for HAVCR2 (TIM-3) and is expressed on various tumor cells. However, it can also interact with other proteins (CLEC7A, CD137, CD40). For example, an interaction with CD40 on T-cells inhibits their proliferation and induces cell death. Galectin-9 also has important cytoplasmic, intracellular functions and controls AMPK in response to lysosomal damage that can occur upon exposure to endogenous and exogenous membrane damaging agents such as crystalline silica, cholesterol crystals, microbial toxins, proteopathic aggregates such as tau fibrils and amyloids, and signaling pathways inducing lysosomal permeabilization such as those initiated by TRAIL. Mild lysosomal damage, such as that caused by the anti-diabetes drug metformin may contribute to the therapeutic action of metformin by activating AMPK. The mechanism of how Galectin-9 activates AMPK involves recognition of exposed lysosomal lumenal glycoproteins such as LAMP1, LAMP2, SCRAB2, TMEM192, etc., repulsion of deubiquitinating enzyme USP9X, increased K63 ubiquitination of TAK1 (MAP3K7) kinase, which in turn phopshorylates AMPK and activates it. This signaling cascade directly links Galectin-9 intracellular function with ubiqutin systems. Galectin-9, through its regulation of AMPK, a kinase that negatively regulates mTOR, cooperates with Galectin-8-based effects to inactivate mTOR downstream of the lysosomal damaging agents and conditions.

Background References

1. Morishita A et al. Galectin-9 in Gastroenterological Cancer. Int J Mol Sci. 2023 Mar

2. Yang R et al. Galectin-9 interacts with PD-1 and TIM-3 to regulate T cell death and is a target for cancer immunotherapy. Nat Commun. 2021 Feb

Subcellular Location

Cytoplasm, Nucleus, Secreted.

UNIPROT

SwissProt: O00182 Human

SwissProt: O08573 Mouse

Synonyms