LANCL2

Official Full Name

LanC like glutathione S-transferase 2

Organism

Homo sapiens

Gene ID

55915

Background

Enables phosphatidylinositol-3-phosphate binding activity; phosphatidylinositol-4-phosphate binding activity; and phosphatidylinositol-5-phosphate binding activity. Involved in negative regulation of DNA-templated transcription and positive regulation of abscisic acid-activated signaling pathway. Located in several cellular components, including cortical actin cytoskeleton; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Feb 2025]

Synonyms

TASP; GPR69B

Cat.No.	Product Name	Price
CSC-DC008541	Panoply™ Human LANCL2 Knockdown Stable Cell Line	Inquiry
CSC-SC008541	Panoply™ Human LANCL2 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD09008Z	Human LANCL2 adenoviral particles	Inquiry
LV16752L	human LANCL2 (NM_018697) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH142027	shRNA set against Human LANCL2(NM_018697.3)	Inquiry
SHH328411	shRNA set against Mouse LANCL2 (NM_133737.2)	Inquiry
SHH328415	shRNA set against Rat LANCL2 (NM_001014187.1)	Inquiry
SHW011216	shRNA set against Danio rerio LANCL2 (NM_001083003)	Inquiry

Cat.No.	Product Name	Price
CDCS414848	Human LANCL2 ORF Clone (BC070049)	Inquiry
CDFG002012	Human LANCL2 cDNA Clone(NM_018697.3)	Inquiry
CDFR003302	Rat Lancl2 cDNA Clone(NM_001014187.1)	Inquiry
MiUTR1H-05569	LANCL2 miRNA 3'UTR clone	Inquiry
MiUTR1R-02957	LANCL2 miRNA 3'UTR clone	Inquiry
CDCB158124	Human LANCL2 ORF clone (BC070049)	Inquiry
CDCB172691	Danio rerio LANCL2 ORF Clone (NM_001083003)	Inquiry
CDCB191487	Rabbit LANCL2 ORF clone (XM_008261841.1)	Inquiry
CDCR265367	Mouse Lancl2 ORF Clone(NM_133737.2)	Inquiry
CDCR304063	Human LANCL2 ORF Clone(NM_018697.3)	Inquiry
CDCR370321	Rat Lancl2 ORF Clone(NM_001014187.1)	Inquiry

Detailed Information

Recent Progress

Abscisic acid (ABA), a well-known phytohormone, has been recently demonstrated to be present also in humans, where it targets cells of the innate immune response, mesenchymal and hemopoietic stem cells and cells involved in the regulation of systemic glucose homeostasis. Lanthionine synthetase component C-like protein 2 (LANCL2) is a member of the LANCL protein family, which is broadly expressed throughout the body. LANCL2 is the molecular target of abscisic acid (ABA), a compound with insulin-sensitizing and immune modulatory actions. LANCL2 is also needed for membrane binding and signaling of ABA in immune cells.

The Serine/Threonine protein kinase Akt controls a wide range of biochemical and cellular processes. In one study researchers identified the LanCL2 protein as a positive regulator of Akt activation in human liver cells. LanCL2 knockdown dampens serum and insulin-stimulated Akt phosphorylation, whereas LanCL2 overexpression enhances it. Moreover, LanCL2 does not function through PP2A, a phosphatase of Akt. Instead, LanCL2 directly interacts with Akt, with a preference for inactive Akt. Plus, it was shown that LanCL2 also binds to the Akt kinase mTORC2, but not PDK1. Recombinant LanCL2 enhances Akt phosphorylation by mTORC2 in vitro. Finally, LanCL2 knockdown increases the rate of apoptosis, which is reversed by the expression of a constitutively active Akt. These findings, taken together, revealed LanCL2 as a novel regulator of Akt, and suggested that LanCL2 facilitates optimal phosphorylation of Akt by mTORC2 via direct physical interactions with both the kinase and the substrate.

In another study, it was shown that N-terminal glycine myristoylation causes LANCL2 localization to the plasmamembrane and to cytoplasmic membrane vesicles, where it interacts with the subunit of a G protein and starts the ABA signaling pathway via activation of adenylate cyclase. Demyristoylation of LANCL2 by chemical or genetic means leads to its nuclear translocation. Nuclear enrichment of native LANCL2 is also induced by ABA treatment. In conclusion, human LANCL2 may be perceived as a non-transmembrane G protein-coupled receptor susceptible to hormone-induced nuclear translocation.

Immune responses to Helicobacter pyloriare organized through complex balances of host-bacterial interactions, including inflammatory and regulatory immune responses that can lead to the development of the gastric disease. To grasp a deeper understanding in regulatory pathways that contribute to preventing inflammatory events during H.pylori infection, researchers generated a computational model incorporating recent developments in the H.pylori-host interactions. Sensitivity analysis revealed that a regulatory macrophage population is critical in maintaining high H.pylori colonization without the generation of an inflammatory response. Modeling studies predicted that LANCL2 is a central regulator of inflammatory and effector pathways and its activation promotes regulatory responses characterized by IL-10 production while suppressing effector responses. The impairment of regulatory macrophage differentiation by the loss of LANCL2 was simulated based on multiscale linkages between the tissue-level gastric mucosa and the intracellular models. The simulated deletion of LANCL2 resulted in a greater clearance of H.pylori, but also greater IFN responses and damage to the epithelium. This study displayed the importance of LANCL2 in the induction of regulatory responses in macrophages and T cells during H.pylori infection.

The therapeutic potential of the LANCL2 pathway ranges from increasing cellular sensitivity to anticancer drugs, insulin sensitizing effects and modulating immune and inflammatory responses in the context of immune-mediated and infectious diseases. A case for LANCL2-based drug discovery and development was illustrated by the anti-inflammatory activity of novel LANCL2 ligands such as NSC61610 against inflammatory bowel disease and influenza-driven inflammation in mice.

References:

Zeng, M., Donk, W. A. V. D., & Chen, J. (2014). Lantibiotic cyclase-like protein 2 (lancl2) is a novel regulator of akt. Molecular Biology of the Cell, 25(24), 3954-3961.
Fresia, C., Vigliarolo, T., Guida, L., Booz, V., Bruzzone, S., & Sturla, L., et al. (2016). G-protein coupling and nuclear translocation of the human abscisic acid receptor lancl2. Scientific Reports, 6(1), 26658.
Carbo, A., Hontecillas, R., Cooper, J., Gandour, R. D., Ehrich, M., & Bassaganya-Riera, J. (2015). Mo1691 lanthionine synthetase c-like receptor 2 (lancl2): a novel therapeutic target for inflammatory bowel disease. Gastroenterology, 148(4), S-686-S-687.
Leber, A., Bassaganya-Riera, J., Tubau-Juni, N., Zoccoli-Rodriguez, V., Viladomiu, M., & Abedi, V., et al. (2016). Modeling the role of lanthionine synthetase c-like 2 (lancl2) in the modulation of immune responses to helicobacter pylori infection. Plos One, 11(12), e0167440.
Lu, P., Hontecillas, R., Philipson, C. W., & Bassaganyariera, J. (2014). Lanthionine synthetase component c-like protein 2: a new drug target for inflammatory diseases and diabetes. Current Drug Targets, 15(6), -.

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