LTF

What is LTF protein?

LTF gene (lactotransferrin) is a protein coding gene which situated on the short arm of chromosome 3 at locus 3p21. This gene is a member of the transferrin family of genes and its protein product is found in the secondary granules of neutrophils. The protein is a major iron-binding protein in milk and body secretions with an antimicrobial activity, making it an important component of the non-specific immune system. The protein demonstrates a broad spectrum of properties, including regulation of iron homeostasis, host defense against a broad range of microbial infections, anti-inflammatory activity, regulation of cellular growth and differentiation and protection against cancer development and metastasis. The LTF protein is consisted of 710 amino acids and LTF molecular weight is approximately 78.2 kDa.

What is the function of LTF protein?

LTF protein is a multifunctional iron-binding glycoprotein belonging to the transferrin family. It plays an important role in many biological processes such as immune regulation, iron metabolism, anti-infection and anti-inflammation. LTF is involved in the host's innate immune response to injury and infection by binding to specific cell surface receptors such as TLR4, CD14, and CD22. LTF plays a key role in controlling acute inflammation and infection by regulating inflammatory responses and reducing the production of inflammatory mediators by inhibiting the NF-κB signaling pathway. In addition, LTF also has anti-tumor activity, which can promote apoptosis and inhibit the proliferation of tumor cells.

Fig1. Protective role of lactoferrin in eukaryotic cell. (Paweł Kowalczyk, 2022)

LTF related signaling pathway

Lactoferrin (LTF) is a multifunctional iron-binding glycoprotein with immunomodulatory, anti-infective and antioxidant activities. LTF is involved in regulating innate immune responses by interacting with a variety of cell surface receptors, including TLR4, CD14, and CD22. It can play a role in controlling inflammation and infection by inhibiting the NF-κB signaling pathway and reducing the production of inflammatory mediators. LTF is also associated with the regulation of cell proliferation, differentiation, and apoptosis, and affects the behavior of tumor cells. In addition, LTF may also reduce blood sugar levels by affecting metabolic processes in adipose tissue, showing potential in diabetes treatment.

LTF related diseases

Lactoferrin (LTF) is a protein with multiple biological functions, and it plays a role in a variety of diseases. LTF has antibacterial, antiviral, antifungal, and antiparasitic activity, inhibiting the growth of pathogens by competing with them for iron or interacting directly with their cell walls. In cancer therapy, LTF has shown the ability to inhibit tumor cell proliferation, promote apoptosis, regulate cell cycle, and influence tumor microenvironment. LTF expression is down-regulated in many cancers, including breast cancer, prostate cancer, gastric cancer and nasopharyngeal cancer, and its expression level is closely related to tumor stage, metastasis and patient prognosis. In addition, LTF is involved in modulating immune responses, enhancing NK cell activity, and inhibiting tumor growth and metastasis by affecting cell signaling pathways such as the AKT/mTOR pathway.

Bioapplications of LTF

The Lactotransferrin protein has a variety of functions in practical applications, including antibacterial, antiviral, antioxidant, anti-inflammatory, and immunomodulatory. Due to its unique structure and biological activity, Lactotransferrin protein is widely used in the food industry, pharmaceutical fields and biotechnology fields. In the food industry, Lactotransferrin protein can act as a natural preservative and antioxidant, extending the shelf life and improving food quality. In the pharmaceutical field, Lactotransferrin protein can be used to prepare antibacterial drugs, antiviral drugs, and immunomodulators for the treatment of infectious diseases and immune system-related diseases. In addition, Lactotransferrin protein can also be used to prepare biomaterials such as bioreactors and biosensors for the detection and processing of biomolecules.

Case Study 1: Carmen Mirabelli, 2021

In response to the global spread of Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) and the related disease COVID-19, interventions that can be quickly detected and translated into clinical treatment are needed. While traditional approaches to drug discovery take a long time and have a low success rate, reusing drugs can significantly speed up the process. Researchers have developed a high-throughput screening method to identify 17 effective agents that inhibit SARS-CoV-2 infection from 1,425 U.S. Food and Drug Administration (FDA) approved drugs and clinical candidates. These agents were analyzed for antiviral activity in a variety of cell lines, including prostate lymph node cancer (LNCaP) cells and alveolar epithelial Type II cells (iAEC2s). In addition, we found that inhibitors of the Ras/Raf/MEK/ERK signaling pathway exacerbate SARS-CoV-2 infection in vitro. Notably, we found that lactoferrin, a glycoprotein present in secretions, including mammalian milk, inhibits SARS-CoV-2 infection in the nanomolar range and has multiple mechanisms of action, including blocking viral binding to cellular heparin sulfate and enhancing interferon response. Native human lactoferrin was used to cluture cells.

Fig1. UMAP embedding and phenotypic clustering of 3 million cells.

Fig2. Antiviral activity of bovine and human lactoferrin, remdesivir, and S1RA was assessed in iAEC2 cells.

Case Study 2: Lulu Hu, 2017

Lactoferrin (LTF) is a pluripotent immune-activating molecule that is often the target of autoimmune reactions. Studies have shown that LTF-containing immune complexes (LTF-ICs) activate monocytes/macrophages to produce TNF-α and IL-1β. These complexes trigger intracellular signaling through CD14 and CD32a receptors, as well as TLR4 - and TLR9-dependent pathways, leading to the production of inflammatory cytokines, a process that can be blocked by inhibitors of caspase-1, NF-κB, and MAPK.

Fig3. The resultant huLTF-specific IgG (RA-IgG) was compared with the sample of flow through and also IVIG in huLTF-based ELISAs.

Fig4. Synergistic effect between huLTF and LTF-Abs.

LTF has several biochemical functions, for example, DNA binding,heparin binding,iron ion binding. Some of the functions are cooperated with other proteins, some of the functions could acted by LTF itself. We selected most functions LTF had, and list some proteins which have the same functions with LTF. You can find most of the proteins on our site.

LTF has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with LTF here. Most of them are supplied by our site. Hope this information will be useful for your research of LTF.

p27958-pro_0000037570;CALM;p27958-pro_0000037569;NCL;p27958-pro_0000037573;SGK1;Dynll1;CDK5RAP3;Ikbip