CLEC4G

Fig1. LSECtin are trans-membrane proteins. (Feng Zhang, 2014)

What is CLEC4G protein?

CLEC4G (C-type lectin domain family 4 member G) gene is a protein coding gene which situated on the short arm of chromosome 19 at locus 19p13. This gene encodes a glycan-binding receptor and member of the C-type lectin family which plays a role in the immune response. C-type lectin receptors are pattern recognition receptors located on immune cells that play a role in the recognition and uptake of both self and non-self glycoproteins as well as mediating cell adhesion, glycoprotein clearance, and cell signaling functions. This gene's protein binds complex-type N-glycans of the viral envelope proteins of Ebola virus, West Nile filovirus, and SARS coronavirus, but not HIV or hepatitis C virus. In mouse, this protein has been shown to recognize activated T-cells and to negatively regulate T-cell receptor-mediated signalling. It also acts as a novel, liver-specific regulator of NK cell-mediated immunity in mouse. The CLEC4G protein is consisted of 293 amino acids and its molecular mass is approximately 32.6 kDa.

What is the function of CLEC4G protein?

CLEC4G has been reported to interact with BACE1, an enzyme that is central to Alzheimer's disease (AD) because it cleaves amyloid precursor protein (APP) to produce amyloid-β (Aβ) peptides, which are toxic and accumulate in the brains of individuals with AD. As a C-type lectin, CLEC4G is likely involved in immune responses, particularly in the recognition and binding of specific carbohydrate structures on the surface of pathogens, contributing to the host's defense mechanisms. CLEC4G may also play a role in cell adhesion and signaling processes, which are crucial for various cellular functions, including cell-cell interactions and cell-matrix interactions.

CLEC4G Related Signaling Pathway

In some diseases, such as sarcoidosis, CLEC4G may be involved in the up-regulation of Th17-related pathways. CLEC4G may be involved in immune regulation, especially in dendritic cells. For example, BDCA2/CLEC4C (from the same C-type lectin family as CLEC4G) is expressed on plasmacytoid dendritic cells (pDC) and is associated with interferon alpha/beta production. CLEC4G interacts with beta-site amyloid precursor protease 1 (BACE1), A key molecule in Alzheimer's disease (AD) that is responsible for cutting the amyloid precursor protein (APP) to produce toxic amyloid beta peptide (Aβ). CLEC4G regulates Aβ production by affecting BACE1 function. CLEC4G may be involved in cell death and clearance processes, affecting inflammation and tissue repair.

CLEC4G Related Diseases

Studies have shown that there is a correlation between the expression of CLEC4G in liver diseases and the clinicopathological features of patients with hepatocellular carcinoma. Specifically, CLEC4G is highly expressed in normal liver tissues, but with the progression of malignant lesions in liver disease, its expression is significantly reduced, and it is rarely expressed in HCC tissues. This suggests that the low expression of CLEC4G is related to tumor vascular metastasis in HCC patients, and may be a pathologic diagnostic marker for HCC. The correlation between the expression of CLEC4G and tumor angiogenesis marker CD34 and its relationship with hepatocellular carcinoma invasion and metastasis is also being studied. CLEC4G has also been linked to diseases such as lymphocytic meningitis and Japanese encephalitis.

Bioapplications of CLEC4G

The recombinant protein of CLEC4G can be used to develop diagnostic reagents, such as ELISA kits, to detect levels of CLEC4G in serum to assist in the diagnosis of diseases such as hepatocellular carcinoma. Because CLEC4G is associated with the development of hepatocellular carcinoma, drug development targeting CLEC4G may help in the treatment of hepatocellular carcinoma. In addition, CLEC4G has been implicated in infection with a variety of pathogens, such as Japanese encephalitis virus, Ebola virus, SARS-CoV, and Lassa virus, so CLEC4G's recombinant proteins may play a role in the development of vaccines or therapeutics against these pathogens.

Case Study 1: Di Liu, 2019

Macrophages have been suggested to contribute to constructing a cancer stem cell (CSC) niche. However, whether and how macrophages regulate the activity of CSCs through juxtacrine signaling are poorly understood. Here the researchers report LSECtin, a transmembrane protein highly expressed on tumor-associated macrophages (TAMs), enhances stemness of breast cancer cells (BCCs). They identified BTN3A3, a B7 family member with previously unknown functions as the receptor for LSECtin on BCCs responsible for stemness-promoting effect of LSECtin. In mice bearing human tumor xenografts, either macrophage-specific ablation of LSECtin or silencing of BTN3A3 in BCCs decreased CSC frequency and tumor growth. Admixture of LSECtin-positive macrophages increased the tumorigenic activity of BCCs dependent on BTN3A3. Disruption of the LSECtin-BTN3A3 axis with BTN3A3-Fc or anti-BTN3A3 mAb has a therapeutic effect on breast cancer.

Fig1. Manders coefficient of LSECtin and CD68 in clinical tumor sections.

Fig2. Binding of LSECtin-Fc recombinant protein at 2 μg/ml to HEK293 cells transfected with BTN3A3 mutations.

Case Study 2: Yasuhiko Kizuka, 2015

β-Site amyloid precursor protein cleaving enzyme-1 (BACE1) is a central molecule in Alzheimer's disease (AD). It cleaves amyloid precursor protein (APP) to produce the toxic amyloid-β (Aβ) peptides. Thus, a novel BACE1 modulator could offer a new therapeutic strategy for AD. We report that C-type lectin-like domain family 4, member g (Clec4g, also designated as LSECtin) interacts with BACE1 in mouse brain and cultured cells. Overexpression of Clec4g suppressed BACE1-mediated Aβ generation, and affected the intracellular distribution of BACE1 but not its catalytic activity. These results highlight a novel role of Clec4g in negatively regulating BACE1 function.

Fig3. Cells were lysed, and BACE1 or Clec4g-myc was immunoprecipitated.

Fig4. Neuro2A cells were transfected with plasmids encoding human BACE1 and/or mouse Clec4g-myc or with an empty plasmid.

CLEC4G has several biochemical functions, for example, polysaccharide binding,protein binding,virus receptor activity. Some of the functions are cooperated with other proteins, some of the functions could acted by CLEC4G itself. We selected most functions CLEC4G had, and list some proteins which have the same functions with CLEC4G. You can find most of the proteins on our site.

CLEC4G 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 CLEC4G here. Most of them are supplied by our site. Hope this information will be useful for your research of CLEC4G.

IFI35;EIF3I;MT-CO1;APOA1;APOH;FTL;SHBG;ASGR1;CAPN1;RPSA;CPN1;ARSA;AZU1;PKLR;NUP214