CLEC4E
Description
The CLEC4E (C-type lectin domain family 4 member E) is a protein-coding gene located on chromosome 12.
Macrophage inducible Ca2+-dependent lectin receptor, (abbreviated to Mincle), is a member of the C-type lectin superfamily encoded by the gene CLEC4E. It is a pattern recognition receptor that can recognize glycolipids including mycobacterial cord factor, trehalose-6,6'-dimycolate (TDM). The mincle receptor binds a range of carbohydrate structures, predominantly containing glucose or mannose, and play an important role in recognition of bacterial glycolipids by the immune system. Upon activation by cord factor, Mincle binds the Fc receptor FcRγ and Syk. Cord factor also binds and activates the related C-type lectin MCL. Upon receptor stimulation is PKC-δ activated, which subsequently phosphorylates CARD9 that triggers recruitment of BCL10 and MALT1, leading to a CARD-CC/BCL10/MALT1 (CBM) signaling complex. This signaling complex in turn triggers downstream recruitment of TRAF6 and NF-κB activation. A wide range of ligands promote signalling through Mincle, including proteins, sterols and glycolipids from altered or damaged self, and various glycolipids from pathogenic and commensal organisms.
== Mincle agonists from self == Crystalline cholesterol, which accumulates in atherosclerotic lesions, can signal through human Mincle. Cholesterol sulfate, which is present in the skin, is a cause of sterile inflammation through agonizing Mincle signalling. The protein SAP130 signal through Mincle. Beta-glucosylceramide, which accumulates as a result of the lysosomal storage disorder Gaucher’s disease, signals through Mincle.
CLEC4E, also known as Mincle, is a calcium-dependent lectin that acts as a pattern recognition receptor (PRR) in the innate immune system. It recognizes both damage-associated molecular patterns (DAMPs) from abnormal self and pathogen-associated molecular patterns (PAMPs) from bacteria and fungi. A notable PAMP is mycobacterial trehalose 6,6'-dimycolate (TDM), a cell wall glycolipid with strong immunomodulatory properties. CLEC4E interacts with the signaling adapter Fc receptor gamma chain (FCER1G) to form a functional complex in myeloid cells. Upon binding of TDM to this complex, the immunoreceptor tyrosine-based activation motif (ITAM) on FCER1G is phosphorylated, triggering activation of SYK, CARD9, and NF-κB. This pathway drives maturation of antigen-presenting cells and shapes the antigen-specific priming of T-cells towards effector T-helper 1 and T-helper 17 cell subtypes. CLEC4E also recognizes alpha-mannose residues on pathogenic fungi of the genus Malassezia, triggering macrophage activation. By recognizing DAMPs released during nonhomeostatic cell death, CLEC4E enables immune sensing of damaged self and promotes inflammatory cell infiltration into damaged tissues.
CLEC4E is also known as CLECSF9, MINCLE.
Associated Diseases
- isolated agammaglobulinemia
- combined immunodeficiency due to moesin deficiency
- agammaglobulinemia 7, autosomal recessive
- acute kidney failure
- severe combined immunodeficiency due to CARD11 deficiency
- immunodeficiency 18
- neutropenia, severe congenital, 1, autosomal dominant
- severe combined immunodeficiency due to CTPS1 deficiency
- common variable immunodeficiency
- hyper-IgM syndrome type 3
- hyper-IgE recurrent infection syndrome 5, autosomal recessive
- agammaglobulinemia 10, autosomal dominant
- nonimmune chronic idiopathic neutropenia of adults
