DCIR

Official Full Name

C-type lectin domain family 4 member A

Organism

Homo sapiens

GeneID

50856

Background

This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may play a role in inflammatory and immune response. Multiple transcript variants encoding distinct isoforms have been identified for this gene. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

Synonyms

CLEC4A; DCIR; LLIR; CD367; DDB27; hDCIR; CLECSF6; HDCGC13P;

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Detailed Information

Dendritic cell immunoreceptor (DCIR), also known as CLEC4A2 (Cluster of Differentiation 4A2), is a highly conserved gene that encodes a receptor protein with important functions in the immune system. The DCIR gene is involved in the regulation of various immune cell signaling pathways and has been implicated in various immune-mediated diseases.

Structure And Function of DCIR

The DCIR gene encodes a type I transmembrane protein that belongs to the C-type lectin superfamily. The extracellular domain of DCIR contains a lectin-like domain, followed by a fibronectin type III (FNIII) domain, a transmembrane domain, and a short cytoplasmic tail. The lectin-like domain of DCIR shares significant homology with other CLEC family members, which suggests that DCIR may have similar functional properties.

In dendritic cells (DCs), the expressed DCIR protein is primarily localized to the cell surface, where it interacts with various ligands to modulate immune cell activation and polarization. The fibronectin type III domain of DCIR has been shown to bind to ICAM-1, a cell adhesion molecule involved in leukocyte migration and trafficking. This interaction enables DCs to efficiently capture and present antigens to T cells, thereby promoting Immune response. Additionally, the lectin-like domain of DCIR has been reported to bind to specific carbohydrates on pathogens, which may contribute to the antigen-presenting function of DCs.

Figure 1. DCIR activity is regulated by the modification of the terminal sialylation of biantennary N-glycans, and this interaction is important for the control of both autoimmune and bone metabolic diseases.

Implications of DCIR in Disease

Several studies have investigated the role of DCIR in disease. In cancer, DCIR has been found to be overexpressed in various tumor tissues compared to normal tissues, suggesting that it may play a role in tumorigenesis and progression. Moreover, reduced DCIR expression has been associated with increased survival in colorectal cancer patients, indicating that DCIR may act as a tumor suppressor gene.

In the context of infectious diseases, DCIR has been shown to be upregulated in response to pathogen stimulation, suggesting that it may play a role in host defense. Indeed, studies have demonstrated that DCIR-deficient mice are more susceptible to bacterial infection, indicating that DCIR is crucial for the development of an effective immune response. Furthermore, DCIR has been implicated in the pathogenesis of autoimmune diseases, as evidenced by increased DCIR expression in patients with systemic lupus erythematosus and rheumatoid arthritis.

The role of DCIR in human health and disease is further underscored by the identification of variants in the DCIR gene that are associated with altered disease risk and severity. For example, a study investigating the role of DCIR in type 1 diabetes found that individuals with a specific DCIR variant were at increased risk of developing the disease. Similarly, DCIR variants have been associated with increased risk of myocardial infarction and reduced renal function.

In conclusion, the DCIR gene encodes a key receptor protein that modulates immune cell function and has been implicated in various human diseases. The structure and function of DCIR suggest that it plays a crucial role in the immune response, with implications for the development of vaccines and therapeutics.

References:

Sun, Haiyang et al. "Blocking DCIR mitigates colitis and prevents colorectal tumors by enhancing the GM-CSF-STAT5 pathway." Cell reports vol. 40,5 (2022): 111158. doi:10.1016/j.celrep.2022.111158
Kaifu, Tomonori et al. "DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis." The Journal of experimental medicine vol. 218,12 (2021): e20210435. doi:10.1084/jem.20210435

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