DARC

Official Full Name

Duffy blood group, chemokine receptor

Background

The protein encoded by this gene is a glycosylated membrane protein and a non-specific receptor for several chemokines. The encoded protein is the receptor for the human malarial parasites Plasmodium vivax and Plasmodium knowlesi. Polymorphisms in this gene are the basis of the Duffy blood group system. Two transcript variants encoding different isoforms have been found for this gene.

Synonyms

DARC; Duffy blood group, chemokine receptor; Duffy blood group , FY; Duffy antigen/chemokine receptor; CCBP1; CD234; Dfy; GPD; glycoprotein D; Fy glycoprotein; Duffy blood group antigen; plasmodium vivax receptor; FY; GpFy; WBCQ1;

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Detailed Information

The Duffy blood group antigen, also known as Duffy antigen receptor for chemokines (DARC), is a glycoprotein receptor that plays a significant role in human immunity and disease. Named after its discovery by the hematologist Terence Hamblin in 1950, the Duffy antigen was initially identified as a blood group system. Individuals can be classified as Duffy positive (Fy^a/b^+) or Duffy negative (Fy^a/b^-), based on the presence or absence of the Duffy antigen on red blood cells.

DARC: A Versatile Chemokine Receptor

Duffy antigen receptor for chemokines (DARC) is known for its unique ability to bind a wide range of chemokines. Chemokines are small signaling proteins secreted by cells to attract immune cells to sites of infection, inflammation, or tissue damage.

The broad binding specificity of DARC allows it to interact with various chemokines, including those involved in immune responses, inflammation, and tissue repair. Through these interactions, DARC influences the movement and positioning of immune cells within the body. By binding and sequestering chemokines, DARC modulates the immune response, controlling the recruitment and activity of immune cells in different tissues and organs. This function not only contributes to normal immune responses but also has implications in various diseases, including inflammatory disorders and infections.

Beyond its blood group function, DARC is primarily recognized as a chemokine receptor, participating in immune responses and inflammation. DARC binds various chemokines, which are small signaling proteins involved in immune cell trafficking and activation. Through its interactions with chemokines, DARC influences the migration and localization of immune cells, playing a crucial role in the immune defense against pathogens and in inflammatory processes.

DARC and Malaria: Unraveling the Parasitic Connection

Duffy Antigen Receptor for Chemokines (DARC) plays a pivotal role in the context of malaria, a life-threatening infectious disease caused by Plasmodium parasites. Plasmodium vivax, a parasite causing malaria, relies on DARC for red blood cell invasion, and the absence of DARC in Duffy-negative individuals provides resistance against P. vivax malaria. Specifically, DARC serves as a receptor on red blood cells, facilitating the invasion of Plasmodium vivax, one of the malaria-causing parasites. Individuals lacking DARC expression, known as Duffy-negative individuals, exhibit a natural resistance to P. vivax malaria. The absence of DARC on the surface of red blood cells prevents the parasite from entering these cells, providing a unique genetic defense mechanism against this particular strain of malaria.

Interestingly, DARC has a unique feature; it lacks the G-protein signaling domain commonly found in other chemokine receptors. Due to this absence, DARC does not initiate typical intracellular signaling pathways upon chemokine binding. Instead, it acts as a "silent" receptor, sequestering chemokines and regulating their availability in the bloodstream. This sequestration function of DARC has implications in various diseases, including malaria.

References:

Łukasik, Ewa, and Kazimiera Waśniowska. "Antygeny układu grupowego Duffy: budowa, właściwości serologiczne i funkcja" [Duffy blood group antigens: structure, serological properties and function]. Postepy higieny i medycyny doswiadczalnej (Online) vol. 70 143-61. 4 Mar. 2016, doi:10.5604/17322693.1196360
Halawani, Amr J et al. "Prevalence of Duffy Blood Group Antigens and Phenotypes among Saudi Blood Donors in Southwestern Saudi Arabia." Clinical laboratory vol. 67,1 (2021): 10.7754/Clin.Lab.2020.200505. doi:10.7754/Clin.Lab.2020.200505

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