IL12A


Description

The IL12A (interleukin 12A) is a protein-coding gene located on chromosome 3.

Interleukin-12 subunit alpha (IL-12 p35) is a protein that in humans is encoded by the IL12A gene. This gene encodes a subunit of the cytokine Interleukin 12 (IL-12) that acts on T and natural killer cells, and has a broad array of biological activities. The cytokine is a disulfide-linked heterodimer composed of the 35-kD subunit encoded by this gene, and a 40-kD subunit that is a member of the cytokine receptor family. This cytokine is required for the T-cell-dependent induction of interferon gamma (IFN-γ), and is important for the differentiation of both Th1 and Th2 cells. The responses of lymphocytes to this cytokine are mediated by the activator of transcription protein STAT4. Nitric oxide synthase 2A (NOS2A/NOS2) is found to be required for the signaling process of this cytokine in innate immunity.

IL12A, also known as IL-12 subunit p35, forms heterodimers with IL12B to create the IL-12 cytokine or with EBI3/IL27B to create the IL-35 cytokine. IL-12 is primarily produced by antigen-presenting cells (APCs), including B-cells, dendritic cells, macrophages, and granulocytes. It regulates T-cell and natural killer-cell responses, induces interferon-gamma (IFN-gamma) production, promotes the differentiation of T-helper 1 (Th1) cells, and is a key link between innate and adaptive immunity. IL-12 functions through a receptor composed of IL12R1 and IL12R2 subunits. Binding triggers tyrosine phosphorylation of cellular substrates, including JAK kinases TYK2 and JAK2. This activates STAT4, which then translocates to the nucleus and regulates cytokine/growth factor-responsive genes. As part of IL-35, IL12A plays a role in maintaining immune homeostasis in the liver and acts as an immune-suppressive cytokine. IL-35 signaling involves unconventional receptors composed of IL12RB2 and gp130/IL6ST heterodimers or homodimers. Signaling requires STAT1 and STAT4, which form a unique heterodimer that binds to distinct DNA sites.

IL12A is also known as CLMF, IL-12A, NFSK, NKSF1, P35.

Associated Diseases


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