Human Signal Regulatory Protein Alpha (SIRPa) Protein

Background

Signal regulatory protein alpha (SIRPA) is a transmembrane glycoprotein encoded by the SIRPA gene in humans, primarily expressed on myeloid cells such as macrophages, dendritic cells, and neutrophils, and to a lesser extent on neurons. SIRPA belongs to the immunoglobulin superfamily (IgSF) and functions as an inhibitory receptor, playing a critical role in immune homeostasis, cellular signaling, and cell-cell interactions. SIRPA interacts primarily with CD47, a widely expressed protein known as the “don’t eat me” signal on host cells. This interaction is fundamental for immune surveillance, as it prevents macrophages and other immune cells from targeting healthy self-cells for phagocytosis, thereby maintaining tolerance to self while supporting immune responses against foreign antigens and damaged cells. SIRPA is integral in modulating immune responses and is implicated in a range of physiological processes, including cell migration, cell adhesion, and tissue homeostasis. Research indicates that SIRPA is not only crucial in the innate immune system but also impacts adaptive immunity. Dysregulation or mutations of SIRPA have been linked to autoimmunity, cancer, and other pathologies due to its role in immune evasion, particularly in the context of cancer, where many tumor cells upregulate CD47 to escape immune clearance.