Signal-regulatory protein alpha

Signal-regulatory protein alpha (SIRPα), also known as CD172a, is a protein that in humans is encoded by the SIRPA gene. SIRPα is a member of the signal-regulatory protein (SIRP) family, and also belongs to the immunoglobulin superfamily. SIRPα is expressed predominantly by myeloid cells and is involved in a range of cellular processes such as neutrophil migration, phagocytosis, and cell adhesion.

Structure[edit | edit source]

SIRPα is a transmembrane protein that consists of three immunoglobulin-like domains, a transmembrane region, and a cytoplasmic region that contains two immunoreceptor tyrosine-based inhibition motifs (ITIMs). The extracellular region of SIRPα interacts with CD47, a widely expressed cell surface protein, to prevent phagocytosis.

Function[edit | edit source]

SIRPα plays a crucial role in the regulation of many cellular processes. It is involved in the negative regulation of receptor tyrosine kinase-coupled signaling processes. SIRPα can also induce cell-cell adhesion when it interacts with CD47, which is present on the surface of many cell types. This interaction is important for the prevention of self-phagocytosis.

Clinical significance[edit | edit source]

Alterations in the expression or function of SIRPα have been implicated in several diseases, including cancer, autoimmune diseases, and neurodegenerative diseases. In cancer, SIRPα-CD47 interaction can be exploited by cancer cells to evade immune surveillance. Therapies that block this interaction are currently being developed and tested in clinical trials.