SIRP1

SIRP1, short for signal-regulatory protein 1, is a designation used for a member of the signal-regulatory protein (SIRP) family of cell-surface receptors in vertebrates. The SIRP family comprises several closely related transmembrane proteins that participate in the regulation of immune cell signaling. In humans, the best studied members are SIRPα (SIRPA), SIRPβ (SIRPB1), and SIRPγ (SIRPG). Some sources historically refer to SIRP1 as an alias for one of these genes, or as a general label for SIRP-family members in non-mammalian species, so the exact identity of SIRP1 can depend on the database or species.

SIRP proteins are type I transmembrane receptors with extracellular immunoglobulin-like domains and a cytoplasmic tail capable of transmitting signals. They typically act as regulators of phagocytosis and inflammatory signaling, modulating responses of macrophages, dendritic cells, and other myeloid cells. The extracellular region mediates ligand interactions; the best characterized ligand in mammals is CD47, which interacts with SIRPα to generate inhibitory signals that restrain phagocytosis. Downstream signaling involves intracellular motifs and associated phosphatases that tune cell activity, though the precise motifs vary among family members.

Evolutionarily, SIRP genes are conserved across jawed vertebrates with lineage-specific expansions producing multiple paralogs. Functional divergence among paralogs underlies differences in ligand recognition, signaling strength, and cell-type distribution.

Clinical relevance arises from the role of SIRP–CD47 signaling in tumor immunology and autoimmunity. Therapeutic strategies aim to block the SIRP–CD47 axis to enhance macrophage-mediated clearance of cancer cells, or to modulate inhibitory signaling in other contexts. See also CD47, SIRP family, SHP phosphatases.