Signal regulatory protein alpha (SIRPA, SHPS1, CD172a) is a transmembrane protein expressed mostly on myeloid cells. CD47, a widely expressed transmembrane protein, is a ligand for SIRP alpha, with the two proteins constituting a cell-cell communication system. The interaction of SIRPA with CD47 is important for the regulation of migration and phagocytosis. SIRPA functions as a docking protein to recruit and activate PTPN6 (SHP-1) or PTPN11 (SHP-2) at the cell membrane in response to extracellular stimuli. SIRPA also binds other intracellular proteins including the adaptor molecules Src kinase-associated protein (SKAP2 SKAP55hom/R), Fyn-binding protein/SLP-76-associated phosphoprotein (FYB/SLAP-130) and the tyrosine kinase PYK2. SIRPA also binds the extracellular proteins, surfactant-A (SP-A) and surfactant-D (SP-D).
The SIRP family members SIRPB and SIRPG show high sequence similarity and similar extracellular structural topology, including three Ig domains, but their ligand binding topology might differ. SIRPB is expressed on myeloid cells, including monocytes, granulocytes and DCs. It has no known natural ligand. SIRPG can bind CD47 but with lower affinity than SIRPA.