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Two closely related proteins, signal regulatory protein alpha (SIRPalpha; SHPS-1/CD172) and SIRPbeta, have been described in humans. The existence of a third SIRP protein has been suggested by cDNA sequence only. We show that this third SIRP is a separate gene that is expressed as a protein with unique characteristics from both alpha and beta genes and suggest that this gene should be termed SIRPgamma. We have expressed the extracellular region of SIRPgamma as a soluble protein and have shown that, like SIRPalpha, it binds CD47, but with a lower affinity (K(d), approximately 23 microM) compared with SIRPalpha (K(d), approximately 2 microM). mAbs specific to SIRPgamma show that it was not expressed on myeloid cells, in contrast to SIRPalpha and -beta, being expressed instead on the majority of T cells and a proportion of B cells. The short cytoplasmic tail of SIRPgamma does not contain any known signaling motifs, nor does it contain a characteristic lysine, as with SIRPbeta, that is required for DAP12 interaction. DAP12 coexpression is a requirement for SIRPbeta surface expression, whereas SIRPgamma is expressed in its absence. The SIRPgamma-CD47 interaction may therefore not be capable of bidirectional signaling as with the SIRPalpha-CD47, but, instead, use unidirectional signaling via CD47 only.

Original publication




Journal article


J Immunol

Publication Date





2562 - 2570


Adaptor Proteins, Signal Transducing, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antibody Specificity, Antigens, CD, Antigens, Differentiation, Apoptosis, CD47 Antigen, Cells, Cultured, Cloning, Molecular, Flow Cytometry, Humans, Jurkat Cells, Lymphocytes, Membrane Glycoproteins, Membrane Proteins, Molecular Sequence Data, Neural Cell Adhesion Molecule L1, Polymerase Chain Reaction, Precipitin Tests, Receptors, Immunologic, Surface Plasmon Resonance, U937 Cells