SIRP alpha, Recombinant, Human (SIRPa, Signal Regulatory Protein, SHPS-1, BIT, p84, CD172a)

Signal regulatory protein alpha (SIRPA, designated CD172a), also called SHPS-1 (SHP substrate 1) and previously, MyD-1 (Myeloid/Dendritic-1), is a monomeric ~90kD type I transmembrane glycoprotein that belongs to the SIRP/SHPS (CD172) family of the immunoglobulin superfamily.1-4 SIRPs are paired receptors, with similar extracellular domains but differing C-termini and functions.1, 2 The 503 amino acid (aa) human SIRPA contains a 342 aa extracellular domain (ECD), with one V-type, and two C1-type Ig domains, and three potential N-glycosylation sites. It has a 110 aa cytoplasmic sequence with ITIM motifs that recruit tyrosine phosphatases SHP-1 and SHP-2 when phosphorylated.4 Human SIRPA has more than 40 described polymorphisms, including the prominent BIT (Brain Ig-like molecule with Tyrosine-based activation motifs, also called SIRPA2 or PTPNS).5 One reported isoform lacks aa 1-101, which eliminates most of the V-type Ig domain. Human SIRPA ECD shares 61%, 60%, 71%, 72% and 73% aa identity with mouse, rat, porcine, bovine and equine SIRPA, respectively; it shares 84% and 76% aa identity with human SIRPB1 and SIRPy, respectively.2 SIRPA is expressed mainly on myeloid cells, including macrophages, neutrophils, dendritic and Langerhans cells.3-6 It is also found on neurons, smooth muscle and endothelial cells.7-9 SIRPA shows adhesion to the ubiquitous CD47/IAP (integrin-associated protein), while SIRPY binds more weakly and SIRPA1 does not bind at all.1, 2 Mouse and human SIRPA-CD47 binding only cross-reacts for specific polymorphisms and influences engraftment of xenotransplanted stem cells.6, 10 SIRPA engagement generally produces a negative regulatory signal.4 Low SIRPA recognition of CD47, which occurs on aged erythrocytes or platelets or xenogenic cells, promotes clearance of CD47low cells from circulation.11-13 SIRPA Arecognition of surfactants SP-A and SP-D in the lung can inhibit alveolar macrophage cytokine production.14 CD47- integrin-SIRPA interaction is reported to promote macrophage fusion during osteoclastogenesis.15\n\nA DNA sequence encoding the extracellular domain of human SIRPa (Gly 27-Arg 370; Accession # NP_542970) was fused to the Fc region of human IgG1 via a polypeptide linker. The chimeric protein was expressed in Chinese hamster ovary cells.\n\nCalculated molecular mass of ~ 64kD. As a result of glycosylation, the recombinant protein migrates as an ~ 70-105kD protein in SDS-PAGE under reducing conditions.\n\nActivity: Measured by the ability of the immobilized protein to support the adhesion of red blood cells (Subramanian S., et al., 2006, Blood 107:2548-2556).\n\nStorage and Stability:\nLyophilized powder may be stored at 4 degrees C for short-term only. Reconstitute to nominal volume by adding sterile PBS and store at -20 degrees C. Reconstituted product is stable for 12 months at -20 degrees C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.

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SPECIFICATIONS

Catalog Number

S1013-86Z

Size

50ug

Form

Supplied as a lyophilized powder in PBS. Reconstitute with PBS to (same/more than)100ug/ml.

Purity

(same/more than) 90%, as determined by SDS-PAGE under reducing conditions and visualized by silver stain.\nEndotoxin: (same/less than) 1EU/1ug.

References

\n1. Barclay, A.N. & M.H. Brown, 2006, Nat. Rev. Immunol. 6:457.\n2. vanBeek, E.M. et al., 2005, J. Immunol. 175:7781.\n3. Liu, Y. et al., 2005, J. Biol. Chem. 280:36132.\n4. Kharitonenkov, A. et al., 1997, Nature 386:181.\n5. Swissprot Accession # P78324.\n6. Miyashita, M. et al., 2004, Mol. Biol. Cell 15:3950.\n7. Wang, X.X. & K.H. Pfenninger, 2005, J. Cell Sci. 119:172.\n8. Maile, L.A. et al., 2003, Mol. Biol. Cell 14:3519.\n9. Johansen, M.L. & E.J. Brown, 2007, J. Biol. Chem. 282:24219.\n10. Takenaka, K. et al., 2007, Nat. Immunol. 8:1313.\n11. Ishikawa-Sekigami, T. et al., 2006, Biochem. Biophys. Res. Commun. 343:1197.\n12. Olsson, M. et al., 2005, Blood 105:3577.\n13. Ide, K. et al., 2007, Proc. Natl. Acad. Sci. USA 104:5062.\n14. Gardai, S.J. et al., 2003, Cell 115:13.\n15. Lundberg, P. et al., 2007, Biochem. Biophys. Res. Commun. 352:444.