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Product Usage Information

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C. Do not aliquot the antibody.

Specificity / Sensitivity

Sharpin Antibody recognizes endogenous levels of total Sharpin protein. This antibody does not cross-react with HOIL-1/RBCK1.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic peptide corresponding to residues near the carboxy terminus of human Sharpin protein. Antibodies are purified by protein A and peptide affinity chromatography.

SHank-Associated RH domain-interacting ProteIN (Sharpin), also known as SIPL1, is a highly conserved gene among many mammalian species and is ubiquitously expressed in various types of cells and tissues. Sharpin harbors multiple functional motifs including an amino terminal coiled-coil (CC) domain, which has been shown to mediate the interaction between sharpin and the scaffold protein shank (1). The other two domains, ubiquitin-like domain (UBL) and NPL4 zinc finger domain (NZF), facilitate ubiquitin-mediated protein recognition and degradation (2). Recent studies have shown that both UBL and NZF domains are essential for sharpin to exert its function in part through ubiquitin-mediated mechanisms (3-5). Although sharpin was initially identified as a scaffold protein within the postsynaptic density of neurons (1), recent studies have identified sharpin as a novel modulator of immune and inflammatory diseases. An emerging mechanistic model suggests that sharpin functions as an important adaptor component of the linear ubiquitin chain assembly complex (LUBAC) that modulates activation of the canonical NF-κB signaling pathway (3,4,6,7), thereby regulating cell survival and apoptosis, cytokine production, and development of lymphoid tissues. Indeed, mice with spontaneous mutations in the Sharpin gene develop chronic proliferative dermatitis that is characterized by eosinophilic inflammation of the skin and dysregulated development of lymphoid tissues (8).

1.  Lim, S. et al. (2001) Mol Cell Neurosci 17, 385-97.

2.  Grabbe, C. and Dikic, I. (2009) Chem Rev 109, 1481-94.

3.  Ikeda, F. et al. (2011) Nature 471, 637-41.

4.  Tokunaga, F. et al. (2011) Nature 471, 633-6.

5.  Iwai, K. (2011) Cell Cycle 10, 3095-104.

6.  Gerlach, B. et al. (2011) Nature 471, 591-6.

7.  Seymour, R.E. et al. (2007) Genes Immun 8, 416-21.

8.  Tokunaga, F. et al. (2009) Nat Cell Biol 11, 123-32.

Entrez-Gene Id 81858
Swiss-Prot Acc. Q9H0F6

For Research Use Only. Not For Use In Diagnostic Procedures.
Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.
Anti-FLAG is a registered trademark of Sigma-Aldrich Biotechnology.

Sharpin Antibody