Sharpin (Sank-associated RH Domain-interacting Protein)

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-kB 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).\n\nApplications: \nSuitable for use in Western Blot and Immunoprecipitation. Other applications not tested.\n\nRecommended Dilution:\nWestern Blot: 1:1000. Incubate membrane with diluted antibody in 5% w/v BSA, 1X TBS, 0.1% Tween-20 at 4 degrees C with gentle shaking, overnight.\nImmunoprecipitation: 1:50\nOptimal dilutions to be determined by the researcher.\n\nStorage and Stability:\nMay be stored at 4 degrees C for short-term only. Aliquot to avoid repeated freezing and thawing. Store at -20 degrees C. Aliquots are stable for 12 months. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap.

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SPECIFICATIONS

Catalog Number

137488

Size

100ul

Applications

IP, WB

Hosts

Rabbit

Reactivities

Hum, NHP

Form

Supplied in 10mM sodium HEPES, pH 7.5, 150mM NaCl, 100ug/ml BSA, 50% glycerol and <0.02% sodium azide

P Type

Mab

Purity

Purified.

Isotype

IgG

References

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. Tokunaga, F. et al. (2009) Nat Cell Biol 11, 123-32. 8. Seymour, R.E. et al. (2007) Genes Immun 8, 416-21.

Additional Info

Recognizes endogenous levels of total human Sharpin. Species Crossreactivity: monkey. Does not react with HOIL-1/RBCK1.