Product Pathways - NF-kB Signaling
Sharpin Antibody #4444
Reactivity Key: H=Human
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.
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.
Western blot analysis of extracts from 293T cells, either mock transfected (-) or transfected with a construct expressing either Myc/DDK-tagged full-length human Sharpin (hSharpin; +) or Myc/DDK-tagged full-length human HOIL-1 (hHOIL-1; +), using Sharpin Antibody (upper) and DYKDDDDK Tag Antibody (Binds to same epitope as Sigma's Anti-FLAG® M2 Antibody) #2368 (lower).
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).
- Lim, S. et al. (2001) Mol Cell Neurosci 17, 385-97.
- Grabbe, C. and Dikic, I. (2009) Chem Rev 109, 1481-94.
- Ikeda, F. et al. (2011) Nature 471, 637-41.
- Tokunaga, F. et al. (2011) Nature 471, 633-6.
- Iwai, K. (2011) Cell Cycle 10, 3095-104.
- Gerlach, B. et al. (2011) Nature 471, 591-6.
- Tokunaga, F. et al. (2009) Nat Cell Biol 11, 123-32.
- Seymour, R.E. et al. (2007) Genes Immun 8, 416-21.
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For Research Use Only. Not For Use In Diagnostic Procedures.