Human Notch-2 Intracellular Domain Biotinylated Antibody
Human Notch-2 Intracellular Domain Biotinylated Antibody Summary
Asp2063-Pro2413
Accession # Q04721
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Applications
Please Note: Optimal dilutions should be determined by each laboratory for each application. General Protocols are available in the Technical Information section on our website.
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Preparation and Storage
- 12 months from date of receipt, -20 to -70 °C as supplied.
- 1 month, 2 to 8 °C under sterile conditions after reconstitution.
- 6 months, -20 to -70 °C under sterile conditions after reconstitution.
Background: Notch-2
Human Notch-2 is a 300 kDa type I transmembrane glycoprotein that is one of four human Notch homologues involved in developmental processes (1‑3). Although Notch proteins are structurally and functionally similar, deletion of either Notch-1 or Notch-2 is lethal, showing that not all functions overlap (4, 5). Mice with hypomorphic Notch-2 show defects in the development of kidney, heart and eyes (6). Notch-2 is up‑regulated in mature B cells and is critical for differentiation to splenic marginal zone B cells (7). Notch-2 is also preferentially expressed in choroid plexus epithelia and neuronal precursors (8, 9). Human Notch-2 is synthesized as a 2471 amino acid (aa) precursor that contains a 25 aa signal sequence, a 1652 aa extracellular domain (ECD), and a 794 aa transmembrane (TM) and cytoplasmic segment. The ECD contains 35 EGF-like repeats and three Lin-12/Notch repeats, while the cytoplasmic region shows six ankyrin repeats, a glutamine-rich domain and a PEST sequence. Binding of ligands, including Jagged and Delta-like molecules in humans, has been localized to the 11th and 12th EGF-like repeats of Notch (10). Notch receptors undergo post-translational furin-type proteolytic cleavage (11). This forms a heterodimer through the interaction of a hydrophobic area in the ligand‑binding extracellular region with the TM/cytoplasmic portion (11, 12). Upon ligand binding, additional sequential proteolysis by TNF-converting enzyme (ADAM‑17) and the presenilin-dependent gamma -secretase results in the release of the Notch intracellular domain (NICD) which translocates into the nucleus, activating transcription of Notch-responsive genes (13). Human Notch-2 ECD (aa 26‑530) shows 93%, 93%, 96% and 96% aa identity with the corresponding regions of mouse, rat, canine, and bovine Notch-2, respectively. This region also exhibits approximately 60% aa identity with human Notch-1 and Notch-3.
- Stifani, S. et al. (1992) Nat. Genet. 2:119.
- Dumortier, A. et al. (2005) Int. J. Hematol. 82:277.
- Yoon, K. and N. Gaiano (2005) Nat. Neurosci. 8:709.
- Hamada, Y. et al. (1999) Development 126:3415.
- Shimizu, K. et al. (2002) Biochem. Biophys. Res. Comm. 291:775.
- McCright, B. et al. (2001) Development 128:491.
- Saito, T. et al. (2003) Immunity 18:675.
- Irvin, D. K. et al. (2001) J. Comp. Neurol. 436:167.
- Solecki, D. J. et al. (2001) Neuron 31:557.
- Hambleton, S. et al. (2004) Structure 12:2173.
- Logeat, F. et al. (1998) Proc. Natl. Acad. Sci. USA 95:8108.
- Sanchez-Irizarry, C. et al. (2004) Mol. Cell. Biol. 24:9265.
- Mumm, J.S. and R. Kopan (2000) Dev. Biol. 228:151.
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