Numb gene with 13 exons is mapped to human chromosome 14q24.3. The protein comprises 651 amino acids. It belongs to the clathrin-associated sorting protein family with two domains namely phosphotyrosine-binding (PTB) and proline-rich region (PRR) domain. Mammalian Numb gene gives rise to at least four alternatively spliced transcripts that produce four protein isoforms Numb1-4, ranging from 65 to 72 kDa.
Numb homolog-NUMB is an adaptor protein and is aberrantly expressed in cancers.
Application
Anti-NUMB (C-terminal) antibody produced in rabbit has been used in immunoblotting.
Biochem/physiol Actions
Numb homolog-NUMB may act as a tumor suppressor. It also takes part in determining the cell fate. NUMB is involved in the endocytosis and trafficking of receptors.
Numb is a critical Notch antagonist and a conserved adapter protein that plays a role in the self-renewal of NSCs and neural differentiation in the central nervous system (CNS). In neural progenitors of CNS, the functional loss of numb is implicated in embryonic lethality accompanied by precocious neuronal differentiation. It has been suggested that a switch in numb isoform expression is a critical step in cortical development. Numb1 or numb3 isoforms that contain an insertion in the proline-rich region (PRRL), promote the proliferation of neural crest stem cells (NCSCs). Numb2 or numb4 isoforms without PRR insertions (PRRS) show ectopic expression and promote neuronal differentiation.
Physical form
Solution in 0.01 M phosphate buffered saline, pH 7.4, containing 15 mM sodium azide.
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The cell fate determinant Numb is aberrantly expressed in cancer. Numb is alternatively spliced, with one isoform containing a long proline-rich region (PRR(L) ) compared to the other with a short PRR (PRR(S) ). Recently, PRR(L) was reported to enhance
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