nb, l(2)03235, dNumb
signaling protein - targeted by Notch signaling - involved in determination of alternate cell fates - regulates the balance between Notch recycling and late endosome targeting in neural progenitor cells
Gene model reviewed during 5.44
Annotated transcripts do not represent all supported alternative splices within 5' UTR.
Gene model reviewed during 5.46
Gene model reviewed during 5.49
3.5, 3.1 (northern blot)
556, 515 (aa); 61, 56 (kD predicted)
The phosphotyrosine binding domains (PID) of most polypeptides studied preferentially bind peptides containing an NPXpY motif (X = any amino acid), whereas the the PID of numb protein binds peptides with a "YIGPY#" motif (# = a hydrophobic amino acid). The affinity of the PID domain for the peptide increases when the second tyrosine is phosphorylated. The GP(p)Y core motif is required for high-affinity binding. The same amino acids in the numb PID are likely to bind both the phosphorylated and non-phosphorylated forms of the peptide.
Interacts with Nak.
PTB domain recognizes multiple ligands by engaging different amounts of surface area dictated by tertiary contacts rather than primary sequence. This may allow interactions with a diverse set of proteins during asymmetric division and specification of cell fate.
Click to get a list of regulatory features (enhancers, TFBS, etc.) and gene disruptions (point mutations, indels, etc.) within or overlapping Dmel\numb using the Feature Mapper tool.
Comment: reported as procephalic ectoderm anlage in statu nascendi
Comment: reported as procephalic ectoderm anlage in statu nascendi
numb protein associates with the plasma membrane of the sensory organ precursor cell and of the neuroblast, and is asymmetrically localized.
numb protein is homogenously distributed along the plasma membrane during interphase and early prophase in embryonic neuroblasts. Beginning in late prophase, numb forms a crescent overlying one of two centromeres and remains in this crescent through later stages of mitosis. During telophase, it segregates into one of the two daughter cells where it is found evenly distributed along the plasma membrane. numb protein localization is microtubule and actin independent.
numb protein localizes in a ring along the plasma membrane of the sensory organ precursor cell, and is distributed asymmetrically to the daughter cell. During neuroblast division, numb protein is asymmetrically localized in the neuroblast, and segregates into the ganglion mother cell. Expression is also detected in epidermal cell membranes.
GBrowse - Visual display of RNA-Seq signalsView Dmel\numb in GBrowse 2
Please Note FlyBase no longer curates genomic clone accessions so this list may not be complete
Please Note This section lists cDNAs and ESTs that fall within the genomic extent of the gene model, which may include cDNAs and ESTs of genes within introns, or of overlapping genes. Please see GBrowse for alignment of the cDNAs and ESTs to the gene model.
For each fully sequenced cDNA the DGRC maintains various forms of the cDNA (e.g tagged or untagged) in several different host vectors for subsequent cloning and expression in Drosophila and Drosophila cell lines.
Source for merge of: numb l(2)03235
mol and numb proteins are colocalised at the plasma membrane in Schneider 2 cells. Inhibition of mol expression in Schneider 2 cells by RNA interference releases numb protein from the plasma membrane to the cytosol.
numb is necessary and sufficient to prevent apoptosis in the abdominal ventral multidendritic neuron 1a lineage.
The abdominal ventral multidendritic neuron 1a is generated by an asymetric divisions in which the numb gene product segregates to the neuron and the other daughter cell dies by apoptosis.
numb is required for correct allocation of cell fate between the Malpighian tubule tip cell and its sibling.
numb functions downstream of cell division genes (CycA, Rca1 and stg) and progression through the cell cycle is required for asymmetric localisation of numb gene product and thus N mediated specification of the sib fate in the RP2/sib division.
Asymmetrical segregation of numb protein into one of the sibling cells produced by division of muscle progenitor cells depends on insc, and is essential for the specification of distinct sibling cell fates.
Changing the dose of maternal numb product directly affects CNS development and suggests that numb may have earlier CNS functions in addition to sibling neuron specification. The numb mutant phenotype is extremely sensitive to the dosage of spdo.
The phosphotyrosine-binding (PTB) domain of numb is required for its function, but this domain is probably not involved in phosphotyrosine- dependent interactions.
Asymmetric localisation, but not membrane localisation, of numb is inhibited by latrunculin A, an inhibitor of actin assembly. Deletion of either the first 41 amino acids or amino acids 41-118 of numb eliminates both localisation to the cell membrane and asymmetric localisation during mitosis, whereas C terminal deletions or deletion of central portions do not affect numb subcellular localisation. The first 227 amino acids of numb are sufficient for asymmetric localisation.
numb PTB domain possesses a unique binding specificity that is distinct from the motifs recognised by other known PTB domains.
The asymmetric distribution of numb protein in muscle progenitors and its asymmetric segregation between sibling cells as each progenitor divides underlies the segregation of cell fates in the myogenic lineages of the Drosophila embryo.
Analysis of the mutant phenotype reveals numb functions in the neuron/sheath cell lineage. numb forms a crescent in the dividing IIa and IIb cells suggesting that asymmetric localisation of numb is important for the cell fate determination in all three asymmetric cell divisions in the sensory organ lineage. Su(H) is required for only a subset of the asymmetric divisions that depend on the function of numb and N. Su(H) appears to act downstream of numb in the same genetic pathway in determining the fates of the IIa daughter cells, the hair cell and the socket cell, and Su(H) is negatively regulated by numb.
A PID, phosphotyrosine interaction domain, has been found in the numb protein. PID is a protein protein interaction motif that binds to the Asn-Pro-X-Tyr(P) motif found in many tyrosine phosphorylated proteins.
pros translocates to the membrane at the beginning of cell division and colocalises with numb throughout mitosis, suggesting a common mechanism for asymmetric segregation. numb and pros localisation is coupled to mitosis and tightly correlated with the position of one of the two centrosomes but independent of microtubules and actin.
numb protein is necessary and sufficient to specify autonomously the dMP2 fate in the MP2 lineage.
The numb product is a membrane associated protein that localizes asymmetrically to one half of the predivisional sensory organ precursor cell. Upon division the numb product segregates preferentially to one of the two daughter cells, which acquire distinct identities.
Analysis of numb mutant embryos determines that growth cones can distinguish between individual muscle fibres during synaptogenesis. Growth cones retain their target preference even when the numbers and patterns of muscle fibres are altered.
In mutants, the precursors of neurons and glial cells in the external sensory (es) organs are, for the most part, transformed into nonneural support cells; some of the es organs are duplicated. Transformation of neuron precursors into nonneural cells also occurs in the chordotonal (ch) organs. Precursors of the multiple dendrite (md) neurons undergo similar changes. Muscle development is abnormal; some muscles are fewer in number than in wild type and show pattern changes.
The numb gene must be able to function in the embryo in order for the peripheral sensory neurons to acquire their correct identity.