NUMB (gene)

NUMBNotch-binding protein
Protein numb homolog is a protein that in humans is encoded by the NUMB gene.wikipedia
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Notch signaling pathway

NotchNotch signalingNotch receptor
Numb’s primary function in cell differentiation is as an inhibitor of Notch signaling which is essential for maintaining self-renewal potential in stem and progenitor cells.
Notch signaling promotes proliferative signaling during neurogenesis, and its activity is inhibited by Numb to promote neural differentiation.

LNX1

LNXp80
The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Numb has demonstrated protein-protein interactions with Adaptor-related protein complex 2, alpha 1, Mdm2, L1, DPYSL2, SIAH1, P53 and LNX1.
LNX1 has been shown to interact with NAGK, NUMB and PAFAH1B3.

Neuroblast

neuroblastsneuroblastic cellsneuronal stem cells
In neuroblasts, both complexes are localized to the apical cortex, causing apical/basal cell division and daughter cells exhibiting strong size asymmetry.
The switch from pluripotent neuroblast to differentiated cell fate is facilitated by the proteins Prospero, Numb, and Miranda.

Mdm2

E3 Ubiquitin-Protein Ligase Mdm2 (MDM2)Hdm2Mdm-2
The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1. Numb has demonstrated protein-protein interactions with Adaptor-related protein complex 2, alpha 1, Mdm2, L1, DPYSL2, SIAH1, P53 and LNX1.

L1 (protein)

L1CAML1CD171
Numb has demonstrated protein-protein interactions with Adaptor-related protein complex 2, alpha 1, Mdm2, L1, DPYSL2, SIAH1, P53 and LNX1.
L1 (protein) has been shown to interact with NUMB.

SIAH1

Siah-1
Numb has demonstrated protein-protein interactions with Adaptor-related protein complex 2, alpha 1, Mdm2, L1, DPYSL2, SIAH1, P53 and LNX1.

P53

TP53p53 genep53 protein
Numb has demonstrated protein-protein interactions with Adaptor-related protein complex 2, alpha 1, Mdm2, L1, DPYSL2, SIAH1, P53 and LNX1. Numb has been posited to have a role in tumor-suppression, through its ability to regulate Notch and TP53.

Adaptor-related protein complex 2, alpha 1

AP2A1adaptor 2 (ADP)AP-2 Alpha
Numb has demonstrated protein-protein interactions with Adaptor-related protein complex 2, alpha 1, Mdm2, L1, DPYSL2, SIAH1, P53 and LNX1.
Adaptor-related protein complex 2, alpha 1 has been shown to interact with DPYSL2 and NUMB.

DPYSL2

Numb has demonstrated protein-protein interactions with Adaptor-related protein complex 2, alpha 1, Mdm2, L1, DPYSL2, SIAH1, P53 and LNX1.
DPYSL2 has been shown to interact with CRMP1, Adaptor-related protein complex 2, alpha 1 and NUMB.

Protein

proteinsproteinaceousstructural proteins
Protein numb homolog is a protein that in humans is encoded by the NUMB gene.

Gene

genesnumber of genesgene sequence
Protein numb homolog is a protein that in humans is encoded by the NUMB gene.

Proteasome

proteasomalproteosomeproteasomes
The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1.

EPS15

The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1.

Notch 1

NOTCH1Notch-1
The encoded protein, whose degradation is induced in a proteasome-dependent manner by MDM2, is a membrane-bound protein that has been shown to associate with EPS15, LNX1, and NOTCH1.

Conserved sequence

sequence conservationconservedhighly conserved
The protein Numb is coded for by the gene, NUMB, whose mechanism appears to be evolutionarily conserved.

Drosophila

fruit fliesfruit flyDrosophilia
Numb has been extensively studied in both invertebrates and mammals, though its function is best understood in Drosophila.

Neurogenesis

neurogenicneural stem cellneural stem cells
During neurogenesis, Numb localizes to one side of the mother cell such that it is distributed selectively to one daughter cell.

Asymmetric cell division

asymmetricasymmetricallyasymmetric divisions
Numb plays a crucial role in asymmetrical cell division during development, allowing for differential cell fate specification in the central and peripheral nervous systems.

Alternative splicing

alternatively splicedtranscript variantssplice variant
In mammals, there are four alternatively spliced forms of the Numb protein.

NUMBL

In addition, there is a Numb homolog called “Numb-like,” or NUMBL.

Phosphorylation

phosphorylatedphosphorylatephosphorylates
It states that a complex phosphorylation cascade enables aPKC to phosphorylate Numb in the pre-mitotic cell, decreasing its affinity for the plasma membrane.

Cell cycle

M phasecell cycle progressioncell-cycle
It states that a complex phosphorylation cascade enables aPKC to phosphorylate Numb in the pre-mitotic cell, decreasing its affinity for the plasma membrane.

Jagged

The human ligands are Delta-like and Jagged, respectively.

Integral membrane protein

integral membrane proteinsintegral proteinintegral
These ligands are themselves integral membrane proteins.

Cytoplasm

cytoplasmiccytosolicintracytoplasmic
Following ligand binding of the Notch receptor, the intracellular fragment of Notch (NICD, or notch intracellular domain) is released into the cytoplasm and transported to the nucleus, where it can form a complex with binding partners such as EP300 and histone acetyltransferase and act as a transcription factor for Notch target genes.