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FLASH GENE

Symbol

NUMBL

contributors: mct - updated : 13-09-2017

HGNC name	numb homolog (Drosophila)-like
HGNC id	8061

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	24.75 kb     10 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

provisional

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_004756 10 - 3561 NP_004747 - 609 - 2017 28067668 NM_001289979 9 - 3483 NP_001276908 - 568 - 2017 28067668 NM_001289980 9 - 3367 NP_001276909 - 568 - 2017 28067668

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine pancreas       highly Nervous nerve       highly Reproductive female system breast mammary gland     Homo sapiens Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Reproductive epithelial cell Homo sapiens

cell lineage	neurons
cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a phosphotyrosine interaction domain in the N terminus
	a single NPF (asparagine-proline-phenylalanine) motif
	putative SH3-binding sites in the C terminus
	eighteen consecutive glutamine residues

conjugated

PhosphoP

HOMOLOGY

interspecies	homolog to Drosophila numb homolog-like
	homolog to C.elegans gene
	homolog to signal transducer Eps15-2 of yeast
	homolog to murine Numbl (95.9pc)
	homolog to rattus Numbl (95.4pc)

Homologene

FAMILY

CATEGORY

regulatory , signaling

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm

basic FUNCTION	required for maintaining radial glial adherens junctions, and for the tissue architecture of neurogenic niches and the cerebral cortex
	negatively regulates NF-kappaB signaling pathways
	role in neurogenesis suggesting that it may contribute to development of glial tumors
	NUMB and NUMBL have evolved to acquire at least partially distinct functions
	implicated in early development of the nervous system
	played an important role in tumorigenesis and invasion by suppressing NFKB1 activation
	importance of NUMB and NUMBL in the control of myoepithelial cell fate determination, epithelial identity, and lactogenesis

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development

text	neurogenesis

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	associating with EPS15 and NOTCH1
	interacting with TAB2 and negatively regulates NF-kappaB signaling pathway
	LNX1 interacts with the cell fate determinant NUMBL, a Numb homolog-like gene involved in the maintenance of neural progenitor cells during embryonic neurogenesis
	binding to TRAF6 and promoting its degradation, leading to the inhibition of NF-kappB signaling pathway
	NUMBL interacted directly with TRAF5, which signals upstream and is required for the activation of NFKB, and committed it to proteasomal degradation by promoting K48-linked polyubiquitination of TRAF5
	potential novel roles of NUMB/NUMBL in regulating heart trabeculation and compaction by inhibiting NOTCH2 and BMP10 signalling
	developmental regulator OFCC1 enables polarized integrin localization by modulating NUMB/NUMBL, thus directing the basal constriction that shapes the vertebrate retina epithelium
	could decrease the expression of TRAF6, CCND1, and MMP9 and increase the expression of CASP3
	NUMB, NUMBL counteract VEGF receptor degradation and promote VEGFR2 recycling back to the plasma membrane
	endocytic adaptor proteins NUMB and NUMBL were required for downregulation of ERBB2 signaling in maturing trabeculae
	NUMB and NUMBL interacted with small GTPase RAB7A to transition ERBB2 from early to late endosome for degradation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in human lung cancer cell lines, especially in metastatic cell lines

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

nestin-CreER transgenic mice where Numb/Numbl are removed have severe damage to brain lateral ventricle integrity