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FLASH GENE

Symbol

NEDD9

contributors: mct - updated : 22-04-2011

HGNC name	neural precursor cell expressed, developmentally down-regulated 9
HGNC id	7733

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006403 7 - 4550 92.9 834 - 1996 8879209 NM_182966 - - 1329 - 174 - 1996 8879209 NM_001142393 8 - 4745 92.9 834 - 1996 8879209 p115 CASL - - - 115 - - 2010 20956287 hyperphosphorylated isoform, p115 CASL is likely necessary for the integration of BCR and S1P-dependent integrin signaling that permits MZ(marginal zone) B cells to be retained in the MZ, whereas dephosphorylation of CASLL contributes to cell detachment and trafficking to the follicle

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 placenta       highly Nervous brain         Respiratory lung       highly Urinary kidney       highly Visual eye lacrimal gland

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial sensory olfactory

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune B cell Lymphoid/Immune lymphocyte Lymphoid/Immune T cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a SH3 domain interacting with two proline-rich regions of focal adhesion kinase and a substrate domain
	multiple SH2-binding motifs
	a C-terminal domain containing a divergent helix-loop-helix (hlh) motif

mono polymer

homomer , heteromer , dimer

HOMOLOGY

interspecies	ortholog to rattus Nedd9 (87.5pc)
	ortholog to murine Nedd9 (89.2pc)

Homologene

FAMILY

CAS family

CATEGORY

adhesion

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
	intracellular,nucleus
text	different location in fibroblasts and in epithelial cells, predominantly in nucleus and in the cell periphery respectively
	recruited to the centrosome during cell cycle progression

basic FUNCTION	focal adhesion-associated signaling protein that undergoes a striking relocalization to the spindle at mitosis
	cell-cycle regulated proteine kinase required for regulation of centrosome structure at the G/M transition
	playing a central coordinating role for tyrosine-kinase-based signaling related to cell adhesion
	may be an important linking element between extracellular signaling and regulation of the cytoskeleton
	playing an important role in the pathophysiology of rheumatoid arthritis
	regulating activation of AURKA and NEK at the centrosome
	enhanced invasion in vitro and metastasis in vivo of both normal and transformed melanocytes
	with ARHGAP22, DOCK3, WASF2, are key molecules regulating RAC1 and RHO signaling that determine the mode of movement driving melanoma cell metastasis
	promotes the migration of neural crest cells in a graded manner and suggest a role for retinoic acid in the control of NEDD9 expression levels (
	required for VEGF-mediated head and neck squamous cell carcinoma (HNSCC) cell migration and invasion, consistent with its recent identification as a metastatic regulator (
	act as scaffolds to regulate protein complexes controlling migration and chemotaxis, apoptosis, cell cycle, and differentiation, and is linked to a role in progenitor cell function
	important role for CAS proteins in cell-cell adhesion signaling in development
	role of NEDD9 as a mediator of the canonical Wnt/CTNNB signaling pathway for cell proliferation, migration, and tumorigenesis, as well as an important player in colorectal tumorigenesis and progression
	new role for CAS proteins in cell-cell adhesion signaling in cancer

CELLULAR PROCESS	cell cycle, progression
	cell life, proliferation/growth

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	component of the cell division control machinery
	CAS scaffolding proteins (NEDD9, BCAR1, and CASS4) regulate cell migration, division and survival, and are often deregulated in cancer

INTERACTION

DNA

RNA

small molecule

protein	PTK2
	NICAL
	interacting with RHOA (impairs M-phase progression by disrupting the RhoA activation cycle)
	interacting with SH2D3C (constitutively bound to NEDD9 in B cells and this association is required for NEDD9 serine/threonine phosphorylation)
	novel Wnt signaling target

cell & other

REGULATION

activated by	induction of cell growth
	WNT3A, CTNNB, and DVL2 in a dose-dependent manner

induced by	two xenobiotic responsive elements present in its promoter

inhibited by	PTPN11 (PTPN11 inhibits tyrosine phosphorylation of Crk-associated substrate lymphocyte type (NEDD9)) (

Other	regulated by TGF-beta1
	phosphorylation dependent on cell adhesion and Src kinase activity
	association with SH2D3C in B cells required for the generation of the hyperphosphorylated p115 CASL (

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   contributes to the metastatic behavior of melanoma and glioblastoma cells tumoral     --over   in colorectal tumor tissues, increased with the tumor grade

Susceptibility

to late-onset Alzheimer and Parkinson disease

Variant & Polymorphism SNP	associated with late-onset Alzheimer's and Parkinson's disease (minor role)
	significant association of a common single nucleotide polymorphism (SNP) rs760678 gene with predisposition to late-onset Alzheimer disease (

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS