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FLASH GENE

Symbol

NTN1

contributors: mct - updated : 28-04-2017

HGNC name	netrin 1
HGNC id	8029

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	17p13.1      Physical location : 8.924.858 - 9.147.316
Synonym name	netrin 1, mouse, homolog of
Synonym symbol(s)	NTN1L, UNC-6

DNA

TYPE	functioning gene
STRUCTURE	222.46 kb     7 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_004822 7 - 5954 NP_004813 67 604 - 2004 14750959

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 Cardiovascular heart       highly Digestive intestine small intestine     highly   intestine large intestine colon   highly   liver       highly   mouth tongue     highly Reproductive female system breast mammary gland   highly   male system prostate     highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Epithelial absorptive excretory digestive epithelium (mucosa)

cells

System Cell Pubmed Species Stage Rna symbol Digestive enterocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	laminin N terminal domain
	VI, V-2, and V-3 domains primarily required for dorsal migrations
	VI and V-3 domains are required for ventral migrations

conjugated

GlycoP

HOMOLOGY

interspecies	homolog to murine Ntn1 (99.2pc)
	homolog to rattus Ntn1 (99.0pc)

Homologene

FAMILY

laminin related secreted proteins family

CATEGORY

signaling growth factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm
text	secreted protein, extracellular space or extracellular matrix

basic FUNCTION	axon outgrow-promoting protein, collaborating with SHH to guide commissural axons to the midline
	playing a major role during nervous system development in mediating chemo-attraction and chemo-repulsion of axons and neurons by interacting with its receptor DCC
	regulating the migratory pathway of LHRH neurons
	involved in colorectal tumorigenesis by regulating apoptosis
	both Slits and NTN1 contribute to floor plate-derived chemorepulsion of cranial motor axons
	recruiting DOCK1 through DCC, which then activates small GTPases
	may regulate the development of placental vessels and plays a key role in the pathogenesis of fetal growth restriction
	potentially required for oligodendroglial migration into the olfactory bulb, but is dispensable for the proliferation of neurosphere forming progenitor cells and for their differentiation
	functionally important for the development of the nervous system
	laminin-related secreted protein, that is highly induced after tissue injury, and may serve as a marker of injury
	bifunctional guidance cue
	NTN1/DCC/UNC5C chemotropism contributes to axonal confinement within the CNS
	NTN1-UNC5C/DCC interaction is involved in controlling the interhemispherical projection in a subset of early born, deep layer callosal neurons

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

development , nervous system

text	survival factor via receptors DCC, UNC5A, B, C
	neuronal development

PATHWAY

metabolism

signaling

cell-cell signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	specifically binding to DCC and mediating axon guidance independently of adenosine A2B receptor activation but through the MAPK activation
	binding to ADORAB, UNC5A, UNC5B, UNC5C
	crucial role for PlTPNA in NTN1-induced neurite outgrowth, revealing a signalling mechanism for DCC/NEO1 and PlTPNA regulation
	requiring MAPK activation of DCC for axon outgrowth
	direct transcriptional target of the transcription factor NFKB
	binds to DCC and DSCAM mediating axon attraction, and UNC5 mediating axon repulsion
	in contrast to callosal neurites, in which NTN1 required GAP43 in order to stimulate both outgrowth and guidance, in ventrolateral efferents, NTN1 required GAP43 only to stimulate outgrowth, but not guidance
	MAPK8 plays an important role in NTN1-mediated axon guidance in the developing nervous system
	combination of DSCAM with DCC or UNC5C plays an important role in NTN1-mediated axon attraction or repulsion
	NTN1-UNC5C/DCC interaction is involved in controlling the interhemispherical projection in a subset of early born, deep layer callosal neurons
	negative regulation of NAA10 towards NTN1 and its receptor UNC5B were also detected upon treatment of all-trans retinoid acid, which was often used to induce morphological differentiation
	disengagement of UNC5C with polymerized TUBB3 plays an essential role in NTN-1/UNC5C-mediated axon repulsion
	NTN1, a canonical guidance cue, induced the interaction of TUBB3 with the netrin receptor DCC
	direct coupling of dynamic TUBB3 in microtubules with netrin receptors is required for NTN1-mediated axon guidance, and the interaction of NTN1 repulsive receptor UNC5C with TUBB3 is involved in NTN1 mediated axonal repulsion

cell & other

REGULATION

inhibited by

netrin attraction is repressed by SLIT through a DCC/ROBO complex

Other

mediated by cytoplasmic Ca2+ signals

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in brain tumor and neuroblastama constitutional     --over   in epithelial cells of ulcerative colitis, and Crohn disease, and required for colorectal cancer progression (Paradisi 2009) tumoral     --over   strongly upregulated in ovarian malignant tumors but not in benign tumors tumoral     --over   in inflammatory bowel diseases is required for colorectal cancer progression (

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	may represent a novel candidate biomarker for ovarian cancer
Therapy target
	System Type Disorder Pubmed cancer digestive colon inhibition of NTN1 could be an innovative target for drug therapy in inflammation-driven colorectal cancers

ANIMAL & CELL MODELS