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FLASH GENE

Symbol

NTRK1

contributors: mct/ - updated : 11-10-2015

HGNC name	neurotrophic tyrosine kinase, receptor, type 1
HGNC id	8031

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	HSAN4 hereditary sensory and autonomic neuropathy, type IV
Location	1q23.1      Physical location : 156.785.541 - 156.851.642
Synonym name	high affinity nerve growth factor receptor
	formed by fusion with TPM3 or TFG (see symbols) in papillary thyroid carcinoma
	tropomyosin-related kinase A
	oncogene TRK
Synonym symbol(s)	HNGFR, TRKA, TRK, MTC, p140-TrkA, DKFZp781I14186, TRK1, p140-TrkA
EC.number	2.7.10.1

DNA

TYPE	functioning gene
STRUCTURE	66.10 kb     17 Exon(s)

Genomic sequence alignment details
10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001012331 16 - 2647 NP_001012331 - 790 non neuronal tissues 2009 19250380 also called variant 1 or TRKA-I NM_002529 17 - 2663 NP_002520 - 796 neuronal tissues 2009 19250380 also called variant 2 or TRKA-II NM_001007792 17 - 2581 NP_001007793 - 760 - 2009 19250380 also called variant 3 or TRKA-III

EXPRESSION

Type	restricted

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 thyroid         Nervous brain         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Nervous central       Homo sapiens Nervous peripherous       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic monocyte Nervous neuron Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a signal peptide
	an extracellular domain with three tandem leucine-rich motifs flanked by two cysteine clusters and two Ig-like domains
	a single transmembrane segment (1TM)
	an intracellular domain possessing a tyrosine-kinase domain

mono polymer

homomer , monomer , dimer

HOMOLOGY

Homologene

FAMILY	protein kinase superfamily
	Tyr protein kinase family
	insulin receptor subfamily

CATEGORY

enzyme , protooncogene , receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,Golgi
	intracellular,cytoplasm,organelle,endosome
	intracellular,nucleus
text	nuclear localization of the intracellular domain of NTRK1 is observed constitutively in liver cells such as hepatocytes and activated stellate cells, while in other cell types it could be induced in response to soluble factors
	NGFR and NTRK1 are localized in the mitochondrial compartment of undifferentiated human podocytes and in all tissues analyzed including central nervous system

basic FUNCTION	nerve growth factor receptor, high affinity (dimeric form)
	involved in the survival differentiation and maintenance of many neural and non neural cell types
	by attracting microtubules to lipid rafts, may mediate other processes such as axon guidance
	positive feedback regulation between LHX8, NTRK1, and NGF is likely an important regulatory mechanism for cholinergic functions of the septum

CELLULAR PROCESS	cell life, differentiation
	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

nervous system

text	apoptotic or antiapoptotic function; key regulator of cell fate and cell shape in CNS

PATHWAY

metabolism

signaling

signal transduction

RUSC1 participates in the NGF-NTRK1 signaling pathway

a component

INTERACTION

DNA

RNA

small molecule

protein	binding nerve growth factor (NGFA, NGFB, NGFC), its high affinity
	binding neurotrophins (NTF3, NTF4)
	associates with TID1
	interaction with KALRN by the pleckstrin homology domain
	NGF is a cognate ligand for the neurotrophic receptor NTRK1, promoting the interaction between CTBP2 and ACIN1 through triggering ACIN1 phosphorylation by AKT1
	APP is phosphorylated by NTRK1 and regulates NGF/NTRK1signaling
	NTRK1 and NGFR collaborate with each other at the plasma membrane to bind NGF
	RASGRF1 binds nerve growth factor (NGF)-activated NTRK1
	RUSC1 RUN domain can directly interact with NTRK1
	NGFR and NTRK1 interact to enhance neurotrophic signaling
	STX8 facilitates NTRK1 transport from the Golgi to the plasma membrane and regulates the surface levels of NTRK1 but not NTRK2 receptors
	LINGO1 functions as a negative feedback regulator of signaling by cognate receptor tyrosine kinases including NTRK1, NTRK2 and NTRK3

cell & other

REGULATION

activated by

RUNX1/RUNX1T1 fusion protein in CD34+ cells and in hematopoietic stem cells

repressed by

MYCN (acts directly to repress NTRK1 and NGFR gene transcription)

ASSOCIATED DISORDERS

corresponding disease(s)

HSAN4

related resource

Mutation Database of Inherited Peripheral Neuropathies

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in association with EPHB6, EFNB2, EFNB3 in low grade neuroblastoma tumoral   deletion     in thyroid tumor tumoral fusion       chimeric protein of fusion between NTRK1 and one among tropomyosin, TRP or TAG in thyroid tumor constitutional         total absence of the expression in keratoconus (repression by Sp3 transcription factor) tumoral     --over   enhances the tumorigenic properties of breast cancer cells constitutional     --low   levels of both NGF protein in seminal plasma and NTRK1 mRNA in spermatozoa are low in samples from oligoasthenozoospermic men

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer hemopathy   potential target for therapeutic in t(8;21) positive leukemia

ANIMAL & CELL MODELS