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FLASH GENE

Symbol

NGFR

contributors: mct/shn/ - updated : 11-10-2017

HGNC name	nerve growth factor receptor
HGNC id	7809

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	19.72 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D17S1868 - D17S797 - NGFR - D17S943 - D17S1795 - qter
Text	see also NTRK1

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002507 6 - 3420 NP_002498 - 427 - -

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 Digestive liver         Homo sapiens Nervous brain       highly Homo sapiens   nerve       predominantly Reproductive female system ovary     highly Respiratory lung       highly Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose white     Homo sapiens Muscular striatum       Homo sapiens Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous optic nerve Nervous Schwann cell

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminal region containing the leucine-rich repeats along with the transmembrane and cytoplasmic domains of LINGO1 are not required for self-interaction or interaction with APP
	an extracellular domain containing four 40-amino acid repeats with 6 cysteine residues at conserved positions
	a serine/threonine-rich region containing the nerve growth factor binding domain
	a single transmembrane domain
	a 155-amino acid cytoplasmic domain
	a cytoplasmic death domain, with unique intracellular structure and downstream signaling partners

mono polymer

homomer , dimer

HOMOLOGY

interspecies	ortholog to Ngfr, Mus musculus
	ortholog to Ngfr, Rattus norvegicus

Homologene

FAMILY

tumor necrosis factor receptor (TNFR) superfamily

CATEGORY

enzyme , signaling cytokine growth factor , receptor

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,cytoskeleton,microtubule
text	type I transmembrane protein (TM1)
	localized along with the SSTR3 receptor to the primary cilia of the granule cells of the murine dentate gyrus, a center of adult neurogenesis
	NGFR and NTRK1 are localized in the mitochondrial compartment of undifferentiated human podocytes and in all tissues analyzed including rat central nervous system

basic FUNCTION	important role in the development and function of sensory neurons
	mediates neurotrophin-dependent apoptosis
	involved in light-mediated photoreceptor apoptosis in vivo
	is the signal transducing element for Myelin-associated glycoprotein
	initiates intracellular signaling leading either to cell survival or to apoptosis
	an essential role for p75(NTR)-related signalling in early embryonic morphogenesis
	role in activity-dependent synaptic plasticity
	receptor tyrosine kinase, class VI, regulating the myelination process in peripheral nervous system
	a negative growth regulator within the context of myelin inhibition 5
	may play a positive role in nerve regeneration
	involved in the control of neuronal survival versus death and axonal regeneration and growth cone collapse
	regulator of liver repair
	binds pro and mature neurotrophins and affects the growth, differentiation and death of the nervous system
	maintains the specificity of neural connectivity
	regulator of glucose uptake and insulin resistance
	unanticipated function of NGFR as a unique regulator of glucose metabolism and insulin sensitivity
	transcriptional activation of NGFR is under circadian regulation in the nervous system and peripheral tissues, and plays an important role in the maintenance of clock and metabolic gene oscillation
	influences the proliferation, survival, and differentiation of neuronal precursors and its expression is induced in injured brain, where it regulates cell survival
	can modulate cell-fate decisions through its highly ramified signaling pathways

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	extracellular signal-regulated protein kinases 1 and 2
	Fas-associated phosphatase-1, FAP-1
	SC-1
	the six tumor necrosis factor receptor-associated factors, TRAF1-6
	caveolin 1, cav1
	zinc finger protein NRIF
	trkA, trkB and trkC
	neurotrophin receptor-interacting MAGE homolog, NRAGE and TrkA, TRKA
	p75NTR-associated cell death executor, NADE
	ganglioside GT1b
	necdin and MAGE-H1
	neurotrophin receptor-interacting MAGE homolog, NRAGE
	NDN and MAGEH1, are interactors for the intracellular domain of NGFR and the interaction is enhanced by ligand stimulation
	interleukin 1 receptor-associated kinase, IRAK
	tumor necrosis factor receptor-associated death domain protein, TRADD, upon nerve growth factor stimulation
	beta catalytic subunit of cAMP-dependent protein kinase, PKACbeta
	nerve growth factor, NGF
	NDN and NSMCE3 target both E2F1 and NGFR to regulate cell viability during brain development
	Nogo receptor and LINGO-1
	brain-expressed X-linked 1, Bex1
	par-3 partitioning defective 3 homolog (C. elegans), PARD3
	MAGED1 (NGFR adaptor protein, required for developmental apoptosis)
	SALL2 (SALL2 is a novel NGFR-interacting protein that links NGF signalling to cell cycle progression and neurite outgrowth)
	serves as a receptor for the pro-forms of theneurotrophins
	NPHS1 and NGFR share a partial overlapping expression pattern in the epicardium and subepicardial coronary vessels
	interactions of RTN4R with its co-receptors LINGO1, NGFR and the myelin inhibitor RTN4 is facilitated by gangliosides
	is required for the signal transduction of PILRB, which interacted with NGFR upon ligand binding
	on oligodendroglial cells, LINGO1 interacts with NGFR to constitutively inhibit multiple aspects of oligodendrocyte differentiation
	RAB5A and RAB31 directly interact with NGFR primarily via helix 4 of the NGFR death domain
	NTRK1 and NGFR collaborate with each other at the plasma membrane to bind NGF
	NGFRAP1 interacts with the death domain of NGFR and mediates apoptosis in neural cells in response to nerve growth factor
	NGFR and NTRK1 interact to enhance neurotrophic signaling
	NGFR associated predominantly with natively expressed LINGO1 containing immature N-glycans, characteristic of protein that has not completed trans-Golgi-mediated processing
	neuronal NRDC critically regulates cardiac sympathetic innervation and circulatory dynamics via modulation of NGFR

cell & other

REGULATION

repressed by

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

Other	phosphorylated by PKACbeta
	regulated by the helix-loop-helix transcription factors CLOCK and ARNTL

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --other   expressed in melanomas

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed diabete type 2   unanticipated function of NGFR as a unique regulator of glucose metabolism and insulin sensitivity

ANIMAL & CELL MODELS

	mice with NGF receptor p75 mutation are viable and fertile display markedly decreased sensory innervation, loss of heat sensitivity associated with ulcers in the distal extremities
	light-induced photoreceptor apoptosis in p75NTR knockout mice is significantly reduced
	impairment of hippocampal long-term potentiation in p75NTR-deficient mouse
	mice depleted for p75NTR exacerbate liver pathology and inhibited hepatocyte proliferation in vivo