Gene Report

Basic Information

Approved Symbol	NGFR
Approved Name	nerve growth factor receptor
Previous Name	nerve growth factor receptor (TNFR superfamily, member 16)
Symbol Alias	TNFRSF16, CD271, p75NTR
Name Alias	low affinity nerve growth factor receptor, "TNFR superfamily, member 16"
Location	17q21-q22
Position	chr17:47572655-47592382 (+)
External Links	Entrez Gene: 4804 Ensembl: ENSG00000064300 UCSC: uc002ioz.4 HGNC ID: 7809
No. of Studies (Positive/Negative)	1(0/1)
Type	Literature-origin; SNP mapped

Positive relationships between NGFR and MDD (count: 0)

Positive relationships between NGFR and other components at different levels (count: 0)

Positive relationship network of NGFR in MK4MDD

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Note:
1. The different color of the nodes denotes the level of the nodes.

Genetic/Epigenetic Locus	Protein and Other Molecule	Cell and Molecular Pathway	Neural System	Cognition and Behavior	Symptoms and Signs	Environment	MDD

2. Besides the component related relationships from literature, gene mapped protein and protein mapped gene are also shown in the network. If the mapped gene or protein is not from literature, square node would be used instead of Circle node. Accordingly, the relationship is marked with dot line.
2. User can drag the nodes to rearrange the layout of the network. Click the node will enter the report page of the node. Right-click will show also the menus to link to the report page of the node and remove the node and related edges. Hover the node will show the level of the node and hover the edge will show the evidence/description of the edge.
3. The network is generated using Cytoscape Web

Negative relationships between NGFR and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
p75NTR	Kunugi H, 2004	Patients and nomal controls	P < 0.05, odds ratio 0.54, 95% CI 0.31-0.94	The minor allele (L205) was significantly decreased in the p...... The minor allele (L205) was significantly decreased in the patients than in the controls (P < 0.05, odds ratio 0.54, 95% CI 0.31-0.94), suggesting that this allele may have a protective effect against the development of major depression. More...

Negative relationships between NGFR and other components at different levels (count: 0)

NGFR related SNPs in MK4MDD (count: 1)

#rs	Location	Annotation	No. of Studies (Positive/Negative)
rs2072446	chr17:47587819(Forward)	downstream_gene_variant; intron_variant; missense_variant; nc_transcript_variant	2(2/0)

NGFR related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Tumor necrosis factor receptor superfamily member 16	P08138	0(0/0)	Gene mapped

NGFR related GO terms (count: 37)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006915	apoptotic process	biological process	TAS

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0004872	receptor activity	molecular function	TAS[3022937]
GO:0004888	transmembrane signaling receptor activity	molecular function	TAS[1846035]
GO:0005576	extracellular region	cellular component	TAS
GO:0005887	integral to plasma membrane	cellular component	TAS[3022937]
GO:0050772	positive regulation of axonogenesis	biological process	TAS
GO:0005654	nucleoplasm	cellular component	TAS
GO:0048146	positive regulation of fibroblast proliferation	biological process	IEA
GO:0031293	membrane protein intracellular domain proteolysis	biological process	TAS
GO:0006886	intracellular protein transport	biological process	ISS
GO:0006917	induction of apoptosis	biological process	IEA
GO:0005035	death receptor activity	molecular function	IEA
GO:0045786	negative regulation of cell cycle	biological process	TAS
GO:0042488	positive regulation of odontogenesis of dentin-containing tooth	biological process	IEA
GO:0007417	central nervous system development	biological process	IEA
GO:0040037	negative regulation of fibroblast growth factor receptor signaling pathway	biological process	IEA
GO:0005515	protein binding	molecular function	IPI
GO:0005886	plasma membrane	cellular component	TAS
GO:0009986	cell surface	cellular component	ISS
GO:0016048	detection of temperature stimulus	biological process	IEA
GO:0004871	signal transducer activity	molecular function	TAS[3022937]
GO:0005829	cytosol	cellular component	TAS
GO:0007411	axon guidance	biological process	IEA
GO:0010468	regulation of gene expression	biological process	IEA
GO:0051799	negative regulation of hair follicle development	biological process	IEA
GO:0050771	negative regulation of axonogenesis	biological process	TAS
GO:0048011	nerve growth factor receptor signaling pathway	biological process	TAS
GO:0031625	ubiquitin protein ligase binding	molecular function	IPI[11279055]
GO:0043588	skin development	biological process	IEA
GO:0042593	glucose homeostasis	biological process	ISS
GO:2001273	regulation of glucose import in response to insulin stimulus	biological process	ISS
GO:0021675	nerve development	biological process	IEA
GO:0031069	hair follicle morphogenesis	biological process	IEA
GO:0017137	Rab GTPase binding	molecular function	ISS
GO:0050770	regulation of axonogenesis	biological process	TAS
GO:0005768	endosome	cellular component	TAS
GO:0048406	nerve growth factor binding	molecular function	IEA

NGFR related KEGG pathways (count: 2)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04722	neurotrophin signaling_pathway	Neurotrophin signaling pathway	Neurotrophins are a family of trophic factors involved in di...... Neurotrophins are a family of trophic factors involved in differentiation and survival of neural cells. The neurotrophin family consists of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), and neurotrophin 4 (NT-4). Neurotrophins exert their functions through engagement of Trk tyrosine kinase receptors or p75 neurotrophin receptor (p75NTR). Neurotrophin/Trk signaling is regulated by connecting a variety of intracellular signaling cascades, which include MAPK pathway, PI-3 kinase pathway, and PLC pathway, transmitting positive signals like enhanced survival and growth. On the other hand, p75NTR transmits both positive and nagative signals. These signals play an important role for neural development and additional higher-order activities such as learning and memory. More...
hsa04060	cytokine cytokine_receptor_interaction	Cytokine-cytokine receptor interaction	Cytokines are soluble extracellular proteins or glycoprotein...... Cytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell growth, differentiation, cell death, angiogenesis, and development and repair processes aimed at the restoration of homeostasis. Cytokines are released by various cells in the body, usually in response to an activating stimulus, and they induce responses through binding to specific receptors on the cell surface of target cells. Cytokines can be grouped by structure into different families and their receptors can likewise be grouped. More...

NGFR related BioCarta pathways (count: 3)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
ERK_PATHWAY	erk pathway	Erk1/Erk2 Mapk Signaling pathway	The p44/42 MAP Kinase pathway consists of a protein kinase c...... The p44/42 MAP Kinase pathway consists of a protein kinase cascade linking growth and differentiation signals with transcription in the nucleus. Growth factor receptors and tyrosine kinases activate Ras which in turn activates c-Raf, MEK, and MAP kinase. Activated p44/42 MAP Kinase translocates to the nucleus and activates transcription by phosphorylation of kinases such as p90 RSK, MSK, and transcription factors such as ELK-1 and Stat3. The importance of this pathway in both growth control and development has been demonstrated via the transforming properties of various mutant forms of Ras, Raf, MEK and by their effects on development. Signal amplification and the potential for crosstalk appear to be important features of this regulatory network. More...
NGF_PATHWAY	ngf pathway	Nerve growth factor pathway (NGF)	Nerve growth factor (NGF) is one of a family of neurotrophin...... Nerve growth factor (NGF) is one of a family of neurotrophins that induce the survival and proliferation of neurons. In cell culture NGF induces the formation of neurite projections and in vivo may stimulate the innervation of tissues. NGF plays a role in the repair, regeneration, and protection of neurons, and as such could serve as a therapeutic agent in neurodegenerative conditions such as Alzheimer's disease. One potential method of NGF application would be through gene therapy or through implantation of cells that have been genetically modified ex vivo. NGF has also been suggested to play a role in other physiological systems and tissues such as the immune system. NGF has two receptors, TrkA and the p75(NTR). NGF may signal its neuroprotective actions through the tyrosine kinase TrkA receptor and trigger apoptosis in some cells through the p75 receptor. High-affinity binding of NGF requires both TrkA and p75(NTR). Binding of NGF to the TrkA receptor causes activation of the receptor tyrosine kinase and downstream signaling cascades. One of the downstream signaling pathways of NGF activates phospholipase C, releasing DAG and IP3 and activating associated downstream pathways such as protein kinase C. Another NGF-activated pathway is the ras-mediated activation of the map kinase pathway. This pathway is initiated through recruitment and activation of Shc, which leads to ras activation through Grb-2 and Sos-1. The Map kinase cascade includes raf, Mek and Erk. The downstream effectors of the ras pathway include activation of fos and jun to form AP-1, activating genes through this transcription factor. Other transcription factors involved in NGF responses include Egr and CREB. The Egr family of transcription factors as well as the Mek/Erk pathway contribute to NGF-induced neurite formation. The CREB family of transcription factors are involved in NGF-induced survival of sympathetic neurons. Further understanding of NGF signaling may be applied to the modulation of NGF responses in neurodegenerative conditions. More...
CDK5_PATHWAY	cdk5 pathway	Phosphorylation of MEK1 by cdk5/p35 down regulates the MAP kinase pathway	Map kinases transduce responses to extracellular signals by ...... Map kinases transduce responses to extracellular signals by a variety of routes, and communicate with other pathways through extensive crosstalk networks. A closely studied Map kinase cascade originates with tyrosine kinase activation, and activation of Ras. Ras activates Raf, Raf activates the Map kinase kinases Mek1 and Mek2 and these kinases activate downstream Map kinases like Erk1 and Erk2. Erk1 and Erk2 in turn activate transgenes like p35 through the Map kinase activated transcription factor EGR-1. Mek1 plays a central role in many different Map kinase pathways. Factors that activate Mek1 include growth factors like NGF, cytokines, chemokines, and phorbol ester, resulting in cellular proliferation and survival. Mek1 activation may also play a role in differentiation in neuronal tissues. In cultured neuronal PC-12 cells, NGF induces neurite outgrowth via Mek1 and the map kinase pathway. Constitutive activation of Mek1 can transform cells and may play a role in cancer. The crucial role of Mek1 in a variety of pathways including cellular transformation suggests that the cell must tightly regulate its activity. Cdk5 is a kinase that regulates the activity of Mek1. Although Cdk5 is a member of the cyclin-dependent kinase gene family, the activity of Cdk5 does not appear to be regulated by cyclins, but is activated by association with p35. Cdk5 does not act as a checkpoint kinase to regulate cell cycle progression, but acts as a regulatory kinase involved in other post-mitotic processes such as neuronal activity such as neuronal migration during development and neurite outgrowth. Mice lacking Cdk5 exhibit defects in neuronal development. One target of Cdk5 is Mek1. Phosphorylation of Mek1 by Cdk5 represses Mek1 activity and blocks downstream cellular responses. The activation of p35 by Map kinase pathways followed by deactivation of Map kinase signaling by the Cdk5/p35 complex completes the loop of a feedback circuit to terminate Map kinase signaling. More...

NGFR related Reactome pathways (count: 9)

ID	Name	Description
Gene mapped Reactome pathways
REACT_13776	p75 ntr_receptor_mediated_signalling	Besides signalling through the tyrosine kinase receptors TRK...... Besides signalling through the tyrosine kinase receptors TRK A, B, and C, the mature neurotrophins NGF, BDNF, and NT3/4 signal through their common receptor p75NTR. NGF binding to p75NTR activates a number of downstream signalling events controlling survival, death, proliferation, and axonogenesis, according to the cellular context. p75NTR is devoid of enzymatic activity, and signals by recruiting other proteins to its own intracellular domain. p75 interacting proteins include NRIF, TRAF2, 4, and 6, NRAGE, necdin, SC1, NADE, RhoA, Rac, ARMS, RIP2, FAP and PLAIDD. Here we annotate only the proteins for which a clear involvement in p75NTR signalling was demonstrated. A peculiarity of p75NTR is the ability to bind the pro-neurotrophins proNGF and proBDNF. Proneurotrophins do not associate with TRK receptors, whereas they efficiently signal cell death by apoptosis through p75NTR. The biological action of neurotrophins is thus regulated by proteolytic cleavage, with proforms preferentially activating p75NTR, mediating apoptosis, and mature forms activating TRK receptors, to promote survival. Moreover, the two receptors are utilised to differentially modulate neuronal plasticity. For instance, proBDNF-p75NTR signalling facilitates LTD, long term depression, in the hippocampus , while BDNF-TRKB signalling promotes LTP (long term potentiation). Many biological observations indicate a functional interaction between p75NTR and TRKA signaling pathways. More...
REACT_11061	signalling by_ngf	Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles i...... Neurotrophins (NGF, BDNF, NT-3, NT-4/5) play pivotal roles in survival, differentiation, and plasticity of neurons in the peripheral and central nervous system. They are produced, and secreted in minute amounts, by a variety of tissues. They signal through two types of receptors: TRK tyrosine kinase receptors (TRKA, TRKB, TRKC), which specifically interact with the different neurotrophins, and p75NTR, which interacts with all neurotrophins. TRK receptors are reported in a variety of tissues in addition to neurons. p75NTRs are also widespread. Neurotrophins and their receptors are synthesized as several different splice variants, which differ in terms of their biological activities. The nerve growth factor (NGF) was the first growth factor to be identified and has served as a model for studying the mechanisms of action of neurotrophins and growth factors. The mechanisms by which NGF generates diverse cellular responses have been studied extensively in the rat pheochromocytoma cell line PC12. When exposed to NGF, PC12 cells exit the cell cycle and differentiate into sympathetic neuron-like cells. Current data show that signalling by the other neurotrophins is similar to NGF signalling. More...
REACT_13443	regulated proteolysis_of_p75ntr	p75NTR undergoes a process of regulated intramembrane proteo...... p75NTR undergoes a process of regulated intramembrane proteolysis (RIP) similar to other transmembrane proteins such as NOTCH, beta-amyloid precursor protein (APP), and ERBB4. Each of these proteins is subjected to two sequential cleavages. The first one occurs in the extracellular part of the protein and is mediated by the metalloproteinase alpha-secretase which causes shedding of the extracellular domain. The second cleavage occurs in the intramembrane region and is mediated by gamma-secretase and causes release of the intracellular domain, ICD, and of a small peptide. The ICD often traffics to the nucleus and, in some instances (e.g. NOTCH), was found to act as transcriptional regulator. Whether the p75NTR ICD does translocate to the nucleus to regulate gene expression in a way similar to the NOTCH receptor remains to be seen. The alpha- and gamma-secretase mediated cleavage of p75 appears to be regulated by neurotrophin (NGF, BDNF) binding to TRKA or TRKB. p75NTR processing also occurs in response to MAG in cerebellar granule neurons. More...
REACT_13643	nrif signals_cell_death_from_the_nucleus	NRIF (nuclear receptor-interacting factor) is a DNA binding ...... NRIF (nuclear receptor-interacting factor) is a DNA binding protein that is essential for p75-mediated apoptosis in retina and sympathetic neurons. Neurotrophin or proneurotrophin binding to p75TR induces nuclear translocation of NRIF, which involves gamma-secretase cleavage of p75NTR ICD (Intra Cellular Domain). Once in the nucleus, NRIF mediates apoptosis, probably by acting as transcription factor. More...
REACT_13696	nf kb_is_activated_and_signals_survival	Upon activation in response to NGF, NF-kB moves to the nucle...... Upon activation in response to NGF, NF-kB moves to the nucleus, where it turns on genes that promote survival, and triggers the expression of HES1/5 to modulate dendritic growth. More...
REACT_13537	p75ntr signals_via_nfkb	The NF-kB pathway is an important pro-survival signalling pa...... The NF-kB pathway is an important pro-survival signalling pathway activated by mature NGF, but not BDNF or NT-3, through p75NTR. It is unclear whether TRKA activity also affects NF-kB activation. More...
REACT_13415	p75ntr recruits_signalling_complexes	NF-kB activation involves recruitment at the cell membrane o...... NF-kB activation involves recruitment at the cell membrane of several proteins such as RIP2, MYD88, IRAK1, TRAF6, p62 and atypical PKC by the NGF:p75NTR complex. More...
REACT_13720	cell death_signalling_via_nrage_nrif_and_nade	p75NTR is a key regulator of neuronal apoptosis, both during...... p75NTR is a key regulator of neuronal apoptosis, both during development and after injury. Apoptosis is triggered by binding of either mature neurotrophin or proneurotrophin (proNGF, proBDNF). ProNGF is at least 10 times more potent than mature NGF in inducing apoptosis. TRKA signalling protects neurons from apoptosis. The molecular mechanisms involved in p75NTR-apoptosis are not well understood. The death signalling requires activation of c-JUN N-terminal Kinase (JNK), as well as transcriptional events. JNK activation appears to involve the receptor interacting proteins TRAF6, NRAGE, and Rac. The transcription events are thought to be regulated by another p75-interacting protein, NRIF. Two other p75-interacting proteins, NADE and Necdin, have been implicated in apoptosis, but their role is less clear. More...
REACT_13638	nrage signals_death_through_jnk	Once bound by either NGF or proNGF, p75NTR interacts with NR...... Once bound by either NGF or proNGF, p75NTR interacts with NRAGE, thus leading to phosphorylation and activation of JUN Kinase (JNK). JNK controls apoptosis in two ways: it induces transcription of pro-apoptotic genes, and directly activates the cell death machinery. Only NGF-bound p75NTR is shown here. More...

NGFR related interactors from protein-protein interaction data in HPRD (count: 32)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
NGFR	NTF4	No	in vivo	7541633
NGFR	RTN4R	No	in vitro;in vivo	12422217
NGFR	NGF	No	in vitro;in vivo	14985763
NGFR	MAGEH1	No	in vivo	12414813
NGFR	SHC1	No	in vivo	7541035
NGFR	TRAF2	No	in vivo	10514511
NGFR	GRB2	No	in vitro;in vivo	9368064
NGFR	MAPK1	Yes	in vitro;in vivo	8407983
NGFR	FSCN1	No	in vitro;in vivo;yeast 2-hybrid	12789270
NGFR	NFKBIB	No	in vitro;in vivo	12034707
NGFR	NDN	No	in vitro;in vivo;yeast 2-hybrid	14593116 , 12716928 , 12414813
NGFR	PTPN13	No	in vitro	10544233
NGFR	KIDINS220	No	in vivo;yeast 2-hybrid	11150334 , 15378608
NGFR	ZNF274	No	in vitro;in vivo	10545116
NGFR	BEX1	No	in vivo	16498402
NGFR	SORT1	Yes	in vivo	14985763
NGFR	MAPK3	No	in vitro;in vivo	8407983
NGFR	NTRK1	No	in vivo	9927421
NGFR	MAGED1	No	in vitro;in vivo;yeast 2-hybrid	10985348
NGFR	NTRK3	Yes	in vivo	9927421
NGFR	TRADD	No	in vivo	12604596
NGFR	TRAF6	No	in vivo	10514511 , 9915784
NGFR	MAG	Yes	in vivo	12011108
NGFR	IL2	Yes	in vitro	1316918
NGFR	RIPK2	No	in vivo	11487608 , 16498402
NGFR	CAV1	No	in vitro	9867838
NGFR	TRA2B	No	in vivo	12604596
NGFR	NGFRAP1	No	in vivo;yeast 2-hybrid	10764727
NGFR	LINGO1	No	in vitro;in vivo	14966521
NGFR	NTRK2	Yes	in vivo	9927421
NGFR	PRKACB	No	in vitro;in vivo;yeast 2-hybrid	12682012
NGFR	TRAF4	No	in vivo	10514511

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways

Gene mapped Reactome pathways