Gene Report

Basic Information

Approved Symbol	TNFRSF1B
Approved Name	tumor necrosis factor receptor superfamily, member 1B
Previous Symbol	TNFR2
Symbol Alias	TNFBR, TNFR80, TNF-R75, TNF-R-II, p75, CD120b
Location	1p36.22
Position	chr1:12267078-12269277 (+)
External Links	Entrez Gene: 7133 Ensembl: ENSG00000028137 UCSC: uc001att.3 HGNC ID: 11917
No. of Studies (Positive/Negative)	2(2/0)
Type	Literature-origin; Protein mapped

Positive relationships between TNFRSF1B and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
TNFR2	Dean B, 2012	patients and normal controls		levels of TNFR2 mRNA was decreased in BA 46 in people with m...... levels of TNFR2 mRNA was decreased in BA 46 in people with mood disorders (MDD=-51%; BD=-67%) More...

Positive relationships between TNFRSF1B and other components at different levels (count: 2)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Relation Description
Name in Literature	Related Components
TNFR2		Depression-like behaviors from animal model(depressive-like behavior)	cognition and behavior	Simen BB, 2006	animal model	We show that deletion of either TNFR1 or TNFR2 leads to an a...... We show that deletion of either TNFR1 or TNFR2 leads to an antidepressant-like response in the forced swim test More...
TNFR2		anhedonic-like behavior from animal model(anhedonic-like behavior)	cognition and behavior	Simen BB, 2006	animal model	mice lacking TNFR2 demonstrate a hedonic response in a sucro...... mice lacking TNFR2 demonstrate a hedonic response in a sucrose drinking test compared with wildtype littermates More...

Positive relationship network of TNFRSF1B 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 TNFRSF1B and MDD (count: 0)

Negative relationships between TNFRSF1B and other components at different levels (count: 1)

Genetic/epigenetic locus					Protein and other molecule			Cell and molecular pathway			Neural system			Cognition and behavior		Symptoms and signs			Environment

Name in Literature	Level	Approved Name (Name in Literature)	Type	Reference	Research Type	Statistical Result	Relation Description
Name in Literature	Related Components
TNFR2		Anxiety-like behaviors from animal model(anxiety-like behavior)	cognition and behavior	Simen BB, 2006	animal model		There were no differences in behavior in anxiety tests for e...... There were no differences in behavior in anxiety tests for either null mutant. More...

TNFRSF1B related SNPs in MK4MDD (count: 0)

TNFRSF1B related proteins in MK4MDD (count: 1)

Approved Name	UniportKB	No. of Studies (Positive/Negative)	Source
Tumor necrosis factor receptor superfamily member 1B	P20333	1(1/0)	Literature-origin

TNFRSF1B related GO terms (count: 27)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006954	inflammatory response	biological process	IBA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0005031	tumor necrosis factor-activated receptor activity	molecular function	IEA
GO:0005886	plasma membrane	cellular component	TAS
GO:0043025	neuronal cell body	cellular component	IEA
GO:0051044	positive regulation of membrane protein ectodomain proteolysis	biological process	IMP[22480688]
GO:0005576	extracellular region	cellular component	IEA
GO:0005634	nucleus	cellular component	IEA
GO:0042127	regulation of cell proliferation	biological process	IBA
GO:0043410	positive regulation of MAPK cascade	biological process	IBA
GO:0050728	negative regulation of inflammatory response	biological process	IEA
GO:0097190	apoptotic signaling pathway	biological process	IBA
GO:0005887	integral component of plasma membrane	cellular component	IBA
GO:0048471	perinuclear region of cytoplasm	cellular component	IEA
GO:0045121	membrane raft	cellular component	IDA[17010968]
GO:0007568	aging	biological process	IEA
GO:0006955	immune response	biological process	IBA
GO:0071222	cellular response to lipopolysaccharide	biological process	IMP[22480688]
GO:0007275	multicellular organism development	biological process	IBA
GO:0043196	varicosity	cellular component	IEA
GO:0008630	intrinsic apoptotic signaling pathway in response to DNA damage	biological process	IEA
GO:0097191	extrinsic apoptotic signaling pathway	biological process	IEA
GO:0050779	RNA destabilization	biological process	IEA
GO:0031625	ubiquitin protein ligase binding	molecular function	IPI[11279055]
GO:0042981	regulation of apoptotic process	biological process	IBA
GO:0033209	tumor necrosis factor-mediated signaling pathway	biological process	TAS
GO:0005515	protein binding	molecular function	IPI[8069916\|10848577\|11244088\|14743216\|24070898]
GO:0071363	cellular response to growth factor stimulus	biological process	IEA

TNFRSF1B related KEGG pathways (count: 3)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
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...
hsa05014	amyotrophic lateral_sclerosis_als	Amyotrophic lateral sclerosis (ALS)	Amyotrophic lateral sclerosis (ALS) is a progressive, lethal...... Amyotrophic lateral sclerosis (ALS) is a progressive, lethal, degenerative disorder of motor neurons. The hallmark of this disease is the selective death of motor neurons in the brain and spinal cord, leading to paralysis of voluntary muscles. Mutant superoxide dismutase 1 (SOD1), as seen in some familial amyotrophic lateral sclerosis (FALS) cases, may be toxic because it is unstable, forming aggregates in the motor neuron cytoplasm, axoplasm and mitochondria. Within mitochondria, mutant SOD1 may interfere with the anti-apoptotic function of Bcl-2, affect mitochondrial import by interfering with the translocation machinery (TOM/TIM), and generate toxic free radicals (ROS) via aberrant superoxide chemistry. These changes may then result in abnormal mitochondrial energy metabolism, Ca2+ handling, and release of pro-apoptotic factors. Reactive oxygen species (ROS), produced within mitochondria, inhibit the function of EAAT2, the main glial glutamate transporter protein, responsible for most of the reuptake of synaptically released glutamate. Glutamate excess causes neurotoxicity by increasing intracellular calcium, which enhances oxidative stress and mitochondrial damage. Mutant SOD1 can also trigger oxidative reactions by various means including by increasing levels of peroxynitrite, which can then cause damage through the formation of hydroxyl radicals or via nitration of tyrosine residues on proteins. Nitration may target neurofilament proteins, disrupting their phosphorylation and affecting axonal transport. Collectively, these mechanisms (or a combination thereof) are predicted to disturb cellular homeostasis (within glial and/or motor neurons), ultimately triggering motor neuron death. More...
hsa04920	adipocytokine signaling_pathway	Adipocytokine signaling pathway	Increased adipocyte volume and number are positively correla...... Increased adipocyte volume and number are positively correlated with leptin production, and negatively correlated with production of adiponectin. Leptin is an important regulator of energy intake and metabolic rate primarily by acting at hypothalamic nuclei. Leptin exerts its anorectic effects by modulating the levels of neuropeptides such as NPY, AGRP, and alpha-MSH. This leptin action is through the JAK kinase, STAT3 phosphorylation, and nuclear transcriptional effect. Adiponectin lowers plasma glucose and FFAs. These effects are partly accounted for by adiponectin-induced AMPK activation, which in turn stimulates skeletal muscle fatty acid oxidation and glucose uptake. Furthermore, activation of AMPK by adiponectin suppresses endogenous glucose production, concomitantly with inhibition of PEPCK and G6Pase expression. The proinflammatory cytokine TNFalpha has been implicated as a link between obesity and insulin resistance. TNFalpha interferes with early steps of insulin signaling. Several data have shown that TNFalpha inhibits IRS1 tyrosine phosphorylation by promoting its serine phosphorylation. Among the serine/threonine kinases activated by TNFalpha, JNK, mTOR and IKK have been shown to be involved in this phosphorylation. More...

TNFRSF1B related BioCarta pathways (count: 8)

ID	Name	Brief Description	Full Description
Gene mapped BioCarta pathways
TNFR2_PATHWAY	tnfr2 pathway	TNFR2 Signaling Pathway	TNFR2 is the receptor for the 171 amino acid 19 kD TNF(beta)...... TNFR2 is the receptor for the 171 amino acid 19 kD TNF(beta) (a.k.a. lymphotoxin). TNF(beta) is produced by activated lymphocytes and can be cytotoxic to many tumor and other cells. In neutrophils, endothelial cells and osteoclasts TNF(beta) can lead to activation while in many other cell types it can lead to increased expression of MHC and adhesion molecules. More...
PML_PATHWAY	pml pathway	Regulation of transcriptional activity by PML	The PML nuclear bodies are ring-shaped nuclear substructures...... The PML nuclear bodies are ring-shaped nuclear substructures associated with the regulation of transcription, transformation, cell growth, and apoptosis and are characterized by the presence of the protein PML. The activities of PML as a tumor suppressor and apoptosis inducing factor are exerted through the numerous proteins it interacts with in the PML-nuclear bodies including the tumor suppressor p53. DNA damage induced activation of p53-dependent apoptosis requires PML. PML acts as a coactivator for p53 and increases acetylation of p53 by the transcriptional coactivator CBP. This acetylation of p53 is reversed by the deacetylase SirT1, the human homolog of the yeast gene Sir2, and this deacetylation opposes the transcriptional activation of p53. The tumor suppressor Rb also interacts with the PML nuclear body, increasing transcriptional repression of genes involved in cell cycle progression, suggesting that PML may affect cellular transformation through more than one mechanism. PML interacts directly with Ubc9, which modifies PML through the attachment of the ubiquitin-like peptide Sumo-1. Sumo-1 modification of PML is not necessary for the nuclear bodies to form, but may affect the recruitment of proteins that interact with PML. PML is involved in non-p53 mediated apoptotic pathways, such as DAXX-mediated apoptosis induced by Fas and TNF and regulates the transcriptional repressor activity of Daxx. The sequestration of Daxx by the PML nuclear bodies relieves the repression of other transcription factors like Pax3 by Daxx. Tumor suppression by PML may in general involve the formation of specific regulatory transcription complexes, including those with DAXX, p53 and CBP. Factors that affect the assembly of PML into the PML nuclear bodies affect the proliferation and transformation of cells. Viral early proteins can interact with PML to disrupt the nuclear bodies, allowing increased proliferation of cells and reduced apoptosis, good conditions for DNA virus infection. Another factor that disrupts the formation of PML nuclear bodies is a translocation between the PML and RAR-alpha genes found in acute promyelocytic leukemia (APL) patients. Binding of retinoic acid to the RAR-alpha steroid hormone receptor activates transcription of retinoic-acid responsive genes. The translocation found in APL patients creates two chimeric proteins, RARalpha-PML and PML-RARalpha. Retinoic acid given to APL patients causes the reappearance of nuclear bodies, and the reversal of cellular transformation, effecting a cure for these patients. More...
SODD_PATHWAY	sodd pathway	SODD/TNFR1 Signaling Pathway	The tumor necrosis factor (TNF) receptor superfamily contain...... The tumor necrosis factor (TNF) receptor superfamily contains several members with homologous cytoplasmic domains known as death domains (DD). The intracellular DD are important in initiating apoptosis and other signaling pathways following ligand binding by the receptors.1 In the absence of ligand, DD-containing receptors are maintained in an inactive state. TNF RI contains a cytoplasmic DD required for signaling pathways associated with apoptosis and NF-kB activation.2,3 Jiang et al.4 identified a widely expressed 60 kDa protein, named SODD (silencer of death domains), associated with the DD of TNF RI and DR3. Overexpression of SODD suppresses TNF-induced cell death and NF-kB activation demonstrating its role as a negative regulatory protein for these signaling pathways. TNF-induced receptor trimerization aggregates the DD of TNF RI and recruits the adapter protein TRADD.3,5 This in turn promotes the recruitment of the DD-containing cytoplasmic proteins FADD, TRAF2 and RIP to form an active TNF RI signaling complex (Figure 1A).6-9 In contrast, SODD acts as a silencer of TNF RI signaling and does not interact with TRADD, FADD, or RIP (Figure 1B).4 It is associated with the DD of TNF RI and maintains TNF RI in an inactive, monomeric state. TNF-induced aggregation of TNF RI promotes the disruption of the SODD-TNF RI complex. SODD does not interact with the DD of other TNF receptor superfamily members such as Fas, DR4, DR5, or TNF RII. SODD association with TNF RI may represent a general model for the prevention of spontaneous TNF signaling by other DD-containing receptors. More...
KERATINOCYTE_PATHWAY	keratinocyte pathway	Keratinocyte Differentiation	The epidermis, which provides a protective barrier that unde...... The epidermis, which provides a protective barrier that undergoes a constant renewal, is a multi-layered tissue with the proliferating cells located in the basal layer. As cells leave the basal layer the underog significant differentiation, biochemical and morphological remodeling. The final differentiation results in the formation of corneocytes. In vitro keratinocytes mimic this process. Several genes mark keratinocyte specific differentiation. Among the most frequently tracked markers are Transglutaminase, Cystatin and Involucrin. The keratinocyte differentiation studies have identified and provided significant detail regarding the involvement of three of the 4 major MAP kinase pathways from several diverse stimuli such as EGF, FAS, TNF and Calicium influx. The p38 cascade is represented twice since both p38alpha (p38) and p38delta (MAPK13) are involved. The keratinocyte differentiation cascased also provide for detailed study of the functions of individual PKC isoforms. It is interesting to note the contrasting functions of the PKC isoforms in this process. In recent studies it has been determined that the cPKC (conventional/classical Protein Kinase C) isoforms, which are calcium-, phospholipid-, and diacylglycerol-dependent are inhibitory where as the nPKC (novel Protein Kinase C) isoforms which are calcium independent are stimulatory for keratinocyte differentiation markers. On the right hand side is an earlier step showing the upregulation loop of TRAF2. This step occurs prior to the activation os ASK1 and the p38 cascade. More...
HIVNEF_PATHWAY	hivnef pathway	HIV-I Nef: negative effector of Fas and TNF	HIV infection leads to drastic declines in CD4 T helper cell...... HIV infection leads to drastic declines in CD4 T helper cells, in part through apoptosis of uninfected cells. Apoptosis of uninfected cells may be induced through the expression of Fas ligand on the surface of HIV-infected cells, stimulating the Fas-dependent apoptotic pathway in cells that come in contact with infected cells. The NEF protein expressed by HIV may play induce the expression of Fas-ligand by infected cells. If this is the case, then a question that arises is how infected cells themselves escape Fas-mediated apoptosis. The NEF protein appears to play a role in this process as well. NEF interacts with the ASK1 kinase (apoptosis signal-regulating kinase) involved in apoptotic signaling by TNF and Fas-ligand. Interaction of NEF with ASK1 prevents phosphorylation of downstream MAP kinases and JNK kinases involved in apoptotic signaling. More...
NFKB_PATHWAY	nfkb pathway	NF-kB Signaling Pathway	Nuclear factor kB (NF-kB) is a nuclear transcription factor ...... Nuclear factor kB (NF-kB) is a nuclear transcription factor that regulates expression of a large number of genes that are critical for the regulation of apoptosis, viral replication, tumorigenesis, inflammation, and various autoimmune diseases. The activation of NF-kB is thought to be part of a stress response as it is activated by a variety of stimuli that include growth factors, cytokines, lymphokines, UV, pharmacological agents, and stress. In its inactive form, NF-kB is sequestered in the cytoplasm, bound by members of the IkB family of inhibitor proteins, which include IkBa, IkBb, IkBg, and IkBe. The various stimuli that activate NF-kB cause phosphorylation of IkB, which is followed by its ubiquitination and subsequent degradation. This results in the exposure of the nuclear localization signals (NLS) on NF-kB subunits and the subsequent translocation of the molecule to the nucleus. In the nucleus, NF-kB binds with a consensus sequence (5'GGGACTTTCC-3') of various genes and thus activates their transcription. IkB proteins are phosphorylated by IkB kinase complex consisting of at least three proteins; IKK1/IKKa, IKK2/IKKb, and IKK3/IKKg. These enzymes phosphorylate IkB leading to its ubiquitination and degradation. Tumor necrosis factor (TNF) which is the best-studied activator binds to its receptor and recruits a protein called TNF receptor death domain (TRADD). TRADD binds to the TNF receptor-associated factor 2 (TRAF-2) that recruits NF-kB-inducible kinase (NIK). Both IKK1 and IKK2 have canonical sequences that can be phosphorylated by the MAP kinase NIK/MEKK1 and both kinases can independently phosphorylate IkBa or IkBb. TRAF-2 also interacts with A20, a zinc finger protein whose expression is induced by agents that activate NF-kB. A20 functions to block TRAF2-mediated NF-kB activation. A20 also inhibits TNF and IL-1 induced activation of NF-kB suggesting that it may act as a general inhibitor of NF-kB activation. More...
TID_PATHWAY	tid pathway	Chaperones modulate interferon Signaling Pathway	Signaling by interferon-gamma stimulates anti-viral response...... Signaling by interferon-gamma stimulates anti-viral responses and tumor suppression through the heterodimeric interferon-gamma receptor. Signaling is initiated by binding of interferon-gamma to its receptor, activating the receptor-associated JAK2 tyrosine kinase to phosphorylate STAT transcription factors that activate interferon responsive genes. Molecular chaperones that modulate or alter protein folding interact with different components of the interferon signaling pathway. One chaperone that modulates interferon signaling is hTid-1, a member of the DnaJ family of chaperones and a cochaperone for the heat shock protein Hsp70, another molecular chaperone. hTid-1 was found in a two-hybrid screen to bind to JAK2 and also to interact with the interferon-gamma receptor. In addition, hTid-1 and JAK2 also interact with Hsp70. Overexpression of hTid-1 represses transcriptional activation by interferon-gamma and Hsp70 dissociates from these proteins when interferon is added to cells, suggesting that Hsp70 holds Jak2 in an inactive conformation prior to ligand activation, and is released in the presence of agonist to allow the activation of Jak-2 and downstream pathways. hTid-1 and Hsp-70 interact with other signaling proteins as well. One of this is Tax, a protein encoded by the HTLV-1 virus that binds to hTid-1. hTid-1 also represses NF-kB activation by blocking the phosphorylation and inactivation of I-kappaB by the IkappaB kinase beta. Hsp70 plays a significant role in protein unfolding for entry into mitochondria and also interacts with tumor suppressor gene products to produce their anti-proliferative activity. One of the actions of interferon is to induce apoptosis of infected target cells, in part through a mitochondrial dependent mechanism. An interaction between interferon signaling and Hsp70 may alter this mitochondrial apoptosis pathway, perhaps playing a role in interferon-mediated apoptosis of infected or transformed cells. The HTLV-1 Tax protein that interacts with Hsp70 blocks mitochondrial induced apoptosis, providing a protection against interferon-mediated cellular defenses. More...
RELA_PATHWAY	rela pathway	Acetylation and Deacetylation of RelA in The Nucleus

TNFRSF1B related Reactome pathways (count: 0)

TNFRSF1B related interactors from protein-protein interaction data in HPRD (count: 14)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
TNFRSF1B	TNF	Yes	in vitro;in vivo	7664431 , 2158863 , 19084540
TNFRSF1B	KRT18	No	in vitro	10747083
TNFRSF1B	BMX	No	in vitro	12370298
TNFRSF1B	HIVEP3	No	in vivo	11804591
TNFRSF1B	STAT1	No	in vitro;in vivo	10848577
TNFRSF1B	CAV1	No	in vivo	11112773
TNFRSF1B	LTA	Yes	in vivo	9552007 , 8123048 , 2160731
TNFRSF1B	TTRAP	No	in vivo;yeast 2-hybrid	10764746
TNFRSF1B	CSNK1A1	No	in vivo	7559483
TNFRSF1B	TRAIP	No	in vitro;in vivo;yeast 2-hybrid	9104814
TNFRSF1B	TRAF1	No	in vitro;in vivo;yeast 2-hybrid	8069916
TNFRSF1B	FANCD2	No	in vitro	14743216
TNFRSF1B	TRAF3	No	in vivo	7859281
TNFRSF1B	TRAF2	No	in vitro;in vivo;yeast 2-hybrid	8069916 , 9461607 , 8702708 , 7639698

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways