Gene Report

Basic Information

Approved Symbol	TNFAIP3
Approved Name	tumor necrosis factor, alpha-induced protein 3
Symbol Alias	A20, OTUD7C
Location	6q23-q25
Position	chr6:138202457-138204449 (+)
External Links	Entrez Gene: 7128 Ensembl: ENSG00000118503 UCSC: uc031spw.1 HGNC ID: 11896
No. of Studies (Positive/Negative)	1(1/0)
Type	Literature-origin

Positive relationships between TNFAIP3 and MDD (count: 1)

Name in Literature	Reference	Research Type	Statistical Result	Relation Description
TNFAIP3	Carvalho LA, 2014	patients and normal controls	FC=2.7; P-value=0.001	Thirty-four of the 47 monocyte inflammatory-related genes w...... Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls More...

Positive relationships between TNFAIP3 and other components at different levels (count: 0)

Positive relationship network of TNFAIP3 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 TNFAIP3 and MDD (count: 0)

Negative relationships between TNFAIP3 and other components at different levels (count: 0)

TNFAIP3 related SNPs in MK4MDD (count: 0)

TNFAIP3 related proteins in MK4MDD (count: 0)

TNFAIP3 related GO terms (count: 73)

ID	Name	Type	Evidence
Literature-origin GO terms
GO:0006954	inflammatory response	biological process	IEA
GO:0006915	apoptotic process	biological process	IEA

ID	Name	Type	Evidence
Gene mapped GO terms
GO:0070530	K63-linked polyubiquitin binding	molecular function	IBA
GO:0003677	DNA binding	molecular function	IEA
GO:0043130	ubiquitin binding	molecular function	IPI[19285159]
GO:0002237	response to molecule of bacterial origin	biological process	IDA[19912257]
GO:0005764	lysosome	cellular component	IEA
GO:0043124	negative regulation of I-kappaB kinase/NF-kappaB signaling	biological process	IDA[11463333\|15258597\|21127049]
GO:0034148	negative regulation of toll-like receptor 5 signaling pathway	biological process	IEA
GO:0008270	zinc ion binding	molecular function	IEA
GO:2000347	positive regulation of hepatocyte proliferation	biological process	IEA
GO:0005634	nucleus	cellular component	IDA[11463333]
GO:0048662	negative regulation of smooth muscle cell proliferation	biological process	IDA[16816117]
GO:0010803	regulation of tumor necrosis factor-mediated signaling pathway	biological process	TAS
GO:0019900	kinase binding	molecular function	IEA
GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors	biological process	IDA[12167698]
GO:0001922	B-1 B cell homeostasis	biological process	ISS
GO:0050728	negative regulation of inflammatory response	biological process	ISS
GO:0006955	immune response	biological process	IBA
GO:0090291	negative regulation of osteoclast proliferation	biological process	NAS[21127049]
GO:0032480	negative regulation of type I interferon production	biological process	TAS
GO:0072573	tolerance induction to lipopolysaccharide	biological process	IMP[21220427]
GO:0070536	protein K63-linked deubiquitination	biological process	IDA[15258597]
GO:0032088	negative regulation of NF-kappaB transcription factor activity	biological process	IDA[18223652]
GO:0034140	negative regulation of toll-like receptor 3 signaling pathway	biological process	IDA[15474016]
GO:0045779	negative regulation of bone resorption	biological process	NAS[21127049]
GO:1903364	positive regulation of cellular protein catabolic process	biological process	IEA
GO:0005737	cytoplasm	cellular component	IBA
GO:0032703	negative regulation of interleukin-2 production	biological process	IMP[18223652]
GO:2000352	negative regulation of endothelial cell apoptotic process	biological process	IDA[12885753]
GO:0032495	response to muramyl dipeptide	biological process	IEA
GO:2000349	negative regulation of CD40 signaling pathway	biological process	IMP[12885753]
GO:0061043	regulation of vascular wound healing	biological process	NAS[16816117]
GO:0071947	protein deubiquitination involved in ubiquitin-dependent protein catabolic process	biological process	IBA
GO:0045732	positive regulation of protein catabolic process	biological process	IDA[21127049]
GO:0070423	nucleotide-binding oligomerization domain containing signaling pathway	biological process	TAS
GO:0005829	cytosol	cellular component	TAS
GO:0034144	negative regulation of toll-like receptor 4 signaling pathway	biological process	NAS[15142865]
GO:0071222	cellular response to lipopolysaccharide	biological process	IDA[19912257\|21127049\|21220427]
GO:0002634	regulation of germinal center formation	biological process	ISS
GO:0070062	extracellular exosome	cellular component	IDA[20458337]
GO:0005515	protein binding	molecular function	IPI[9299557\|11463333\|15142865\|15231748\|15474016\|19131965\|20392859\|21988832\|23032186\|25416956]
GO:0043621	protein self-association	molecular function	IDA[8797804\|15474016]
GO:0002020	protease binding	molecular function	IPI[18223652]
GO:0035871	protein K11-linked deubiquitination	biological process	IDA[23827681]
GO:0045087	innate immune response	biological process	TAS
GO:0070301	cellular response to hydrogen peroxide	biological process	ISS
GO:0045736	negative regulation of cyclin-dependent protein serine/threonine kinase activity	biological process	IEA
GO:0045824	negative regulation of innate immune response	biological process	ISS
GO:0016579	protein deubiquitination	biological process	TAS[20392859]
GO:0050691	regulation of defense response to virus by host	biological process	NAS[15142865]
GO:0032715	negative regulation of interleukin-6 production	biological process	ISS
GO:0016874	ligase activity	molecular function	IEA
GO:0070433	negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	biological process	IEA
GO:0004842	ubiquitin-protein transferase activity	molecular function	IDA[15258597]
GO:0032691	negative regulation of interleukin-1 beta production	biological process	IEA
GO:0051259	protein oligomerization	biological process	NAS[15474016]
GO:0031397	negative regulation of protein ubiquitination	biological process	IDA[20392859]
GO:0007166	cell surface receptor signaling pathway	biological process	TAS
GO:0071108	protein K48-linked deubiquitination	biological process	IDA[23827681]
GO:0070936	protein K48-linked ubiquitination	biological process	IDA[15258597]
GO:0050727	regulation of inflammatory response	biological process	IBA
GO:0008234	cysteine-type peptidase activity	molecular function	IEA
GO:0070429	negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway	biological process	IEA
GO:0035872	nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway	biological process	TAS
GO:0004843	thiol-dependent ubiquitin-specific protease activity	molecular function	IDA[15258597\|23827681]; TAS[20392859]
GO:0002677	negative regulation of chronic inflammatory response	biological process	IEA
GO:0034136	negative regulation of toll-like receptor 2 signaling pathway	biological process	NAS[15142865]
GO:0072666	establishment of protein localization to vacuole	biological process	IEA
GO:0033209	tumor necrosis factor-mediated signaling pathway	biological process	TAS
GO:0050869	negative regulation of B cell activation	biological process	ISS
GO:0032720	negative regulation of tumor necrosis factor production	biological process	ISS
GO:0045088	regulation of innate immune response	biological process	IBA

TNFAIP3 related KEGG pathways (count: 1)

ID	Name	Brief Description	Full Description
Gene mapped KEGG pathways
hsa04621	nod like_receptor_signaling_pathway	NOD-like receptor signaling pathway	Specific families of pattern recognition receptors are respo...... Specific families of pattern recognition receptors are responsible for detecting various pathogens and generating innate immune responses. The intracellular NOD-like receptor (NLR) family contains more than 20 members in mammals and plays a pivotal role in the recognition of intracellular ligands. NOD1 and NOD2, two prototypic NLRs, sense the cytosolic presence of the bacterial peptidoglycan fragments that escaped from endosomal compartments, driving the activation of NF-{kappa}B and MAPK, cytokine production and apoptosis. On the other hand, a different set of NLRs induces caspase-1 activation through the assembly of multiprotein complexes called inflammasomes. These NLRs include NALP1, NALP3 and Ipaf. The inflammasomes are critical for generating mature proinflammatory cytokines in concert with Toll-like receptor signaling pathway. More...

TNFAIP3 related BioCarta pathways (count: 3)

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...
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...
CD40_PATHWAY	cd40 pathway	CD40L Signaling Pathway	The CD40 receptor was first associated with expression in B ...... The CD40 receptor was first associated with expression in B cells and the role it plays through its ligand CD40L (CD154) in moderating T cell activation. Broader expression may indicate a broader role for CD40 and CD40L in immune function and disease states such as transplant rejection and HIV infection. Disruption of CD40 interaction with CD40L may prove therapeutic in the treatment of autoimmune disorders or heart disease and modulation of the interaction may in the future be exploited in cancer treatment. As a member of the TNF receptor family, CD40 relies on interaction with TRAF proteins to mediate an intracellular signal in response to CD40L binding. The pathway downstream of TRAFs activates the transcription factor NF-kappaB through a kinase pathway involving map kinases, NIK (NF-kappaB inducing kinase) and I-kappa B kinases. Some CD40 responses like regulation of immunoglobulin expression might be mediated by NF-kappaB transcriptional activation. More...

TNFAIP3 related Reactome pathways (count: 0)

TNFAIP3 related interactors from protein-protein interaction data in HPRD (count: 21)

Gene	Interactor	Interactor in MK4MDD?	Experiment Type	PMID
TNFAIP3	CHUK	No	in vitro;in vivo	11594795
TNFAIP3	IKBKB	No	in vitro;in vivo	11594795
TNFAIP3	TAX1BP1	No	in vivo;yeast 2-hybrid	10435631 , 11389905
TNFAIP3	TICAM1	No	in vivo	15474016
TNFAIP3	YWHAB	No	in vitro;in vivo;yeast 2-hybrid	8702721
TNFAIP3	TRAF2	No	in vivo;yeast 2-hybrid	8692885
TNFAIP3	LAPTM5	No	yeast 2-hybrid	15231748
TNFAIP3	TNFAIP3	Yes	in vitro;in vivo;yeast 2-hybrid	8692885 , 11389905 , 8797804
TNFAIP3	CCDC50	No	in vitro	18029035
TNFAIP3	YWHAH	No	in vitro;in vivo;yeast 2-hybrid	8702721 , 9299557
TNFAIP3	TNIP1	No	in vivo;yeast 2-hybrid	10385526 , 12965196
TNFAIP3	ZFAND5	No	in vivo	14754897
TNFAIP3	YWHAG	No	in vivo;yeast 2-hybrid	8702721
TNFAIP3	TRAF6	No	in vivo	9928991
TNFAIP3	YWHAE	Yes	in vivo	8702721
TNFAIP3	YWHAZ	No	yeast 2-hybrid	9299557
TNFAIP3	RNF11	No	in vivo;yeast 2-hybrid	15231748 , 19131965
TNFAIP3	TNIP2	No	in vivo;yeast 2-hybrid	11390377 , 10385526 , 11389905
TNFAIP3	RIPK1	No	in vitro;in vivo	15258597
TNFAIP3	IKBKG	No	in vitro;in vivo;yeast 2-hybrid	10755617 , 11389905
TNFAIP3	TRAF1	No	in vivo;yeast 2-hybrid	8692885

Gene Report

Literature-origin GO terms

Gene mapped GO terms

Gene mapped KEGG pathways

Gene mapped BioCarta pathways