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FLASH GENE

Symbol

TNFAIP3

contributors: mct - updated : 13-06-2017

HGNC name	tumor necrosis factor, alpha-induced protein 3
HGNC id	11896

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	6q23.3      Physical location : 138.188.580 - 138.204.445
Synonym name	tumor necrosis factor inducible protein A20
	putative DNA-binding protein A20
	zinc finger protein A20
Synonym symbol(s)	A20, TNFA1P2, MGC138687, MGC138688, OTUD7C, MGC104522
EC.number	3.-.-.-

DNA

TYPE	functioning gene
STRUCTURE	15.87 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

provisional

Map	cen - D6S472 - D6S1722 - D6S292 - PEX7 - TNFAIP3 - D6S1684 - D6S453 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006290 9 - 4446 NP_006281 89.5 790 - 1996 8663499

EXPRESSION

Type	ubiquitous

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 Cardiovascular heart         Digestive liver         Lymphoid/Immune lymph node       highly Nervous brain         Reproductive male system prostate       Respiratory respiratory tract larynx     highly   respiratory tract trachea     highly Urinary kidney       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / Hematopoietic bone marrow       Lymphoid         Muscular striatum skeletal

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	zinc finger protein containing multiple Cys2/Cys2 finger motifs
	one OTU domain

mono polymer

homomer , dimer

HOMOLOGY

interspecies	ortholog to murine Tnfaip3
	homolog to C.elegans F21C3.2

Homologene

FAMILY

peptidase C64 family

CATEGORY

structural protein

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,organelle,lysosome
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus
text	a fraction of endogenous and ectopically expressed TNFAIP3 is localized to an endocytic membrane compartment that is in association with the lysosome

basic FUNCTION	inhibiting NF-kappa B activation as well as TNF-mediated apoptosis
	critical for limiting inflammation by terminating TNF-induced NF-kappa B responses
	may be involvement of a lysosome-associated mechanism in TNFAIP3-dependent termination of NFkappaB signaling
	playing a role in the function of the lymphoid system
	contribute to the in vivo effects of TNF
	inhibitor of NF-kB signaling that may play an important role in lymphomagenesis
	having a function in the regulation of CARD10 and BCL10 activity in lymphoid and non-lymphoid cells
	ubiquitin modifying enzyme that restricts NF-kappaB signals and protects cells against tumor necrosis factor (TNF)-induced programmed cell death
	plays a key role in the negative regulation of inflammation and immunity
	negatively regulates NFkappaB (nuclear factor kappaB) signaling induced by TNF receptor family and Toll-like receptors
	negatively regulates TRAF3-stimulated IRF7 ubiquitination and activity in Epstein-Barr virus latency, and its deubiquitinase activity is indispensable for this function
	tightly regulates NFKB signaling by acting as an Ub editor
	involved in the negative feedback regulation of NFKB signaling in response to specific proinflammatory stimuli in different cell types
	TNIP1 cooperates with TAX1BP1 and TNFAIP3 to restrict antiviral signaling
	plays a critical role in the termination of NFKB signaling after activation

CELLULAR PROCESS	cell life, antiapoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

binding

RNA

small molecule	metal binding,
	Zn2+

protein	binding to NAF1, TRAF1 and TRAF2
	binding to TAX1BP1 (functioning as a negative regulator of ubiquitination of key signaling molecules that are also targeted by TNFAIP3)
	TAX1BP1 is a key regulator of TNFAIP3 function in terminating signaling to IRF3
	TNIP1 requires its ubiquitin binding domain and cooperates with TAX1BP1 and TNFAIP3 to restrict antiviral signaling
	RNF11 and TNFAIP3 interact in a microglial cell line, suggesting the presence of TNFAIP3 ubiquitin-editing protein complex in microglial cells
	ASH1L suppresses interleukin-6 production and inflammatory autoimmune diseases by inducing the ubiquitin-editing enzyme TNFAIP3
	inhibits non-canonical TGFB1 signalling by recruiting the deubiquitinase TNFAIP3 to TRAF6
	KCNIP3 bound to the promoter of the gene encoding TNFAIP3 to repress expression of this deubiquitinase that suppresses inflammatory NFKB1 signaling
	ESRRA regulated macrophage inflammatory responses by directly binding the promoter region of TNFAIP3, a deubiquitinating enzyme in TLR signaling
	TNFAIP3 is a key endogenous suppressor of MAP3K5 activation, and TNFAIP3 directly interacts with and deubiquitinates MAP3K5 in hepatocytes

cell & other

REGULATION

induced by

the tumor necrosis factor (TNF) rapidly

repressed by

PML

Other

different mechanisms of regulation, including phosphorylation, proteolytic processing, and association with ubiquitin binding proteins

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   deletion     in ocular adnexal marginal zone B cell lymphoma constitutional     --low   reduced expression predisposes to autoimmunity

Susceptibility

to systemic lupus erythematosus (SLE) or rheumatoid arthritis

Variant & Polymorphism other	polymorphisms increasing the risk of systemic lupus erythematosus or rheumatoid arthritis
	association of rs2230926 G allele with SLE

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

Knockout A20 mice