TNFAIP3
entrez
7128
canonical
uniprot
P21580
canonical
ensembl
ENSG00000118503
resolver
ensp
ENSP00000237289
resolver
ensp
ENSP00000393577
resolver
ensp
ENSP00000401562
resolver
ensp
ENSP00000409845
resolver
ensp
ENSP00000481570
resolver
ensp
ENSP00000576296
resolver
ensp
ENSP00000576297
resolver
ensp
ENSP00000576298
resolver
ensp
ENSP00000576299
resolver
ensp
ENSP00000576300
resolver
ensp
ENSP00000576301
resolver
ensp
ENSP00000641952
resolver
ensp
ENSP00000641953
resolver
enst
ENST00000237289
resolver
enst
ENST00000420009
resolver
enst
ENST00000421450
resolver
enst
ENST00000433680
resolver
enst
ENST00000612899
resolver
enst
ENST00000906237
resolver
enst
ENST00000906238
resolver
enst
ENST00000906239
resolver
enst
ENST00000906240
resolver
enst
ENST00000906241
resolver
enst
ENST00000906242
resolver
enst
ENST00000971893
resolver
enst
ENST00000971894
resolver
genesymbol
TNFAIP3
resolver
genesymbol_syn
OTUD7C
resolver
hgnc
HGNC:11896
resolver
uniprot
B2R767
resolver
uniprot
E1P588
resolver
uniprot
Q2HIX9
resolver
uniprot
Q5VXQ7
resolver
uniprot
Q9NSR6
resolver
uniprot_entry
TNAP3_HUMAN
resolver
uniprot_sec
B2R767
resolver
uniprot_sec
E1P588
resolver
uniprot_sec
Q2HIX9
resolver
uniprot_sec
Q5VXQ7
resolver
uniprot_sec
Q9NSR6
resolver
amino_acid_sequence
MAEQVLPQALYLSNMRKAVKIRERTPEDIFKPTNGIIHHFKTMHRYTLEMFRTCQFCPQFREIIHKALIDRNIQATLESQKKLNWCREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDLVLRKALFSTLKETDTRNFKFRWQLESLKSQEFVETGLCYDTRNWNDEWDNLIKMASTDTPMARSGLQYNSLEEIHIFVLCNILRRPIIVISDKMLRSLESGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLVTLKDSGPEIRAVPLVNRDRGRFEDLKVHFLTDPENEMKEKLLKEYLMVIEIPVQGWDHGTTHLINAAKLDEANLPKEINLVDDYFELVQHEYKKWQENSEQGRREGHAQNPMEPSVPQLSLMDVKCETPNCPFFMSVNTQPLCHECSERRQKNQNKLPKLNSKPGPEGLPGMALGASRGEAYEPLAWNPEESTGGPHSAPPTAPSPFLFSETTAMKCRSPGCPFTLNVQHNGFCERCHNARQLHASHAPDHTRHLDPGKCQACLQDVTRTFNGICSTCFKRTTAEASSSLSTSLPPSCHQRSKSDPSRLVRSPSPHSCHRAGNDAPAGCLSQAARTPGDRTGTSKCRKAGCVYFGTPENKGFCTLCFIEYRENKHFAAASGKVSPTASRFQNTIPCLGRECGTLGSTMFEGYCQKCFIEAQNQRFHEAKRTEEQLRSSQRRDVPRTTQSTSRPKCARASCKNILACRSEELCMECQHPNQRMGPGAHRGEPAPEDPPKQRCRAPACDHFGNAKCNGYCNECFQFKQMYG
uniprot
proteins
disease_involvement
DISEASE: Autoinflammatory syndrome, familial, Behcet-like 1 (AIFBL1) [MIM:616744]: An autosomal dominant, autoinflammatory disorder with early onset, characterized by ulceration of mucosal surfaces, particularly in the oral and genital areas. Additional variable features include skin rash, uveitis, and polyarthritis. {ECO:0000269|PubMed:26642243, ECO:0000269|PubMed:27175295}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
2.3.2.-
uniprot
proteins
ec_number
3.4.19.12
uniprot
proteins
function
FUNCTION: Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of pro-inflammatory cytokines and IFN beta in LPS-tolerized macrophages. {ECO:0000269|PubMed:14748687, ECO:0000269|PubMed:15258597, ECO:0000269|PubMed:16684768, ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:18164316, ECO:0000269|PubMed:18952128, ECO:0000269|PubMed:19494296, ECO:0000269|PubMed:22099304, ECO:0000269|PubMed:23827681, ECO:0000269|PubMed:8692885, ECO:0000269|PubMed:9299557, ECO:0000269|PubMed:9882303}.
uniprot
proteins
mass_dalton
89614
uniprot
proteins
mutagenesis
MUTAGEN 70; /note="D->A: Minor effect on 'Lys-48' deubiquitinase activity. Strongly reduced 'Lys-63' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:18164316"; MUTAGEN 97; /note="T->A: Minor effect on 'Lys-48' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 100; /note="D->A: Strongly reduced deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 103; /note="C->A: Loss of deubiquitinase activity."; /evidence="ECO:0000269|PubMed:14748687, ECO:0000269|PubMed:15258597, ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:18164316"; MUTAGEN 103; /note="C->S: Loss of 'Lys-63' deubiquitinating activity. Down-regulation of TNF-induced NF-kappa-B activity less effective."; /evidence="ECO:0000269|PubMed:14748687, ECO:0000269|PubMed:15258597, ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:18164316"; MUTAGEN 106; /note="H->A: Reduces deubiquitinase activity."; /evidence="ECO:0000269|PubMed:27732584"; MUTAGEN 157; /note="L->A: Strongly reduced 'Lys-48' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 159; /note="Y->A: Strongly reduced 'Lys-48' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 190; /note="S->A: Strongly reduced 'Lys-48' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 192; /note="E->A: Strongly reduced 'Lys-48' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 224; /note="F->A: Strongly reduced 'Lys-48' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 227; /note="L->A: Strongly reduced 'Lys-48' deubiquitinase activity."; /evidence="ECO:0000269|PubMed:18164316"; MUTAGEN 256; /note="H->A: Loss of deubiquitinase activity."; /evidence="ECO:0000269|PubMed:17961127, ECO:0000269|PubMed:27732584"; MUTAGEN 521; /note="C->A: No effect on ubiquitin ligase activity; when associated with A-524."; /evidence="ECO:0000269|PubMed:15258597"; MUTAGEN 524; /note="C->A: No effect on ubiquitin ligase activity; when associated with A-521."; /evidence="ECO:0000269|PubMed:15258597"; MUTAGEN 562; /note="R->A: Abolishes interactionj with YWHAZ and YWHAH; no effect on inhibitory activity of TNF-induced NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:9299557"; MUTAGEN 565; /note="S->A: Abolishes interactionj with YWHAZ and YWHAH; no effect on inhibitory activity of TNF-induced NF-kappa-B activation."; /evidence="ECO:0000269|PubMed:9299557"; MUTAGEN 614; /note="Y->A: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-615 or R-626."; /evidence="ECO:0000269|PubMed:21095585"; MUTAGEN 615; /note="F->A: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-614."; /evidence="ECO:0000269|PubMed:21095585"; MUTAGEN 624; /note="C->A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-627."; /evidence="ECO:0000269|PubMed:15258597"; MUTAGEN 626; /note="L->R: Impairs ubiquitination activity. Loss of down-regulation of NF-kappa-B activity; when associated with A-614."; /evidence="ECO:0000269|PubMed:21095585"; MUTAGEN 627; /note="C->A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation; when associated with A-624."; /evidence="ECO:0000269|PubMed:15258597"; MUTAGEN 770..771; /note="FG->AA: Impairs polyubiquitin binding, abolishes inhibition of IKK activation."; /evidence="ECO:0000269|PubMed:22099304"; MUTAGEN 779; /note="C->A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-782."; /evidence="ECO:0000269|PubMed:22099304"; MUTAGEN 782; /note="C->A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation; when associated with A-779."; /evidence="ECO:0000269|PubMed:22099304
uniprot
proteins
post_translational_modification
PTM: Proteolytically cleaved by MALT1 upon TCR stimulation; disrupts NF-kappa-B inhibitory function and results in increased IL-2 production. It is proposed that only a fraction of TNFAIP3 colocalized with TCR and CBM complex is cleaved, leaving the main TNFAIP3 pool intact. {ECO:0000269|PubMed:18223652, ECO:0000269|PubMed:20804738}.
uniprot
proteins
protein_family
Peptidase C64 family
uniprot
proteins
pubmed
10435631
uniprot
proteins
pubmed
11463333
uniprot
proteins
pubmed
14574404
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
14748687
uniprot
proteins
pubmed
15258597
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16684768
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17961127
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
18164316
uniprot
proteins
pubmed
18223652
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18952128
uniprot
proteins
pubmed
19131965
uniprot
proteins
pubmed
19494296
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20804738
uniprot
proteins
pubmed
21095585
uniprot
proteins
pubmed
2118515
uniprot
proteins
pubmed
22099304
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23827681
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
26642243
uniprot
proteins
pubmed
27175295
uniprot
proteins
pubmed
27732584
uniprot
proteins
pubmed
8692885
uniprot
proteins
pubmed
9299557
uniprot
proteins
pubmed
9882303
uniprot
proteins
sequence_length
790
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Lysosome.; SUBCELLULAR LOCATION: [A20p50]: Cytoplasm.
uniprot
proteins