TNAP3_MOUSE
ID TNAP3_MOUSE Reviewed; 775 AA.
AC Q60769; Q3U968;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Tumor necrosis factor alpha-induced protein 3;
DE Short=TNF alpha-induced protein 3;
DE EC=2.3.2.-;
DE EC=3.4.19.12;
DE AltName: Full=Putative DNA-binding protein A20;
DE AltName: Full=Zinc finger protein A20;
GN Name=Tnfaip3; Synonyms=Tnfip3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=7836754;
RA Tewari M., Wolf F.W., Seldin M.F., O'Shea K.S., Dixit V.M., Turka L.A.;
RT "Lymphoid expression and regulation of A20, an inhibitor of programmed cell
RT death.";
RL J. Immunol. 154:1699-1706(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=10385526; DOI=10.1083/jcb.145.7.1471;
RA Heyninck K., De Valck D., Vanden Berghe W., Van Criekinge W., Contreras R.,
RA Fiers W., Haegeman G., Beyaert R.;
RT "The zinc finger protein A20 inhibits TNF-induced NF-B-dependent gene
RT expression by interfering with an RIP- or TRAF2-mediated transactivation
RT signal and directly binds to a novel NF-B-inhibiting protein ABIN.";
RL J. Cell Biol. 145:1471-1482(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP FUNCTION, AND INTERACTION WITH TNIP2; TAX1BP1; IKBKG AND TNIP1.
RX PubMed=11389905; DOI=10.1016/s0014-5793(01)02504-2;
RA Klinkenberg M., Van Huffel S., Heyninck K., Beyaert R.;
RT "Functional redundancy of the zinc fingers of A20 for inhibition of NF-
RT kappaB activation and protein-protein interactions.";
RL FEBS Lett. 498:93-97(2001).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF ASP-100 AND CYS-103.
RX PubMed=15334086; DOI=10.1038/ni1110;
RA Boone D.L., Turer E.E., Lee E.G., Ahmad R.C., Wheeler M.T., Tsui C.,
RA Hurley P., Chien M., Chai S., Hitotsumatsu O., McNally E., Pickart C.,
RA Ma A.;
RT "The ubiquitin-modifying enzyme A20 is required for termination of Toll-
RT like receptor responses.";
RL Nat. Immunol. 5:1052-1060(2004).
RN [6]
RP ERRATUM OF PUBMED:15334086.
RA Boone D.L., Turer E.E., Lee E.G., Ahmad R.C., Wheeler M.T., Tsui C.,
RA Hurley P., Chien M., Chai S., Hitotsumatsu O., McNally E., Pickart C.,
RA Ma A.;
RL Nat. Immunol. 6:114-114(2005).
RN [7]
RP FUNCTION.
RX PubMed=18342009; DOI=10.1016/j.immuni.2008.02.002;
RA Hitotsumatsu O., Ahmad R.C., Tavares R., Wang M., Philpott D., Turer E.E.,
RA Lee B.L., Shiffin N., Advincula R., Malynn B.A., Werts C., Ma A.;
RT "The ubiquitin-editing enzyme A20 restricts nucleotide-binding
RT oligomerization domain containing 2-triggered signals.";
RL Immunity 28:381-390(2008).
RN [8]
RP INTERACTION WITH TAX1BP1; RNF11 AND RIPK1.
RX PubMed=19131965; DOI=10.1038/emboj.2008.285;
RA Shembade N., Parvatiyar K., Harhaj N.S., Harhaj E.W.;
RT "The ubiquitin-editing enzyme A20 requires RNF11 to downregulate NF-kappaB
RT signalling.";
RL EMBO J. 28:513-522(2009).
RN [9]
RP FUNCTION, INTERACTION WITH UBE2N, AND MUTAGENESIS OF CYS-103.
RX PubMed=20185725; DOI=10.1126/science.1182364;
RA Shembade N., Ma A., Harhaj E.W.;
RT "Inhibition of NF-kappaB signaling by A20 through disruption of ubiquitin
RT enzyme complexes.";
RL Science 327:1135-1139(2010).
RN [10]
RP FUNCTION, AND INDUCTION.
RX PubMed=23609450; DOI=10.1074/jbc.m113.454538;
RA Li Y., Zhang P., Wang C., Han C., Meng J., Liu X., Xu S., Li N., Wang Q.,
RA Shi X., Cao X.;
RT "Immune responsive gene 1 (IRG1) promotes endotoxin tolerance by increasing
RT A20 expression in macrophages through ROS.";
RL J. Biol. Chem. 288:16225-16234(2013).
CC -!- FUNCTION: Ubiquitin-editing enzyme that contains both ubiquitin ligase
CC and deubiquitinase activities. Involved in immune and inflammatory
CC responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or
CC pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B
CC activity. Essential component of a ubiquitin-editing protein complex,
CC comprising also RNF11, ITCH and TAX1BP1, that ensures the transient
CC nature of inflammatory signaling pathways. In cooperation with TAX1BP1
CC promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-
CC 1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2
CC and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In
CC cooperation with TAX1BP1 promotes ubiquitination of UBE2N and
CC proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation,
CC deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes
CC the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1
CC proteasomal degradation and consequently termination of the TNF- or
CC LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably
CC acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-
CC mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin
CC chains on MALT1 thereby mediating disassociation of the CBM
CC (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK
CC activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by
CC TNIP1 and leads to inhibition of NF-kappa-B activation. Upon
CC stimulation by bacterial peptidoglycans, probably deubiquitinates
CC RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic
CC mechanism which involves polyubiquitin; polyubiquitin promotes
CC association with IKBKG and prevents IKK MAP3K7-mediated
CC phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able
CC to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin
CC chains. Inhibitor of programmed cell death. Has a role in the function
CC of the lymphoid system. Required for LPS-induced production of pro-
CC inflammatory cytokines and IFN beta in LPS-tolerized macrophages.
CC {ECO:0000269|PubMed:10385526, ECO:0000269|PubMed:11389905,
CC ECO:0000269|PubMed:15334086, ECO:0000269|PubMed:18342009,
CC ECO:0000269|PubMed:20185725, ECO:0000269|PubMed:23609450}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide
CC and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-
CC residue protein attached to proteins as an intracellular targeting
CC signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:15334086};
CC -!- SUBUNIT: Homodimer. Interacts with TNIP1, TAX1BP1 and TRAF2. Interacts
CC with RNF11, ITCH and TAX1BP1 only after TNF stimulation; these
CC interaction are transient and they are lost after 1 hour of stimulation
CC with TNF (By similarity). Interacts with YWHAZ and YWHAH. Interacts
CC with IKBKG; the interaction is induced by TNF stimulation and by
CC polyubiquitin. Interacts with RIPK1. Interacts with UBE2N; the
CC interaction requires TAX1BP1. Interacts with TRAF6 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC Q60769; Q9CYZ8: Ssbp2; NbExp=2; IntAct=EBI-646595, EBI-309962;
CC Q60769; Q9WUU8: Tnip1; NbExp=4; IntAct=EBI-646595, EBI-6126152;
CC Q60769; P39429: Traf2; NbExp=3; IntAct=EBI-646595, EBI-520016;
CC Q60769; P01375: TNF; Xeno; NbExp=2; IntAct=EBI-646595, EBI-359977;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Lysosome {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Found in most tissues during development.
CC Strikingly high levels are found in lymphoid organs, including the
CC thymus, spleen, and gut-associated lymphoid tissue. Constitutively
CC expressed in immature and mature thymocyte subpopulations as well as in
CC resting peripheral T-cells; activation of these leads to down-
CC regulation.
CC -!- INDUCTION: By cytokines. TNF-alpha may regulate expression in the
CC thymus. Up-regulated in presence of reactive oxygen species (ROS), like
CC H(2)O(2), in LPS-tolerized macrophages. {ECO:0000269|PubMed:23609450}.
CC -!- DOMAIN: The A20-type zinc fingers mediate the ubiquitin ligase
CC activity. The A20-type zinc finger 4 selectively recognizes 'Lys-63'-
CC linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to
CC bind polyubiquitin (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The OTU domain mediates the deubiquitinase activity.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the peptidase C64 family. {ECO:0000305}.
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DR EMBL; U19463; AAC52153.1; -; mRNA.
DR EMBL; AK151921; BAE30799.1; -; mRNA.
DR CCDS; CCDS23715.1; -.
DR PIR; I49237; I49237.
DR RefSeq; NP_033423.3; NM_009397.3.
DR RefSeq; XP_006512765.1; XM_006512702.2.
DR PDB; 5DQ6; X-ray; 2.80 A; A/B=1-360.
DR PDBsum; 5DQ6; -.
DR AlphaFoldDB; Q60769; -.
DR SMR; Q60769; -.
DR BioGRID; 204243; 27.
DR DIP; DIP-41120N; -.
DR IntAct; Q60769; 11.
DR MINT; Q60769; -.
DR STRING; 10090.ENSMUSP00000019997; -.
DR iPTMnet; Q60769; -.
DR PhosphoSitePlus; Q60769; -.
DR EPD; Q60769; -.
DR MaxQB; Q60769; -.
DR PaxDb; Q60769; -.
DR PRIDE; Q60769; -.
DR ProteomicsDB; 259139; -.
DR Antibodypedia; 1049; 513 antibodies from 45 providers.
DR DNASU; 21929; -.
DR Ensembl; ENSMUST00000019997; ENSMUSP00000019997; ENSMUSG00000019850.
DR Ensembl; ENSMUST00000105527; ENSMUSP00000101167; ENSMUSG00000019850.
DR GeneID; 21929; -.
DR KEGG; mmu:21929; -.
DR UCSC; uc007ena.3; mouse.
DR CTD; 7128; -.
DR MGI; MGI:1196377; Tnfaip3.
DR VEuPathDB; HostDB:ENSMUSG00000019850; -.
DR eggNOG; KOG4345; Eukaryota.
DR GeneTree; ENSGT00940000158448; -.
DR HOGENOM; CLU_019606_0_0_1; -.
DR InParanoid; Q60769; -.
DR OMA; QFKQLYG; -.
DR PhylomeDB; Q60769; -.
DR TreeFam; TF323312; -.
DR Reactome; R-MMU-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-MMU-5357786; TNFR1-induced proapoptotic signaling.
DR Reactome; R-MMU-5357905; Regulation of TNFR1 signaling.
DR Reactome; R-MMU-5357956; TNFR1-induced NFkappaB signaling pathway.
DR Reactome; R-MMU-5689896; Ovarian tumor domain proteases.
DR Reactome; R-MMU-936440; Negative regulators of DDX58/IFIH1 signaling.
DR BioGRID-ORCS; 21929; 23 hits in 74 CRISPR screens.
DR ChiTaRS; Tnfaip3; mouse.
DR PRO; PR:Q60769; -.
DR Proteomes; UP000000589; Chromosome 10.
DR RNAct; Q60769; protein.
DR Bgee; ENSMUSG00000019850; Expressed in retinal neural layer and 148 other tissues.
DR ExpressionAtlas; Q60769; baseline and differential.
DR Genevisible; Q60769; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0004843; F:cysteine-type deubiquitinase activity; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0019900; F:kinase binding; IDA:BHF-UCL.
DR GO; GO:0061578; F:Lys63-specific deubiquitinase activity; ISO:MGI.
DR GO; GO:0002020; F:protease binding; ISO:MGI.
DR GO; GO:0008022; F:protein C-terminus binding; IDA:ARUK-UCL.
DR GO; GO:0043621; F:protein self-association; ISO:MGI.
DR GO; GO:0043130; F:ubiquitin binding; ISO:MGI.
DR GO; GO:0004842; F:ubiquitin-protein transferase activity; ISS:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0001922; P:B-1 B cell homeostasis; IMP:BHF-UCL.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; ISS:BHF-UCL.
DR GO; GO:0007010; P:cytoskeleton organization; IBA:GO_Central.
DR GO; GO:0072666; P:establishment of protein localization to vacuole; IDA:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0002315; P:marginal zone B cell differentiation; NAS:BHF-UCL.
DR GO; GO:0010507; P:negative regulation of autophagy; NAS:BHF-UCL.
DR GO; GO:0050869; P:negative regulation of B cell activation; IDA:BHF-UCL.
DR GO; GO:2000349; P:negative regulation of CD40 signaling pathway; ISS:BHF-UCL.
DR GO; GO:0060548; P:negative regulation of cell death; IMP:BHF-UCL.
DR GO; GO:0002677; P:negative regulation of chronic inflammatory response; IMP:BHF-UCL.
DR GO; GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISO:MGI.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR GO; GO:0002632; P:negative regulation of granuloma formation; NAS:BHF-UCL.
DR GO; GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; NAS:BHF-UCL.
DR GO; GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB signaling; IMP:BHF-UCL.
DR GO; GO:0050728; P:negative regulation of inflammatory response; IDA:UniProtKB.
DR GO; GO:0045824; P:negative regulation of innate immune response; IMP:UniProtKB.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:BHF-UCL.
DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISO:MGI.
DR GO; GO:0032715; P:negative regulation of interleukin-6 production; IMP:BHF-UCL.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISO:MGI.
DR GO; GO:0070429; P:negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway; IMP:BHF-UCL.
DR GO; GO:0070433; P:negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:BHF-UCL.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISO:MGI.
DR GO; GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISS:BHF-UCL.
DR GO; GO:0034140; P:negative regulation of toll-like receptor 3 signaling pathway; ISO:MGI.
DR GO; GO:0034148; P:negative regulation of toll-like receptor 5 signaling pathway; IDA:BHF-UCL.
DR GO; GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:BHF-UCL.
DR GO; GO:2000347; P:positive regulation of hepatocyte proliferation; IDA:BHF-UCL.
DR GO; GO:0045732; P:positive regulation of protein catabolic process; IDA:MGI.
DR GO; GO:0030177; P:positive regulation of Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0016579; P:protein deubiquitination; IDA:BHF-UCL.
DR GO; GO:0071947; P:protein deubiquitination involved in ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:0035871; P:protein K11-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0035523; P:protein K29-linked deubiquitination; IBA:GO_Central.
DR GO; GO:1990168; P:protein K33-linked deubiquitination; IBA:GO_Central.
DR GO; GO:0071108; P:protein K48-linked deubiquitination; ISS:UniProtKB.
DR GO; GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0070536; P:protein K63-linked deubiquitination; IDA:MGI.
DR GO; GO:0002634; P:regulation of germinal center formation; IMP:BHF-UCL.
DR GO; GO:0002637; P:regulation of immunoglobulin production; IC:BHF-UCL.
DR GO; GO:0045088; P:regulation of innate immune response; IC:BHF-UCL.
DR GO; GO:0002237; P:response to molecule of bacterial origin; IDA:BHF-UCL.
DR GO; GO:0032495; P:response to muramyl dipeptide; IMP:BHF-UCL.
DR GO; GO:0009611; P:response to wounding; NAS:BHF-UCL.
DR GO; GO:0072573; P:tolerance induction to lipopolysaccharide; ISO:MGI.
DR InterPro; IPR033478; A20.
DR InterPro; IPR003323; OTU_dom.
DR InterPro; IPR002653; Znf_A20.
DR PANTHER; PTHR13367:SF3; PTHR13367:SF3; 1.
DR Pfam; PF02338; OTU; 1.
DR Pfam; PF01754; zf-A20; 5.
DR SMART; SM00259; ZnF_A20; 7.
DR PROSITE; PS50802; OTU; 1.
DR PROSITE; PS51036; ZF_A20; 7.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Cytoplasm; DNA-binding; Hydrolase;
KW Inflammatory response; Lysosome; Metal-binding; Multifunctional enzyme;
KW Nucleus; Phosphoprotein; Protease; Reference proteome; Repeat;
KW Thiol protease; Transferase; Ubl conjugation pathway; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P21580"
FT CHAIN 2..775
FT /note="Tumor necrosis factor alpha-induced protein 3"
FT /id="PRO_0000188793"
FT DOMAIN 92..263
FT /note="OTU"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00139"
FT ZN_FING 381..416
FT /note="A20-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT ZN_FING 464..499
FT /note="A20-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT ZN_FING 500..533
FT /note="A20-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT ZN_FING 586..621
FT /note="A20-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT ZN_FING 636..671
FT /note="A20-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT ZN_FING 695..730
FT /note="A20-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT ZN_FING 741..775
FT /note="A20-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT REGION 58..300
FT /note="TRAF-binding"
FT /evidence="ECO:0000250"
FT REGION 157..159
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000250"
FT REGION 190..192
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000250"
FT REGION 224..227
FT /note="Interaction with ubiquitin"
FT /evidence="ECO:0000250"
FT REGION 369..775
FT /note="Interaction with TNIP1"
FT /evidence="ECO:0000269|PubMed:11389905"
FT REGION 386..445
FT /note="Interaction with RIPK1"
FT /evidence="ECO:0000250"
FT REGION 415..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 567..590
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 590..640
FT /note="Required for proteosomal degradation of UBE2N and
FT UBE2D3, TRAF6 deubiquitination, and TAX1BP1 interaction
FT with UBE2N"
FT /evidence="ECO:0000269|PubMed:20185725"
FT REGION 591..775
FT /note="Sufficient for inhibitory activity of TNF-induced
FT NF-kappa-B activity"
FT REGION 682..775
FT /note="Required for lysosomal localization and for TRAF2
FT lysosomal degradation"
FT /evidence="ECO:0000250"
FT ACT_SITE 100
FT /evidence="ECO:0000250"
FT ACT_SITE 103
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 256
FT /note="Proton acceptor"
FT /evidence="ECO:0000250"
FT BINDING 387
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 392
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 404
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 407
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 470
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 475
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 487
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 490
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 506
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 509
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 521
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 524
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 592
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 597
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 609
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 612
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 642
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 647
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 659
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 662
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 701
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 706
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 718
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 721
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 747
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 752
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 764
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT BINDING 767
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00451"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P21580"
FT MOD_RES 451
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P21580"
FT MUTAGEN 100
FT /note="D->A: Loss of deubiquitinating activity."
FT /evidence="ECO:0000269|PubMed:15334086"
FT MUTAGEN 103
FT /note="C->A: Loss of deubiquitinating activity, does not
FT disassemble TRAF6:UBE2N ubiquitin ligase complex,
FT abolioshes TAX1BP1 interaction with UBE2N."
FT /evidence="ECO:0000269|PubMed:15334086,
FT ECO:0000269|PubMed:20185725"
FT CONFLICT 627
FT /note="E -> A (in Ref. 1; AAC52153)"
FT /evidence="ECO:0000305"
FT TURN 10..14
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 15..24
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 26..28
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 39..42
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 43..45
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 58..68
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 71..78
FT /evidence="ECO:0007829|PDB:5DQ6"
FT TURN 79..81
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 93..95
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 103..113
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 121..132
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 136..145
FT /evidence="ECO:0007829|PDB:5DQ6"
FT TURN 146..150
FT /evidence="ECO:0007829|PDB:5DQ6"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 167..174
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 183..185
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 193..203
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 207..209
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 231..233
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 248..255
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 257..261
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 272..279
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 282..285
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 293..297
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 299..302
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 305..307
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 322..325
FT /evidence="ECO:0007829|PDB:5DQ6"
FT STRAND 327..329
FT /evidence="ECO:0007829|PDB:5DQ6"
FT TURN 337..339
FT /evidence="ECO:0007829|PDB:5DQ6"
FT HELIX 342..356
FT /evidence="ECO:0007829|PDB:5DQ6"
SQ SEQUENCE 775 AA; 87654 MW; 32349928908B3185 CRC64;
MAEQLLPQAL YLSNMRKAVK IRERTPEDIF KPTNGIIYHF KTMHRYTLEM FRTCQFCPQF
REIIHKALID RSVQASLESQ KKLNWCREVR KLVALKTNGD GNCLMHAACQ YMWGVQDTDL
VLRKALCSTL KETDTRNFKF RWQLESLKSQ EFVETGLCYD TRNWNDEWDN LVKMASADTP
AARSGLQYNS LEEIHIFVLS NILRRPIIVI SDKMLRSLES GSNFAPLKVG GIYLPLHWPA
QECYRYPIVL GYDSQHFVPL VTLKDSGPEL RAVPLVNRDR GRFEDLKVHF LTDPENEMKE
KLLKEYLIVM EIPVQGWDHG TTHLINAAKL DEANLPKEIN LVDDYFELVQ HEYKKWQENS
DQARRAAHAQ NPLEPSTPQL SLMDIKCETP NCPFFMSVNT QPLCHECSER RQKNQSKLPK
LNSKLGPEGL PGVGLGSSNW SPEETAGGPH SAPPTAPSLF LFSETTAMKC RSPGCPFTLN
VQHNGFCERC HARQINASHT ADPGKCQACL QDVTRTFNGI CSTCFKRTTA EPSSSLTSSI
PASCHQRSKS DPSQLIQSLT PHSCHRTGNV SPSGCLSQAA RTPGDRAGTS KCRKAGCMYF
GTPENKGFCT LCFIEYRENK QSVTASEKAG SPAPRFQNNV PCLGRECGTL GSTMFEGYCQ
KCFIEAQNQR FHEARRTEEQ LRSSQHRDMP RTTQVASRLK CARASCKNIL ACRSEELCME
CQHLSQRVGS VAHRGEPTPE EPPKQRCRAP ACDHFGNAKC NGYCNECYQF KQMYG
