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 24-JAN-2024, entry version 188. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 29. DR DIP; DIP-41120N; -. DR IntAct; Q60769; 11. DR MINT; Q60769; -. DR STRING; 10090.ENSMUSP00000019997; -. DR GlyGen; Q60769; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q60769; -. DR PhosphoSitePlus; Q60769; -. DR EPD; Q60769; -. DR MaxQB; Q60769; -. DR PaxDb; 10090-ENSMUSP00000019997; -. DR ProteomicsDB; 259139; -. DR Antibodypedia; 1049; 577 antibodies from 45 providers. DR DNASU; 21929; -. DR Ensembl; ENSMUST00000019997.11; ENSMUSP00000019997.5; ENSMUSG00000019850.12. DR Ensembl; ENSMUST00000105527.2; ENSMUSP00000101167.2; ENSMUSG00000019850.12. DR GeneID; 21929; -. DR KEGG; mmu:21929; -. DR UCSC; uc007ena.3; mouse. DR AGR; MGI:1196377; -. 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; NAKCSGY; -. DR OrthoDB; 2909231at2759; -. 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 NF-kappa-B 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 79 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 150 other cell types or tissues. DR ExpressionAtlas; Q60769; baseline and differential. 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:0061578; F:K63-linked deubiquitinase activity; 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:0002020; F:protease binding; ISO:MGI. 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:0043124; P:negative regulation of canonical NF-kappaB signal transduction; IMP:BHF-UCL. DR GO; GO:2000349; P:negative regulation of CD40 signaling pathway; ISS: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:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:BHF-UCL. 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: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: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:0035871; P:protein K11-linked deubiquitination; ISS:UniProtKB. 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; ISS:UniProtKB. DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW. 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 CDD; cd22766; OTU_TNFAIP3; 1. DR Gene3D; 1.20.5.4770; -; 1. DR Gene3D; 3.90.70.80; -; 1. DR Gene3D; 4.10.240.30; -; 3. DR InterPro; IPR003323; OTU_dom. DR InterPro; IPR002653; Znf_A20. DR PANTHER; PTHR13367:SF3; TUMOR NECROSIS FACTOR ALPHA-INDUCED PROTEIN 3; 1. DR PANTHER; PTHR13367; UBIQUITIN THIOESTERASE; 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. DR Genevisible; Q60769; MM. 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 proteasomal 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 //