| IED ID | IndEnz0002008744 |
| Enzyme Type ID | protease008744 |
| Protein Name |
Tumor necrosis factor alpha-induced protein 3 TNF alpha-induced protein 3 EC 2.3.2.- EC 3.4.19.12 Putative DNA-binding protein A20 Zinc finger protein A20 |
| Gene Name | Tnfaip3 Tnfip3 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MAEQLLPQALYLSNMRKAVKIRERTPEDIFKPTNGIIYHFKTMHRYTLEMFRTCQFCPQFREIIHKALIDRSVQASLESQKKLNWCREVRKLVALKTNGDGNCLMHAACQYMWGVQDTDLVLRKALCSTLKETDTRNFKFRWQLESLKSQEFVETGLCYDTRNWNDEWDNLVKMASADTPAARSGLQYNSLEEIHIFVLSNILRRPIIVISDKMLRSLESGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSQHFVPLVTLKDSGPELRAVPLVNRDRGRFEDLKVHFLTDPENEMKEKLLKEYLIVMEIPVQGWDHGTTHLINAAKLDEANLPKEINLVDDYFELVQHEYKKWQENSDQARRAAHAQNPLEPSTPQLSLMDIKCETPNCPFFMSVNTQPLCHECSERRQKNQSKLPKLNSKLGPEGLPGVGLGSSNWSPEETAGGPHSAPPTAPSLFLFSETTAMKCRSPGCPFTLNVQHNGFCERCHARQINASHTADPGKCQACLQDVTRTFNGICSTCFKRTTAEPSSSLTSSIPASCHQRSKSDPSQLIQSLTPHSCHRTGNVSPSGCLSQAARTPGDRAGTSKCRKAGCMYFGTPENKGFCTLCFIEYRENKQSVTASEKAGSPAPRFQNNVPCLGRECGTLGSTMFEGYCQKCFIEAQNQRFHEARRTEEQLRSSQHRDMPRTTQVASRLKCARASCKNILACRSEELCMECQHLSQRVGSVAHRGEPTPEEPPKQRCRAPACDHFGNAKCNGYCNECYQFKQMYG |
| Enzyme Length | 775 |
| Uniprot Accession Number | Q60769 |
| Absorption | |
| Active Site | ACT_SITE 100; /evidence=ECO:0000250; ACT_SITE 103; /note=Nucleophile; /evidence=ECO:0000250; ACT_SITE 256; /note=Proton acceptor; /evidence=ECO:0000250 |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).; EC=3.4.19.12; Evidence={ECO:0000269|PubMed:15334086}; |
| DNA Binding | |
| EC Number | 2.3.2.-; 3.4.19.12 |
| Enzyme 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-alpha 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 proinflammatory cytokines and IFN beta in LPS-tolerized macrophages. {ECO:0000269|PubMed:10385526, ECO:0000269|PubMed:11389905, ECO:0000269|PubMed:15334086, ECO:0000269|PubMed:18342009, ECO:0000269|PubMed:20185725, ECO:0000269|PubMed:23609450}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Beta strand (13); Chain (1); Domain (1); Helix (14); Initiator methionine (1); Metal binding (28); Modified residue (2); Mutagenesis (2); Region (11); Sequence conflict (1); Turn (5); Zinc finger (7) |
| Keywords | 3D-structure;Acetylation;Apoptosis;Cytoplasm;DNA-binding;Hydrolase;Inflammatory response;Lysosome;Metal-binding;Multifunctional enzyme;Nucleus;Phosphoprotein;Protease;Reference proteome;Repeat;Thiol protease;Transferase;Ubl conjugation pathway;Zinc;Zinc-finger |
| Interact With | Q9CYZ8; Q9WUU8; P39429; P01375 |
| Induction | INDUCTION: By cytokines. TNF-alpha may regulate expression in the thymus. Up-regulated in presence of reactive oxygen species (ROS), like H(2)O(2), in LPS-tolerized macrophages. {ECO:0000269|PubMed:23609450}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}. Lysosome {ECO:0000250}. |
| Modified Residue | MOD_RES 2; /note=N-acetylalanine; /evidence=ECO:0000250|UniProtKB:P21580; MOD_RES 451; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:P21580 |
| Post Translational Modification | |
| Signal Peptide | |
| Structure 3D | X-ray crystallography (1) |
| Cross Reference PDB | 5DQ6; |
| Mapped Pubmed ID | 11009421; 11390377; 11973313; 12586352; 14614151; 15102471; 15163632; 15226823; 15618518; 15962316; 16919269; 16936197; 17389268; 17703191; 17709380; 17982095; 18006655; 18223652; 18239685; 18246070; 18268035; 18676814; 18952128; 19060883; 19252225; 19412163; 19570823; 19826422; 19877201; 19912257; 20059953; 20211142; 20430393; 20501938; 20530205; 20577653; 20705491; 21088135; 21151899; 21167234; 21206085; 21321094; 21335489; 21341261; 21566665; 21723156; 21765415; 21841782; 21885437; 21934070; 22012122; 22019834; 22031828; 22396652; 22595989; 22685311; 22733818; 22736257; 22826618; 22975135; 23029542; 23032187; 23145026; 23238769; 23602765; 23671587; 23677497; 23922952; 24012418; 24023826; 24055365; 24236890; 24453940; 24487321; 24498102; 24832470; 24859449; 24878851; 25024217; 25026958; 25043000; 25190567; 25234043; 25267258; 25433453; 25472594; 25607459; 25609235; 25624445; 25911380; 25939025; 25976305; 25989384; 26043155; 26159495; 26200012; 26339029; 26437781; 26546835; 26549234; 26561336; 26649818; 26652732; 26815999; 26940588; 26952977; 27028905; 27177019; 27253414; 27443844; 27551052; 27551157; 27783947; 27825134; 27986908; 28004776; 28094437; 28116503; 28355611; 28363868; 28465464; 28562353; 28569771; 28658319; 28683286; 28765172; 28842469; 28892081; 29143862; 29203883; 29440643; 29608924; 29678181; 29733654; 29789522; 29796309; 29868491; 29887373; 29891719; 29930103; 30067782; 30171721; 30209212; 30463008; 30760622; 31015422; 31057558; 31086261; 31101885; 31114134; 31151831; 31295268; 31296735; 31477755; 31545817; 31630621; 31755338; 31811410; 32023471; 32205880; 32205881; 32234376; 32325694; 32471718; 32540868; 32748687; 32755457; 32951573; 33224133; 33460648; 33613524; 33746949; 33981308; 34023381; 34062371; 34288802; 34315113; 34381441; 34413280; 34943932; 9610637; |
| Motif | |
| Gene Encoded By | |
| Mass | 87,654 |
| Kinetics | |
| Metal Binding | METAL 387; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 392; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 404; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 407; /note=Zinc 1; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 470; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 475; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 487; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 490; /note=Zinc 2; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 506; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 509; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 521; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 524; /note=Zinc 3; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 592; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 597; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 609; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 612; /note=Zinc 4; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 642; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 647; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 659; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 662; /note=Zinc 5; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 701; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 706; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 718; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 721; /note=Zinc 6; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 747; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 752; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 764; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451; METAL 767; /note=Zinc 7; /evidence=ECO:0000255|PROSITE-ProRule:PRU00451 |
| Rhea ID | |
| Cross Reference Brenda |