Uniprot ID:P21580	Protein name: Tumor necrosis factor alpha-induced protein 3	Gene : TNFAIP3 OTUD7C
Protein Family:Peptidase C64 family	Squence Length : 790

Sequnce	>P21580 791 MAEQVLPQALYLSNMRKAVKIRERTPEDIFKPTNGIIHHFKTMHRYTLEMFRTCQFCPQFREIIHKALIDRNIQATLESQKKLNWCREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDLVLRKALFSTLKETDTRNFKFRWQLESLKSQEFVETGLCYDTRNWNDEWDNLIKMASTDTPMARSGLQYNSLEEIHIFVLCNILRRPIIVISDKMLRSLESGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLVTLKDSGPEIRAVPLVNRDRGRFEDLKVHFLTDPENEMKEKLLKEYLMVIEIPVQGWDHGTTHLINAAKLDEANLPKEINLVDDYFELVQHEYKKWQENSEQGRREGHAQNPMEPSVPQLSLMDVKCETPNCPFFMSVNTQPLCHECSERRQKNQNKLPKLNSKPGPEGLPGMALGASRGEAYEPLAWNPEESTGGPHSAPPTAPSPFLFSETTAMKCRSPGCPFTLNVQHNGFCERCHNARQLHASHAPDHTRHLDPGKCQACLQDVTRTFNGICSTCFKRTTAEASSSLSTSLPPSCHQRSKSDPSRLVRSPSPHSCHRAGNDAPAGCLSQAARTPGDRTGTSKCRKAGCVYFGTPENKGFCTLCFIEYRENKHFAAASGKVSPTASRFQNTIPCLGRECGTLGSTMFEGYCQKCFIEAQNQRFHEAKRTEEQLRSSQRRDVPRTTQSTSRPKCARASCKNILACRSEELCMECQHPNQRMGPGAHRGEPAPEDPPKQRCRAPACDHFGNAKCNGYCNECFQFKQMYG
A20-type domains repeats	ZN_FING 381 416 A20-type 1 ZN_FING 472 507 A20-type 2 ZN_FING 515 548 A20-type 3 ZN_FING 601 636 A20-type 4 ZN_FING 651 686 A20-type 5 ZN_FING 710 745 A20-type 6 ZN_FING 756 790 A20-type 7
Domin repeated regions	381 - 416 SLMDVKCETPNCPFFMSVNTQPLCHECSERRQKNQN 472 - 507 ETTAMKCRSPGCPFTLNVQHNGFCERCHNARQLHAS 515 - 548 HLDPGKCQACLQDVTRTFNGICSTCFKRTTAEAS 601 - 636 RTGTSKCRKAGCVYFGTPENKGFCTLCFIEYRENKH 651 - 686 FQNTIPCLGRECGTLGSTMFEGYCQKCFIEAQNQRF 710 - 745 STSRPKCARASCKNILACRSEELCMECQHPNQRMGP 756 - 790 DPPKQRCRAPACDHFGNAKCNGYCNECFQFKQMYG
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"
Active Site	ACT_SITE 100 100 . ACT_SITE 103 103 Nucleophile. ACT_SITE 256 256 Proton acceptor
Mutation	"70 70 D->A: Minor effect on 'Lys-48' deubiquitinase activity 97 97 T->A: Minor effect on 'Lys-48' deubiquitinase activity 100 100 D->A: Strongly reduced deubiquitinase activity 103 103 C->A: Loss of deubiquitinase activity 103 103 C->S: Loss of 'Lys-63' deubiquitinating activity 106 106 H->A: Reduces deubiquitinase activity 157 157 L->A: Strongly reduced 'Lys-48' deubiquitinase activity 159 159 Y->A: Strongly reduced 'Lys-48' deubiquitinase activity 190 190 S->A: Strongly reduced 'Lys-48' deubiquitinase activity 192 192 E->A: Strongly reduced 'Lys-48' deubiquitinase activity 224 224 F->A: Strongly reduced 'Lys-48' deubiquitinase activity 227 227 L->A: Strongly reduced 'Lys-48' deubiquitinase activity 256 256 H->A: Loss of deubiquitinase activity 521 521 C->A: No effect on ubiquitin ligase activity when associated with A-524 524 524 C->A: No effect on ubiquitin ligase activity when associated with A-521 562 562 R->A: Abolishes interactionj with YWHAZ AND YWHAH no effect on inhibitory activity of TNF-induced NF-kappa-B activation 565 565 S->A: Abolishes interactionj with YWHAZ AND YWHAH no effect on inhibitory activity of TNF-induced NF-kappa-B activation 614 614 Y->A: Impairs ubiquitination activity when associated with A-615 or R-626 615 615 F->A: Impairs ubiquitination activity when associated with A-614 624 624 C->A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation when associated with A-627 626 626 L->R: Impairs ubiquitination activity when associated with A-614 627 627 C->A: Marked attenuation of ubiquitin ligase activity and inhibition of RIPK1 degradation when associated with A-624 770 771 FG->AA: Impairs polyubiquitin binding, abolishes inhibition of IKK activation 779 779 C->A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation when associated with A-782 782 782 C->A: Impairs polyubiquitin binding, abolishes inhibition of IKK activation when associated with A-779"
Disease	"DISEASE: Autoinflammatory syndrome, familial, Behcet-like (AISBL) [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 Note=The disease is caused by mutations affecting the gene represented in this entry"

P21580 of Proteins A20-type domain repeats