CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-014252
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Tumor necrosis factor alpha-induced protein 3 
Protein Synonyms/Alias
 TNF alpha-induced protein 3; Putative DNA-binding protein A20; Zinc finger protein A20 
Gene Name
 Tnfaip3 
Gene Synonyms/Alias
 Tnfip3 
Created Date
 July 27, 2013 
Organism
 Mus musculus (Mouse) 
NCBI Taxa ID
 10090 
Lysine Modification
Position
Peptide
Type
References
81QASLESQKKLNWCREubiquitination[1]
628QSVTASEKAGSPAPRubiquitination[1]
707KCARASCKNILACRSubiquitination[1]
Reference
 [1] BTB-ZF factors recruit the E3 ligase cullin 3 to regulate lymphoid effector programs.
 Mathew R, Seiler MP, Scanlon ST, Mao AP, Constantinides MG, Bertozzi-Villa C, Singer JD, Bendelac A.
 Nature. 2012 Nov 22;491(7425):618-21. [PMID: 23086144] 
Functional Description
 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. Deubiquinates 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. Deubiquinates 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 both '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. 
Sequence Annotation
 DOMAIN 92 263 OTU.
 REPEAT 286 317 1.
 REPEAT 324 356 2.
 ZN_FING 381 416 A20-type 1.
 ZN_FING 464 499 A20-type 2.
 ZN_FING 500 533 A20-type 3.
 ZN_FING 586 621 A20-type 4.
 ZN_FING 636 671 A20-type 5.
 ZN_FING 695 730 A20-type 6.
 ZN_FING 741 775 A20-type 7.
 REGION 58 300 TRAF-binding (By similarity).
 REGION 157 159 Interaction with ubiquitin (By
 REGION 190 192 Interaction with ubiquitin (By
 REGION 224 227 Interaction with ubiquitin (By
 REGION 286 356 2 X approximate repeats.
 REGION 369 775 Interaction with TNIP1.
 REGION 386 445 Interaction with RIPK1 (By similarity).
 REGION 590 640 Required for proteosomal degradation of
 REGION 591 775 Sufficient for inhibitory activity of
 REGION 682 775 Required for lysosomal localization and
 ACT_SITE 103 103 Nucleophile (By similarity).
 ACT_SITE 256 256 Proton acceptor (By similarity).
 MOD_RES 451 451 Phosphoserine (By similarity).  
Keyword
 Apoptosis; Complete proteome; Cytoplasm; DNA-binding; Hydrolase; Inflammatory response; Ligase; Lysosome; Metal-binding; Multifunctional enzyme; Nucleus; Phosphoprotein; Protease; Reference proteome; Repeat; Thiol protease; Ubl conjugation pathway; Zinc; Zinc-finger. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 775 AA 
Protein Sequence
MAEQLLPQAL YLSNMRKAVK IRERTPEDIF KPTNGIIYHF KTMHRYTLEM FRTCQFCPQF 60
REIIHKALID RSVQASLESQ KKLNWCREVR KLVALKTNGD GNCLMHAACQ YMWGVQDTDL 120
VLRKALCSTL KETDTRNFKF RWQLESLKSQ EFVETGLCYD TRNWNDEWDN LVKMASADTP 180
AARSGLQYNS LEEIHIFVLS NILRRPIIVI SDKMLRSLES GSNFAPLKVG GIYLPLHWPA 240
QECYRYPIVL GYDSQHFVPL VTLKDSGPEL RAVPLVNRDR GRFEDLKVHF LTDPENEMKE 300
KLLKEYLIVM EIPVQGWDHG TTHLINAAKL DEANLPKEIN LVDDYFELVQ HEYKKWQENS 360
DQARRAAHAQ NPLEPSTPQL SLMDIKCETP NCPFFMSVNT QPLCHECSER RQKNQSKLPK 420
LNSKLGPEGL PGVGLGSSNW SPEETAGGPH SAPPTAPSLF LFSETTAMKC RSPGCPFTLN 480
VQHNGFCERC HARQINASHT ADPGKCQACL QDVTRTFNGI CSTCFKRTTA EPSSSLTSSI 540
PASCHQRSKS DPSQLIQSLT PHSCHRTGNV SPSGCLSQAA RTPGDRAGTS KCRKAGCMYF 600
GTPENKGFCT LCFIEYRENK QSVTASEKAG SPAPRFQNNV PCLGRECGTL GSTMFEGYCQ 660
KCFIEAQNQR FHEARRTEEQ LRSSQHRDMP RTTQVASRLK CARASCKNIL ACRSEELCME 720
CQHLSQRVGS VAHRGEPTPE EPPKQRCRAP ACDHFGNAKC NGYCNECYQF KQMYG 775 
Gene Ontology
 GO:0005813; C:centrosome; IEA:Compara.
 GO:0005737; C:cytoplasm; IDA:MGI.
 GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
 GO:0019900; F:kinase binding; IDA:BHF-UCL.
 GO:0004221; F:ubiquitin thiolesterase activity; ISS:UniProtKB.
 GO:0004842; F:ubiquitin-protein ligase activity; ISS:UniProtKB.
 GO:0004843; F:ubiquitin-specific protease activity; ISS:UniProtKB.
 GO:0008270; F:zinc ion binding; IEA:InterPro.
 GO:0001922; P:B-1 B cell homeostasis; IMP:BHF-UCL.
 GO:0070301; P:cellular response to hydrogen peroxide; IMP:UniProtKB.
 GO:0071222; P:cellular response to lipopolysaccharide; ISS:BHF-UCL.
 GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
 GO:0002315; P:marginal zone B cell differentiation; NAS:BHF-UCL.
 GO:0043066; P:negative regulation of apoptotic process; NAS:BHF-UCL.
 GO:0010507; P:negative regulation of autophagy; NAS:BHF-UCL.
 GO:0050869; P:negative regulation of B cell activation; IDA:BHF-UCL.
 GO:2000349; P:negative regulation of CD40 signaling pathway; ISS:BHF-UCL.
 GO:0002677; P:negative regulation of chronic inflammatory response; IMP:BHF-UCL.
 GO:0045736; P:negative regulation of cyclin-dependent protein serine/threonine kinase activity; IDA:BHF-UCL.
 GO:0043154; P:negative regulation of cysteine-type endopeptidase activity involved in apoptotic process; ISS:BHF-UCL.
 GO:2000352; P:negative regulation of endothelial cell apoptotic process; IEA:Compara.
 GO:0002632; P:negative regulation of granuloma formation; NAS:BHF-UCL.
 GO:0034115; P:negative regulation of heterotypic cell-cell adhesion; NAS:BHF-UCL.
 GO:0043124; P:negative regulation of I-kappaB kinase/NF-kappaB cascade; ISS:UniProtKB.
 GO:0045824; P:negative regulation of innate immune response; IMP:UniProtKB.
 GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:BHF-UCL.
 GO:0032703; P:negative regulation of interleukin-2 production; IEA:Compara.
 GO:0032715; P:negative regulation of interleukin-6 production; IMP:BHF-UCL.
 GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IEA:Compara.
 GO:0070429; P:negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway; IMP:BHF-UCL.
 GO:0070433; P:negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway; IDA:BHF-UCL.
 GO:0031397; P:negative regulation of protein ubiquitination; IEA:Compara.
 GO:0048662; P:negative regulation of smooth muscle cell proliferation; ISS:BHF-UCL.
 GO:0034140; P:negative regulation of toll-like receptor 3 signaling pathway; IEA:Compara.
 GO:0034148; P:negative regulation of toll-like receptor 5 signaling pathway; IDA:BHF-UCL.
 GO:0032720; P:negative regulation of tumor necrosis factor production; IMP:BHF-UCL.
 GO:2000347; P:positive regulation of hepatocyte proliferation; IDA:BHF-UCL.
 GO:0045732; P:positive regulation of protein catabolic process; ISS:BHF-UCL.
 GO:0070936; P:protein K48-linked ubiquitination; ISS:UniProtKB.
 GO:0070536; P:protein K63-linked deubiquitination; ISS:UniProtKB.
 GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
 GO:0002634; P:regulation of germinal center formation; IMP:BHF-UCL.
 GO:0002637; P:regulation of immunoglobulin production; IC:BHF-UCL.
 GO:0032495; P:response to muramyl dipeptide; IMP:BHF-UCL.
 GO:0009611; P:response to wounding; NAS:BHF-UCL.
 GO:0072573; P:tolerance induction to lipopolysaccharide; IEA:Compara. 
Interpro
 IPR003323; OTU.
 IPR002653; Znf_A20. 
Pfam
 PF02338; OTU
 PF01754; zf-A20 
SMART
 SM00259; ZnF_A20 
PROSITE
 PS50802; OTU
 PS51036; ZF_A20 
PRINTS