5V3P,3DKB,3ZJD,5DQ6,5LRX,2VFJ,5V3B,3ZJE


Conserved Protein Domain Family
OTU_TNFAIP3

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cd22766: OTU_TNFAIP3 
Click on image for an interactive view with Cn3D
OTU (ovarian tumor) domain of tumor necrosis factor alpha induced protein 3
Tumor necrosis factor (TNF) alpha-induced protein 3 (TNFAIP3) is also called OTU domain-containing protein 7C (OTUD7C), DNA-binding protein A20, or zinc finger protein A20. It is a ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) activities. It antagonizes IKK [IkappaB (inhibitor of kappaB) kinase] activation by modulating Lys63-linked polyubiquitination of cytokine-receptor-associated factors including TRAF2/6 (tumour-necrosis-factor-receptor-associated factor 2/6) and RIP1 (receptor-interacting protein 1). It can also inhibit IKK through a non-catalytic mechanism which involves polyubiquitin. In vitro, TNFAIP3 is able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. TNFAIP3 contains several A20-type zinc fingers that mediate the ubiquitin ligase activity and an OTU (ovarian tumor) domain that contains the DUB activity. It belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. It is classified as a family C64 cysteine protease by MEROPS.
Statistics
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PSSM-Id: 438603
Aligned: 28 rows
Threshold Bit Score: 320.36
Created: 21-Sep-2020
Updated: 17-Oct-2022
Structure
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Program:
Drawing:
Aligned Rows:
 
polypeptideactive site
Conserved site includes 31 residues -Click on image for an interactive view with Cn3D
Feature 1:polypeptide substrate binding site [polypeptide binding site]
Evidence:
  • Structure:5LRX: Human TNFAIP3 OTU domain binds ubiquitin; contacts at 4A

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                      ## ###             
5V3P_A         41 KTMHRYTLEMFRTC-QFCPQFREIIHKAliDRNIQATLESQKKLNW---CREVRKLVALKTNGDGNXLMHATSQYMWGVQ 116 
5LRX_A         46 KTMHRYTLEMFRTC-QFCPQFREIIHKAliDRNIQATLESQKKLNW---CREVRKLVALKTNGDGNCLMHATSQYMWGVQ 121  human
XP_006816095   50 LGSTSVTLTLPPLN-VFPEEFQTFLYQDliDKQMLATLYNAGELNW---CSAVKRVLPLQTTADGNCLLHAVCMAMWGID 125  Saccoglossus ...
XP_007902490   56 LNMNMHTLQLHSMR-EYQPQFRRTLEQSlmDQVTSKALADAGTLNW---CKELRKQFPLKVSGDGNSLLHSLSLCMWGVK 131  elephant shark
XP_014343667   44 RTLHRHSLQVPDLQ-SYSSPVRDMVDKSlfDQHARRVLEKSGGLNW---CKDISPLVPLSFTGDGNSLLHAISVYLWGVS 119  coelacanth
AGQ17408       45 GAMTGHSLMLPCIK-LFPLDFQEILNKQliDRFVQKTLEEAKVLNW---CRASRPLTPVQTTGDGNCLLHAVSQYMWGIH 120  Branchiostoma...
PIK44277       50 QQLPMYTAALPYHWvLYPEDMTRFLQREitEPAIKRQFEKEGLINWstsLPTLYPLLPQNIGGDGNCLLHAVALYMWGIE 129  Japanese sea ...
XP_011670661   56 AEMQNATAILPNYWqLYPSDFAKYLKQElcDLHMSKFLEDKKVLNW---CPGFTKLYSLNATGDGNCLLHAISLALWGVE 132  purple sea ur...
XP_022081813   55 LHMATFTSLLPPHWeSFPPELKMFLEKEmfDPVLLYILEREGLMNW---CPSVRKVYPLITPGDGNCLLHAVSLAMWGIE 131  crown-of-thor...
XP_020376854   43 NRLHEYTLQLYSTK-GYQRRFRRIVEQAlfDQEVCQTLQEARVLNW---SREVRRQFPLKVPGEGNSLLHSVSLYMWGVQ 118  whale shark
Feature 1                                           ###     ## ##       #   #  #                ##
5V3P_A        117 DTDLVLRKALFSTLKETD--TRNFKFRWQLESLKSQEfv--eTGLCYDTRNWNDEWDNLIKMASTdtpma-rsglQYNSL 191 
5LRX_A        122 DTDLVLRKALFSTLKETD--TRNFKFRWQLESLKSQEfv--eTGLCYDTRNWNDEWDNLIKMASTdtpma-rsglQYNSL 196  human
XP_006816095  126 DSNLFLRRHLYRGLVETEefTESMKKRWENERKKQDVai-pgGGLRYNSTQWNGEWETMIRIAAAdrkpasdgglPYECL 204  Saccoglossus ...
XP_007902490  132 DTDLTLSKTFHEALTKTN--SVNFRLRWQTEHGAGQHyp--tTGLCDQSAIWDAEWQNMIDSSAPvs------qaCTSLY 201  elephant shark
XP_014343667  120 DADMFLHKVLHEALTKTN--TTSFKLRYQREKGKIPEhk--lPHRPPDPEVWEEEWNKVVDTADPhtkg---hssLYNAY 192  coelacanth
AGQ17408      121 DRDLTLRRLLNRTMVADM--TEDMKQRWNRSCKSHNQh----VHLEYASLEWRQEWNIIVSMTDPtpnppeandlPYKSL 194  Branchiostoma...
PIK44277      130 DTELFLRTSLWESMVNGSf-SDNNMPRWQAERSSVDQaa-msFEFRYNTKEWNEEYDMLKTMAAPiadds-gynlPYKSL 206  Japanese sea ...
XP_011670661  133 DTDLWLRKVLHSVMKGEY--AEANERRWRRERNQFDTthipgQGFRYNTKEWSAEWQIVVDISSPerrldqtmglPYECL 210  purple sea ur...
XP_022081813  132 DDELVLRTALFRLLRDDK--NERNRLRWQRERMRVDSai-pgSGLVYNTIEWESEWDMIKTMASPerrlttaqglPYESL 208  crown-of-thor...
XP_020376854  119 DTDLVLQKIFHEALVKTH--DTNFKLRLQTEYRKDQGfl--dPDLLHQPKIWDQEWQNVIESSNPaspa---ghpFANIY 191  whale shark
Feature 1         #                     ## ###   ### #                        #  ###    
5V3P_A        192 EEIHIFVLCNILRRPIIVISDKMLRSLEsgsNFAPLKVGGIYLPLHWPaQECYRYPIVLGYDsHHFVPLV 261 
5LRX_A        197 EEIHIFVLCNILRRPIIVISDKMLRSLEsgsNFAPLKVGGIYLPLHWPaQECYRYPIVLGYDsHHFVPLV 266  human
XP_006816095  205 DEFHIFLLSNIIRRPIIVAAEKMWRDLDg-hSFQPQNFGGVYLPLCWEpKDCVKTPLLLAYDsMHFTPLV 273  Saccoglossus kowalevskii
XP_007902490  202 QDMHLFILANIARRPIIVIAESSKGNSKk-vSDKTSSPAGIYLPLHWPaEQCFTYPILLSYTqQRFTPLV 270  elephant shark
XP_014343667  193 QDIYIFILANIIRRPIIVIAGNHKETASd-sAYSFSDPSGIFLPLHWHsEECFHSPVILGHVdRIFRALV 261  coelacanth
AGQ17408      195 EEFHIFVLANLLRRPIIILAEDVLHNFEg-hTFAPIHFSGIYLPLRWKpEECVRSPIVLGYLqQHFTPLL 263  Branchiostoma belcheri ...
PIK44277      207 EEFHIYALANMLRRPIMIISNDKIRNLEg-aSLQPQSVSGLYLPLDWDpSLCCKFPIVLGFYhSHFFPLV 275  Japanese sea cucumber
XP_011670661  211 EEFHIFVMANILRRPIIVLAENMWRDAAg-kSLQPLNFSGIYLPLGWDsKDCFHHPILLGYHhQHFSPLL 279  purple sea urchin
XP_022081813  209 EQFHIFMLANMLRRPIIVVAQDMMRSQLg-hSLQPQDLHGIYLPLNWDpATCYRHPILLGFHqNHFTPLL 277  crown-of-thorns starfish
XP_020376854  192 QDVHIFVLANIVRRPIVVVGKSEGRPKTv-sETMMSSPAGIYLPLHWPpHRCYAYPILLGYArQYFTPLI 260  whale shark

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