OTU (ovarian tumor) domain of ubiquitin thioesterase OTU1 and similar proteins; Ubiquitin thioesterase (EC 3.4.19.12) OTU1 is also called OTU domain-containing protein 1 in yeast, while human OTU1 is also called HIV-1-induced protease 7 (HIN7), DUBA-8, or OTU domain-containing protein 2 (OTUD2). OTU1 is a deubiquitinase (DUB) that catalyzes the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. OTU1 has been implicated in the ER-associated degradation (ERAD) pathway. In yeast, it counteracts the activity of Ufd2 by deubiquitinating Ufd2 substrates; Ufd2 is a E4 ubiquitin ligase that interacts with Cdc48, an AAA ATPase that plays a central role in the ERAD pathway by chaperoning proteins to the proteasome for destruction. OTU1 also functions as a substrate-processing factor of valosin-containing protein (VCP, the mammalian counterpart of yeast Cdc48) that is required for the retrotranslocation of the ERAD pathway. OTU1 has been shown to preferentially hydrolyze polyubiquitin chains with Lys48 linkages. It contains ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a C2H2-type zinc finger, and an OTU (ovarian tumor) domain. This model represents the OTU domain that interacts with ubiquitin and possesses catalytic activity. OTU1 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. This family also contains plant OTU1 and OTU2.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 108 VLSVHPVLDDNSCLFHAIAYGIFK--QDSVRDLREMVSKEVLNNPVKFNDAILDKPNKDYAQWILKMESWGGAIEIGIIS 185
Cdd:cd22745   2 YLVRRVVPDDNSCLFTSISYLLEGglLDSAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSILS 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 186 DALAVAIYVVDIDAVKIEKFNEDK-FDNYILILFNGIHYDSLTMNEF--------KTVFNKnqpESDDVLTAALQLASNL 256
Cdd:cd22745  82 KHFGVEICVVDVQTGRVDRFGEDKgYSKRIFLLYSGIHYDALALNPSldapedfdVTVFSV---SDDEVLEAALELAKEL 158

                ..
gi 14318475 257 KQ 258
Cdd:cd22745 159 KA 160

OTU (ovarian tumor) domain of ubiquitin thioesterase OTU1 and similar proteins; Ubiquitin thioesterase (EC 3.4.19.12) OTU1 is also called OTU domain-containing protein 1 in yeast, while human OTU1 is also called HIV-1-induced protease 7 (HIN7), DUBA-8, or OTU domain-containing protein 2 (OTUD2). OTU1 is a deubiquitinase (DUB) that catalyzes the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. OTU1 has been implicated in the ER-associated degradation (ERAD) pathway. In yeast, it counteracts the activity of Ufd2 by deubiquitinating Ufd2 substrates; Ufd2 is a E4 ubiquitin ligase that interacts with Cdc48, an AAA ATPase that plays a central role in the ERAD pathway by chaperoning proteins to the proteasome for destruction. OTU1 also functions as a substrate-processing factor of valosin-containing protein (VCP, the mammalian counterpart of yeast Cdc48) that is required for the retrotranslocation of the ERAD pathway. OTU1 has been shown to preferentially hydrolyze polyubiquitin chains with Lys48 linkages. It contains ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a C2H2-type zinc finger, and an OTU (ovarian tumor) domain. This model represents the OTU domain that interacts with ubiquitin and possesses catalytic activity. OTU1 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. This family also contains plant OTU1 and OTU2.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 108 VLSVHPVLDDNSCLFHAIAYGIFK--QDSVRDLREMVSKEVLNNPVKFNDAILDKPNKDYAQWILKMESWGGAIEIGIIS 185
Cdd:cd22745   2 YLVRRVVPDDNSCLFTSISYLLEGglLDSAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSILS 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 186 DALAVAIYVVDIDAVKIEKFNEDK-FDNYILILFNGIHYDSLTMNEF--------KTVFNKnqpESDDVLTAALQLASNL 256
Cdd:cd22745  82 KHFGVEICVVDVQTGRVDRFGEDKgYSKRIFLLYSGIHYDALALNPSldapedfdVTVFSV---SDDEVLEAALELAKEL 158

                ..
gi 14318475 257 KQ 258
Cdd:cd22745 159 KA 160

OTU (ovarian tumor) domain family; The OTU family of cysteine proteases use a conserved cysteine and histidine, and in most cases an aspartate, as the catalytic triad. OTU domains typically function as deubiquitinases (DUBs)/ubiquitin thiolesterases (EC 3.4.19.12) that catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. These DUBs may play important regulatory roles at the level of protein turnover by preventing degradation.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 110 SVHPVLDDNSCLFHAIAYGIFK-QDSVRDLREMVSKEVLNNPVKFNDAILDK--PNKDYAQWILKME---SWGGAIEIGI 183
Cdd:cd22744   1 RVVDVPGDGNCLFRALAHALYGdQESHRELRQEVVDYLRENPDLYEPAELADedDGEDFDEYLQRMRkpgTWGGELELQA 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 14318475 184 ISDALAVAIYVVDIDAVKIE----KFNEDKFDNYILILFNGI-HYDSL 226
Cdd:cd22744  81 LANALNVPIVVYSEDGGFLPvsvfGPGPGPSGRPIHLLYTGGnHYDAL 128

OTU (ovarian tumor) domain of viral RNA-directed RNA polymerase L; RNA-directed RNA polymerase L is also called protein L, large structural protein, replicase, transcriptase, or ubiquitin thioesterase. It displays RNA-directed RNA polymerase (EC 2.7.7.48), deubiquitinase (DUB)/ubiquitin thiolesterase (EC 3.4.19.12), and deISGylating activities. It is a viral homolog of ovarian tumor protease (vOTU) that has been implicated in the downregulation of type I interferon immune response by removing post-translational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15) from host cellular proteins. The attachment of Ub and ISG15 to cellular proteins mediates important innate antiviral responses, and their removal inhibits these antiviral pathways. This subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 111 VHPVLDDNSCLFHAIAYGIFK-QDSVRDLREMVSKEVLNNPVKFNDAILDKPNKD-YAQWILKMESWGGAIEIGIISDAL 188
Cdd:cd21880  24 IERVPGDGNCFFRSIAELLFDtEDEWRLVKNTIESYARANWDECPEARLYYLSLEeYLRDAMKDGYWGGSLEAEILSKAL 103

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*
gi 14318475 189 AVAIY--VVDiDAVKIE---KFNEDKFDNYILILFNGIHYDSLTM 228
Cdd:cd21880 104 GITIIiwVVD-DSDWVTaavRFGDGDVSTSLNLLHSGGHFDALRL 147

OTU (ovarian tumor) domain of Arabidopsis thaliana deubiquitinating enzyme OTU7 and similar proteins; Arabidopsis thaliana deubiquitinating enzyme OTU7, also called OTU domain-containing protein 7, is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that shows a preference for 'Lys-63' over 'Lys-48' over 'Met-1'-linked ubiquitin (UB) tetramers as substrates. DUBs catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. These DUBs may play important regulatory roles at the level of protein turnover by preventing degradation. OTU7 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 109 LSVHPVLDDNSCLFHAIA---YGIfkQDSVRDLREMVSKEVLNNPVKFNDAILDK-PNKDYAQWILKMESWGGAIEIGII 184
Cdd:cd22771   2 LRIRDVEGDGNCLFRALAdqlYGD--EERHAELRKKVVDYMEAHEEDFEPFFEDDeTFEDYVSRMREDGTWGGNLELQAA 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 14318475 185 SDALAVAI--YVVDIDAVKIEKFNEDKFDNYILILFNGIHYDS 225
Cdd:cd22771  80 SLVYRVNIvvHQLGQPRWEIENFPDKGARTIHLSYHDGEHYNS 122

OTU (ovarian tumor) domain of Caenorhabditis elegans deubiquitylating enzyme with USP/UBP and OTU domains, and similar proteins; This subfamily is composed of mostly uncharacterized proteins containing an OTU domain, similar to Caenorhabditis elegans deubiquitylating enzyme with USP/UBP and OTU domains. OTU domain-containing proteins function as deubiquitinases (DUBs)/ubiquitin thiolesterases (EC 3.4.19.12) that catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. These DUBs may play important regulatory roles at the level of protein turnover by preventing degradation. They belong to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 111 VHPVLDDNSCLFHAIAYGIF-KQDSVRDLREMVSKEVLNNPVKFNdAILDKPNKDYAQWILKME-----SWGGAIEIGII 184
Cdd:cd22755   3 TIKIVGDGNCFFRALSYAITgSEKYHRKIRKAIVDFLEKNPDEFR-NLLRSDYESVEEYLEKSRmrydgTWATDVEIFAA 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 14318475 185 SDALAVAIYVVDIDAVKIEKFNEDKFD-------NYI-LILFNGIHYD 224
Cdd:cd22755  82 ATLLGVDIYVYSKGGYKWLLYSPRFKLgkrngsrEAIyLKNTNGNHFE 129

OTU (ovarian tumor) domain of OTU domain-containing proteins 6A and 6B and similar proteins; This subfamily is composed of mammalian OTU domain-containing protein 6A (OTUD6A, also called DUBA-2) and vertebrate OTU domain-containing protein 6B (OTUD6B, also called DUBA-5), which are deubiquitinating enzymes/ubiquitinyl hydrolases (EC 3.4.19.12). OTUD6A hydrolyzes 'Lys-27'-, 'Lys-29'-, and 'Lys-33'-linked polyubiquitin chains, and may also be able to hydrolyze 'Lys-11'-linked ubiquitin chains. It deubiquitylates and stabilizes dynamin-related protein 1 (Drp1), a cytosolic protein responsible for mitochondrial fission and is essential in the initiation and development of several human diseases including cancer, thereby facilitating tumorigenesis. OTUD6B is a functional deubiquitinase in in vitro enzyme assays. It may play a role in the ubiquitin-dependent regulation of protein synthesis downstream of mTORC1, and may modify the ubiquitination of the protein synthesis initiation complex to repress translation. Biallelic variants in OTUD6B cause an intellectual disability syndrome that is associated with seizures and dysmorphic features. This subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 109 LSVHPVLDDNSCLFHAIAY---GIFKQDSVRDLREMVSKEVLNNPvkfNDAI--LDKPN-------KDYAQWILKMES-- 174
Cdd:cd22761  10 LKIHEIPSDGDCLYNAIAHqlsLRGIETSVEELRKQTADYMRENK---DDFLpfLTNPDtgdplteEEFEKYCDDVENtg 86

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14318475 175 -WGGAIEIGIISDALAVAIYVVDIDAVKIeKFNED-KFDNYILILFN------GIHYDSLT 227
Cdd:cd22761  87 aWGGQLELRALSHVLKRPIEVIQAEGPPI-IIGEEfKSGKPLILTYHrhayglGEHYNSVE 146

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU4 from plants and similar proteins; Deubiquitinating enzyme OTU4, also called OTU domain-containing protein 4, is a deubiquitinase (DUB) or ubiquitin thiolesterase (EC 3.4.19.12) that catalyzes the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. OTU4 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU4 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 109 LSVHPVLDDNSCLFHAIAYGI------FKQDSVRD------LREMVSKEVlnnpVKFNDAILDKPNKDYAQWILKME--- 173
Cdd:cd22760   2 YRVHGIAGDGRCLFRAVAHGEclargkAAPDEEREreladeLRTRAADEL----VKRREETEWFIEGDFDEYVARMRrpg 77

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14318475 174 SWGGAIEIGIISDALAVAI--YVVDIDAVKIEKF----NEDKFDNYILILFNGI-HYDSLT 227
Cdd:cd22760  78 VWGGEPELLMLSHVLQRPItvYMADEGEGGLISIaeygQEYGKGNPIRVLFHGFgHYEALL 138

OTU (ovarian tumor) domain of the potexviruses/carlaviruses RNA replication protein family; RNA replication polyprotein (RDRP) is a viral homolog of ovarian tumor protease (vOTU), which displays RNA helicase (EC 3.6.4.13), RNA-directed RNA polymerase (EC 2.7.7.48), viral methyltransferase, Fe(2+) 2-oxoglutarate dioxygenase and protease activities. The central part of this protein possibly functions as an ATP-binding helicase. It is an RNA-directed RNA polymerase involved in viral RNA replication. It also acts as a thiol protease that cleaves the polyprotein. This subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 111 VHPVLDDNSCLFHAIAYgiFKQDSVRDLREMVSKevlnnpVKFNDAILDKPnkdyAQWILKMESWGGAIEIGIISDALAV 190
Cdd:cd22792   2 VVPVPGDGNCFWHSLGH--FLGLSALELKKLLRD------SLFDDPELDEE----LDEQLEPGVYAEDEAIAAAAKLFGV 69

                        90       100       110
                ....*....|....*....|....*....|....
gi 14318475 191 AIYVVDIDAVKIEKFNEDKFDNYILILFNGIHYD 224
Cdd:cd22792  70 NICVHDPDEGVLYTFTPNESSKSIHLLLENEHFE 103

OTU (ovarian tumor) domain of OTU domain-containing protein 4 and similar proteins; OTU domain-containing protein 4 (OTUD4), also called HIV-1-induced protein HIN-1, is a deubiquitinase that specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein upon phosphorylation, triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators. OTUD4 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14318475 113 PVLDDNSCLFHAIAYGIF---------KQDSVRDLREmvskevlnNPVKFnDAILDKPNKDYAQWILKMESWGGAIEIGI 183
Cdd:cd22794  14 QIAKDGSCLFRAVAEQVFhtqsrhlevRKACVDYLRR--------NREKF-EAFIEGPFEQYLKNLENPKEWAGQVEISA 84

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 14318475 184 ISDalavaIYVVD------IDAVKIeKFNEDKFDNYILILF-NGIHYDS 225
Cdd:cd22794  85 LSL-----MYKRDfiiyqePGKPPS-NVTENGFPDKILLCFsNGNHYDS 127