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 62751964 148 VLTRTVVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWGGAIEISI 227
Cdd:cd22745   2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62751964 228 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 305
Cdd:cd22745  80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                ..
gi 62751964 306 RR 307
Cdd:cd22745 160 AK 161

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 62751964 148 VLTRTVVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWGGAIEISI 227
Cdd:cd22745   2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62751964 228 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 305
Cdd:cd22745  80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                ..
gi 62751964 306 RR 307
Cdd:cd22745 160 AK 161

ubiquitin-like (Ubl) domain found in ubiquitin thioesterase OTU1 and similar proteins; OTU1 (EC 3.4.19.12), also termed YOD1, or DUBA-8, or HIV-1-induced protease 7 (HIN-7), or OTU domain-containing protein 2 (OTUD2), is a p97-associated deubiquitinylase that functions as a key player in endoplasmic reticulum-associated degradation (ERAD). Its deubiquitinylase activity is also required for negatively regulating cholera toxin A1 (CTA1) retro-translocation. OTU1 contains a conserved ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a C2H2-type zinc finger, and an OTU domain.

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 62751964  47 WRLRCKAKDGTHVLQGLSSRTRVRELQGQIAAITGIAPGGQRILVGYPPECLDLSNGDTILEDLPIQSGDMLIIE 121
Cdd:cd17059   1 MRLRVRSKGGQHVLSLLTDTSTVGELQDRIAALTGIPPSSQKILYGFPPKPLDLSDEEASLESLGIQSGDTLIVE 75

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 62751964 148 VLTRTVVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWGGAIEISI 227
Cdd:cd22745   2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62751964 228 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 305
Cdd:cd22745  80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                ..
gi 62751964 306 RR 307
Cdd:cd22745 160 AK 161

Predicted cysteine protease (OTU family) [Posttranslational modification, protein turnover, chaperones];

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62751964  91 VGYPPE-----CLDLSNGDTILEDLPIQSGDMLIIEEDQTRPRSS----PAFTKRGAS----SYVRETLPVLTRTVVPAD 157
Cdd:COG5539  41 FGRPPQrlngkCLDLSYALSQKDEVEIEKAPKLRAETNEADQEDSltplQNIPELGISsfekSVSQQSINVLEDMPGQDD 120

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62751964 158 NSCLFTSVYYVveggvLNPACAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWG-GAIEISILSKFYQCEI 236
Cdd:COG5539 121 NSRLFQAERYS-----LRDASVAKLREVVSLEVLSNPDLYNPAILEIDVIAYATWIVKPDSQGdGCIEIAIISDQLPVRI 195

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62751964 237 CVVDTQTVRIDRFGEDAgYTKRVLLIYDGIHYDPLQRNFPDPDTPPLTIFSSNDDIVLVQALELADEARRRRQFTDVNRF 316
Cdd:COG5539 196 HVVDVDKDSEDRYNSHP-YVQRISILFTGIHFDEETLAMVLWDTYVNEVLFDASDGITIEIQQLASLLKNPHYYTNTASP 274

                       250       260       270
                ....*....|....*....|....*....|.
gi 62751964 317 TLRCMVCQKGLTGQAEAREHAKETGHTNFGE 347
Cdd:COG5539 275 SIKCNICGTGFVGEKDYYAHALATGHYNFGE 305

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 62751964 154 VPADNSCLFTSVYYVVEGgvlNPACAPEMRRLIAQIVASDPDFYSEAIL-----GKTNQEYCDWIKRDDTWGGAIEISIL 228
Cdd:cd22744   5 VPGDGNCLFRALAHALYG---DQESHRELRQEVVDYLRENPDLYEPAELadeddGEDFDEYLQRMRKPGTWGGELELQAL 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 62751964 229 SKFYQCEICVV--DTQTVRIDRFGEDAGYTKRVL-LIYDGI-HYDPL 271
Cdd:cd22744  82 ANALNVPIVVYseDGGFLPVSVFGPGPGPSGRPIhLLYTGGnHYDAL 128

OTU (ovarian tumor) domain of OTU domain-containing proteins 6A, 6B, and similar proteins; This subfamily is composed of mammalian OTU domain-containing protein 6A (OTUD6A, also called DUBA-2, vertebrate OTU domain-containing protein 6B (OTUD6B, also called DUBA-5), fungal OTU domain-containing protein 2 (OTU2), and similar proteins. OTUD6A, OTUD6B, and Schizosaccharomyces pombe OTU2 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 62751964 154 VPADNSCLFTSVYY--VVEGGVLNPACAPEMRRLIAQ------------IVASDPDFYSEAILgktnQEYCDWIKRDDTW 219
Cdd:cd22748  11 IPPDGHCLYRAIADqlKLRGGSEEPYSYKELRKLAADymrahrddflpfLTNDDGDLMTEEEF----EEYCDKIENTAEW 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 62751964 220 GGAIEISILSKFYQCEICVVDTQTVRIdRFGEDaGYTKRVLLI 262
Cdd:cd22748  87 GGQLELRALSKALKRPIHVYQAGSPPL-VIGEE-FDSGEPLRL 127

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 62751964 154 VPADNSCLFTSV---YYVVEGGVLnpacapEMRRLIAQIVASDPDFYSEAIL-GKTNQEYCDWIKRDDTWGGAIEISILS 229
Cdd:cd21880  27 VPGDGNCFFRSIaelLFDTEDEWR------LVKNTIESYARANWDECPEARLyYLSLEEYLRDAMKDGYWGGSLEAEILS 100

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 62751964 230 KFYQCEI---CVVDTQTVRID-RFGEDaGYTKRVLLIYDGIHYDPL 271
Cdd:cd21880 101 KALGITIiiwVVDDSDWVTAAvRFGDG-DVSTSLNLLHSGGHFDAL 145

OTU (ovarian tumor) domain of Invertebrate iridescent virus putative ubiquitin thioesterase 232R and similar proteins; This subfamily contains putative ubiquitin thioesterases 232R from Invertebrate iridescent virus and L96 from Tipula iridescent virus (TIV), Dictyostelium discoideum OTU domain-containing protein DDB_G0284757, and similar proteins. L96 may be involved in TIV genomic DNA packaging in a manner related to the Gag polyproteins of the mammalian viruses. Proteins in this subfamily contain an OTU domain. 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. 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 62751964 154 VPADNSCLFTSV---YYvvegGVLNPACAPEMRRLIAQIVASDPDFYSEAILGKTN-----QEYCDWIKRDDTWGGAIEI 225
Cdd:cd22758  11 VPGDGNCFFHAVsdqLY----GNGIEHSHKELRQQAVNYLRENPELYDGFFLSEFDeeeswEEYLNRMSKDGTWGDHIIL 86

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 62751964 226 SILSKFYQCEICVVDT-QTVRIDRFGEDAGYTKRVLLI--YDGIHY 268
Cdd:cd22758  87 QAAANLFNVRIVIISSdGSDETTIIEPGNSKNGRTIYLghIGENHY 132

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU3 from plants and similar proteins; Deubiquitinating enzyme OTU3, also called OTU domain-containing protein 3, 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. OTU3 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU3 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 62751964 149 LTRTVVPADNSCLFTSV---YYVVEGGVLNP----ACAPEMRRLIAQIVASDP---DFYSEAILGKTNQE----YCDWIK 214
Cdd:cd22759   3 YTVVRVKGDGRCMFRALvkgLAANKGIFLSGreeeQEADELRLAVAEALCRSEerrRDYEEALIAITVEGsldrYCRRIQ 82

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 62751964 215 RDDTWGGAIEISILSKFYQCEICVV-----------DTQTVRIDRFGED-----AGYTKR--VLLIYDG-IHYDPL 271
Cdd:cd22759  83 RPDFWGGESELLVLSKMLKQPIIVYipeseaknggwGSGFIPIQKYGEEfakgtKGRKGRkpVRLLYSGsNHYDLL 158

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 62751964 207 QEYCDWIKRDDTWGGAIEISILSKFYQCEICVVDTQTVRIdRFGEDAGYTKRVLLIYD------GIHYD 269
Cdd:cd22761  76 EKYCDDVENTGAWGGQLELRALSHVLKRPIEVIQAEGPPI-IIGEEFKSGKPLILTYHrhayglGEHYN 143

OTU (ovarian tumor) domain of OTU domain-containing protein 3 and similar proteins; This subfamily includes bilaterial OTU domain-containing protein 3 (OTUD3), Arabidopsis thaliana deubiquitinating enzyme OTU7, also called OTU domain-containing protein 7, and similar proteins. OTUD3 is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that hydrolyzes 'Lys-6'- and 'Lys-11'-linked polyubiquitin. It is an acetylation-dependent deubiquitinase that restricts innate antiviral immune signaling. It directly hydrolyzes lysine 63 (Lys63)-linked polyubiquitination of MAVS (mitochondrial antiviral-signaling protein) and shuts off innate antiviral immune response. OTUD3 can elicit tumor-suppressing or tumor-promoting activities in a cell- and tissue-dependent manner. It is a DUB for PTEN (phosphatase and tension homologue deleted on chromosome 10); the OTUD3-PTEN signaling axis plays a critical role in suppression of breast tumorigenesis. OTUD3 is also a DUB for glucose-regulated protein GRP78, stabilizing it and promoting lung tumorigenesis. OTU7 is a DUB that shows a preference for 'Lys-63' over 'Lys-48' over 'Met-1'-linked ubiquitin (UB) tetramers as substrates. 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 62751964 154 VPADNSCLFTSV---YYvvegGvlNPACAPEMRRLIAQIVASDPDFY-------SEAILGKTNQEYCDWIKRDDTWGGAI 223
Cdd:cd22756   5 ITGDGNCLFRALsdqLY----G--DPDRHLEIRAEVVEYMRANPDDFkpfseaaTFAEDDEAFEDYLARMAKDGTYGDNL 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 62751964 224 EISILSKFYQCEICV--VDTQTVRIDRFGEDAGYTKRVLLI--YDGIHY 268
Cdd:cd22756  79 EIVAFARAYNVDVKVyqPDPVYVISAPEDGSPGPARRVLHIayHNWEHY 127

OTU (ovarian tumor) domain of OTU domain-containing protein 5 and similar proteins; OTU domain-containing protein 5 (OTUD5), also called deubiquitinating enzyme A (DUBA), is a phosphorylation-dependent deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that can hydrolyze 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, and may function as negative regulator of the innate immune system. It limits type I interferon production in macrophages and suppresses interleukin-17A production in T cells. OTUD5 also functions in an apoptotic signaling cascade by mediating the sequential activation of PDCD5 (programmed cell death 5) and p53 in response to genotoxic stress. In Drosophila, OTUD5/DUBA is essential for spermatogenesis. This subfamily also includes Arabidopsis thaliana OTU domain-containing protein 6, also called deubiquitinating enzyme OTU6 or otubain-like deubiquitinase 1 (OTLD1), which binds chromatin and has enzymatic histone deubiquitinase activity specific for the H2B histone. This subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. It also includes plant OTU6.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 62751964 154 VPADNSCLFTSVYYVVEGGvlnpacaPEMRRLIAQI----VASDPDFYSEAILGKTNqEYCDWIKRDDTWGGAIEISILS 229
Cdd:cd22752   7 MEEDGNCLFRAVADQVYGD-------QEMHDVVRKHcmdyMEKNRDYFSQFVTEDFE-EYINRKRQDGVWGNHIEIQAMS 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 62751964 230 KFYQCEICVVDTQTVRIDRFGE--DAGYTKRVLLIYDGIHYD 269
Cdd:cd22752  79 ELYNRPIEVYAYSTEPINTFHEasSSDNEPIRLSYHGNSHYN 120