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 2319158784 143 VLTRTAVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDLYSEAILGKTNEEYCDWIRRDDTWGGAIEISI 222
Cdd:cd22745     2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158784 223 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 300
Cdd:cd22745    80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                  ..
gi 2319158784 301 RK 302
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 2319158784 143 VLTRTAVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDLYSEAILGKTNEEYCDWIRRDDTWGGAIEISI 222
Cdd:cd22745     2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158784 223 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 300
Cdd:cd22745    80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                  ..
gi 2319158784 301 RK 302
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 2319158784  42 WRLRCKAKGGTHVLQGLSNRTRLRELQGQIAAITGIAPGSQRILVGYPPECLDLSDRDITLGDLPIQSGDMLIVE 116
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 2319158784 143 VLTRTAVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDLYSEAILGKTNEEYCDWIRRDDTWGGAIEISI 222
Cdd:cd22745     2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158784 223 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 300
Cdd:cd22745    80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                  ..
gi 2319158784 301 RK 302
Cdd:cd22745   160 AK 161

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158784  72 AAITGIAPGSQRILVGYPPE-----CLDLSDrDITLGD-LPIQSGDMLIVEEDQTRPKAS----PAFSKHG----APSYV 137
Cdd:COG5539    27 DLQTKITRIMKQLTFGRPPQrlngkCLDLSY-ALSQKDeVEIEKAPKLRAETNEADQEDSltplQNIPELGissfEKSVS 105

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158784 138 RETLPVLTRTAVPADNSCLFTSVYYVveggvLNPACAPEMRRLIAQIVASDPDLYSEAILGKTNEEYCDWIRRDDTWG-G 216
Cdd:COG5539   106 QQSINVLEDMPGQDDNSRLFQAERYS-----LRDASVAKLREVVSLEVLSNPDLYNPAILEIDVIAYATWIVKPDSQGdG 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2319158784 217 AIEISILSKFYQCEICVVDTQTVRIDRFGEDAgYTKRVLLIYDGIHYDPLQRNFPDPDTPPLTIFSSNDDIVLVQALELA 296
Cdd:COG5539   181 CIEIAIISDQLPVRIHVVDVDKDSEDRYNSHP-YVQRISILFTGIHFDEETLAMVLWDTYVNEVLFDASDGITIEIQQLA 259

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 2319158784 297 DEARRKRQFTDVNRFTLRCMLCQKGLTGQAEARDHARETGHTNFGE 342
Cdd:COG5539   260 SLLKNPHYYTNTASPSIKCNICGTGFVGEKDYYAHALATGHYNFGE 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 2319158784 145 TRTAVPADNSCLFTSVYYVVEGgvlNPACAPEMRRLIAQIVASDPDLYSEAIL-----GKTNEEYCDWIRRDDTWGGAIE 219
Cdd:cd22744     1 RVVDVPGDGNCLFRALAHALYG---DQESHRELRQEVVDYLRENPDLYEPAELadeddGEDFDEYLQRMRKPGTWGGELE 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 2319158784 220 ISILSKFYQCEICVV--DTQTVRIDRFGEDAGYTKRVL-LIYDGI-HYDPL 266
Cdd:cd22744    78 LQALANALNVPIVVYseDGGFLPVSVFGPGPGPSGRPIhLLYTGGnHYDAL 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 2319158784 149 VPADNSCLFTSVYY--VVEGGVLNPACAPEMRRLIAQ------------IVASDPDLYSEAILgktnEEYCDWIRRDDTW 214
Cdd:cd22748    11 IPPDGHCLYRAIADqlKLRGGSEEPYSYKELRKLAADymrahrddflpfLTNDDGDLMTEEEF----EEYCDKIENTAEW 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2319158784 215 GGAIEISILSKFYQCEICVVDTQTVRIdRFGEDaGYTKRVLLI 257
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 2319158784 149 VPADNSCLFTSVYYVVEGGvlnpacaPEMRRLIAQIVASDPDLY----SEAIL-GKTNEEYCDWIRRDDTWGGAIEISIL 223
Cdd:cd21880    27 VPGDGNCFFRSIAELLFDT-------EDEWRLVKNTIESYARANwdecPEARLyYLSLEEYLRDAMKDGYWGGSLEAEIL 99

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2319158784 224 SKFYQCEI---CVVDTQTVRID-RFGEDaGYTKRVLLIYDGIHYDPL 266
Cdd:cd21880   100 SKALGITIiiwVVDDSDWVTAAvRFGDG-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 2319158784 149 VPADNSCLFTSV---YYvvegGVLNPACAPEMRRLIAQIVASDPDLYSEAILGKTN-----EEYCDWIRRDDTWGGAIEI 220
Cdd:cd22758    11 VPGDGNCFFHAVsdqLY----GNGIEHSHKELRQQAVNYLRENPELYDGFFLSEFDeeeswEEYLNRMSKDGTWGDHIIL 86

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2319158784 221 SILSKFYQCEICVVDT-QTVRIDRFGEDAGYTKRVLLI--YDGIHY 263
Cdd:cd22758    87 QAAANLFNVRIVIISSdGSDETTIIEPGNSKNGRTIYLghIGENHY 132

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 2319158784 145 TRTAVPADNSCLFTSVYYVVEGGVLnpacapEMRRLIAQIVASDPDLYSE--AILGktneeycdwirrDDTWGGAIEISI 222
Cdd:cd22792     1 KVVPVPGDGNCFWHSLGHFLGLSAL------ELKKLLRDSLFDDPELDEEldEQLE------------PGVYAEDEAIAA 62

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2319158784 223 LSKFYQCEICVVDTQTVRIDRFGEDaGYTKRVLLIYDGIHYDPL 266
Cdd:cd22792    63 AAKLFGVNICVHDPDEGVLYTFTPN-ESSKSIHLLLENEHFEPL 105

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 2319158784 144 LTRTAVPADNSCLFTSVYY--VVEGGVLNpacAPEMRRLIAQIV-------------ASDPDLYSEAILgktnEEYCDWI 208
Cdd:cd22761    10 LKIHEIPSDGDCLYNAIAHqlSLRGIETS---VEELRKQTADYMrenkddflpfltnPDTGDPLTEEEF----EKYCDDV 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2319158784 209 RRDDTWGGAIEISILSKFYQCEICVVDTQTVRIdRFGEDAGYTKRVLLIYD------GIHYD 264
Cdd:cd22761    83 ENTGAWGGQLELRALSHVLKRPIEVIQAEGPPI-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 2319158784 149 VPADNSCLFTSV---YYvvegGvlNPACAPEMRRLIAQIVASDPDLY-------SEAILGKTNEEYCDWIRRDDTWGGAI 218
Cdd:cd22756     5 ITGDGNCLFRALsdqLY----G--DPDRHLEIRAEVVEYMRANPDDFkpfseaaTFAEDDEAFEDYLARMAKDGTYGDNL 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2319158784 219 EISILSKFYQCEICV--VDTQTVRIDRFGEDAGYTKRVLLI--YDGIHY 263
Cdd:cd22756    79 EIVAFARAYNVDVKVyqPDPVYVISAPEDGSPGPARRVLHIayHNWEHY 127

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 2319158784 149 VPADNSCLFTSVYYVVEGgvlNPACAPEMRRLIAQIVASDPDLYSEaILGKTNEEYCDWIRR-----DDTWGGAIEISIL 223
Cdd:cd22755     6 IVGDGNCFFRALSYAITG---SEKYHRKIRKAIVDFLEKNPDEFRN-LLRSDYESVEEYLEKsrmryDGTWATDVEIFAA 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2319158784 224 SKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLL---IY----DGIHYDP 265
Cdd:cd22755    82 ATLLGVDIYVYSKGGYKWLLYSPRFKLGKRNGSreaIYlkntNGNHFEP 130

ubiquitin-like (Ubl) domain 1 found in interferon-stimulated gene 15 (ISG15) and similar proteins; ISG15, also termed interferon-induced 15 kDa protein, or interferon-induced 17 kDa protein (IP17), or ubiquitin cross-reactive protein (UCRP), is an antiviral interferon-induced ubiquitin-like protein (Ubl) that upon viral infection, modifies cellular and viral proteins by mechanisms similar to ubiquitination. Although ISG15 has properties similar to those of other Ubl molecules, it is a unique member of the Ubl superfamily, whose expression and conjugation to target proteins are tightly regulated by specific signaling pathways, indicating it may have specialized functions in the immune system. ISG15 contains two tandem Ubl domains with a beta-grasp Ubl fold. This family corresponds to the first Ubl domain.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 2319158784  42 WRLRCKAKGGTHVLQGLSNRTRLRELQGQIAAITGIAPGSQRILVgyPPECLDLSDRdITLGDLPI--QSGDMLIVEE 117
Cdd:cd01792     1 WDLTVKMLTGNEFQVSVSPSMTVSELKAQITQKIGVPAFQQRLAV--QPSGVELQDG-VRLASQGLgpSSTVLLVVKK 75

ubiquitin-like (Ubl) domain found in ubiquitin-specific-processing protease 48 (USP48) and similar proteins; USP48, also termed USP31, or deubiquitinating enzyme 48, or ubiquitin thioesterase 48, or ubiquitin carboxyl-terminal hydrolase 48, belongs to the ubiquitin specific protease (USP) family that is one of at least seven deubiquitylating enzyme (DUB) families capable of deconjugating ubiquitin (Ub)and ubiquitin-like (Ubl) adducts. While the USP proteins have a conserved catalytic core domain, USP48 differs in its domain architecture. It contains an N-terminal USP domain, three DUSP (domain present in ubiquitin-specific protease) domains, and a C-terminal Ubl domain with a beta-grasp Ubl fold, a common structure involved in protein-protein interactions. USP48 is a deubiquitinating enzyme that interacts with TNF receptor-associated factor 2 (TRAF2) and has been implicated in activation of nuclear factor-kappaB (NF-kappaB). Moreover, as a nuclear deubiquitinase regulated by casein kinase 2 (CK2), USP48 controls the ubiquitin/proteasome-system (UPS)-dependent turnover of activated NF-kappaB/RelA in the nucleus together with the COP9 signalosome, suggesting a role of USP48 in a timely control of immune responses.

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gi 2319158784  47 KAKGGTHVLQGLSNRTrLRELQGQIAAITGIAPGSQRILVGyppeCLDLSDRDITLGDLPIQSGDMLIVEEDQ 119
Cdd:cd01795     2 RVRGERKSLTVSSTTT-LKELKLQIMEKFSVAPFDQHLYFN----GRELTDDSATLADLGILPGDVLYLKVDE 69

OTU (ovarian tumor) domain of nucleopolyhedrovirus P87/VP80 protein and similar proteins; The VP80 protein is a capsid-associated structural protein that was first identified as P87 in Orgyia pseudotsugata multicapsid nuclear polyhedrosis virus (OpMNPV); its homologs are found only in NPV genomes. The Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV) VP80 protein is essential for the formation of both budded virus (BV) and occlusion-derived virus (ODV). It has also been shown to interact with the virus-triggered, nuclear F-actin cytoskeleton. P87/VP80 contains an N-terminal 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.

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gi 2319158784 149 VPADNSCLFTSVYYVVEGGVLNpacAPEMRRLIAQIVASDPDLYSEAIL------GKTNEEYCDWIRRDDTWGGAIEISI 222
Cdd:cd22757     6 IPGDGACLFRALSYLLYGTQSR---HLEVRKEVVDYVVNNWDEFSIYTHdsegnnYKSAEEYRADMSKPGTYGTLCELVA 82

                  ....*.
gi 2319158784 223 LSKFYQ 228
Cdd:cd22757    83 AAELYP 88