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 442630318 148 GILLKKVVPADNSCLFTSIRFVLNGKVDNEGSEMmRHIIAQEVAADPQSYNDAVLGKSNAEYCAWIQKADSWGGAIEVSI 227
Cdd:cd22745    1 GYLVRRVVPDDNSCLFTSISYLLEGGLLDSAPEL-REIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630318 228 LSNYYGIEIDVVDIQNAIINRFGEDKNFGLRVFLLFDGIHYDPLYMETSPSAAPA---TIFPVEELGVYQQAEQLANEAQ 304
Cdd:cd22745   80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLDAPEDfdvTVFSVSDDEVLEAALELAKELK 159

                 ..
gi 442630318 305 SS 306
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 442630318 148 GILLKKVVPADNSCLFTSIRFVLNGKVDNEGSEMmRHIIAQEVAADPQSYNDAVLGKSNAEYCAWIQKADSWGGAIEVSI 227
Cdd:cd22745    1 GYLVRRVVPDDNSCLFTSISYLLEGGLLDSAPEL-REIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630318 228 LSNYYGIEIDVVDIQNAIINRFGEDKNFGLRVFLLFDGIHYDPLYMETSPSAAPA---TIFPVEELGVYQQAEQLANEAQ 304
Cdd:cd22745   80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLDAPEDfdvTVFSVSDDEVLEAALELAKELK 159

                 ..
gi 442630318 305 SS 306
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 442630318   5 FSVKLKSKKGQFIVNDLNEHTTLGELKTKIVQATDIEATQLHVLVGYPPKPLDLSqqQEQRALKAVGINSGETLIVE 81
Cdd:cd17059    1 MRLRVRSKGGQHVLSLLTDTSTVGELQDRIAALTGIPPSSQKILYGFPPKPLDLS--DEEASLESLGIQSGDTLIVE 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 442630318 148 GILLKKVVPADNSCLFTSIRFVLNGKVDNEGSEMmRHIIAQEVAADPQSYNDAVLGKSNAEYCAWIQKADSWGGAIEVSI 227
Cdd:cd22745    1 GYLVRRVVPDDNSCLFTSISYLLEGGLLDSAPEL-REIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630318 228 LSNYYGIEIDVVDIQNAIINRFGEDKNFGLRVFLLFDGIHYDPLYMETSPSAAPA---TIFPVEELGVYQQAEQLANEAQ 304
Cdd:cd22745   80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLDAPEDfdvTVFSVSDDEVLEAALELAKELK 159

                 ..
gi 442630318 305 SS 306
Cdd:cd22745  160 AK 161

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630318 158 DNSCLFTSIRFvlnGKVDNEGSEMmRHIIAQEVAADPQSYNDAVLGKSNAEYCAWIQKADSWG-GAIEVSILSNYYGIEI 236
Cdd:COG5539  120 DNSRLFQAERY---SLRDASVAKL-REVVSLEVLSNPDLYNPAILEIDVIAYATWIVKPDSQGdGCIEIAIISDQLPVRI 195

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 442630318 237 DVVDIQNAIINRFGEDkNFGLRVFLLFDGIHYDPLYMETSP-SAAPATIFPVEELGVYQQAEQLANEAQSSRQYTNVDKF 315
Cdd:COG5539  196 HVVDVDKDSEDRYNSH-PYVQRISILFTGIHFDEETLAMVLwDTYVNEVLFDASDGITIEIQQLASLLKNPHYYTNTASP 274

                        170       180       190
                 ....*....|....*....|....*....|.
gi 442630318 316 TLRCMQCDVRLVGQVQAQEHAKQTGHKNFGE 346
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 442630318 155 VPADNSCLFTSIRFVLNGkvDNEGSEMMRHIIAQEVAADPQSYNDAVL-----GKSNAEYCAWIQKADSWGGAIEVSILS 229
Cdd:cd22744    5 VPGDGNCLFRALAHALYG--DQESHRELRQEVVDYLRENPDLYEPAELadeddGEDFDEYLQRMRKPGTWGGELELQALA 82

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 442630318 230 NYYGIEIDVVDIQNAIINR--FGEDKNFGLR-VFLLFDGI-HYDPL 271
Cdd:cd22744   83 NALNVPIVVYSEDGGFLPVsvFGPGPGPSGRpIHLLYTGGnHYDAL 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 442630318 155 VPADNSCLFTSIRFVLngkVDNEGS-EMMRHIIAQEVAADPQSYNDAVL-GKSNAEYCAWIQKADSWGGAIEVSILSNYY 232
Cdd:cd21880   27 VPGDGNCFFRSIAELL---FDTEDEwRLVKNTIESYARANWDECPEARLyYLSLEEYLRDAMKDGYWGGSLEAEILSKAL 103

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 442630318 233 GIEI------DVVDIQNAIinRFGEDKNFGlRVFLLFDGIHYDPLYM 273
Cdd:cd21880  104 GITIiiwvvdDSDWVTAAV--RFGDGDVST-SLNLLHSGGHFDALRL 147

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 442630318 155 VPADNSCLFTSIRFVLNGKVDNEGSEMMRHIIAQEVAADPQSYNDAVLGKSNA-----EYCAWIQKADSWGGAIEVSILS 229
Cdd:cd22758   11 VPGDGNCFFHAVSDQLYGNGIEHSHKELRQQAVNYLRENPELYDGFFLSEFDEeesweEYLNRMSKDGTWGDHIILQAAA 90

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 442630318 230 NYYGIEIDVV----DIQNAIINRFGEDKNfglRVFLL--FDGIHY 268
Cdd:cd22758   91 NLFNVRIVIIssdgSDETTIIEPGNSKNG---RTIYLghIGENHY 132

ubiquitin-like (Ubl) domain found in ubiquitin and ubiquitin-like Ubl proteins; Ubiquitin-like (Ubl) proteins have a similar ubiquitin (Ub) beta-grasp fold and attach to other proteins in a Ubl manner but with biochemically distinct roles. Ub and Ubl proteins conjugate and deconjugate via ligases and peptidases to covalently modify target polypeptides. Some Ubl domains have adaptor roles in Ub-signaling by mediating protein-protein interaction. Prokaryotic sulfur carrier proteins are Ub-related proteins that can be activated in an ATP-dependent manner. Polyubiquitination signals for a diverse set of cellular events via different isopeptide linkages formed between the C terminus of one ubiquitin (Ub) and the epsilon-amine of K6, K11, K27, K29, K33, K48, or K63 of a second Ub. One of these seven lysine residues (K27, Ub numbering) is conserved in this Ubl_ubiquitin_like family. K27-linked Ub chains are versatile and can be recognized by several downstream receptor proteins. K27 has roles beyond chain linkage, such as in Ubl NEDD8 (which contains many of the same lysines (K6, K11, K27, K33, K48) as Ub) where K27 has a role (other than conjugation) in the mechanism of protein neddylation.

                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 442630318   7 VKLKSKKGQFIVNDLNEHTTLGELKTKIVQATDIEATQLHVLvgYPPKPLdlsqqQEQRALKAVGINSGETLIV 80
Cdd:cd17039    1 ITVKTLDGKTYTVEVDPDDTVADLKEKIEEKTGIPVEQQRLI--YNGKEL-----KDDKTLSDYGIKDGSTIHL 67