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 444299626 104 VLTRTVVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWGGAIEISI 183
Cdd:cd22745    2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444299626 184 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 261
Cdd:cd22745   80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                 ..
gi 444299626 262 RR 263
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 444299626 104 VLTRTVVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWGGAIEISI 183
Cdd:cd22745    2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444299626 184 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 261
Cdd:cd22745   80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                 ..
gi 444299626 262 RR 263
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
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 444299626  13 SFTVEGLSSRTRVRELQGQIAAITGIAPGGQRILVGYPPECLDLSNGDTILEDLPIQSGDMLIIE 77
Cdd:cd17059   11 QHVLSLLTDTSTVGELQDRIAALTGIPPSSQKILYGFPPKPLDLSDEEASLESLGIQSGDTLIVE 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 444299626 104 VLTRTVVPADNSCLFTSVYYVVEGGVLNpaCAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWGGAIEISI 183
Cdd:cd22745    2 YLVRRVVPDDNSCLFTSISYLLEGGLLD--SAPELREIVADAILSDPDTYNEAILGKPPDEYCAWILKPDSWGGAIELSI 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444299626 184 LSKFYQCEICVVDTQTVRIDRFGEDAGYTKRVLLIYDGIHYDPLQRNFPD--PDTPPLTIFSSNDDIVLVQALELADEAR 261
Cdd:cd22745   80 LSKHFGVEICVVDVQTGRVDRFGEDKGYSKRIFLLYSGIHYDALALNPSLdaPEDFDVTVFSVSDDEVLEAALELAKELK 159

                 ..
gi 444299626 262 RR 263
Cdd:cd22745  160 AK 161

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444299626  47 VGYPPE-----CLDLSNGDTILEDLPIQSGDMLIIEEDQTRPRSS----PAFTKRGAS----SYVRETLPVLTRTVVPAD 113
Cdd:COG5539   41 FGRPPQrlngkCLDLSYALSQKDEVEIEKAPKLRAETNEADQEDSltplQNIPELGISsfekSVSQQSINVLEDMPGQDD 120

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444299626 114 NSCLFTSVYYVveggvLNPACAPEMRRLIAQIVASDPDFYSEAILGKTNQEYCDWIKRDDTWG-GAIEISILSKFYQCEI 192
Cdd:COG5539  121 NSRLFQAERYS-----LRDASVAKLREVVSLEVLSNPDLYNPAILEIDVIAYATWIVKPDSQGdGCIEIAIISDQLPVRI 195

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 444299626 193 CVVDTQTVRIDRFGEDAgYTKRVLLIYDGIHYDPLQRNFPDPDTPPLTIFSSNDDIVLVQALELADEARRRRQFTDVNRF 272
Cdd:COG5539  196 HVVDVDKDSEDRYNSHP-YVQRISILFTGIHFDEETLAMVLWDTYVNEVLFDASDGITIEIQQLASLLKNPHYYTNTASP 274

                        250       260       270
                 ....*....|....*....|....*....|.
gi 444299626 273 TLRCMVCQKGLTGQAEAREHAKETGHTNFGE 303
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 444299626 110 VPADNSCLFTSVYYVVEGgvlNPACAPEMRRLIAQIVASDPDFYSEAIL-----GKTNQEYCDWIKRDDTWGGAIEISIL 184
Cdd:cd22744    5 VPGDGNCLFRALAHALYG---DQESHRELRQEVVDYLRENPDLYEPAELadeddGEDFDEYLQRMRKPGTWGGELELQAL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 444299626 185 SKFYQCEICVV--DTQTVRIDRFGEDAGYTKRVL-LIYDGI-HYDPL 227
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 444299626 110 VPADNSCLFTSVYY--VVEGGVLNPACAPEMRRLIAQ------------IVASDPDFYSEAILgktnQEYCDWIKRDDTW 175
Cdd:cd22748   11 IPPDGHCLYRAIADqlKLRGGSEEPYSYKELRKLAADymrahrddflpfLTNDDGDLMTEEEF----EEYCDKIENTAEW 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|...
gi 444299626 176 GGAIEISILSKFYQCEICVVDTQTVRIdRFGEDaGYTKRVLLI 218
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 444299626 110 VPADNSCLFTSV---YYVVEGGVLnpacapEMRRLIAQIVASDPDFYSEAIL-GKTNQEYCDWIKRDDTWGGAIEISILS 185
Cdd:cd21880   27 VPGDGNCFFRSIaelLFDTEDEWR------LVKNTIESYARANWDECPEARLyYLSLEEYLRDAMKDGYWGGSLEAEILS 100

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 444299626 186 KFYQCEI---CVVDTQTVRID-RFGEDaGYTKRVLLIYDGIHYDPL 227
Cdd:cd21880  101 KALGITIiiwVVDDSDWVTAAvRFGDG-DVSTSLNLLHSGGHFDAL 145

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 444299626 106 TRTVVPADNSCLFTSVYYVVEGGVLnpacapEMRRLIAQIVASDPDFYSEAilgktnqeycDWIKRDDTWGGAIEISILS 185
Cdd:cd22792    1 KVVPVPGDGNCFWHSLGHFLGLSAL------ELKKLLRDSLFDDPELDEEL----------DEQLEPGVYAEDEAIAAAA 64

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 444299626 186 KFYQCEICVVDTQTVRIDRFGEDaGYTKRVLLIYDGIHYDPL 227
Cdd:cd22792   65 KLFGVNICVHDPDEGVLYTFTPN-ESSKSIHLLLENEHFEPL 105

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 444299626 105 LTRTVVPADNSCLFTSV---YYVVEGGVLNP----ACAPEMRRLIAQIVASDP---DFYSEAILGKTNQE----YCDWIK 170
Cdd:cd22759    3 YTVVRVKGDGRCMFRALvkgLAANKGIFLSGreeeQEADELRLAVAEALCRSEerrRDYEEALIAITVEGsldrYCRRIQ 82

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 444299626 171 RDDTWGGAIEISILSKFYQCEICVV-----------DTQTVRIDRFGED-----AGYTKR--VLLIYDG-IHYDPL 227
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 444299626 163 QEYCDWIKRDDTWGGAIEISILSKFYQCEICVVDTQTVRIdRFGEDAGYTKRVLLIYD------GIHYD 225
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 444299626 110 VPADNSCLFTSV---YYvvegGvlNPACAPEMRRLIAQIVASDPDFY-------SEAILGKTNQEYCDWIKRDDTWGGAI 179
Cdd:cd22756    5 ITGDGNCLFRALsdqLY----G--DPDRHLEIRAEVVEYMRANPDDFkpfseaaTFAEDDEAFEDYLARMAKDGTYGDNL 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 444299626 180 EISILSKFYQCEICV--VDTQTVRIDRFGEDAGYTKRVLLI--YDGIHY 224
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 444299626 110 VPADNSCLFTSVYYVVEGGvlnpacaPEMRRLIAQI----VASDPDFYSEAILGKTNqEYCDWIKRDDTWGGAIEISILS 185
Cdd:cd22752    7 MEEDGNCLFRAVADQVYGD-------QEMHDVVRKHcmdyMEKNRDYFSQFVTEDFE-EYINRKRQDGVWGNHIEIQAMS 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 444299626 186 KFYQCEICVVDTQTVRIDRFGE--DAGYTKRVLLIYDGIHYD 225
Cdd:cd22752   79 ELYNRPIEVYAYSTEPINTFHEasSSDNEPIRLSYHGNSHYN 120