OTU (ovarian tumor) domain of plant deubiquitinating enzyme OTU9 and similar proteins; This subfamily contains Arabidopsis thaliana deubiquitinating enzymes OTU8, OTU9, OTU10, OTU11, and OTU12, and similar proteins from plants and other eukaryotes. OTU8-OTU12 are 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 18403314  92 LSGRLATYGLAELQMEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKL-YEEYVPMKYRHYTRKMKKHGEWGDH 170
Cdd:cd22751   1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPELyYEFYVPEEYDEYLKKMSKDGEWGDE 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 18403314 171 VTLQAAADRFEAKICLVTSFRDQSYIEILPHN-KNPLREAWLSFWSEVHYNSLY 223
Cdd:cd22751  81 LTLQAAADAFGVKIHVITSFEDNWFLEIEPRGlVRSKRVLFLSYWAEVHYNSIY 134

OTU (ovarian tumor) domain of plant deubiquitinating enzyme OTU9 and similar proteins; This subfamily contains Arabidopsis thaliana deubiquitinating enzymes OTU8, OTU9, OTU10, OTU11, and OTU12, and similar proteins from plants and other eukaryotes. OTU8-OTU12 are 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 18403314  92 LSGRLATYGLAELQMEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKL-YEEYVPMKYRHYTRKMKKHGEWGDH 170
Cdd:cd22751   1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPELyYEFYVPEEYDEYLKKMSKDGEWGDE 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 18403314 171 VTLQAAADRFEAKICLVTSFRDQSYIEILPHN-KNPLREAWLSFWSEVHYNSLY 223
Cdd:cd22751  81 LTLQAAADAFGVKIHVITSFEDNWFLEIEPRGlVRSKRVLFLSYWAEVHYNSIY 134

OTU (ovarian tumor) domain of plant deubiquitinating enzyme OTU9 and similar proteins; This subfamily contains Arabidopsis thaliana deubiquitinating enzymes OTU8, OTU9, OTU10, OTU11, and OTU12, and similar proteins from plants and other eukaryotes. OTU8-OTU12 are 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 18403314  92 LSGRLATYGLAELQMEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKL-YEEYVPMKYRHYTRKMKKHGEWGDH 170
Cdd:cd22751   1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPELyYEFYVPEEYDEYLKKMSKDGEWGDE 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 18403314 171 VTLQAAADRFEAKICLVTSFRDQSYIEILPHN-KNPLREAWLSFWSEVHYNSLY 223
Cdd:cd22751  81 LTLQAAADAFGVKIHVITSFEDNWFLEIEPRGlVRSKRVLFLSYWAEVHYNSIY 134

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18403314 100 GLAELQMEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKLYEEYVP--MKYRHYTRKMKKHGEWGDHVTLQAAA 177
Cdd:cd22771   1 GLRIRDVEGDGNCLFRALADQLYGDEERHAELRKKVVDYMEAHEEDFEPFFEddETFEDYVSRMREDGTWGGNLELQAAS 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....
gi 18403314 178 DRFEAKICLVTSfrDQSYIEILPHNKNPLREAWLSFWSEVHYNS 221
Cdd:cd22771  81 LVYRVNIVVHQL--GQPRWEIENFPDKGARTIHLSYHDGEHYNS 122

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 18403314 100 GLAELQMEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKLYEEYVPMKYRHYTRKMKKHGEWGDHVTLQAAADR 179
Cdd:cd22752   1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSEL 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 18403314 180 FEAKICLVTSFRDQSYI--EILPHNKNPLReawLSFWSEVHYNSLY 223
Cdd:cd22752  81 YNRPIEVYAYSTEPINTfhEASSSDNEPIR---LSYHGNSHYNSIV 123

OTU (ovarian tumor) domain of bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 and similar proteins; Bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 is alco called asparagine-linked glycosylation 13 homolog, glycosyltransferase 28 domain-containing protein 1 (GLT28D1), or UDP-N-acetylglucosamine transferase subunit ALG13 homolog. It displays both glycosyltransferase (EC 2.4.1.141) and deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) activities. With ALG14, it forms a UDP-N-acetylglucosamine transferase that catalyzes the second step of eukaryotic N-linked glycosylation in the endoplasmic reticulum. ALG13 variants cause a form of early infantile epileptic encephalopathy known as EIEE36 refractory seizures, neurodevelopmental impairment, and poor prognosis; given the essential role of ALG13 in glycosylation, it is also considered a congenital disorder of glycosylation (CDG). This subfamily also contains OTU domain-containing protein 4 (OTUD4), also called HIV-1-induced protein HIN-1, a DUB that specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein upon phosphorylation, triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators. 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 18403314 109 DGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKLYEEYVPMKYRHYTRKMKKHGEWGDHVTLQAAADRFEAKICLvt 188
Cdd:cd22753  18 DGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKEWGGLLELEALSLLYKVDFIV-- 95

                        90       100       110
                ....*....|....*....|....*....|....*
gi 18403314 189 sFRDQSYIEILPHNKNPLREAWLSFWSEVHYNSLY 223
Cdd:cd22753  96 -YSIPDQPPSNITNNGYPKKIMLCYSGGNHYDSVY 129

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18403314  96 LATYGLAELQMEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKLYEEYVPMKYRHYTRKMKKHGEWGDHVTLQA 175
Cdd:cd22794   5 LRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQVEISA 84

                ....*
gi 18403314 176 AADRF 180
Cdd:cd22794  85 LSLMY 89

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU6 from plants and similar proteins; Deubiquitinating enzyme OTU6, also called OTU domain-containing protein 6 or otubain-like deubiquitinase 1 (OTLD1), 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. OTU6 binds chromatin and has enzymatic histone deubiquitinase activity specific for the H2B histone. OTU6 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 18403314 100 GLAELQMEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKLYEEYVPMKYRHYTRKMKKHGEWGDHVTLQAAADR 179
Cdd:cd22796   4 GLEIRRMDGDGNCLFRAVADQVYGDQEMHDEVREMCMDYMEKERDHFSQFVTEDFTQYVKRKRRDRVFGNNLEIQAMSEI 83

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 18403314 180 FEAKIcLVTSFRDQSYIEIL----PHNKNPLReawLSFWSEVHYNSLY 223
Cdd:cd22796  84 YNRPI-EVYSYSNGEPINIFhgsyEGDDPPIR---LSYHDGNHYNSII 127

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.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18403314 106 MEGDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKLYEEYVPMK----YR---HYTRKMKKHGEWGDHVTLQAAAD 178
Cdd:cd22757   6 IPGDGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIYTHDSegnnYKsaeEYRADMSKPGTYGTLCELVAAAE 85

                        90
                ....*....|....*....
gi 18403314 179 RFeaKICLVTsFRDQSYIE 197
Cdd:cd22757  86 LY--PFHFEV-YRNGKLYA 101

OTU-like cysteine protease; This family is comprised of a group of predicted cysteine proteases, homologous to the Ovarian Tumour (OTU) gene in Drosophila. Members include proteins from eukaryotes, viruses and pathogenic bacterium. The conserved cysteine and histidine, and possibly the aspartate, represent the catalytic residues in this putative group of proteases.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18403314   108 GDGNCQFRALADQLFRNAD-----YHKHVRKHVVKQLKQQRKLYEEYVPMKYRHYTRKMKKHGEWGDHVTLQAAADRFEA 182
Cdd:pfam02338   2 GDGNCLYRSISHQLWGVHDvlrkmLVQELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFALAHILRR 81

                          90
                  ....*....|
gi 18403314   183 KICLVTSFRD 192
Cdd:pfam02338  82 PIIVYKSEGG 91

OTU (ovarian tumor) domain of vertnin and similar proteins; Vertnin (VRTN) is an OTU domain-containing protein that is required for the development of thoracic vertebrae in mammals. 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. Vertnin and some subfamily members do not possess the conserved catalytic residues and may not have DUB activity. VRTN gene is associated with variations in vertebral number.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 18403314 108 GDGNCQFRALADQLFRNADYHKHVRKHVVKQLKQQRKLYEEYvpmkYRHYTRKMKKHGEWGDHVTLQAAADRFEAKICLV 187
Cdd:cd22791   8 GDGNCLFRAASLLLFGDESLHLELRLRTVLELVLNSEFYEAI----YEAEIKATCKPGSYSGIWHIYALSSVLQRPIFSV 83

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 18403314  96 LATYGLAELQMEGDGNCQFRALADQLfrnadyHKHVRKHVVKQLKQQ-----RKLYEEYVPM-------------KYRHY 157
Cdd:cd22761   5 LKERGLKIHEIPSDGDCLYNAIAHQL------SLRGIETSVEELRKQtadymRENKDDFLPFltnpdtgdplteeEFEKY 78

                        90       100
                ....*....|....*....|....*..
gi 18403314 158 TRKMKKHGEWGDHVTLQAAADRFEAKI 184
Cdd:cd22761  79 CDDVENTGAWGGQLELRALSHVLKRPI 105

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 18403314 105 QMEGDGNCQFRALADQLFRNADYHKHVRKHVV-------KQLKQQRKLYEEYVpmkyrHYTRKMKKHGEWG 168
Cdd:cd21880  26 RVPGDGNCFFRSIAELLFDTEDEWRLVKNTIEsyaranwDECPEARLYYLSLE-----EYLRDAMKDGYWG 91