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 209977067   1 MKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVE 80
Cdd:cd22752    7 MEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSELYNRPIE 86

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 209977067  81 VYQYSTEPINTFHGIHQNEDEPIRVSYHRNIHYNSVVN 118
Cdd:cd22752   87 VYAYSTEPINTFHEASSSDNEPIRLSYHGNSHYNSIVD 124

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 209977067   1 MKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVE 80
Cdd:cd22752    7 MEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSELYNRPIE 86

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 209977067  81 VYQYSTEPINTFHGIHQNEDEPIRVSYHRNIHYNSVVN 118
Cdd:cd22752   87 VYAYSTEPINTFHEASSSDNEPIRLSYHGNSHYNSIVD 124

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 209977067   1 MKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVE 80
Cdd:cd22752    7 MEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSELYNRPIE 86

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 209977067  81 VYQYSTEPINTFHGIHQNEDEPIRVSYHRNIHYNSVVN 118
Cdd:cd22752   87 VYAYSTEPINTFHEASSSDNEPIRLSYHGNSHYNSIVD 124

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 209977067   1 MKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSN------YVTEDFTTYINRKRKNNCHGNHIEMQAMAEM 74
Cdd:cd22744    5 VPGDGNCLFRALAHALYGDQESHRELRQEVVDYLRENPDLYEPaeladeDDGEDFDEYLQRMRKPGTWGGELELQALANA 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 209977067  75 YNRPVEVYQYST--EPINTFHGIHQNEDEPIRVSYHRNIHYNSV 116
Cdd:cd22744   85 LNVPIVVYSEDGgfLPVSVFGPGPGPSGRPIHLLYTGGNHYDAL 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 209977067   4 DGACLFRAVADQV-----YGDQDMHEVVRKHCMDYLMKNADYFSNYVT---------EDFTTYINRKRKNNCHGNHIEMQ 69
Cdd:cd22748   14 DGHCLYRAIADQLklrggSEEPYSYKELRKLAADYMRAHRDDFLPFLTnddgdlmteEEFEEYCDKIENTAEWGGQLELR 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 209977067  70 AMAEMYNRPVEVYQYSTEPINtfHGIHQNEDEPIRVSYHRNI-----HYNSVV 117
Cdd:cd22748   94 ALSKALKRPIHVYQAGSPPLV--IGEEFDSGEPLRLSYHRHAyglgeHYNSVV 144

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 209977067   3 EDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVY 82
Cdd:cd22753   17 RDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKEWGGLLELEALSLLYKVDFIVY 96

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 209977067  83 Q-YSTEPINTFHGIHQNEdepIRVSYHRNIHYNSVV 117
Cdd:cd22753   97 SiPDQPPSNITNNGYPKK---IMLCYSGGNHYDSVY 129

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 209977067   4 DGACLFRAVADQVYGDQ--DMHEVVRKHCMDYLMKNADYFSNYV------TEDFTTYINRKRKNNCHGNHIEMQAMAEMY 75
Cdd:cd22758   14 DGNCFFHAVSDQLYGNGieHSHKELRQQAVNYLRENPELYDGFFlsefdeEESWEEYLNRMSKDGTWGDHIILQAAANLF 93

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 209977067  76 NRPVEVY-QYSTEPINTFHGIHQNEDEPIRVSYHRNIHYNSV 116
Cdd:cd22758   94 NVRIVIIsSDGSDETTIIEPGNSKNGRTIYLGHIGENHYVSL 135

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 209977067    4 DGACLFRAVADQVYGDQDM-----HEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRP 78
Cdd:pfam02338   3 DGNCLYRSISHQLWGVHDVlrkmlVQELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFALAHILRRP 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 209977067   79 VEVYQySTEPINT----FHGIHQNE--DEPIRVSYHRNIHYNS 115
Cdd:pfam02338  83 IIVYK-SEGGEELgglkEYGIYLPLgwDPSLCLVYPRHLYYLG 124

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 209977067   2 KEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTT---YINRKRKNNCH--GNHIEMQAMAEMYN 76
Cdd:cd22755    7 VGDGNCFFRALSYAITGSEKYHRKIRKAIVDFLEKNPDEFRNLLRSDYESveeYLEKSRMRYDGtwATDVEIFAAATLLG 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 209977067  77 rpVEVYQYSTEPI-------NTFHGIHQNEDEPIRVSYHRNIHYNSVV 117
Cdd:cd22755   87 --VDIYVYSKGGYkwllyspRFKLGKRNGSREAIYLKNTNGNHFEPVV 132

OTU (ovarian tumor) domain of fungal OTU domain-containing protein 2 and similar proteins; This subfamily includes Schizosaccharomyces pombe and Saccharomyces cerevisiae OTU domain-containing protein 2 (OTU2) and similar proteins. S. pombe OTU2 is a ubiquitin thioesterase/hydrolase (EC 3.4.19.12) that can remove conjugated ubiquitin from protein substrates and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Fungal OTU2 bbelongs 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 209977067   2 KEDGACLFRAVADQ---VYGDQDM-HEVVRKHCMDYLMKNADYFSNYVTE------DFTTYINRKRKNNCHGNHIEMQAM 71
Cdd:cd22762   13 KPDGHCLFAAIADQlqlRGSEINLdYKELRKLAAEYIRKHPDDFEPFLFEetdeleDIDEYCKKIENTAEWGGELELLAL 92

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 209977067  72 AEMYNRPVEVYQYSTEPInTFHGIHQNEDEPIRVSYHRNI-----HYNSVV 117
Cdd:cd22762   93 AKAFGVPIHVVQAEGRVI-KINEEGDSDKPELWLAYYKHSyglgeHYNSLR 142

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU5 from plants and similar proteins; Deubiquitinating enzyme OTU5, also called OTU domain-containing protein 6, 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. OTU5 is an inactive cysteine protease. It regulates gene expression by contributing to chromatin organization and DNA methylation patterns (e.g. H3K4me3 and H3K27me3). It is required for phosphate (Pi) homeostasis. OTU5 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 209977067   2 KEDGACLFRAVADQVYGDQDMHEVV-----RKHCMDYLMKNADYFSNYV---------TEDFTTYINRKRKNNCHGNHIE 67
Cdd:cd22797   16 KADGHCLYRAVEDQLQLRGGGAPAPdyqqlRELAADYMRAHPDDFLPFLededeggdgDEAFEAYCREVESTAAWGGQLE 95

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 209977067  68 MQAMAEMYNRPVEVYQySTEPINTFHGIHQNEDEPIRVSYHRNI-----HYNSVV 117
Cdd:cd22797   96 LGALAHALRRHIKVYS-AGMPDVEMGEEYAGTGPPLRLCYHRHAfglgeHYNSVV 149

OTU (ovarian tumor) domain of OTU domain-containing protein 3 and similar proteins; OTU domain-containing protein 3 (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. It 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 209977067   4 DGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTED--FTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEV 81
Cdd:cd22770   22 DGNCLFRALGDQLEGHSRNHLKHRQETVQYMIEHREDFEPFVEDDvpFDKHVANLSKPGTYAGNDAIVAFARLHQVNVVI 101

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 209977067  82 YQYSTePINTFHGIHQNEDEPIRVSYHRNIHYNSV 116
Cdd:cd22770  102 HQLNA-PLWQIRGTEKSSSRELHISYHNGDHYSSV 135

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU4 from plants and similar proteins; Deubiquitinating enzyme OTU4, also called OTU domain-containing protein 4, 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. OTU4 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU4 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 209977067   4 DGACLFRAVAdqvYG----------DQDMHEV----VRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQ 69
Cdd:cd22760   10 DGRCLFRAVA---HGeclargkaapDEEREREladeLRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWGGEPELL 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 209977067  70 AMAEMYNRPVEVY--QYSTEPINTF--HGIHQNEDEPIRVSYHRNIHYNSVV 117
Cdd:cd22760   87 MLSHVLQRPITVYmaDEGEGGLISIaeYGQEYGKGNPIRVLFHGFGHYEALL 138