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 768033267   1 MHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQYSTgtsavEPINTFHGIH 80
Cdd:cd22752   28 MHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSELYNRPIEVYAYST-----EPINTFHEAS 102

                         90       100
                 ....*....|....*....|..
gi 768033267  81 QNEDEPIRVSYHRNIHYNSVVN 102
Cdd:cd22752  103 SSDNEPIRLSYHGNSHYNSIVD 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 768033267   1 MHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQYSTgtsavEPINTFHGIH 80
Cdd:cd22752   28 MHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSELYNRPIEVYAYST-----EPINTFHEAS 102

                         90       100
                 ....*....|....*....|..
gi 768033267  81 QNEDEPIRVSYHRNIHYNSVVN 102
Cdd:cd22752  103 SSDNEPIRLSYHGNSHYNSIVD 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 768033267   1 MHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQYSTgtsavEPINTFHGIH 80
Cdd:cd22752   28 MHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSELYNRPIEVYAYST-----EPINTFHEAS 102

                         90       100
                 ....*....|....*....|..
gi 768033267  81 QNEDEPIRVSYHRNIHYNSVVN 102
Cdd:cd22752  103 SSDNEPIRLSYHGNSHYNSIVD 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 768033267   1 MHEVVRKHCMDYLMKNADYFSN------YVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQYSTGTsavEPIN 74
Cdd:cd22744   26 SHRELRQEVVDYLRENPDLYEPaeladeDDGEDFDEYLQRMRKPGTWGGELELQALANALNVPIVVYSEDGGF---LPVS 102

                         90       100
                 ....*....|....*....|....*.
gi 768033267  75 TFHGIHQNEDEPIRVSYHRNIHYNSV 100
Cdd:cd22744  103 VFGPGPGPSGRPIHLLYTGGNHYDAL 128

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 768033267   2 HEVVRKHCMDYLMKNADYFSNYVT--EDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQYStgtsavEPINTFhgi 79
Cdd:cd22771   29 HAELRKKVVDYMEAHEEDFEPFFEddETFEDYVSRMREDGTWGGNLELQAASLVYRVNIVVHQLG------QPRWEI--- 99

                         90       100
                 ....*....|....*....|....*
gi 768033267  80 hQNEDEP----IRVSYHRNIHYNSV 100
Cdd:cd22771  100 -ENFPDKgartIHLSYHDGEHYNSV 123

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 768033267   6 RKHCMDYLMKNADYF----SN------YVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQySTGTSavepinT 75
Cdd:cd22761   43 RKQTADYMRENKDDFlpflTNpdtgdpLTEEEFEKYCDDVENTGAWGGQLELRALSHVLKRPIEVIQ-AEGPP------I 115

                         90       100       110
                 ....*....|....*....|....*....|.
gi 768033267  76 FHGIHQNEDEPIRVSYHRNI-----HYNSVV 101
Cdd:cd22761  116 IIGEEFKSGKPLILTYHRHAyglgeHYNSVE 146

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 768033267   1 MHEVVRKHCMDYLMKNADYFSNYVT--------EDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQYstgtSAVEP 72
Cdd:cd22756   26 RHLEIRAEVVEYMRANPDDFKPFSEaatfaeddEAFEDYLARMAKDGTYGDNLEIVAFARAYNVDVKVYQP----DPVYV 101

                         90       100
                 ....*....|....*....|....*....
gi 768033267  73 I-NTFHGIHQNEDEPIRVSYHRNIHYNSV 100
Cdd:cd22756  102 IsAPEDGSPGPARRVLHIAYHNWEHYSSV 130

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 768033267   2 HEVVRKHCMDYLMKNADYFSNYVTEDFTT---YINRKRKNNCH--GNHIEMQAMAEMYNrpVEVYQYSTGTSAVEPI--N 74
Cdd:cd22755   28 HRKIRKAIVDFLEKNPDEFRNLLRSDYESveeYLEKSRMRYDGtwATDVEIFAAATLLG--VDIYVYSKGGYKWLLYspR 105

                         90       100
                 ....*....|....*....|....*..
gi 768033267  75 TFHGIHQNEDEPIRVSYHRNIHYNSVV 101
Cdd:cd22755  106 FKLGKRNGSREAIYLKNTNGNHFEPVV 132

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 768033267   2 HEVVRKHCMDYLMKNADYFSNYV---------TEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYqystgtSAVEP 72
Cdd:cd22797   42 YQQLRELAADYMRAHPDDFLPFLededeggdgDEAFEAYCREVESTAAWGGQLELGALAHALRRHIKVY------SAGMP 115

                         90       100       110
                 ....*....|....*....|....*....|....
gi 768033267  73 INTFHGIHQNEDEPIRVSYHRNI-----HYNSVV 101
Cdd:cd22797  116 DVEMGEEYAGTGPPLRLCYHRHAfglgeHYNSVV 149

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 768033267   2 HEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQystgTSAVEPIN-TFHGIh 80
Cdd:cd22794   37 HLEVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQVEISALSLMYKRDFIIYQ----EPGKPPSNvTENGF- 111

                         90       100
                 ....*....|....*....|
gi 768033267  81 qneDEPIRVSYHRNIHYNSV 100
Cdd:cd22794  112 ---PDKILLCFSNGNHYDSV 128

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 768033267   6 RKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEMYNRPVEVYQYSTGTSAVEPINTFhGIHQNEDE 85
Cdd:cd22760   44 RTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWGGEPELLMLSHVLQRPITVYMADEGEGGLISIAEY-GQEYGKGN 122

                         90
                 ....*....|....*.
gi 768033267  86 PIRVSYHRNIHYNSVV 101
Cdd:cd22760  123 PIRVLFHGFGHYEALL 138