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 564398713 285 GFIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEM 364
Cdd:cd22752    1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSEL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 564398713 365 YNRPVEVYQYSTEPINTFHGIHQNEDEPIRVSYHRNIHYNSVVN 408
Cdd:cd22752   81 YNRPIEVYAYSTEPINTFHEASSSDNEPIRLSYHGNSHYNSIVD 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 564398713 285 GFIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEM 364
Cdd:cd22752    1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSEL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 564398713 365 YNRPVEVYQYSTEPINTFHGIHQNEDEPIRVSYHRNIHYNSVVN 408
Cdd:cd22752   81 YNRPIEVYAYSTEPINTFHEASSSDNEPIRLSYHGNSHYNSIVD 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 564398713 285 GFIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAEM 364
Cdd:cd22752    1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSEL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 564398713 365 YNRPVEVYQYSTEPINTFHGIHQNEDEPIRVSYHRNIHYNSVVN 408
Cdd:cd22752   81 YNRPIEVYAYSTEPINTFHEASSSDNEPIRLSYHGNSHYNSIVD 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 564398713 288 IKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSN------YVTEDFTTYINRKRKNNCHGNHIEMQAM 361
Cdd:cd22744    2 VVDVPGDGNCLFRALAHALYGDQESHRELRQEVVDYLRENPDLYEPaeladeDDGEDFDEYLQRMRKPGTWGGELELQAL 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 564398713 362 AEMYNRPVEVYQYST--EPINTFHGIHQNEDEPIRVSYHRNIHYNSV 406
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 564398713 283 KKGFIIKQMKEDGACLFRAVADQV---YGDQDMHEV--VRKHCMDYLMKNADYFSNYVT---------EDFTTYINRKRK 348
Cdd:cd22748    3 PLGLRIKEIPPDGHCLYRAIADQLklrGGSEEPYSYkeLRKLAADYMRAHRDDFLPFLTnddgdlmteEEFEEYCDKIEN 82

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 564398713 349 NNCHGNHIEMQAMAEMYNRPVEVYQYSTEPINtfHGIHQNEDEPIRVSYHRNI-----HYNSVV 407
Cdd:cd22748   83 TAEWGGQLELRALSKALKRPIHVYQAGSPPLV--IGEEFDSGEPLRLSYHRHAyglgeHYNSVV 144

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 564398713 288 IKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVT--------EDFTTYINRKRKNNCHGNHIEMQ 359
Cdd:cd22756    2 AKDITGDGNCLFRALSDQLYGDPDRHLEIRAEVVEYMRANPDDFKPFSEaatfaeddEAFEDYLARMAKDGTYGDNLEIV 81

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 564398713 360 AMAEMYNRPVEVYQ-YSTEPI-NTFHGIHQNEDEPIRVSYHRNIHYNSV 406
Cdd:cd22756   82 AFARAYNVDVKVYQpDPVYVIsAPEDGSPGPARRVLHIAYHNWEHYSSV 130

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 564398713 285 GFIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNAD-YFSNYVTEDFTTYINRKRKNNCHGNHIEMQAMAE 363
Cdd:cd22751    9 GLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPElYYEFYVPEEYDEYLKKMSKDGEWGDELTLQAAAD 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 564398713 364 MYNRPVEVYQ-YSTEPINTFHgiHQNEDEPIRV---SYHRNIHYNSV 406
Cdd:cd22751   89 AFGVKIHVITsFEDNWFLEIE--PRGLVRSKRVlflSYWAEVHYNSI 133

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 564398713 282 DKKGFIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQAM 361
Cdd:cd22794    6 RSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQVEISAL 85

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564398713 362 AEMYNRPVEVYQ-------YSTEpiNTFhgihqneDEPIRVSYHRNIHYNSV 406
Cdd:cd22794   86 SLMYKRDFIIYQepgkppsNVTE--NGF-------PDKILLCFSNGNHYDSV 128

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 564398713 288 IKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTEDFTT---YINRKRKNNCH--GNHIEMQAMA 362
Cdd:cd22755    3 TIKIVGDGNCFFRALSYAITGSEKYHRKIRKAIVDFLEKNPDEFRNLLRSDYESveeYLEKSRMRYDGtwATDVEIFAAA 82

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564398713 363 EMYNrpVEVYQYSTEPI-------NTFHGIHQNEDEPIRVSYHRNIHYNSVV 407
Cdd:cd22755   83 TLLG--VDIYVYSKGGYkwllyspRFKLGKRNGSREAIYLKNTNGNHFEPVV 132

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 564398713 286 FIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTE-DFTTYINRKR------KNNCHGNHIEM 358
Cdd:cd22757    1 FRVIPIPGDGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIYTHDsEGNNYKSAEEyradmsKPGTYGTLCEL 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 564398713 359 QAMAEMYNRPVEVYQySTEPINTFhGIHQNEDEPIRVSYH-RNIHYN 404
Cdd:cd22757   81 VAAAELYPFHFEVYR-NGKLYASF-GDPSNPVKRLKFSGDlSNGHFD 125

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 564398713 285 GFIIKQMKEDGACLFRAVADQVYGDQDMHEVV-----RKHCMDYLMKNADYFSNYV---------TEDFTTYINRKRKNN 350
Cdd:cd22797    9 GLAIKEIKADGHCLYRAVEDQLQLRGGGAPAPdyqqlRELAADYMRAHPDDFLPFLededeggdgDEAFEAYCREVESTA 88

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564398713 351 CHGNHIEMQAMAEMYNRPVEVYQySTEPINTFHGIHQNEDEPIRVSYHRNI-----HYNSVV 407
Cdd:cd22797   89 AWGGQLELGALAHALRRHIKVYS-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 564398713 285 GFIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFSNYVTED--FTTYINRKRKNNCHGNHIEMQAMA 362
Cdd:cd22770   13 GLKLRDIPGDGNCLFRALGDQLEGHSRNHLKHRQETVQYMIEHREDFEPFVEDDvpFDKHVANLSKPGTYAGNDAIVAFA 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 564398713 363 EMYNRPVEVYQYSTePINTFHGIHQNEDEPIRVSYHRNIHYNSV 406
Cdd:cd22770   93 RLHQVNVVIHQLNA-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 564398713 294 DGACLFRAVAdqvYG----------DQDMHEV----VRKHCMDYLMKNADYFSNYVTEDFTTYINRKRKNNCHGNHIEMQ 359
Cdd:cd22760   10 DGRCLFRAVA---HGeclargkaapDEEREREladeLRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWGGEPELL 86

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564398713 360 AMAEMYNRPVEVY--QYSTEPINTF--HGIHQNEDEPIRVSYHRNIHYNSVV 407
Cdd:cd22760   87 MLSHVLQRPITVYmaDEGEGGLISIaeYGQEYGKGNPIRVLFHGFGHYEALL 138

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 564398713 286 FIIKQMKEDGACLFRAVADQVYGDQDMHEVVRKHCMDYLMKNADYFS----NYVTEDftTYINRKRKNNCHGNHIEMQAM 361
Cdd:cd21880   22 FEIERVPGDGNCFFRSIAELLFDTEDEWRLVKNTIESYARANWDECPearlYYLSLE--EYLRDAMKDGYWGGSLEAEIL 99

                 ....*...
gi 564398713 362 AEMYNRPV 369
Cdd:cd21880  100 SKALGITI 107