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 1783531732  70 PGDGNCLFRALGDQLEGHSRNHLKH-----RQETVDYMIRQREDFEPFVEDDipFEKHVASLSKPGTFAGndAIVAFARN 144
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHDVLRKMlvqelRETLAEYMREHKEEFEPFLEDD--ETGDIIEIEQTGAWGG--EIEIFALA 76

                          90       100
                  ....*....|....*....|....*..
gi 1783531732 145 HQLNVVIHQLNAPlwqiRGTDKGSTRE 171
Cdd:pfam02338  77 HILRRPIIVYKSE----GGEELGGLKE 99

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 1783531732  65 KLREVPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEPF------VEDDIPFEKHVASLSKPGTFAGNDAI 138
Cdd:cd22756     1 YAKDITGDGNCLFRALSDQLYGDPDRHLEIRAEVVEYMRANPDDFKPFseaatfAEDDEAFEDYLARMAKDGTYGDNLEI 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1783531732 139 VAFARNHQLNVVIHQLNaPLWQIRGTDKGST----RELHIAYRYGEHYDSVR 186
Cdd:cd22756    81 VAFARAYNVDVKVYQPD-PVYVISAPEDGSPgparRVLHIAYHNWEHYSSVR 131

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 1783531732  65 KLREVPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEP----FVEDDIPFEKHVASLSKPGTFAGNDAIVA 140
Cdd:cd22744     1 RVVDVPGDGNCLFRALAHALYGDQESHRELRQEVVDYLRENPDLYEPaelaDEDDGEDFDEYLQRMRKPGTWGGELELQA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1783531732 141 FARNHQLNVVIHQLNAPLWQ---IRGTDKGSTRELHIAYRYGEHYDSV 185
Cdd:cd22744    81 LANALNVPIVVYSEDGGFLPvsvFGPGPGPSGRPIHLLYTGGNHYDAL 128

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 1783531732  59 LQALGLKLREVPGDGNCLFRALGDQLE--GHSRNHLKHRQETVDYMIRQREDFEPF----VEDDIPFEKHVASLSKPGTF 132
Cdd:cd22758     1 AKENGFEIRDVPGDGNCFFHAVSDQLYgnGIEHSHKELRQQAVNYLRENPELYDGFflseFDEEESWEEYLNRMSKDGTW 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1783531732 133 AGNDAIVAFARNHQLNVVIHQLNAPLWQ--IRGTDKGSTRELHIAYRYGEHYDSV 185
Cdd:cd22758    81 GDHIILQAAANLFNVRIVIISSDGSDETtiIEPGNSKNGRTIYLGHIGENHYVSL 135

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 1783531732  57 NQLQALGLKLREVPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEPFVEddIPFEKHVASLSKPGTFAGND 136
Cdd:cd22753     3 EYLDSLGLYRKHIPRDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSE--ISFDDYLERLSDPKEWGGLL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 1783531732 137 AIVAFARNHQLNVVIHQLNAPLwQIRGTDKGSTRELHIAYRYGEHYDSV 185
Cdd:cd22753    81 ELEALSLLYKVDFIVYSIPDQP-PSNITNNGYPKKIMLCYSGGNHYDSV 128

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 1783531732  63 GLKLREVPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEPFVEDDipFEKHVASLSKPGTFAGNDAIVAFA 142
Cdd:cd22752     1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTED--FEEYINRKRQDGVWGNHIEIQAMS 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1783531732 143 RNHQLNVVIHQ-LNAPLWQIRGTDKGSTRELHIAYRYGEHYDSVR 186
Cdd:cd22752    79 ELYNRPIEVYAySTEPINTFHEASSSDNEPIRLSYHGNSHYNSIV 123

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 1783531732  63 GLKLREVPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEPFVEDDipFEKHVASLSKPGTFAGNDAIVAFA 142
Cdd:cd22796     4 GLEIRRMDGDGNCLFRAVADQVYGDQEMHDEVREMCMDYMEKERDHFSQFVTED--FTQYVKRKRRDRVFGNNLEIQAMS 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1783531732 143 R--NHQLNVVIHQLNAPLWQIRGTDKGSTRELHIAYRYGEHYDSV 185
Cdd:cd22796    82 EiyNRPIEVYSYSNGEPINIFHGSYEGDDPPIRLSYHDGNHYNSI 126

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 1783531732  56 ANQLQALGLKLREVPGDGNCLFRALGDQL-----EGHSRNHLKHRQETVDYMIRQREDFEPFVEDDIP-------FEKHV 123
Cdd:cd22797     2 RAKLAPLGLAIKEIKADGHCLYRAVEDQLqlrggGAPAPDYQQLRELAADYMRAHPDDFLPFLEDEDEggdgdeaFEAYC 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1783531732 124 ASLSKPGTFAGNDAIVAFARNHQLNVVIHQLNAPLWQIRGTDKGSTRELHIAY-RY----GEHYDSVR 186
Cdd:cd22797    82 REVESTAAWGGQLELGALAHALRRHIKVYSAGMPDVEMGEEYAGTGPPLRLCYhRHafglGEHYNSVV 149

OTU (ovarian tumor) domain of bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13; Bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 is also 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). ALG13 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 1783531732  59 LQALGLKLREVPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEPFVEDdiPFEKHVASLSKPGTFAGNDAI 138
Cdd:cd22795     5 LGSLGLYRKLTAKDASCLFRAVSEQLFLCQIHHLEIRKACVSYMRANQCNFESYVEG--SFEKYLERLEDPKESAGQLEI 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1783531732 139 VAFARNHQLNVVIHQL-NAPLWQIrgTDKGSTRELHIAYRYGEHYDSV 185
Cdd:cd22795    83 SALSLIYNRDFILYRYpGKPPTYA--TDNGFEDKILLCCSSNGHYDSV 128

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 1783531732  65 KLREVPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEPFVEDD-----IPFEKHVASLSKPGTFAGNDAIV 139
Cdd:cd22757     2 RVIPIPGDGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIYTHDSegnnyKSAEEYRADMSKPGTYGTLCELV 81

                          90
                  ....*....|....
gi 1783531732 140 AFARNHQLNVVIHQ 153
Cdd:cd22757    82 AAAELYPFHFEVYR 95

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 1783531732  65 KLREVPGDGNCLFRALGDQLEGHSRnHLKHRqetvdymIRQREdfepfvEDDIPFEKHVASLSKPGTFAGNDAIVAFARN 144
Cdd:cd22792     1 KVVPVPGDGNCFWHSLGHFLGLSAL-ELKKL-------LRDSL------FDDPELDEELDEQLEPGVYAEDEAIAAAAKL 66

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1783531732 145 HQLNVVIHQLNAP-LWQIrgTDKGSTRELHIAYRyGEHYD 183
Cdd:cd22792    67 FGVNICVHDPDEGvLYTF--TPNESSKSIHLLLE-NEHFE 103

OTU (ovarian tumor) domain of deubiquitinating enzymes OTU3 and OTU4 from plants, and similar proteins; Deubiquitinating enzyme OTU3 (also called OTU domain-containing protein 3) and deubiquitinating enzyme OTU4 (also called OTU domain-containing protein 4) are deubiquitinases (DUBs) or 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. OTU3 and OTU4 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 1783531732  64 LKLREVPGDGNCLFRAL---------GDQLEGHS--RNHLKHRQETVDYMIRQREDFEP---FVEDDipFEKHVASLSKP 129
Cdd:cd22746     2 LRVVPVKGDGRCLFRAVarglalatgGRPLSERRerADADALRKAVVEEIRKRRDELFEgslVIEGD--FDAYCQRMSHP 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1783531732 130 GTFAGNDAIVAFArnHQLNVVI-----HQLNAPLWQIR--GTDKGSTRELHIAYRYGEHYD 183
Cdd:cd22746    80 DTWGGEPELLMLA--DVLQRPIavylpTPGKGGLRKIQeyGEEYLGGEPIRLLYNGGNHYD 138

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1783531732  69 VPGDGNCLFRALGDQLEGHSRNHLKHRQETVDYMIRQREDFEPfveddiPFEKHVASLSKPGTFAGNDAIVAFA 142
Cdd:cd22791     6 VTGDGNCLFRAASLLLFGDESLHLELRLRTVLELVLNSEFYEA------IYEAEIKATCKPGSYSGIWHIYALS 73