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 1034660683  37 LAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYTPEEFQKYCE 116
Cdd:cd22761     1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034660683 117 DIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEY-SKKPLILVYMRHAYGLGEHYNSVT 181
Cdd:cd22761    81 DVENTGAWGGQLELRALSHVLKRPIEVIQAEGPPIIIGEEFkSGKPLILTYHRHAYGLGEHYNSVE 146

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 1034660683  37 LAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYTPEEFQKYCE 116
Cdd:cd22761     1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034660683 117 DIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEY-SKKPLILVYMRHAYGLGEHYNSVT 181
Cdd:cd22761    81 DVENTGAWGGQLELRALSHVLKRPIEVIQAEGPPIIIGEEFkSGKPLILTYHRHAYGLGEHYNSVE 146

Predicted cysteine protease (OTU family) [Posttranslational modification, protein turnover, chaperones];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034660683  32 MESEKLAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCAL---TVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMytp 108
Cdd:COG5539   157 PAILEIDVIAYATWIVKPDSQGDGCIEIAIISDQLPVRIHVVdvdKDSEDRYNSHPYVQRISILFTGIHFDEETLAM--- 233

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034660683 109 EEFQKYCEDIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEYSKKPLILVYMRHAYGLGeHYNS 179
Cdd:COG5539   234 VLWDTYVNEVLFDASDGITIEIQQLASLLKNPHYYTNTASPSIKCNICGTGFVGEKDYYAHALATG-HYNF 303

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 1034660683  37 LAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYTPEEFQKYCE 116
Cdd:cd22761     1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034660683 117 DIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEY-SKKPLILVYMRHAYGLGEHYNSVT 181
Cdd:cd22761    81 DVENTGAWGGQLELRALSHVLKRPIEVIQAEGPPIIIGEEFkSGKPLILTYHRHAYGLGEHYNSVE 146

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 1034660683  37 LAQILAARQLEIKQIPSDGHCMYKAIEDQLKEK---DCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDmyTPEE-FQ 112
Cdd:cd22797     1 LRAKLAPLGLAIKEIKADGHCLYRAVEDQLQLRgggAPAPDYQQLRELAADYMRAHPDDFLPFLEDEDEGG--DGDEaFE 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034660683 113 KYCEDIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEYSKK--PLILVYMRHAYGLGEHYNSV 180
Cdd:cd22797    79 AYCREVESTAAWGGQLELGALAHALRRHIKVYSAGMPDVEMGEEYAGTgpPLRLCYHRHAFGLGEHYNSV 148

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 1034660683  52 PSDGHCMYKAIEDQL---KEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYtpeefqkyceDIVNTAAWGGQL 128
Cdd:pfam02338   1 PGDGNCLYRSISHQLwgvHDVLRKMLVQELRETLAEYMREHKEEFEPFLEDDETGDII----------EIEQTGAWGGEI 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034660683 129 ELRALSHILQTPIEIIQADSPPIIVG-EEYS-------KKPLILVYMRHAYGLGEHY 177
Cdd:pfam02338  71 EIFALAHILRRPIIVYKSEGGEELGGlKEYGiylplgwDPSLCLVYPRHLYYLGGHY 127

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 1034660683  47 EIKQIPSDGHCMYKAIEDQLKEKDCalTVVALRSQTAEYMQSHVEDFLPFltnpNTGDMYTPEEFQKYCEDIVNTAAWGG 126
Cdd:cd22744     1 RVVDVPGDGNCLFRALAHALYGDQE--SHRELRQEVVDYLRENPDLYEPA----ELADEDDGEDFDEYLQRMRKPGTWGG 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034660683 127 QLELRALSHILQTPIEIIQADS---PPIIVGEEY--SKKPLILVYMRhayglGEHYNSV 180
Cdd:cd22744    75 ELELQALANALNVPIVVYSEDGgflPVSVFGPGPgpSGRPIHLLYTG-----GNHYDAL 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 1034660683  46 LEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDmytpEEFQKYCEDIVNTAAWG 125
Cdd:cd22758     6 FEIRDVPGDGNCFFHAVSDQLYGNGIEHSHKELRQQAVNYLRENPELYDGFFLSEFDEE----ESWEEYLNRMSKDGTWG 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034660683 126 GQLELRALSHILQTPIEIIQAD--SPPIIV--GEEYSKKPLILVYMRhayglGEHYNSV 180
Cdd:cd22758    82 DHIILQAAANLFNVRIVIISSDgsDETTIIepGNSKNGRTIYLGHIG-----ENHYVSL 135

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 1034660683  45 QLEIKQIPSDGHCMYKAIEDQLKEKDCALTVValRSQTAEYMQSHVEDFLPFLTnpntgdmytpEEFQKYCEDIVNTAAW 124
Cdd:cd22752     1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVV--RKHCMDYMEKNRDYFSQFVT----------EDFEEYINRKRQDGVW 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1034660683 125 GGQLELRALSHILQTPIEIIQADSPPIIVGEEYSKK---PLILVYMRHAyglgeHYNSV 180
Cdd:cd22752    69 GNHIEIQAMSELYNRPIEVYAYSTEPINTFHEASSSdnePIRLSYHGNS-----HYNSI 122

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 1034660683  43 ARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVValRSQTAEYMQSHVEDFLPFLTnpntgdmytpEEFQKYCEDIVNTA 122
Cdd:cd22796     2 KKGLEIRRMDGDGNCLFRAVADQVYGDQEMHDEV--REMCMDYMEKERDHFSQFVT----------EDFTQYVKRKRRDR 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034660683 123 AWGGQLELRALSHILQTPIEIIQ--ADSPPIIVGEEYSKK--PLILVYMRhayglGEHYNSV 180
Cdd:cd22796    70 VFGNNLEIQAMSEIYNRPIEVYSysNGEPINIFHGSYEGDdpPIRLSYHD-----GNHYNSI 126

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 1034660683  41 LAARQLEIKQIPSDGHCMYKAIEDQLKekDCALTVVALRSQTAEYMQSHVEDFLPFLTNPntgdmytpeeFQKYCEDIVN 120
Cdd:cd22794     5 LRSLGLYRKQIAKDGSCLFRAVAEQVF--HTQSRHLEVRKACVDYLRRNREKFEAFIEGP----------FEQYLKNLEN 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034660683 121 TAAWGGQLELRALSHILQTPIEIIQ-ADSPPIIVGEE-YSKKPLIlvymrhAYGLGEHYNSV 180
Cdd:cd22794    73 PKEWAGQVEISALSLMYKRDFIIYQePGKPPSNVTENgFPDKILL------CFSNGNHYDSV 128

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 1034660683  37 LAQILAARQLEIKQIPSDGHCMYKAIEDQL-KEKDCALTVvalRSQTAEYMQSHVEDFLPFltnpntgdmYTPEEFQKYC 115
Cdd:cd22751     1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLfGTQDHHAEV---RELVVKQLRAHPELYYEF---------YVPEEYDEYL 68

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034660683 116 EDIVNTAAWGGQLELRALSHILQTPIEIIQ--ADSPPIIV---GEEYSKKPLILVYMRHayglgEHYNSVT 181
Cdd:cd22751    69 KKMSKDGEWGDELTLQAAADAFGVKIHVITsfEDNWFLEIeprGLVRSKRVLFLSYWAE-----VHYNSIY 134

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 1034660683  45 QLEIKQIPSDGHCMYKAI---------EDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPfltnpntGDMYTPEEFQKYC 115
Cdd:cd22746     1 SLRVVPVKGDGRCLFRAVarglalatgGRPLSERRERADADALRKAVVEEIRKRRDELFE-------GSLVIEGDFDAYC 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034660683 116 EDIVNTAAWGGQLELRALSHILQTPIE--IIQADSP---PIIV-GEEYSKKPLIlvymRHAYGLGEHY 177
Cdd:cd22746    74 QRMSHPDTWGGEPELLMLADVLQRPIAvyLPTPGKGglrKIQEyGEEYLGGEPI----RLLYNGGNHY 137

OTU (ovarian tumor) domain of ubiquitin thioesterase OTU1 and similar proteins; Ubiquitin thioesterase (EC 3.4.19.12) OTU1 is also called OTU domain-containing protein 1 in yeast, while human OTU1 is also called HIV-1-induced protease 7 (HIN7), DUBA-8, or OTU domain-containing protein 2 (OTUD2). OTU1 is a deubiquitinase (DUB) 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. OTU1 has been implicated in the ER-associated degradation (ERAD) pathway. In yeast, it counteracts the activity of Ufd2 by deubiquitinating Ufd2 substrates; Ufd2 is a E4 ubiquitin ligase that interacts with Cdc48, an AAA ATPase that plays a central role in the ERAD pathway by chaperoning proteins to the proteasome for destruction. OTU1 also functions as a substrate-processing factor of valosin-containing protein (VCP, the mammalian counterpart of yeast Cdc48) that is required for the retrotranslocation of the ERAD pathway. OTU1 has been shown to preferentially hydrolyze polyubiquitin chains with Lys48 linkages. It contains ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a C2H2-type zinc finger, and an OTU (ovarian tumor) domain. This model represents the OTU domain that interacts with ubiquitin and possesses catalytic activity. OTU1 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. This family also contains plant OTU1 and OTU2.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034660683  46 LEIKQIPSDGHCMYKAIeDQLKEKDCALTVVALRSQTAEYMQSHVEDF-LPFLTNPNtgdmytpeefQKYCEDIVNTAAW 124
Cdd:cd22745     3 LVRRVVPDDNSCLFTSI-SYLLEGGLLDSAPELREIVADAILSDPDTYnEAILGKPP----------DEYCAWILKPDSW 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034660683 125 GGQLELRALSHILQTPIEIIQADSPPIIV-GEE-YSKKPLILVYMrhayglGEHYNSVTR 182
Cdd:cd22745    72 GGAIELSILSKHFGVEICVVDVQTGRVDRfGEDkGYSKRIFLLYS------GIHYDALAL 125

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU3 from plants and similar proteins; Deubiquitinating enzyme OTU3, also called OTU domain-containing protein 3, 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. OTU3 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU3 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 1034660683 109 EEFQKYCEDIVNTAAWGGQLELRALSHILQTPIEIIQADSP-----------PII-VGEEYSK--------KPLILVY 166
Cdd:cd22759    72 GSLDRYCRRIQRPDFWGGESELLVLSKMLKQPIIVYIPESEaknggwgsgfiPIQkYGEEFAKgtkgrkgrKPVRLLY 149

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034660683  46 LEIKQIPSDGHCMYKAIedqlkekdcALTV-------VALRSQTAEYMQSHVEDFLPFLTNPNTgdmyTPEE-FQKYCED 117
Cdd:cd22755     1 CKTIKIVGDGNCFFRAL---------SYAItgsekyhRKIRKAIVDFLEKNPDEFRNLLRSDYE----SVEEyLEKSRMR 67

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034660683 118 IVNTaaWGGQLELRALSHILQTPIEIIQAD-------SPPIIVGEEYSKKPLIlvYMRHAYglGEHYNSVT 181
Cdd:cd22755    68 YDGT--WATDVEIFAAATLLGVDIYVYSKGgykwllySPRFKLGKRNGSREAI--YLKNTN--GNHFEPVV 132

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU1 and OTU2 from plants and similar proteins; Deubiquitinating enzyme OTU2, also called OTU domain-containing protein 2, 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. OTU2 exhibited equivalent binding affinities for K48- and K63-linked ubiquitin chains and no cleavage activity toward linear UB chains. It may also be involved in endoplasmic-reticulum-associated protein degradation (ERAD). OTU2 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 1034660683  51 IPSDGHCMYKAI----EDQLKEKDCALTVVA--LRSQTAEYMQShvedflpFLTNPNTGdmytpeefqkYCEDIVNTAAW 124
Cdd:cd22793     8 IDSDNSCLFNAVgyvmEGSRKKAPELRQVIAdaVLSDPFEYNEA-------FLGKSNKE----------YCEWILNPNSW 70

                          90
                  ....*....|
gi 1034660683 125 GGQLELRALS 134
Cdd:cd22793    71 GGAIELSILS 80