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 1424027020 138 LAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYTPEEFQKYCE 217
Cdd:cd22761     1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1424027020 218 DIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEY-SKKPLILVYMRHAYGLGEHYNSVT 282
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 1424027020 138 LAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYTPEEFQKYCE 217
Cdd:cd22761     1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1424027020 218 DIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEY-SKKPLILVYMRHAYGLGEHYNSVT 282
Cdd:cd22761    81 DVENTGAWGGQLELRALSHVLKRPIEVIQAEGPPIIIGEEFkSGKPLILTYHRHAYGLGEHYNSVE 146

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1424027020  18 RHRKEKKELQAKIQGMKNAVPKNDKKRR-----------------------KQLTEDVAKLEKEMEQKHREELEQLKLTT 74
Cdd:COG5539    20 KQRFELKDLQTKITRIMKQLTFGRPPQRlngkcldlsyalsqkdeveiekaPKLRAETNEADQEDSLTPLQNIPELGISS 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1424027020  75 KENKIDSVAVNisnlVLENQPPRISKAQKRREKKAALEKEREE---RIAEAEIENLTGARHMESEKLAQILAARQLEIKQ 151
Cdd:COG5539   100 FEKSVSQQSIN----VLEDMPGQDDNSRLFQAERYSLRDASVAklrEVVSLEVLSNPDLYNPAILEIDVIAYATWIVKPD 175

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1424027020 152 IPSDGHCMYKAIEDQLKEKDCAL---TVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMytpEEFQKYCEDIVNTAAWGGQ 228
Cdd:COG5539   176 SQGDGCIEIAIISDQLPVRIHVVdvdKDSEDRYNSHPYVQRISILFTGIHFDEETLAM---VLWDTYVNEVLFDASDGIT 252

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1424027020 229 LELRALSHILQTPIEIIQADSPPIIVGEEYSKKPLILVYMRHAYGLGeHYNS 280
Cdd:COG5539   253 IEIQQLASLLKNPHYYTNTASPSIKCNICGTGFVGEKDYYAHALATG-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 1424027020 138 LAQILAARQLEIKQIPSDGHCMYKAIEDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYTPEEFQKYCE 217
Cdd:cd22761     1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1424027020 218 DIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEY-SKKPLILVYMRHAYGLGEHYNSVT 282
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 1424027020 138 LAQILAARQLEIKQIPSDGHCMYKAIEDQLK---EKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDmyTPEE-FQ 213
Cdd:cd22797     1 LRAKLAPLGLAIKEIKADGHCLYRAVEDQLQlrgGGAPAPDYQQLRELAADYMRAHPDDFLPFLEDEDEGG--DGDEaFE 78

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1424027020 214 KYCEDIVNTAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEYSKK--PLILVYMRHAYGLGEHYNSV 281
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 1424027020 153 PSDGHCMYKAIEDQL---KEKDCALTVVALRSQTAEYMQSHVEDFLPFLTNPNTGDMYtpeefqkyceDIVNTAAWGGQL 229
Cdd:pfam02338   1 PGDGNCLYRSISHQLwgvHDVLRKMLVQELRETLAEYMREHKEEFEPFLEDDETGDII----------EIEQTGAWGGEI 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1424027020 230 ELRALSHILQTPIEIIQADSPPIIVG-EEYS-------KKPLILVYMRHAYGLGEHY 278
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 1424027020 148 EIKQIPSDGHCMYKAIEDQLKEKDCalTVVALRSQTAEYMQSHVEDFLPFltnpNTGDMYTPEEFQKYCEDIVNTAAWGG 227
Cdd:cd22744     1 RVVDVPGDGNCLFRALAHALYGDQE--SHRELRQEVVDYLRENPDLYEPA----ELADEDDGEDFDEYLQRMRKPGTWGG 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1424027020 228 QLELRALSHILQTPIEIIQADS---PPIIVGEEY--SKKPLILVYMRhayglGEHYNSV 281
Cdd:cd22744    75 ELELQALANALNVPIVVYSEDGgflPVSVFGPGPgpSGRPIHLLYTG-----GNHYDAL 128

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 1424027020 149 IKQIPSDGHCMYKAIEDQL-------KEkdcaltvvaLRSQTAEYMQSHVEDFLPFLTNPNTGDMytPEEFQKYCEDIVN 221
Cdd:cd22756     2 AKDITGDGNCLFRALSDQLygdpdrhLE---------IRAEVVEYMRANPDDFKPFSEAATFAED--DEAFEDYLARMAK 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1424027020 222 TAAWGGQLELRALSHILQTPIEIIQADSPPIIVGEEY-----SKKPLILVYmrHAYglgEHYNSV 281
Cdd:cd22756    71 DGTYGDNLEIVAFARAYNVDVKVYQPDPVYVISAPEDgspgpARRVLHIAY--HNW---EHYSSV 130

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 1424027020 146 QLEIKQIPSDGHCMYKAIEDQLKEKDCALTVValRSQTAEYMQSHVEDFLPFLTnpntgdmytpEEFQKYCEDIVNTAAW 225
Cdd:cd22752     1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVV--RKHCMDYMEKNRDYFSQFVT----------EDFEEYINRKRQDGVW 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1424027020 226 GGQLELRALSHILQTPIEIIQADSPPIIVGEEYSKK---PLILVYMRHAyglgeHYNSV 281
Cdd:cd22752    69 GNHIEIQAMSELYNRPIEVYAYSTEPINTFHEASSSdnePIRLSYHGNS-----HYNSI 122

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 1424027020 140 QILAARQLEIKQIPSDGHCMYKAIEDQLkeKDCALTVVALRSQTAEYMQSHVEDFLPFLtnpntgdmytPEEFQKYCEDI 219
Cdd:cd22753     3 EYLDSLGLYRKHIPRDGSCLFRAVSEQL--FFTQSYHQQVRQACVEYLEKNREEFEKFS----------EISFDDYLERL 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1424027020 220 VNTAAWGGQLELRALSHILQTPIEIIQ-ADSPPIIVGEEYSKKPLILVYMrhaygLGEHYNSV 281
Cdd:cd22753    71 SDPKEWGGLLELEALSLLYKVDFIVYSiPDQPPSNITNNGYPKKIMLCYS-----GGNHYDSV 128

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 1424027020 142 LAARQLEIKQIPSDGHCMYKAIEDQLKekDCALTVVALRSQTAEYMQSHVEDFLPFLTNPntgdmytpeeFQKYCEDIVN 221
Cdd:cd22794     5 LRSLGLYRKQIAKDGSCLFRAVAEQVF--HTQSRHLEVRKACVDYLRRNREKFEAFIEGP----------FEQYLKNLEN 72

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1424027020 222 TAAWGGQLELRALSHILQTPIEIIQ-ADSPPIIVGEE-YSKKPLIlvymrhAYGLGEHYNSV 281
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 1424027020 138 LAQILAARQLEIKQIPSDGHCMYKAIEDQL-KEKDCALTVvalRSQTAEYMQSHVEDFLPFltnpntgdmYTPEEFQKYC 216
Cdd:cd22751     1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLfGTQDHHAEV---RELVVKQLRAHPELYYEF---------YVPEEYDEYL 68

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1424027020 217 EDIVNTAAWGGQLELRALSHILQTPIEIIQ--ADSPPIIV---GEEYSKKPLILVYMRHayglgEHYNSVT 282
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 1424027020 146 QLEIKQIPSDGHCMYKAI---------EDQLKEKDCALTVVALRSQTAEYMQSHVEDFLPfltnpntGDMYTPEEFQKYC 216
Cdd:cd22746     1 SLRVVPVKGDGRCLFRAVarglalatgGRPLSERRERADADALRKAVVEEIRKRRDELFE-------GSLVIEGDFDAYC 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1424027020 217 EDIVNTAAWGGQLELRALSHILQTPIE--IIQADSP---PIIV-GEEYSKKPLIlvymRHAYGLGEHY 278
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 1424027020 147 LEIKQIPSDGHCMYKAIeDQLKEKDCALTVVALRSQTAEYMQSHvedflPFLTNPNTGDMyTPEEfqkYCEDIVNTAAWG 226
Cdd:cd22745     3 LVRRVVPDDNSCLFTSI-SYLLEGGLLDSAPELREIVADAILSD-----PDTYNEAILGK-PPDE---YCAWILKPDSWG 72

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1424027020 227 GQLELRALSHILQTPIEIIQADSPPIIV-GEE-YSKKPLILVYMrhayglGEHYNSVTR 283
Cdd:cd22745    73 GAIELSILSKHFGVEICVVDVQTGRVDRfGEDkGYSKRIFLLYS------GIHYDALAL 125

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 1424027020 147 LEIKQIPSDGHCMYKAIedqlkekdcALTV-------VALRSQTAEYMQSHVEDFLPFLTNPNTgdmyTPEE-FQKYCED 218
Cdd:cd22755     1 CKTIKIVGDGNCFFRAL---------SYAItgsekyhRKIRKAIVDFLEKNPDEFRNLLRSDYE----SVEEyLEKSRMR 67

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1424027020 219 IVNTaaWGGQLELRALSHILQTPIEIIQAD-------SPPIIVGEEYSKKPLIlvYMRHAYglGEHYNSVT 282
Cdd:cd22755    68 YDGT--WATDVEIFAAATLLGVDIYVYSKGgykwllySPRFKLGKRNGSREAI--YLKNTN--GNHFEPVV 132

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 1424027020 148 EIKQIPSDGHCMYKAIEDQLKEKDcaLTVVALRSQTAEYMQSHVEDFLPFLTNPNTgdmytPEEfqkYCEDIVNTAAWGG 227
Cdd:cd21880    23 EIERVPGDGNCFFRSIAELLFDTE--DEWRLVKNTIESYARANWDECPEARLYYLS-----LEE---YLRDAMKDGYWGG 92

                          90       100
                  ....*....|....*....|...
gi 1424027020 228 QLELRALSHILQTPIEIIQADSP 250
Cdd:cd21880    93 SLEAEILSKALGITIIIWVVDDS 115