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 564350425 169 LAQILAARELEIKHIPSDGHCMYGALEDQLREQDSALTVATLRRQTAEYMQSHSDDFLPFLTNPNTGDMYTPEEFGKYCD 248
Cdd:cd22761    1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564350425 249 DIVNTAAWGGQLELRALSHILKTPIEILQADAPPIIVGEEY-PRNPLVLVYMRHAYGLGEHYNSVT 313
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 564350425 169 LAQILAARELEIKHIPSDGHCMYGALEDQLREQDSALTVATLRRQTAEYMQSHSDDFLPFLTNPNTGDMYTPEEFGKYCD 248
Cdd:cd22761    1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564350425 249 DIVNTAAWGGQLELRALSHILKTPIEILQADAPPIIVGEEY-PRNPLVLVYMRHAYGLGEHYNSVT 313
Cdd:cd22761   81 DVENTGAWGGQLELRALSHVLKRPIEVIQAEGPPIIIGEEFkSGKPLILTYHRHAYGLGEHYNSVE 146

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564350425  43 EEQLMRRHRKEKKELQAKIQGMKNAVPKNDKKRRKQLTedVAKLEREMEQKHREELEQLKL----TFKDSKIDSVAV--N 116
Cdd:COG5539   14 MESLTEKQRFELKDLQTKITRIMKQLTFGRPPQRLNGK--CLDLSYALSQKDEVEIEKAPKlraeTNEADQEDSLTPlqN 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564350425 117 VSNLVLDSQPPRISKA-------QKRREKKAALEKEREERIAEAEIENLSGARHLESEKLA-----------QILAAREL 178
Cdd:COG5539   92 IPELGISSFEKSVSQQsinvledMPGQDDNSRLFQAERYSLRDASVAKLREVVSLEVLSNPdlynpaileidVIAYATWI 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564350425 179 EIKHIPSDGHCMYGALEDQLREQDSALTVAT---LRRQTAEYMQSHSDDFLPFLTNPNTGDMytpEEFGKYCDDIVNTAA 255
Cdd:COG5539  172 VKPDSQGDGCIEIAIISDQLPVRIHVVDVDKdseDRYNSHPYVQRISILFTGIHFDEETLAM---VLWDTYVNEVLFDAS 248

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 564350425 256 WGGQLELRALSHILKTPIEILQAdAPPIIVGEEYPRNP-LVLVYMRHAYGLGeHYNS 311
Cdd:COG5539  249 DGITIEIQQLASLLKNPHYYTNT-ASPSIKCNICGTGFvGEKDYYAHALATG-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 564350425 169 LAQILAARELEIKHIPSDGHCMYGALEDQLREQDSALTVATLRRQTAEYMQSHSDDFLPFLTNPNTGDMYTPEEFGKYCD 248
Cdd:cd22761    1 IKKILKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDFLPFLTNPDTGDPLTEEEFEKYCD 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 564350425 249 DIVNTAAWGGQLELRALSHILKTPIEILQADAPPIIVGEEY-PRNPLVLVYMRHAYGLGEHYNSVT 313
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 564350425 169 LAQILAARELEIKHIPSDGHCMYGALEDQL---REQDSALTVATLRRQTAEYMQSHSDDFLPFLTNPNTGDmyTPEE-FG 244
Cdd:cd22797    1 LRAKLAPLGLAIKEIKADGHCLYRAVEDQLqlrGGGAPAPDYQQLRELAADYMRAHPDDFLPFLEDEDEGG--DGDEaFE 78

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564350425 245 KYCDDIVNTAAWGGQLELRALSHILKTPIEILQADAPPIIVGEEY--PRNPLVLVYMRHAYGLGEHYNSV 312
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 564350425  184 PSDGHCMYGALEDQL---REQDSALTVATLRRQTAEYMQSHSDDFLPFLTNPNTGDMYtpeefgkycdDIVNTAAWGGQL 260
Cdd:pfam02338   1 PGDGNCLYRSISHQLwgvHDVLRKMLVQELRETLAEYMREHKEEFEPFLEDDETGDII----------EIEQTGAWGGEI 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 564350425  261 ELRALSHILKTPIEILQADAPPIIVGEEY--------PRNPLVLVYMRHAYGLGEHY 309
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 564350425 179 EIKHIPSDGHCMYGALEDQLreQDSALTVATLRRQTAEYMQSHSDDFLPFltnpNTGDMYTPEEFGKYCDDIVNTAAWGG 258
Cdd:cd22744    1 RVVDVPGDGNCLFRALAHAL--YGDQESHRELRQEVVDYLRENPDLYEPA----ELADEDDGEDFDEYLQRMRKPGTWGG 74

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 564350425 259 QLELRALSHILKTPIEILQADA---PPIIVGEEY--PRNPLVLVYMRhayglGEHYNSV 312
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 564350425 180 IKHIPSDGHCMYGALEDQLR-EQDSAltvATLRRQTAEYMQSHSDDFLPFLTNPNTGDMytPEEFGKYCDDIVNTAAWGG 258
Cdd:cd22756    2 AKDITGDGNCLFRALSDQLYgDPDRH---LEIRAEVVEYMRANPDDFKPFSEAATFAED--DEAFEDYLARMAKDGTYGD 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 564350425 259 QLELRALSHILKTPIEILQADAPPIIVGEEYPRNPL---VLvymrH-AYGLGEHYNSV 312
Cdd:cd22756   77 NLEIVAFARAYNVDVKVYQPDPVYVISAPEDGSPGParrVL----HiAYHNWEHYSSV 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 564350425 177 ELEIKHIPSDGHCMYGALEDQLREQDSALTVatLRRQTAEYMQSHSDDFLPFLTnpntgdmytpEEFGKYCDDIVNTAAW 256
Cdd:cd22752    1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDV--VRKHCMDYMEKNRDYFSQFVT----------EDFEEYINRKRQDGVW 68

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 564350425 257 GGQLELRALSHILKTPIEILQADAPPIIVG-EEYPRN--PLVLVYMRHAyglgeHYNSV 312
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 564350425 175 ARELEIKHIPSDGHCMYGALEDQLREQDSALTVAtlRRQTAEYMQSHSDDFLPFLTnpntgdmytpEEFGKYCDDIVNTA 254
Cdd:cd22796    2 KKGLEIRRMDGDGNCLFRAVADQVYGDQEMHDEV--REMCMDYMEKERDHFSQFVT----------EDFTQYVKRKRRDR 69

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564350425 255 AWGGQLELRALSHILKTPIEILQ--ADAPPIIVGEEYPRN--PLVLVYMRhayglGEHYNSV 312
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 564350425 173 LAARELEIKHIPSDGHCMYGALEDQ-LREQDSALTVatlRRQTAEYMQSHSDDFLPFLTNPntgdmytpeeFGKYCDDIV 251
Cdd:cd22794    5 LRSLGLYRKQIAKDGSCLFRAVAEQvFHTQSRHLEV---RKACVDYLRRNREKFEAFIEGP----------FEQYLKNLE 71

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 564350425 252 NTAAWGGQLELRALSHILKTPIEILQ-ADAPPIIVGEEYPRNPLVLVYMRhayglGEHYNSV 312
Cdd:cd22794   72 NPKEWAGQVEISALSLMYKRDFIIYQePGKPPSNVTENGFPDKILLCFSN-----GNHYDSV 128

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 564350425 171 QILAARELEIKHIPSDGHCMYGALEDQLreQDSALTVATLRRQTAEYMQSHSDDFLPFLtnpntgdmytPEEFGKYCDDI 250
Cdd:cd22753    3 EYLDSLGLYRKHIPRDGSCLFRAVSEQL--FFTQSYHQQVRQACVEYLEKNREEFEKFS----------EISFDDYLERL 70

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 564350425 251 VNTAAWGGQLELRALSHILKTPIEILQ-ADAPPIIVGEEYPRNPLVLVYMrhaygLGEHYNSV 312
Cdd:cd22753   71 SDPKEWGGLLELEALSLLYKVDFIVYSiPDQPPSNITNNGYPKKIMLCYS-----GGNHYDSV 128

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 564350425 183 IPSDGHCMYGAL---------EDQLREQDSALTVATLRRQTAEYMQSHSDDFLPfltnpntGDMYTPEEFGKYCDDIVNT 253
Cdd:cd22746    7 VKGDGRCLFRAVarglalatgGRPLSERRERADADALRKAVVEEIRKRRDELFE-------GSLVIEGDFDAYCQRMSHP 79

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 564350425 254 AAWGGQLELRALSHILKTPIEIL-----QADAPPIIV-GEEYPR-NPLVLVY 298
Cdd:cd22746   80 DTWGGEPELLMLADVLQRPIAVYlptpgKGGLRKIQEyGEEYLGgEPIRLLY 131

Otubain subfamily of ubiquitin thioesterases; The otubain subfamily is composed of otubain-1 (also called ubiquitin thioesterase OTUB1 or OTU domain-containing ubiquitin aldehyde-binding protein 1), otubain-2 (also called ubiquitin thioesterase OTUB2 or OTU domain-containing ubiquitin aldehyde-binding protein 2), and similar proteins. They function as deubiquitylases (DUBs)/ubiquitin thioesterases (EC 3.4.19.12). OTUB1 can specifically remove 'Lys-48'-linked conjugated ubiquitin from protein substrates, while OTUB2 mediates the deubiquitination of 'Lys-11'-,'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains. The otubain subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. Members of this subfamily are classified as family C65 cysteine proteases by MEROPS.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564350425 194 LEDQLREQD-SALTVATLRRQTAEYMQSHSDDFLPFLTNPNTGDMYTPEE---FGKYCDdivntaawggQLELRALSHIL 269
Cdd:cd22749  117 LLELFNDEEtSNYIVVFLRLLTSAYLKTNADDYEPFLFEGMSVEEFCEREvepMGKEAD----------HLQITALANAL 186

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 564350425 270 KTPIEI--LQADAPPIIVGEEYPRN------PLVLVYMRhayglgEHYN 310
Cdd:cd22749  187 GVPVRVeyLDRSAGGEVNFHEFPPEdsdslpVITLLYRP------GHYD 229

Peptidase C65 Otubain; This family of proteins conserved from plants to humans is a highly specific ubiquitin iso-peptidase that removes ubiquitin from proteins. The modification of cellular proteins by ubiquitin (Ub) is an important event that underlies protein stability and function in eukaryote being a dynamic and reversible process. Otubain carries several key conserved domains: (i) the OTU (ovarian tumour domain) in which there is an active cysteine protease triad (ii) a nuclear localization signal, (iii) a Ub interaction motif (UIM)-like motif phi-xx-A-xxxs-xx-Ac (where phi indicates an aromatic amino acid, x indicates any amino acid and Ac indicates an acidic amino acid), (iv) a Ub-associated (UBA)-like domain and (v) the LxxLL motif.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564350425  179 EIKHIPSDGHCMYGALEDQLREQDSA-LTVATLRRQTAEYMQSHSDDFLPFLTNPNTGDMYTPEE---FGKYCDdivnta 254
Cdd:pfam10275 106 LLKKVEDGVSTSESELLQAFNDQETSdYIVYFLRLLTSAYLKTHADEYEPFIDGGGTVEEFCQQEvepMNKEAD------ 179

                          90       100
                  ....*....|....*....|.
gi 564350425  255 awggQLELRALSHILKTPIEI 275
Cdd:pfam10275 180 ----HLQIIALAEALGVPVRV 196

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.

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                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 564350425 179 EIKHIPSDGHCMYGALEDQLreQDSALTVATLRRQTAEYMQSHSDDFLPFLTNPNTgdmytPEEfgkYCDDIVNTAAWGG 258
Cdd:cd21880   23 EIERVPGDGNCFFRSIAELL--FDTEDEWRLVKNTIESYARANWDECPEARLYYLS-----LEE---YLRDAMKDGYWGG 92

                         90       100
                 ....*....|....*....|...
gi 564350425 259 QLELRALSHILKTPIEILQADAP 281
Cdd:cd21880   93 SLEAEILSKALGITIIIWVVDDS 115