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 2130318174 238 RAKGFEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEGFTSYCKRKRRDKVYGNNVEIQAL 317
Cdd:cd22796     1 KKKGLEIRRMDGDGNCLFRAVADQVYGDQEMHDEVREMCMDYMEKERDHFSQFVTEDFTQYVKRKRRDRVFGNNLEIQAM 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2130318174 318 SEMYNRPIHIYSYTT-EPINIFHGSYRTDTPPIRLSYHHGNHYNSLVD 364
Cdd:cd22796    81 SEIYNRPIEVYSYSNgEPINIFHGSYEGDDPPIRLSYHDGNHYNSIID 128

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 2130318174 238 RAKGFEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEGFTSYCKRKRRDKVYGNNVEIQAL 317
Cdd:cd22796     1 KKKGLEIRRMDGDGNCLFRAVADQVYGDQEMHDEVREMCMDYMEKERDHFSQFVTEDFTQYVKRKRRDRVFGNNLEIQAM 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2130318174 318 SEMYNRPIHIYSYTT-EPINIFHGSYRTDTPPIRLSYHHGNHYNSLVD 364
Cdd:cd22796    81 SEIYNRPIEVYSYSNgEPINIFHGSYEGDDPPIRLSYHDGNHYNSIID 128

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130318174 220 VSSYDDLERERQFEID-IRRAKGFEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCL-----DYMERERDHFSQFITE 293
Cdd:COG5539   148 VLSNPDLYNPAILEIDvIAYATWIVKPDSQGDGCIEIAIISDQLPVRIHVVDVDKDSEDrynshPYVQRISILFTGIHFD 227

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130318174 294 G-------FTSYCKRKRRDKVYGNNVEIQALSEMYNRPIHIYSyTTEPINIFHGSyrTDTPPIRLSYH-HG---NHYNSL 362
Cdd:COG5539   228 EetlamvlWDTYVNEVLFDASDGITIEIQQLASLLKNPHYYTN-TASPSIKCNIC--GTGFVGEKDYYaHAlatGHYNFG 304

                  ..
gi 2130318174 363 VD 364
Cdd:COG5539   305 ED 306

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 2130318174 238 RAKGFEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEGFTSYCKRKRRDKVYGNNVEIQAL 317
Cdd:cd22796     1 KKKGLEIRRMDGDGNCLFRAVADQVYGDQEMHDEVREMCMDYMEKERDHFSQFVTEDFTQYVKRKRRDRVFGNNLEIQAM 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 2130318174 318 SEMYNRPIHIYSYTT-EPINIFHGSYRTDTPPIRLSYHHGNHYNSLVD 364
Cdd:cd22796    81 SEIYNRPIEVYSYSNgEPINIFHGSYEGDDPPIRLSYHDGNHYNSIID 128

OTU (ovarian tumor) domain of Arabidopsis thaliana deubiquitinating enzyme OTU7 and similar proteins; Arabidopsis thaliana deubiquitinating enzyme OTU7, also called OTU domain-containing protein 7, is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that shows a preference for 'Lys-63' over 'Lys-48' over 'Met-1'-linked ubiquitin (UB) tetramers as substrates. DUBs 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. OTU7 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 2130318174 241 GFEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEG--FTSYCKRKRRDKVYGNNVEIQALS 318
Cdd:cd22771     1 GLRIRDVEGDGNCLFRALADQLYGDEERHAELRKKVVDYMEAHEEDFEPFFEDDetFEDYVSRMREDGTWGGNLELQAAS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 2130318174 319 EMYNRPIHIYSYTTEPINIFHgSYRTDTPPIRLSYHHGNHYNS 361
Cdd:cd22771    81 LVYRVNIVVHQLGQPRWEIEN-FPDKGARTIHLSYHDGEHYNS 122

OTU (ovarian tumor) domain of OTU domain-containing proteins 6A, 6B, and similar proteins; This subfamily is composed of mammalian OTU domain-containing protein 6A (OTUD6A, also called DUBA-2, vertebrate OTU domain-containing protein 6B (OTUD6B, also called DUBA-5), fungal OTU domain-containing protein 2 (OTU2), and similar proteins. OTUD6A, OTUD6B, and Schizosaccharomyces pombe OTU2 are deubiquitinating enzymes/ubiquitinyl hydrolases (EC 3.4.19.12). OTUD6A hydrolyzes 'Lys-27'-, 'Lys-29'-, and 'Lys-33'-linked polyubiquitin chains, and may also be able to hydrolyze 'Lys-11'-linked ubiquitin chains. It deubiquitylates and stabilizes dynamin-related protein 1 (Drp1), a cytosolic protein responsible for mitochondrial fission and is essential in the initiation and development of several human diseases including cancer, thereby facilitating tumorigenesis. OTUD6B is a functional deubiquitinase in in vitro enzyme assays. It may play a role in the ubiquitin-dependent regulation of protein synthesis downstream of mTORC1, and may modify the ubiquitination of the protein synthesis initiation complex to repress translation. Biallelic variants in OTUD6B cause an intellectual disability syndrome that is associated with seizures and dysmorphic features. This subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130318174 238 RAKGFEVKKMLEDGNCLFRAIADQV-----YGDSEAYDLVRQMCLDYMERERDHFSQFIT---------EGFTSYCKRKR 303
Cdd:cd22748     2 KPLGLRIKEIPPDGHCLYRAIADQLklrggSEEPYSYKELRKLAADYMRAHRDDFLPFLTnddgdlmteEEFEEYCDKIE 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 2130318174 304 RDKVYGNNVEIQALSEMYNRPIHIYSYTTEPINIfhGSYRTDTPPIRLSYHH-----GNHYNSLV 363
Cdd:cd22748    82 NTAEWGGQLELRALSKALKRPIHVYQAGSPPLVI--GEEFDSGEPLRLSYHRhayglGEHYNSVV 144

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 2130318174 238 RAKGFEVKKMLEDGNCLFRAIADQVYGD--SEAYDLVRQMCLDYMERERDHF------SQFITEGFTSYCKRKRRDKVYG 309
Cdd:cd22758     2 KENGFEIRDVPGDGNCFFHAVSDQLYGNgiEHSHKELRQQAVNYLRENPELYdgfflsEFDEEESWEEYLNRMSKDGTWG 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 2130318174 310 NNVEIQALSEMYNRPIHIY-SYTTEPINIFHGSYRTDTPPIRLSYHHGNHYNSL 362
Cdd:cd22758    82 DHIILQAAANLFNVRIVIIsSDGSDETTIIEPGNSKNGRTIYLGHIGENHYVSL 135

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 2130318174 238 RAKGFEVKKMLEDGNCLFRAIADQVYgDSEAYDL-VRQMCLDYMERERDHFSQFITEGFTSYCKRKRRDKVYGNNVEIQA 316
Cdd:cd22794     6 RSLGLYRKQIAKDGSCLFRAVAEQVF-HTQSRHLeVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQVEISA 84

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2130318174 317 LSEMYNRPIHIY-SYTTEPINIFHGSYrtdTPPIRLSYHHGNHYNS 361
Cdd:cd22794    85 LSLMYKRDFIIYqEPGKPPSNVTENGF---PDKILLCFSNGNHYDS 127

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 2130318174 235 DIRRAKGFEVKKMLEDGNCLFRAIADQ--VYGDSEAYDLVRQMCLDYMERERDHFSQFIT----------EGFTSYCKRK 302
Cdd:cd22761     3 KILKERGLKIHEIPSDGDCLYNAIAHQlsLRGIETSVEELRKQTADYMRENKDDFLPFLTnpdtgdplteEEFEKYCDDV 82

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2130318174 303 RRDKVYGNNVEIQALSEMYNRPIHIYSYTTEPINIfhGSYRTDTPPIRLSYHH-----GNHYNSLV 363
Cdd:cd22761    83 ENTGAWGGQLELRALSHVLKRPIEVIQAEGPPIII--GEEFKSGKPLILTYHRhayglGEHYNSVE 146

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 2130318174 250 DGNCLFRAIADQVYGDSEA-----YDLVRQMCLDYMERERDHFSQFITEGFTSYCKRKRRDKVYGNNVEIQALSEMYNRP 324
Cdd:pfam02338   3 DGNCLYRSISHQLWGVHDVlrkmlVQELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFALAHILRRP 82

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 2130318174 325 IHIYsYTTEPINI----FHGSYRTDT--PPIRLSYH-----HGNHY 359
Cdd:pfam02338  83 IIVY-KSEGGEELgglkEYGIYLPLGwdPSLCLVYPrhlyyLGGHY 127

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 2130318174 243 EVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEGFTSYCK-----RKRRDKVYGNNVEIQAL 317
Cdd:cd22755     2 KTIKIVGDGNCFFRALSYAITGSEKYHRKIRKAIVDFLEKNPDEFRNLLRSDYESVEEyleksRMRYDGTWATDVEIFAA 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 2130318174 318 SEMYNRPIHIYS------YTTEPiNIFHGSYRTDTPPIRLSYHHGNHYN 360
Cdd:cd22755    82 ATLLGVDIYVYSkggykwLLYSP-RFKLGKRNGSREAIYLKNTNGNHFE 129

OTU (ovarian tumor) domain of OTU domain-containing protein 3 and similar proteins; OTU domain-containing protein 3 (OTUD3) is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that hydrolyzes 'Lys-6'- and 'Lys-11'-linked polyubiquitin. It is an acetylation-dependent deubiquitinase that restricts innate antiviral immune signaling. It directly hydrolyzes lysine 63 (Lys63)-linked polyubiquitination of MAVS (mitochondrial antiviral-signaling protein) and shuts off innate antiviral immune response. OTUD3 can elicit tumor-suppressing or tumor-promoting activities in a cell- and tissue-dependent manner. It is a DUB for PTEN (phosphatase and tension homologue deleted on chromosome 10); the OTUD3-PTEN signaling axis plays a critical role in suppression of breast tumorigenesis. OTUD3 is also a DUB for glucose-regulated protein GRP78, stabilizing it and promoting lung tumorigenesis. It belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130318174 241 GFEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEG--FTSYCKRKRRDKVYGNNVEIQALS 318
Cdd:cd22770    13 GLKLRDIPGDGNCLFRALGDQLEGHSRNHLKHRQETVQYMIEHREDFEPFVEDDvpFDKHVANLSKPGTYAGNDAIVAFA 92

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2130318174 319 EMYNRPIHIYSYTTEPINIfHGSYRTDTPPIRLSYHHGNHYNSLvdpRRL 368
Cdd:cd22770    93 RLHQVNVVIHQLNAPLWQI-RGTEKSSSRELHISYHNGDHYSSV---RKL 138

OTU (ovarian tumor) domain of viral RNA-directed RNA polymerase L; RNA-directed RNA polymerase L is also called protein L, large structural protein, replicase, transcriptase, or ubiquitin thioesterase. It displays RNA-directed RNA polymerase (EC 2.7.7.48), deubiquitinase (DUB)/ubiquitin thiolesterase (EC 3.4.19.12), and deISGylating activities. It is a viral homolog of ovarian tumor protease (vOTU) that has been implicated in the downregulation of type I interferon immune response by removing post-translational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15) from host cellular proteins. The attachment of Ub and ISG15 to cellular proteins mediates important innate antiviral responses, and their removal inhibits these antiviral pathways. This subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130318174 242 FEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEGFTS--YCKRKRRDKVYGNNVEIQALSE 319
Cdd:cd21880    22 FEIERVPGDGNCFFRSIAELLFDTEDEWRLVKNTIESYARANWDECPEARLYYLSLeeYLRDAMKDGYWGGSLEAEILSK 101

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 2130318174 320 MYNRPIHIysYTTEPINIFHGSYRTDTPPIRLSY---HHGNHYNSLV 363
Cdd:cd21880   102 ALGITIII--WVVDDSDWVTAAVRFGDGDVSTSLnllHSGGHFDALR 146

OTU (ovarian tumor) domain of OTU domain-containing protein 1 and similar proteins; OTU domain-containing protein 1 (OTUD1), also called DUBA-7 in humans, is a deubiquitinating enzyme/ubiquitinyl hydrolase (EC 3.4.19.12) that specifically hydrolyzes 'Lys-63'-linked polyubiquitin to monoubiquitin; this specificity is facilitated by the C-terminal Ub-interacting motif (UIM) of OTUD1. It interacts and promotes the deubiquitination of myeloid cell leukemia 1 (MCL1), a pro-survival Bcl-2 family protein that plays important roles in cell survival, proliferation, differentiation and tumorigenesis. OTUD1 also deubiquitinates IFN regulatory factor 3 (IRF3) and attenuates its function; IRF3 is critical for the transcription of type I IFNs in defensing virus and promoting inflammatory responses. Loss-of-function mutations of OTUD1 associated with multiple autoimmune diseases including systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), ulcerative colitis (UC) and Hashimoto's thyroiditis (HT). OTUD1 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 2130318174 250 DGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEGFTSYCKRKRRDKVYGNNVEIQALSEMYNRPIHIys 329
Cdd:cd22747    29 DGNCLYRAVSKAVYGDQALHRELREQTVHYIADHLDEFNPIIEGDVGEFLIKAAQDGAWAGYPELLAMGQMLNVNIRL-- 106

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 2130318174 330 yTT-----EPI--NIFH--GSYRTDTPPIRLSYHHGNHYNSLVD 364
Cdd:cd22747   107 -TTggsleSPTvsTMVHylGPEDSGKPSIWLSWLSNGHYDAVFD 149

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 2130318174 242 FEVKKMLEDGNCLFRAIADQVYGDSEAYDLVRQMCLDYMERERDHFSQFITEG----FTS---YCKRKRRDKVYGNNVEI 314
Cdd:cd22757     1 FRVIPIPGDGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIYTHDSegnnYKSaeeYRADMSKPGTYGTLCEL 80

                          90
                  ....*....|....
gi 2130318174 315 QALSEMYNRPIHIY 328
Cdd:cd22757    81 VAAAELYPFHFEVY 94

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 2130318174 250 DGNCLFRAIADQVYGD-SEAYDLvRQMCLDYMERERDHFSqfitEGF-----TSYCKRKRRDKVYGNNVEIQALSEMYNR 323
Cdd:cd22793    11 DNSCLFNAVGYVMEGSrKKAPEL-RQVIADAVLSDPFEYN----EAFlgksnKEYCEWILNPNSWGGAIELSILSDHYGR 85

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 2130318174 324 PIHIYSYTTEPINIFhGSYRTDTPPIRLSYhHGNHYNSLV 363
Cdd:cd22793    86 EIAAFDIQTKRCDVY-GEGKGYTERVMLIY-DGLHYDALA 123

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.

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                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2130318174 242 FEVKKMLEDGNCLFRAIADQVYGD--SEAYDLvRQMCLDYMERERDHFsqfiTEGF-----TSYCKRKRRDKVYGNNVEI 314
Cdd:cd22745     3 LVRRVVPDDNSCLFTSISYLLEGGllDSAPEL-REIVADAILSDPDTY----NEAIlgkppDEYCAWILKPDSWGGAIEL 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 2130318174 315 QALSEMYNrpIHIYSYTTEPINIFH-GSYRTDTPPIRLSYhHGNHYNSLV 363
Cdd:cd22745    78 SILSKHFG--VEICVVDVQTGRVDRfGEDKGYSKRIFLLY-SGIHYDALA 124