OTU (ovarian tumor) domain of deubiquitinating enzyme OTU4 from plants and similar proteins; Deubiquitinating enzyme OTU4, also called OTU domain-containing protein 4, 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. OTU4 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU4 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 1002294325 159 DYSVTGIPGDGRCLFRSVAHGACIRSGK-RPDDDLQRKMADDLRAMVADEFIKRRAETEWFVEGDFDAYVSRIRKPHVWG 237
Cdd:cd22760     1 DYRVHGIAGDGRCLFRAVAHGECLARGKaAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1002294325 238 GEPELLMASHVLRMPITVYMHDKEAGGLIAIAEYGQEYGKEDPIQVLFHGFGHYDALQ 295
Cdd:cd22760    81 GEPELLMLSHVLQRPITVYMADEGEGGLISIAEYGQEYGKGNPIRVLFHGFGHYEALL 138

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU4 from plants and similar proteins; Deubiquitinating enzyme OTU4, also called OTU domain-containing protein 4, 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. OTU4 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU4 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 1002294325 159 DYSVTGIPGDGRCLFRSVAHGACIRSGK-RPDDDLQRKMADDLRAMVADEFIKRRAETEWFVEGDFDAYVSRIRKPHVWG 237
Cdd:cd22760     1 DYRVHGIAGDGRCLFRAVAHGECLARGKaAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1002294325 238 GEPELLMASHVLRMPITVYMHDKEAGGLIAIAEYGQEYGKEDPIQVLFHGFGHYDALQ 295
Cdd:cd22760    81 GEPELLMLSHVLQRPITVYMADEGEGGLISIAEYGQEYGKGNPIRVLFHGFGHYEALL 138

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002294325 165 IPGDGRCLFRSVAHGACIR--SGKRPDDDLQRKMADDLRAMVADEFIKRRAETEWFVEGDFDAYVSRIRKPHVWGGEPEL 242
Cdd:COG5539   176 SQGDGCIEIAIISDQLPVRihVVDVDKDSEDRYNSHPYVQRISILFTGIHFDEETLAMVLWDTYVNEVLFDASDGITIEI 255

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1002294325 243 LMASHVLRMPITVYMhdkEAGGLIAIAEYGQEY-GKEDPIQVLFhGFGHYDALQ 295
Cdd:COG5539   256 QQLASLLKNPHYYTN---TASPSIKCNICGTGFvGEKDYYAHAL-ATGHYNFGE 305

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU4 from plants and similar proteins; Deubiquitinating enzyme OTU4, also called OTU domain-containing protein 4, 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. OTU4 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU4 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 1002294325 159 DYSVTGIPGDGRCLFRSVAHGACIRSGK-RPDDDLQRKMADDLRAMVADEFIKRRAETEWFVEGDFDAYVSRIRKPHVWG 237
Cdd:cd22760     1 DYRVHGIAGDGRCLFRAVAHGECLARGKaAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1002294325 238 GEPELLMASHVLRMPITVYMHDKEAGGLIAIAEYGQEYGKEDPIQVLFHGFGHYDALQ 295
Cdd:cd22760    81 GEPELLMLSHVLQRPITVYMADEGEGGLISIAEYGQEYGKGNPIRVLFHGFGHYEALL 138

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 1002294325 166 PGDGRCLFRSVAHGACIRSGKRPDDDLQrkmadDLRAMVADEFIKRRAETEWFVEGDFDAYVSRIRKPHVWGGEPELLMA 245
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHDVLRKMLVQ-----ELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFAL 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1002294325 246 SHVLRMPITVYMHDK-EAGGLIAIAEYGQEYGKEDPIQVLFHG-----FGHY 291
Cdd:pfam02338  76 AHILRRPIIVYKSEGgEELGGLKEYGIYLPLGWDPSLCLVYPRhlyylGGHY 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 1002294325 165 IPGDGRCLFRSVAHGACirsgkrpdddLQRKMADDLRAMVADEFIKRRAETE------WFVEGDFDAYVSRIRKPHVWGG 238
Cdd:cd22744     5 VPGDGNCLFRALAHALY----------GDQESHRELRQEVVDYLRENPDLYEpaeladEDDGEDFDEYLQRMRKPGTWGG 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1002294325 239 EPELLMASHVLRMPITVYMHDKEAGGLIAIAEYGQEYGKedPIQVLFHGFGHYDAL 294
Cdd:cd22744    75 ELELQALANALNVPIVVYSEDGGFLPVSVFGPGPGPSGR--PIHLLYTGGNHYDAL 128

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 1002294325 165 IPGDGRCLFRSVAHGACIRSGKRPDDDLQRKMADDLRAMVAD--EFIKRRAETEWFVEGDFDAYVSRIRKPHVWGGEPEL 242
Cdd:cd22761    15 IPSDGDCLYNAIAHQLSLRGIETSVEELRKQTADYMRENKDDflPFLTNPDTGDPLTEEEFEKYCDDVENTGAWGGQLEL 94

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1002294325 243 LMASHVLRMPITVYMHDkeaGGLIAIaeyGQEYGKEDPIQVLFH----GFG-HYD 292
Cdd:cd22761    95 RALSHVLKRPIEVIQAE---GPPIII---GEEFKSGKPLILTYHrhayGLGeHYN 143

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 1002294325 165 IPGDGRCLFRSVAH---GacirsgkrpDDDlqrkMADDLRAMVADEFIKRRAETEWFVEGDFDAYVSRIRKPHVWGGEPE 241
Cdd:cd22752     7 MEEDGNCLFRAVADqvyG---------DQE----MHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIE 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1002294325 242 LLMASHVLRMPITVYMHDKEAgglIAIAEYGQEYGKEdPIQVLFHGFGHYDAL 294
Cdd:cd22752    74 IQAMSELYNRPIEVYAYSTEP---INTFHEASSSDNE-PIRLSYHGNSHYNSI 122

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 1002294325 165 IPGDGRCLFRSVAHGACIRSGKRPDDDLQ--RKMA--------DDLRAMVADEFIKRRAETEWfvegdfDAYVSRIRKPH 234
Cdd:cd22797    15 IKADGHCLYRAVEDQLQLRGGGAPAPDYQqlRELAadymrahpDDFLPFLEDEDEGGDGDEAF------EAYCREVESTA 88

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1002294325 235 VWGGEPELLMASHVLRMPITVYmhdkeAGGLiAIAEYGQEYGKED-PIQVLF--HGFG---HYDALQ 295
Cdd:cd22797    89 AWGGQLELGALAHALRRHIKVY-----SAGM-PDVEMGEEYAGTGpPLRLCYhrHAFGlgeHYNSVV 149

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 1002294325 165 IPGDGRCLFRSVAHgacirsgkrpdddlQ----RKMADDLRAMVADEFIKRRAETEWF--------VEGDFDAYVSRIRK 232
Cdd:cd22756     5 ITGDGNCLFRALSD--------------QlygdPDRHLEIRAEVVEYMRANPDDFKPFseaatfaeDDEAFEDYLARMAK 70

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1002294325 233 PHVWGGEPELLMASHVLRMPITVYmhdkEAGGLIAI--AEYGQEYGKEDPIQVLFHGFGHY 291
Cdd:cd22756    71 DGTYGDNLEIVAFARAYNVDVKVY----QPDPVYVIsaPEDGSPGPARRVLHIAYHNWEHY 127

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 1002294325 159 DYSVTGIPGDGRCLFRSVAHgaCIRSGKRPDDdlqrkmADDLRAMVADEFIKRRAET------EWFVEGDFDAYVSRIRK 232
Cdd:cd22758     5 GFEIRDVPGDGNCFFHAVSD--QLYGNGIEHS------HKELRQQAVNYLRENPELYdgfflsEFDEEESWEEYLNRMSK 76

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1002294325 233 PHVWGGEPELLMASHVLRMPITVYMHDkEAGGLIAIAEygQEYGKEDPIQVLFHGFGHYDAL 294
Cdd:cd22758    77 DGTWGDHIILQAAANLFNVRIVIISSD-GSDETTIIEP--GNSKNGRTIYLGHIGENHYVSL 135

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 1002294325 165 IPGDGRCLFRSVAHgaCIRSGkrpdddlQRKMADDLRAMVADEfIKRRAET--EWFVEGDFDAYVSRIRKPHVWGGEPEL 242
Cdd:cd22745     8 VPDDNSCLFTSISY--LLEGG-------LLDSAPELREIVADA-ILSDPDTynEAILGKPPDEYCAWILKPDSWGGAIEL 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1002294325 243 LMASHVLRMPITVYmhDKEAGgliAIAEYGQEYGKEDPIQVLFHGFgHYDAL 294
Cdd:cd22745    78 SILSKHFGVEICVV--DVQTG---RVDRFGEDKGYSKRIFLLYSGI-HYDAL 123

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 1002294325 165 IPGDGRCLFRSVAHGacIRSGKRPDDDLQRK----MADDLramvaDEFikrraetEWFVEGDFDAYVSRIRKPHVWGGEP 240
Cdd:cd22747    26 IIPDGNCLYRAVSKA--VYGDQALHRELREQtvhyIADHL-----DEF-------NPIIEGDVGEFLIKAAQDGAWAGYP 91

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1002294325 241 ELLMASHVLRmpITVYMHDKEAGGLIAIAEYGQEYGKEDP----IQVLFHGFGHYDAL 294
Cdd:cd22747    92 ELLAMGQMLN--VNIRLTTGGSLESPTVSTMVHYLGPEDSgkpsIWLSWLSNGHYDAV 147

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 1002294325 165 IPGDGRCLFRSVA---------HgacirsgkrpdddlqrkmaDDLRAMVADEFIKRRAETEWFVEGDFDAYVSRIRKPHV 235
Cdd:cd22753    15 IPRDGSCLFRAVSeqlfftqsyH-------------------QQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKE 75

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1002294325 236 WGGEPELLMASHVLRMPITVY-MHDKEAgglIAIAEYGQeygkEDPIQVLFHGFGHYD 292
Cdd:cd22753    76 WGGLLELEALSLLYKVDFIVYsIPDQPP---SNITNNGY----PKKIMLCYSGGNHYD 126

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 1002294325 166 PGDGRCLFRSVAhgacirsgkrpdddlqRKMADDLramvaDEF------IKRRAETEW-------FVEGDFDAYVSRIRK 232
Cdd:cd21880    28 PGDGNCFFRSIA----------------ELLFDTE-----DEWrlvkntIESYARANWdecpearLYYLSLEEYLRDAMK 86

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1002294325 233 PHVWGGEPELLMASHVLRMPITVYMHDkeAGGLIaiaEYGQEYGKEDPIQV--LFHGFGHYDALQI 296
Cdd:cd21880    87 DGYWGGSLEAEILSKALGITIIIWVVD--DSDWV---TAAVRFGDGDVSTSlnLLHSGGHFDALRL 147

OTU (ovarian tumor) domain of vertnin and similar proteins; Vertnin (VRTN) is an OTU domain-containing protein that is required for the development of thoracic vertebrae in mammals. OTU domains typically function as deubiquitinases (DUBs)/ubiquitin thiolesterases (EC 3.4.19.12) that catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. These DUBs may play important regulatory roles at the level of protein turnover by preventing degradation. Vertnin and some subfamily members do not possess the conserved catalytic residues and may not have DUB activity. VRTN gene is associated with variations in vertebral number.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1002294325 165 IPGDGRCLFRSVAHGACirsGkrpDDDLqrkmADDLRAMVADEFIKRRAetewFVEGDFDAYVSRIRKPHVWGGEPELLM 244
Cdd:cd22791     6 VTGDGNCLFRAASLLLF---G---DESL----HLELRLRTVLELVLNSE----FYEAIYEAEIKATCKPGSYSGIWHIYA 71

                          90
                  ....*....|...
gi 1002294325 245 ASHVLRMPI-TVY 256
Cdd:cd22791    72 LSSVLQRPIfSVY 84