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 186520008 195 LFQRLQLYGLVENKIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREI-YEGYVPMAYNDYLKAMKRNGEWGDH 273
Cdd:cd22751    1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPELyYEFYVPEEYDEYLKKMSKDGEWGDE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 186520008 274 VTLQAAADLFGVRMFVITSFKDTCYIEILPHF-QKSNRLICLSFWAEVHYNSIY 326
Cdd:cd22751   81 LTLQAAADAFGVKIHVITSFEDNWFLEIEPRGlVRSKRVLFLSYWAEVHYNSIY 134

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 186520008 195 LFQRLQLYGLVENKIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREI-YEGYVPMAYNDYLKAMKRNGEWGDH 273
Cdd:cd22751    1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPELyYEFYVPEEYDEYLKKMSKDGEWGDE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 186520008 274 VTLQAAADLFGVRMFVITSFKDTCYIEILPHF-QKSNRLICLSFWAEVHYNSIY 326
Cdd:cd22751   81 LTLQAAADAFGVKIHVITSFEDNWFLEIEPRGlVRSKRVLFLSYWAEVHYNSIY 134

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186520008 203 GLVENKIEGDGNCQFRSLSDQLyrsPEHHNFV-----REQVVNQLAYNREIYEGYVPMAY----------NDYLKAMKRN 267
Cdd:COG5539  170 WIVKPDSQGDGCIEIAIISDQL---PVRIHVVdvdkdSEDRYNSHPYVQRISILFTGIHFdeetlamvlwDTYVNEVLFD 246

                         90
                 ....*....|....*.
gi 186520008 268 GEWGDHVTLQAAADLF 283
Cdd:COG5539  247 ASDGITIEIQQLASLL 262

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 186520008 195 LFQRLQLYGLVENKIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREI-YEGYVPMAYNDYLKAMKRNGEWGDH 273
Cdd:cd22751    1 LLRRLDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPELyYEFYVPEEYDEYLKKMSKDGEWGDE 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 186520008 274 VTLQAAADLFGVRMFVITSFKDTCYIEILPHF-QKSNRLICLSFWAEVHYNSIY 326
Cdd:cd22751   81 LTLQAAADAFGVKIHVITSFEDNWFLEIEPRGlVRSKRVLFLSYWAEVHYNSIY 134

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 186520008 199 LQLYGLVENKIEGDGNCQFRSLSDQLYR--SPEHHNFVREQVVNQLAYNREIYEGYVPM------AYNDYLKAMKRNGEW 270
Cdd:cd22758    1 AKENGFEIRDVPGDGNCFFHAVSDQLYGngIEHSHKELRQQAVNYLRENPELYDGFFLSefdeeeSWEEYLNRMSKDGTW 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 186520008 271 GDHVTLQAAADLFGVRMFVITSFKDTCYIEILPHFQKSNRLICLSFWAEVHYNSI 325
Cdd:cd22758   81 GDHIILQAAANLFNVRIVIISSDGSDETTIIEPGNSKNGRTIYLGHIGENHYVSL 135

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 186520008 208 KIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREIYEGYVPM--------AYNDYLKAMKRNGEWGDHVTLQAA 279
Cdd:cd22756    4 DITGDGNCLFRALSDQLYGDPDRHLEIRAEVVEYMRANPDDFKPFSEAatfaeddeAFEDYLARMAKDGTYGDNLEIVAF 83

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 186520008 280 ADLFGVRMFVITsfKDTCYI---EILPHFQKSNRLICLSFWAEVHYNSI 325
Cdd:cd22756   84 ARAYNVDVKVYQ--PDPVYVisaPEDGSPGPARRVLHIAYHNWEHYSSV 130

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 186520008 203 GLVENKIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREIYEGYVPMAYNDYLKAMKRNGEWGDHVTLQAAADL 282
Cdd:cd22753    9 GLYRKHIPRDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKEWGGLLELEALSLL 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 186520008 283 FGVRmFVITSFKDTcyieiLPHFQKSNRL---ICLSFWAEVHYNSIYP 327
Cdd:cd22753   89 YKVD-FIVYSIPDQ-----PPSNITNNGYpkkIMLCYSGGNHYDSVYS 130

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 186520008 203 GLVENKIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREIYEGYVPMAYNDYLKAMKRNGEWGDHVTLQAAADL 282
Cdd:cd22794    9 GLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQVEISALSLM 88

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*...
gi 186520008 283 FGvRMFVItsFKDtcyIEILPHFQKSNRL---ICLSFWAEVHYNSIYP 327
Cdd:cd22794   89 YK-RDFII--YQE---PGKPPSNVTENGFpdkILLCFSNGNHYDSVYP 130

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 186520008 208 KIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREIYEGYVPMAY-------NDYLKAMKRNGEWGDHVTLQAAA 280
Cdd:cd22757    5 PIPGDGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIYTHDSEgnnyksaEEYRADMSKPGTYGTLCELVAAA 84

                         90
                 ....*....|
gi 186520008 281 DLFGVRMFVI 290
Cdd:cd22757   85 ELYPFHFEVY 94

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 186520008 209 IEGDGNCQFRSLSDQL---YRSPEHHNF--VREQVVNQLAYNREIY---------EGYVPMAYNDYLKAMKRNGEWGDHV 274
Cdd:cd22748   11 IPPDGHCLYRAIADQLklrGGSEEPYSYkeLRKLAADYMRAHRDDFlpfltnddgDLMTEEEFEEYCDKIENTAEWGGQL 90

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 186520008 275 TLQAAADLFGVRMFVITSFKDTcyIEILPHFqKSNRLICLSF-----WAEVHYNSI 325
Cdd:cd22748   91 ELRALSKALKRPIHVYQAGSPP--LVIGEEF-DSGEPLRLSYhrhayGLGEHYNSV 143

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 186520008  211 GDGNCQFRSLSDQLY-RSPEH----HNFVREQVVNQLAYNREIYEGYVPMAYNDYLKAMKRNGEWGDHVTLQAAADLFGV 285
Cdd:pfam02338   2 GDGNCLYRSISHQLWgVHDVLrkmlVQELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFALAHILRR 81

                          90
                  ....*....|
gi 186520008  286 RMFVITSFKD 295
Cdd:pfam02338  82 PIIVYKSEGG 91

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 186520008 208 KIEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREIYEGYvpmaYNDYLKAMKRNGEWGDHVTLQAAADLFGVRM 287
Cdd:cd22791    5 RVTGDGNCLFRAASLLLFGDESLHLELRLRTVLELVLNSEFYEAI----YEAEIKATCKPGSYSGIWHIYALSSVLQRPI 80

                         90       100
                 ....*....|....*....|....*.
gi 186520008 288 FVItsFKDTCYIEILPHFqksNRLIC 313
Cdd:cd22791   81 FSV--YPEVGNQKIRPLL---NRTIR 101

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 186520008 209 IEGDGNCQFRSLSDQLYRSPEHHNFVREQVVNQLAYNREIYEGYVPMAYNDYLKAMKRNGEWGDHVTLQAAADLFGVRMF 288
Cdd:cd22747   26 IIPDGNCLYRAVSKAVYGDQALHRELREQTVHYIADHLDEFNPIIEGDVGEFLIKAAQDGAWAGYPELLAMGQMLNVNIR 105

                 ...
gi 186520008 289 VIT 291
Cdd:cd22747  106 LTT 108

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 186520008 203 GLVENKIEGDGNCQFRSLSDQLyrsPEHHNFV-----REQVVNQLAYNREIYEGYVPMAY----------NDYLKAMKRN 267
Cdd:COG5539  170 WIVKPDSQGDGCIEIAIISDQL---PVRIHVVdvdkdSEDRYNSHPYVQRISILFTGIHFdeetlamvlwDTYVNEVLFD 246

                         90
                 ....*....|....*.
gi 186520008 268 GEWGDHVTLQAAADLF 283
Cdd:COG5539  247 ASDGITIEIQQLASLL 262

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 186520008 193 ERLFQR-LQLYglvenKIEGDGNCQFRSLSDQLYRSPEHHNF--VREQVVNQLAYNREIY----------EGYVPMAYND 259
Cdd:cd22761    3 KILKERgLKIH-----EIPSDGDCLYNAIAHQLSLRGIETSVeeLRKQTADYMRENKDDFlpfltnpdtgDPLTEEEFEK 77

                         90       100       110
                 ....*....|....*....|....*....|.
gi 186520008 260 YLKAMKRNGEWGDHVTLQAAADLFGVRMFVI 290
Cdd:cd22761   78 YCDDVENTGAWGGQLELRALSHVLKRPIEVI 108