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 223941923 289 KLALYLAEVEKQDKYLRQRNKYRFHIIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEGDVGEFIIA 368
Cdd:cd22747    1 KLALYLAEVEKQDKYLRERNKYRFHIIPDGNCLYRAVSKAVYGDQALHRELREQTVHYIADHLDEFNPIIEGDVGEFLIK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 223941923 369 AAQDGAWAGYPELLAMGQMLNVNIHLTTGGRLESPTVSTMIHYLGPEDSLRPSIWLSWLSNGHYDAVFD 437
Cdd:cd22747   81 AAQDGAWAGYPELLAMGQMLNVNIRLTTGGSLESPTVSTMVHYLGPEDSGKPSIWLSWLSNGHYDAVFD 149

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 223941923 289 KLALYLAEVEKQDKYLRQRNKYRFHIIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEGDVGEFIIA 368
Cdd:cd22747    1 KLALYLAEVEKQDKYLRERNKYRFHIIPDGNCLYRAVSKAVYGDQALHRELREQTVHYIADHLDEFNPIIEGDVGEFLIK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 223941923 369 AAQDGAWAGYPELLAMGQMLNVNIHLTTGGRLESPTVSTMIHYLGPEDSLRPSIWLSWLSNGHYDAVFD 437
Cdd:cd22747   81 AAQDGAWAGYPELLAMGQMLNVNIRLTTGGSLESPTVSTMVHYLGPEDSGKPSIWLSWLSNGHYDAVFD 149

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 223941923 289 KLALYLAEVEKQDKYLRQRNKYRFHIIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEGDVGEFIIA 368
Cdd:cd22747    1 KLALYLAEVEKQDKYLRERNKYRFHIIPDGNCLYRAVSKAVYGDQALHRELREQTVHYIADHLDEFNPIIEGDVGEFLIK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 223941923 369 AAQDGAWAGYPELLAMGQMLNVNIHLTTGGRLESPTVSTMIHYLGPEDSLRPSIWLSWLSNGHYDAVFD 437
Cdd:cd22747   81 AAQDGAWAGYPELLAMGQMLNVNIRLTTGGSLESPTVSTMVHYLGPEDSGKPSIWLSWLSNGHYDAVFD 149

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 223941923 314 IIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLI------EGDVGEFIIAAAQDGAWAGYPELLAMGQM 387
Cdd:cd22744    5 VPGDGNCLFRALAHALYGDQESHRELRQEVVDYLRENPDLYEPAEladeddGEDFDEYLQRMRKPGTWGGELELQALANA 84

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 223941923 388 LNVNIH-LTTGGRLESPTVstmihYLGPEDSLRPSIWLSWLSNGHYDAV 435
Cdd:cd22744   85 LNVPIVvYSEDGGFLPVSV-----FGPGPGPSGRPIHLLYTGGNHYDAL 128

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 223941923 314 IIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEGDVGEFIIAAAQDGAWAGYPELLAMGQMLNVNIH 393
Cdd:cd22752    7 MEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSELYNRPIE 86

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 223941923 394 LTtggrleSPTVSTMIHYLGPEDSLRPSIWLSWLSNGHYDAVFD 437
Cdd:cd22752   87 VY------AYSTEPINTFHEASSSDNEPIRLSYHGNSHYNSIVD 124

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 223941923 306 QRNKYRFH-IIPDGNCLYRAVSKTVYGDQSL--HRELREQTVHYIADHLDHF--SPLIEGDVGE----FIIAAAQDGAWA 376
Cdd:cd22758    2 KENGFEIRdVPGDGNCFFHAVSDQLYGNGIEhsHKELRQQAVNYLRENPELYdgFFLSEFDEEEsweeYLNRMSKDGTWG 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 223941923 377 GYPELLAMGQMLNVNIHLTTGGRLESPTVstmIHYLGPEDslRPSIWLSWLSNGHYDAV 435
Cdd:cd22758   82 DHIILQAAANLFNVRIVIISSDGSDETTI---IEPGNSKN--GRTIYLGHIGENHYVSL 135

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 223941923 301 DKYLRQRNKYRFHIIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEGDVGEFIIAAAQDGAWAGYPE 380
Cdd:cd22753    2 DEYLDSLGLYRKHIPRDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKEWGGLLE 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 223941923 381 LLAMGQMLNVNIHLTTGGRLEsPTVSTMIHYLGPedslrpsIWLSWLSNGHYDAVFD 437
Cdd:cd22753   82 LEALSLLYKVDFIVYSIPDQP-PSNITNNGYPKK-------IMLCYSGGNHYDSVYS 130

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 223941923 310 YRFHIIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEGDVGEFIIAA--------AQDGAWAGYPEL 381
Cdd:cd22756    1 YAKDITGDGNCLFRALSDQLYGDPDRHLEIRAEVVEYMRANPDDFKPFSEAATFAEDDEAfedylarmAKDGTYGDNLEI 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 223941923 382 LAMGQMLNVN--IHLTTGGRLESPTVStmihylGPEDSLRPSIWLSWLSNGHYDAV 435
Cdd:cd22756   81 VAFARAYNVDvkVYQPDPVYVISAPED------GSPGPARRVLHIAYHNWEHYSSV 130

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 223941923 312 FHIIPDGNCLYRAVS---KTVYGDQSL--HRELREQTVHYIADHLDHFSPLIEGDVGEFIIAA---------AQDGAWAG 377
Cdd:cd22748    9 KEIPPDGHCLYRAIAdqlKLRGGSEEPysYKELRKLAADYMRAHRDDFLPFLTNDDGDLMTEEefeeycdkiENTAEWGG 88

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 223941923 378 YPELLAMGQMLNVNIHLTTGGrleSPTVsTMihylGPEDSLRPSIWLSWLSN-----GHYDAV 435
Cdd:cd22748   89 QLELRALSKALKRPIHVYQAG---SPPL-VI----GEEFDSGEPLRLSYHRHayglgEHYNSV 143

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 223941923 315 IP-DGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLDHFSPLIEGDVG--EFIIAAAQDGAWAGYPELLAMGQM--LN 389
Cdd:cd22770   19 IPgDGNCLFRALGDQLEGHSRNHLKHRQETVQYMIEHREDFEPFVEDDVPfdKHVANLSKPGTYAGNDAIVAFARLhqVN 98

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 223941923 390 VNIHlttggRLESPtvstMIHYLGPEDSLRPSIWLSWLSNGHYDAV 435
Cdd:cd22770   99 VVIH-----QLNAP----LWQIRGTEKSSSRELHISYHNGDHYSSV 135

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 223941923 304 LRQRNKY----RFHIIPDGNCLYRAVSKTVYGDQSLHRELREQTVHYIADHLD-HFSPLIEGDVGEFIIAAAQDGAWAGY 378
Cdd:cd22751    1 LLRRLDLyglvERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPElYYEFYVPEEYDEYLKKMSKDGEWGDE 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 223941923 379 PELLAMGQMLNVNIHLTTggrleSpTVSTMIHYLGPEDSLRPS--IWLSWLSNGHYDAVF 436
Cdd:cd22751   81 LTLQAAADAFGVKIHVIT-----S-FEDNWFLEIEPRGLVRSKrvLFLSYWAEVHYNSIY 134

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 223941923 302 KYLRQRNKYRFHIIPDGNCLYRAVSK--TVYGDQSLHRELREQTVHYIADHLDHFSP-LIEGDVGEFIIAA--------- 369
Cdd:cd22761    3 KILKERGLKIHEIPSDGDCLYNAIAHqlSLRGIETSVEELRKQTADYMRENKDDFLPfLTNPDTGDPLTEEefekycddv 82

                         90       100
                 ....*....|....*....|...
gi 223941923 370 AQDGAWAGYPELLAMGQMLNVNI 392
Cdd:cd22761   83 ENTGAWGGQLELRALSHVLKRPI 105

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 223941923 312 FHII---PDGNCLYRAVSKTVYGDQSLHRELREQTVHYiADHldHFSPLIE-----GDVGEFIIAAAQDGAWAGYPE--L 381
Cdd:cd21880   22 FEIErvpGDGNCFFRSIAELLFDTEDEWRLVKNTIESY-ARA--NWDECPEarlyyLSLEEYLRDAMKDGYWGGSLEaeI 98

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 223941923 382 LAmgQMLNVNIHLTTGGRLEspTVSTMIHYlGPEDsLRPSIWLSwLSNGHYDA 434
Cdd:cd21880   99 LS--KALGITIIIWVVDDSD--WVTAAVRF-GDGD-VSTSLNLL-HSGGHFDA 144

OTU (ovarian tumor) domain of the potexviruses/carlaviruses RNA replication protein family; RNA replication polyprotein (RDRP) is a viral homolog of ovarian tumor protease (vOTU), which displays RNA helicase (EC 3.6.4.13), RNA-directed RNA polymerase (EC 2.7.7.48), viral methyltransferase, Fe(2+) 2-oxoglutarate dioxygenase and protease activities. The central part of this protein possibly functions as an ATP-binding helicase. It is an RNA-directed RNA polymerase involved in viral RNA replication. It also acts as a thiol protease that cleaves the polyprotein. 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 223941923 317 DGNCLYRAVSKtvYGDQSlHRELREQtvhyIADHLDHfspliEGDVGEFIIAAAQDGAWAGYPELLAMGQMLNVNIHLTT 396
Cdd:cd22792    8 DGNCFWHSLGH--FLGLS-ALELKKL----LRDSLFD-----DPELDEELDEQLEPGVYAEDEAIAAAAKLFGVNICVHD 75

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|
gi 223941923 397 GGrlesptvSTMIHYLGPEDSlRPSIWLsWLSNGHYDAVF 436
Cdd:cd22792   76 PD-------EGVLYTFTPNES-SKSIHL-LLENEHFEPLV 106