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 778684853 187 DYSVIGIPGDGRCLFRSVAHGACLRSGKPAPSESLQRDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPHVWG 266
Cdd:cd22760    1 DYRVHGIAGDGRCLFRAVAHGECLARGKAAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 778684853 267 GEPELFMASHVLQAPIIVYMYDKDSGGLISIAEYGDEYGKENPIRVLYHGFGHYDALQ 324
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 778684853 187 DYSVIGIPGDGRCLFRSVAHGACLRSGKPAPSESLQRDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPHVWG 266
Cdd:cd22760    1 DYRVHGIAGDGRCLFRAVAHGECLARGKAAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 778684853 267 GEPELFMASHVLQAPIIVYMYDKDSGGLISIAEYGDEYGKENPIRVLYHGFGHYDALQ 324
Cdd:cd22760   81 GEPELLMLSHVLQRPITVYMADEGEGGLISIAEYGQEYGKGNPIRVLFHGFGHYEALL 138

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778684853 193 IPGDGRCLFRSVAHGACLR-SGKPAPSESLQRDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPHVWGGEPEL 271
Cdd:COG5539  176 SQGDGCIEIAIISDQLPVRiHVVDVDKDSEDRYNSHPYVQRISILFTGIHFDEETLAMVLWDTYVNEVLFDASDGITIEI 255

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 778684853 272 FMASHVLQAPIIVYMYDKDSgglISIAEYGdeYGKENPIRVLYHGF--GHYDALQ 324
Cdd:COG5539  256 QQLASLLKNPHYYTNTASPS---IKCNICG--TGFVGEKDYYAHALatGHYNFGE 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 778684853 187 DYSVIGIPGDGRCLFRSVAHGACLRSGKPAPSESLQRDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPHVWG 266
Cdd:cd22760    1 DYRVHGIAGDGRCLFRAVAHGECLARGKAAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 778684853 267 GEPELFMASHVLQAPIIVYMYDKDSGGLISIAEYGDEYGKENPIRVLYHGFGHYDALQ 324
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 778684853  194 PGDGRCLFRSVAHGACLRSGkpapseSLQRDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPHVWGGEPELFM 273
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHD------VLRKMLVQELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFA 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 778684853  274 ASHVLQAPIIVY-MYDKDSGGLISIAEYGDEYGKENPIRVLYHG-----FGHY 320
Cdd:pfam02338  75 LAHILRRPIIVYkSEGGEELGGLKEYGIYLPLGWDPSLCLVYPRhlyylGGHY 127

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU3 from plants and similar proteins; Deubiquitinating enzyme OTU3, also called OTU domain-containing protein 3, 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. OTU3 may play an important regulatory role at the level of protein turnover by preventing degradation. OTU3 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 778684853 188 YSVIGIPGDGRCLFRSVAHGACLRSGKPAPSESLQRDlADELRSNVAD----EFIKRREETEWFV----EGDFDTYMSNM 259
Cdd:cd22759    3 YTVVRVKGDGRCMFRALVKGLAANKGIFLSGREEEQE-ADELRLAVAEalcrSEERRRDYEEALIaitvEGSLDRYCRRI 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 778684853 260 RNPHVWGGEPELFMASHVLQAPIIVYMYDKDSG------GLISIAEYGDEYGKE-------NPIRVLYHGFGHYDAL 323
Cdd:cd22759   82 QRPDFWGGESELLVLSKMLKQPIIVYIPESEAKnggwgsGFIPIQKYGEEFAKGtkgrkgrKPVRLLYSGSNHYDLL 158

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 778684853 193 IPGDGRCLFRSVAHGACLRsGKPAPSESLQRDLADELRSNVAD--EFIKRREETEWFVEGDFDTYMSNMRNPHVWGGEPE 270
Cdd:cd22761   15 IPSDGDCLYNAIAHQLSLR-GIETSVEELRKQTADYMRENKDDflPFLTNPDTGDPLTEEEFEKYCDDVENTGAWGGQLE 93

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 778684853 271 LFMASHVLQAPIIVYMYDkdsGGLISIaeyGDEYGKENPIRVLYH----GFG-HYD 321
Cdd:cd22761   94 LRALSHVLKRPIEVIQAE---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 778684853 190 VIGIPGDGRCLFRSVAHGAclrSGKPapseslqrDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPHVWGGEP 269
Cdd:cd22752    4 IKEMEEDGNCLFRAVADQV---YGDQ--------EMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHI 72

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 778684853 270 ELFMASHVLQAPIIVYMYDKdsgglISIAEYGDEYGKEN-PIRVLYHGFGHYDAL 323
Cdd:cd22752   73 EIQAMSELYNRPIEVYAYST-----EPINTFHEASSSDNePIRLSYHGNSHYNSI 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 778684853 193 IPGDGRCLFRSVAHGACLRSGK-PAPS-ESLQRDLADELRSNvADEFIKRREETEWFVEGD--FDTYMSNMRNPHVWGGE 268
Cdd:cd22797   15 IKADGHCLYRAVEDQLQLRGGGaPAPDyQQLRELAADYMRAH-PDDFLPFLEDEDEGGDGDeaFEAYCREVESTAAWGGQ 93

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 778684853 269 PELFMASHVLQAPIIVYmydkdSGGLiSIAEYGDEYGKEN-PIRVLY--HGFG---HYDALQ 324
Cdd:cd22797   94 LELGALAHALRRHIKVY-----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 778684853 193 IPGDGRCLFRSVA---------HGAcLRsgkpapseslqRDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPH 263
Cdd:cd22756    5 ITGDGNCLFRALSdqlygdpdrHLE-IR-----------AEVVEYMRANPDDFKPFSEAATFAEDDEAFEDYLARMAKDG 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 778684853 264 VWGGEPELFMASHVLQAPIIVY----MYDkdsgglISIAEYGDEYGKENPIRVLYHGFGHY 320
Cdd:cd22756   73 TYGDNLEIVAFARAYNVDVKVYqpdpVYV------ISAPEDGSPGPARRVLHIAYHNWEHY 127

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 778684853 193 IPGDGRCLFRSVA----HgaclrsgkpAPSESLQRDLA--DELRSNvadefikrREETEWFVEGDFDTYMSNMRNPHVWG 266
Cdd:cd22794   15 IAKDGSCLFRAVAeqvfH---------TQSRHLEVRKAcvDYLRRN--------REKFEAFIEGPFEQYLKNLENPKEWA 77

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 778684853 267 GEPELFMASHVLQAPIIVYmydKDSGGLISIAEygdEYGKENPIRVLYHGFGHYDA 322
Cdd:cd22794   78 GQVEISALSLMYKRDFIIY---QEPGKPPSNVT---ENGFPDKILLCFSNGNHYDS 127

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 778684853 193 IPGDGRCLFRSVahgaclrsgkpapSESL----------QRDLADELRSNvadefikrREETEWFVEGDFDTYMSNMRNP 262
Cdd:cd22753   15 IPRDGSCLFRAV-------------SEQLfftqsyhqqvRQACVEYLEKN--------REEFEKFSEISFDDYLERLSDP 73

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 778684853 263 HVWGGEPELFMASHVLQAPIIVY-MYDKDSgglISIAEYGDeygkENPIRVLYHGFGHYD 321
Cdd:cd22753   74 KEWGGLLELEALSLLYKVDFIVYsIPDQPP---SNITNNGY----PKKIMLCYSGGNHYD 126

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 778684853 190 VIGIPGDGRCLFRSVAHgaCLrSGkpapSESLQRdladELRSNVADEFIKRREETEWFVEGDFDTY-----MSNMRNPHV 264
Cdd:cd22755    3 TIKIVGDGNCFFRALSY--AI-TG----SEKYHR----KIRKAIVDFLEKNPDEFRNLLRSDYESVeeyleKSRMRYDGT 71

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 778684853 265 WGGEPELFMASHVLQAPIIVYMyDKDSGGLI--SIAEYGDEYGKENPIRVLYHGFGHYD 321
Cdd:cd22755   72 WATDVEIFAAATLLGVDIYVYS-KGGYKWLLysPRFKLGKRNGSREAIYLKNTNGNHFE 129

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 778684853 193 IPGDGRCLFRSVAHGAclrsgkpAPSESLQRDLADELRSNVADEfikrREETEWFVEGDFDTYMSNMRNPHVWGGEPELF 272
Cdd:cd22747   26 IIPDGNCLYRAVSKAV-------YGDQALHRELREQTVHYIADH----LDEFNPIIEGDVGEFLIKAAQDGAWAGYPELL 94

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 778684853 273 MASHVLQapIIVYMYDKDSGGLISIAEYGDEYGKENPIR----VLYHGFGHYDAL 323
Cdd:cd22747   95 AMGQMLN--VNIRLTTGGSLESPTVSTMVHYLGPEDSGKpsiwLSWLSNGHYDAV 147

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 778684853 193 IPGDGRCLFRSVAHgaCL-RSGKPAPSesLQRDLADELRSNvADEFikrreeTEWFVEGDFDTYMSNMRNPHVWGGEPEL 271
Cdd:cd22793    8 IDSDNSCLFNAVGY--VMeGSRKKAPE--LRQVIADAVLSD-PFEY------NEAFLGKSNKEYCEWILNPNSWGGAIEL 76

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....
gi 778684853 272 FMASHVLQAPIIVYMYDKDSGGLisiaeYGDEYGKENPIRVLYHGFgHYDALQI 325
Cdd:cd22793   77 SILSDHYGREIAAFDIQTKRCDV-----YGEGKGYTERVMLIYDGL-HYDALAI 124

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 778684853 165 DDNEENSDSSHVKLShgkkvYTDY-SVIGIPGDGRCLFRSVAhgaCLRSGKPapseslqrdlaDELRS--NVADEFIKRR 241
Cdd:cd21880    3 EEVGEGQYVSNPRFN-----LRDYfEIERVPGDGNCFFRSIA---ELLFDTE-----------DEWRLvkNTIESYARAN 63

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778684853 242 EETEWFVEGDFDT---YMSNMRNPHVWGGEPELFMASHVLQAPIIVYMYDkDSGGLISIAEYGDeyGKENPIRVLYHGFG 318
Cdd:cd21880   64 WDECPEARLYYLSleeYLRDAMKDGYWGGSLEAEILSKALGITIIIWVVD-DSDWVTAAVRFGD--GDVSTSLNLLHSGG 140

                 ....*..
gi 778684853 319 HYDALQI 325
Cdd:cd21880  141 HFDALRL 147

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 778684853 193 IPGDGRCLFRSVAHGACLR-SGKPAPSESLQRDLADELRSNVADEFIKRREETEWFVEGDFDTYMSNMRNPHVWGGEPEL 271
Cdd:COG5539  176 SQGDGCIEIAIISDQLPVRiHVVDVDKDSEDRYNSHPYVQRISILFTGIHFDEETLAMVLWDTYVNEVLFDASDGITIEI 255

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 778684853 272 FMASHVLQAPIIVYMYDKDSgglISIAEYGdeYGKENPIRVLYHGF--GHYDALQ 324
Cdd:COG5539  256 QQLASLLKNPHYYTNTASPS---IKCNICG--TGFVGEKDYYAHALatGHYNFGE 305