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 1063717448 167 DYSIIGIPGDGRCLFRSVAHGFCLRSGKLAPGEKMQRELADELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVWG 246
Cdd:cd22760     1 DYRVHGIAGDGRCLFRAVAHGECLARGKAAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063717448 247 GEPELFMASHVLQMPITVYMKDDKAGGLISIAEYGQEYGKDDPIRVLYHGFGHYDALL 304
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 1063717448 167 DYSIIGIPGDGRCLFRSVAHGFCLRSGKLAPGEKMQRELADELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVWG 246
Cdd:cd22760     1 DYRVHGIAGDGRCLFRAVAHGECLARGKAAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063717448 247 GEPELFMASHVLQMPITVYMKDDKAGGLISIAEYGQEYGKDDPIRVLYHGFGHYDALL 304
Cdd:cd22760    81 GEPELLMLSHVLQRPITVYMADEGEGGLISIAEYGQEYGKGNPIRVLFHGFGHYEALL 138

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063717448 173 IPGDGRCLFRSVAHGFCLR--SGKLAPGEKMqRELADELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVWGGEPE 250
Cdd:COG5539   176 SQGDGCIEIAIISDQLPVRihVVDVDKDSED-RYNSHPYVQRISILFTGIHFDEETLAMVLWDTYVNEVLFDASDGITIE 254

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1063717448 251 LFMASHVLQMPITVYMkddKAGGLISIAEYGQEY-GKDDPIRVLYhGFGHYDAL 303
Cdd:COG5539   255 IQQLASLLKNPHYYTN---TASPSIKCNICGTGFvGEKDYYAHAL-ATGHYNFG 304

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 1063717448 167 DYSIIGIPGDGRCLFRSVAHGFCLRSGKLAPGEKMQRELADELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVWG 246
Cdd:cd22760     1 DYRVHGIAGDGRCLFRAVAHGECLARGKAAPDEERERELADELRTRAADELVKRREETEWFIEGDFDEYVARMRRPGVWG 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063717448 247 GEPELFMASHVLQMPITVYMKDDKAGGLISIAEYGQEYGKDDPIRVLYHGFGHYDALL 304
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 1063717448 174 PGDGRCLFRSVAHGFCLRSGklaPGEKMQREladELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVWGGEPELFM 253
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHD---VLRKMLVQ---ELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFA 74

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1063717448 254 ASHVLQMPITVY-MKDDKAGGLISIAEYGQEYGKDDPIRVLYHG-----FGHY 300
Cdd:pfam02338  75 LAHILRRPIIVYkSEGGEELGGLKEYGIYLPLGWDPSLCLVYPRhlyylGGHY 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 1063717448 169 SIIGIPGDGRCLFRSVAHGFClrsgklapgekMQRELADELRTRVADEFIQRRQETE------WFVEGDFDTYVRQIRDP 242
Cdd:cd22744     1 RVVDVPGDGNCLFRALAHALY-----------GDQESHRELRQEVVDYLRENPDLYEpaeladEDDGEDFDEYLQRMRKP 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1063717448 243 HVWGGEPELFMASHVLQMPITVYMKDDKAGGLISIAEYGQEYGKddPIRVLYHGFGHYDAL 303
Cdd:cd22744    70 GTWGGELELQALANALNVPIVVYSEDGGFLPVSVFGPGPGPSGR--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 1063717448 169 SIIGIPGDGRCLFRSVAHGFCLRSGKLaPGEKMQRELADELRTRVAD--EFIQRRQETEWFVEGDFDTYVRQIRDPHVWG 246
Cdd:cd22761    11 KIHEIPSDGDCLYNAIAHQLSLRGIET-SVEELRKQTADYMRENKDDflPFLTNPDTGDPLTEEEFEKYCDDVENTGAWG 89

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063717448 247 GEPELFMASHVLQMPITVYMKDdkaGGLISIaeyGQEYGKDDPIRVLYH----GFG-HYD 301
Cdd:cd22761    90 GQLELRALSHVLKRPIEVIQAE---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 1063717448 170 IIGIPGDGRCLFRSVAHgfclrsgklapgekmQ----RELADELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVW 245
Cdd:cd22752     4 IKEMEEDGNCLFRAVAD---------------QvygdQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVW 68

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063717448 246 GGEPELFMASHVLQMPITVYMKDDKAgglISIAeYGQEYGKDDPIRVLYHGFGHYDAL 303
Cdd:cd22752    69 GNHIEIQAMSELYNRPIEVYAYSTEP---INTF-HEASSSDNEPIRLSYHGNSHYNSI 122

OTU (ovarian tumor) domain of Arabidopsis thaliana deubiquitinating enzyme OTU7 and similar proteins; Arabidopsis thaliana deubiquitinating enzyme OTU7, also called OTU domain-containing protein 7, is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that shows a preference for 'Lys-63' over 'Lys-48' over 'Met-1'-linked ubiquitin (UB) tetramers as substrates. DUBs catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. These DUBs may play important regulatory roles at the level of protein turnover by preventing degradation. OTU7 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1063717448 169 SIIGIPGDGRCLFRSVAHGFClrsgklapGEkmQRELAdELRTRVADeFIQRRQET-EWFVEGD--FDTYVRQIRDPHVW 245
Cdd:cd22771     3 RIRDVEGDGNCLFRALADQLY--------GD--EERHA-ELRKKVVD-YMEAHEEDfEPFFEDDetFEDYVSRMREDGTW 70

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1063717448 246 GGEPELFMASHVLQMPITVYMKDDkaggliSIAEYGQEYGKDDP-IRVLYHGFGHYD 301
Cdd:cd22771    71 GGNLELQAASLVYRVNIVVHQLGQ------PRWEIENFPDKGARtIHLSYHDGEHYN 121

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 1063717448 173 IPGDGRCLFRSVAHgfclrsgKLAPGEKMQRELadelRTRV-------ADEFIQR-RQETEWFVEGDFDTYVRQIRDPHV 244
Cdd:cd22756     5 ITGDGNCLFRALSD-------QLYGDPDRHLEI----RAEVveymranPDDFKPFsEAATFAEDDEAFEDYLARMAKDGT 73

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1063717448 245 WGGEPELFMASHVLQMPITVYmkddKAGGLISI--AEYGQEYGKDDPIRVLYHGFGHY 300
Cdd:cd22756    74 YGDNLEIVAFARAYNVDVKVY----QPDPVYVIsaPEDGSPGPARRVLHIAYHNWEHY 127

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 1063717448 173 IPGDGRCLFRSVahGFCLRSGKLapgekmqreLADELRTRVADEFIQRRQE-TEWFVEGDFDTYVRQIRDPHVWGGEPEL 251
Cdd:cd22793     8 IDSDNSCLFNAV--GYVMEGSRK---------KAPELRQVIADAVLSDPFEyNEAFLGKSNKEYCEWILNPNSWGGAIEL 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1063717448 252 FMASHVLQMPITVYmkdDKAGGLISIaeYGQEYGKDDPIRVLYHGFgHYDALLLH 306
Cdd:cd22793    77 SILSDHYGREIAAF---DIQTKRCDV--YGEGKGYTERVMLIYDGL-HYDALAIA 125

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 1063717448 173 IPGDGRCLFRSVAhgfclrsgklapgEKMQRELADELRTRVA-DEFIQRRQET-EWFVEGDFDTYVRQIRDPHVWGGEPE 250
Cdd:cd22794    15 IAKDGSCLFRAVA-------------EQVFHTQSRHLEVRKAcVDYLRRNREKfEAFIEGPFEQYLKNLENPKEWAGQVE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1063717448 251 LFMASHVLQMPITVYMKDDKAGGLISiaeygqEYGKDDPIRVLYHGFGHYDA 302
Cdd:cd22794    82 ISALSLMYKRDFIIYQEPGKPPSNVT------ENGFPDKILLCFSNGNHYDS 127

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 1063717448 151 HHSSDGKFHNGKRV-YTDY-SIIGIPGDGRCLFRSVAhgfCLrsgkLAPGEKMQRELADELRtRVADEFIQRRQETEWFV 228
Cdd:cd21880     3 EEVGEGQYVSNPRFnLRDYfEIERVPGDGNCFFRSIA---EL----LFDTEDEWRLVKNTIE-SYARANWDECPEARLYY 74

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1063717448 229 EgDFDTYVRQIRDPHVWGGEPELFMASHVLQMPITVYMKDDkaGGLISIAeygQEYGKDDPIRV--LYHGFGHYDALLL 305
Cdd:cd21880    75 L-SLEEYLRDAMKDGYWGGSLEAEILSKALGITIIIWVVDD--SDWVTAA---VRFGDGDVSTSlnLLHSGGHFDALRL 147

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 1063717448 168 YSIIGIPGDGRCLFRSVAHgfCLRSGKlapgekmqrELADELRTRVADEFIQRRQETEWFV---EGDF----DTYVRQIR 240
Cdd:cd22757     1 FRVIPIPGDGACLFRALSY--LLYGTQ---------SRHLEVRKEVVDYVVNNWDEFSIYThdsEGNNyksaEEYRADMS 69

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1063717448 241 DPHVWGGEPELFMASHVLQMPITVYmKDDKAgglisIAEYGQEygkDDPIRVLYH----GFGHYDALL 304
Cdd:cd22757    70 KPGTYGTLCELVAAAELYPFHFEVY-RNGKL-----YASFGDP---SNPVKRLKFsgdlSNGHFDVLE 128

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 1063717448 173 IPGDGRCLFRSVAHGfclrsgklAPGEKMQREladELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVWGGEPELF 252
Cdd:cd22747    26 IIPDGNCLYRAVSKA--------VYGDQALHR---ELREQTVHYIADHLDEFNPIIEGDVGEFLIKAAQDGAWAGYPELL 94

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1063717448 253 MASHVLQmpITVYMKDDKAGGLISIAEYGQEYGKDDPIR----VLYHGFGHYDALL 304
Cdd:cd22747    95 AMGQMLN--VNIRLTTGGSLESPTVSTMVHYLGPEDSGKpsiwLSWLSNGHYDAVF 148

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 1063717448 171 IGIPGDGRCLFRSVAHGFClrsgklapgekMQRELADELRTRVADEFIQRRQetewFVEGDFDTYVRQIRDPHVWGGEPE 250
Cdd:cd22791     4 LRVTGDGNCLFRAASLLLF-----------GDESLHLELRLRTVLELVLNSE----FYEAIYEAEIKATCKPGSYSGIWH 68

                          90
                  ....*....|....*.
gi 1063717448 251 LFMASHVLQMPI-TVY 265
Cdd:cd22791    69 IYALSSVLQRPIfSVY 84

OTU (ovarian tumor) domain of bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13; Bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 is also 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). ALG13 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 1063717448 176 DGRCLFRSVAHG-FCLRSGKLapgekmqreladELRTRVADEFIQRRQETEWFVEGDFDTYVRQIRDPHVWGGEPELFMA 254
Cdd:cd22795    18 DASCLFRAVSEQlFLCQIHHL------------EIRKACVSYMRANQCNFESYVEGSFEKYLERLEDPKESAGQLEISAL 85

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 1063717448 255 SHVLQMPITVYMKDDKAgglisiAEYGQEYGKDDPIRVLYHGFGHYDALL 304
Cdd:cd22795    86 SLIYNRDFILYRYPGKP------PTYATDNGFEDKILLCCSSNGHYDSVY 129