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 1480008125   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQV 104
Cdd:cd22794      1 MDEYLRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1480008125  105 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 154
Cdd:cd22794     81 EISALSLMYKRDFIIYQEPGKPPSNVTENGFPDKILLCFSNGNHYDSVYP 130

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  543 TVSSPSKSKKLECPSPAEQKPAEHVSLSNPAPLLVSPEVHLTPavPSLPATVPAWPS--EPTTFGPTGVPAPIPVLSVTq 620
Cdd:PHA03247  2643 PPTVPPPERPRDDPAPGRVSRPRRARRLGRAAQASSPPQRPRR--RAARPTVGSLTSlaDPPPPPPTPEPAPHALVSAT- 2719

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  621 TLTTGPDSAVSQAHLTPSpVPVSIQAVNQPLMPL-------PQTLSLYQDPLYPGFPCNEKGDRAIVPPY-SLCQTGEDL 692
Cdd:PHA03247  2720 PLPPGPAAARQASPALPA-APAPPAVPAGPATPGgparparPPTTAGPPAPAPPAAPAAGPPRRLTRPAVaSLSESRESL 2798

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  693 PKDKNILRFFFNLGVKAYSCPMWAPHSYLYPLHQAYLAACRMYPKVPVP--------VYPHNPwFQEAPAAQNESDCTCT 764
Cdd:PHA03247  2799 PSPWDPADPPAAVLAPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPpslplggsVAPGGD-VRRRPPSRSPAAKPAA 2877

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  765 DAHFPMQteasvngQMPQPEIGPPTFSSPLviPPSQVSESHGQLSYQADLESETPGQLLHADYEESLSGKnmfPQPSFGP 844
Cdd:PHA03247  2878 PARPPVR-------RLARPAVSRSTESFAL--PPDQPERPPQPQAPPPPQPQPQPPPPPQPQPPPPPPPR---PQPPLAP 2945

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1480008125  845 NPFLGPVPIAPPFFPHVWYGYPFQGFIENPVMRQNIVLPSDE 886
Cdd:PHA03247  2946 TTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSRE 2987

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 1480008125   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQV 104
Cdd:cd22794      1 MDEYLRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1480008125  105 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 154
Cdd:cd22794     81 EISALSLMYKRDFIIYQEPGKPPSNVTENGFPDKILLCFSNGNHYDSVYP 130

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 1480008125   42 DGSCLFRAVAEQV-----LHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISALSLMYRKD 116
Cdd:pfam02338    3 DGNCLYRSISHQLwgvhdVLRKMLVQELRETLAEYMREHKEEFEPFLEDDETGDIIEIEQTGAWGGEIEIFALAHILRRP 82

                   ....*
gi 1480008125  117 FIIYR 121
Cdd:pfam02338   83 IIVYK 87

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  530 PSTLENITDDkyatvSSPSKSKKLECPSPAEQkpAEHVSLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEPTTFGPTGV 609
Cdd:pfam03154  149 PSPQDNESDS-----DSSAQQQILQTQPPVLQ--AQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQT 221

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  610 PAPIPVLSVTQTLTT-------GPDSAVSQAHLTPSPVPVSIQAVNQPLM-----PLPQTL----SLYQDPLYP-GFPCN 672
Cdd:pfam03154  222 QSTAAPHTLIQQTPTlhpqrlpSPHPPLQPMTQPPPPSQVSPQPLPQPSLhgqmpPMPHSLqtgpSHMQHPVPPqPFPLT 301

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  673 EKGDRAIVPPYSLCQ------------------TGEDLPKDKNILRFFFNL-GVKAYSC----PMWAPHSYLYPLHQAYL 729
Cdd:pfam03154  302 PQSSQSQVPPGPSPAapgqsqqrihtppsqsqlQSQQPPREQPLPPAPLSMpHIKPPPTtpipQLPNPQSHKHPPHLSGP 381

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  730 AACRMYPKVPVPvyphnpwfqeaPAAQNESDCTC---TDAHFPMQTEASVNGQMPQPEIGPPTFSSPLVIPPSqvSESHG 806
Cdd:pfam03154  382 SPFQMNSNLPPP-----------PALKPLSSLSThhpPSAHPPPLQLMPQSQQLPPPPAQPPVLTQSQSLPPP--AASHP 448

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1480008125  807 QLSYQADLESETPgqllhadyeeslsgknmFPQPSFGPNpflGPVPIAPPFFP 859
Cdd:pfam03154  449 PTSGLHQVPSQSP-----------------FPQHPFVPG---GPPPITPPSGP 481

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 1480008125   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQV 104
Cdd:cd22794      1 MDEYLRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAFIEGPFEQYLKNLENPKEWAGQV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1480008125  105 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 154
Cdd:cd22794     81 EISALSLMYKRDFIIYQEPGKPPSNVTENGFPDKILLCFSNGNHYDSVYP 130

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 1480008125   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQV 104
Cdd:cd22795      1 MDEYLGSLGLYRKLTAKDASCLFRAVSEQLFLCQIHHLEIRKACVSYMRANQCNFESYVEGSFEKYLERLEDPKESAGQL 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1480008125  105 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 154
Cdd:cd22795     81 EISALSLIYNRDFILYRYPGKPPTYATDNGFEDKILLCCSSNGHYDSVYT 130

Tudor domain found in OTU domain-containing protein 4 (OTUD4); OTUD4, also called HIV-1-induced protein HIN-1, is a phospho-activated K63 deubiquitinase that hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein. It may negatively regulate inflammatory and pathogen recognition signaling in innate immune response. It contains one Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1480008125  275 DYSIAAGLQYEVGDKCQVRLDHNGKFLNADVQGIHSENGPVLV--EELGKKHTS--KNLKAPPP 334
Cdd:cd20448      1 DFSIAAGMQYSVGDKCKVRLDHNGKFYNAHIQEVSPENGPVVVfvEELGKKHTVplKNLKPPPQ 64

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 1480008125   33 GLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISALSLM 112
Cdd:cd22752      1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTEDFEEYINRKRQDGVWGNHIEIQAMSEL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1480008125  113 YRKDFIIY---REP-NVSPSQVTENNFPekVLLCFSNGNHYDIVYP 154
Cdd:cd22752     81 YNRPIEVYaysTEPiNTFHEASSSDNEP--IRLSYHGNSHYNSIVD 124

OTU (ovarian tumor) domain of deubiquitinating enzyme OTU6 from plants and similar proteins; Deubiquitinating enzyme OTU6, also called OTU domain-containing protein 6 or otubain-like deubiquitinase 1 (OTLD1), 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. OTU6 binds chromatin and has enzymatic histone deubiquitinase activity specific for the H2B histone. OTU6 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 1480008125   30 RKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVEISAL 109
Cdd:cd22796      1 KKKGLEIRRMDGDGNCLFRAVADQVYGDQEMHDEVREMCMDYMEKERDHFSQFVTEDFTQYVKRKRRDRVFGNNLEIQAM 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1480008125  110 SLMYRKDFIIYREPNVSP-----SQVTENNFPekVLLCFSNGNHYDIVY 153
Cdd:cd22796     81 SEIYNRPIEVYSYSNGEPinifhGSYEGDDPP--IRLSYHDGNHYNSII 127

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 1480008125   29 LRKLGLYRKLVAKDGSCLFRAVAEQVLH-----SQSRHVEVRMACIHYLRENREKFEAFI---------EGSFEEYLKRL 94
Cdd:cd22748      1 LKPLGLRIKEIPPDGHCLYRAIADQLKLrggseEPYSYKELRKLAADYMRAHRDDFLPFLtnddgdlmtEEEFEEYCDKI 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1480008125   95 ENPQEWVGQVEISALSLMYRKDFIIYREPnvSPSQVTENNFPEK--VLLCF-----SNGNHY 149
Cdd:cd22748     81 ENTAEWGGQLELRALSKALKRPIHVYQAG--SPPLVIGEEFDSGepLRLSYhrhayGLGEHY 140

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 1480008125   26 DAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEGSFEEYLKRLENPQEWVGQVE 105
Cdd:cd22747     13 DKYLRERNKYRFHIIPDGNCLYRAVSKAVYGDQALHRELREQTVHYIADHLDEFNPIIEGDVGEFLIKAAQDGAWAGYPE 92

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1480008125  106 ISALSLMYRKDfiIYREPNVSPSQVT----------ENNFPEKVLLCF-SNGnHYDIVY 153
Cdd:cd22747     93 LLAMGQMLNVN--IRLTTGGSLESPTvstmvhylgpEDSGKPSIWLSWlSNG-HYDAVF 148

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 1480008125   42 DGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFI---EGSF----EEYLKRLENPQEWVGQVEISALSLMYR 114
Cdd:cd22757      9 DGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIYThdsEGNNyksaEEYRADMSKPGTYGTLCELVAAAELYP 88

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1480008125  115 KDFIIYREPNVsPSQVTENNFPEKVLLC---FSNGnHYDiVY 153
Cdd:cd22757     89 FHFEVYRNGKL-YASFGDPSNPVKRLKFsgdLSNG-HFD-VL 127

Tudor domain found in Tudor domain-containing protein 13 (TDRD13) and similar proteins; The TDRD13 family includes TDRD13 and OTU domain-containing protein 4 (OTUD4). TDRD13, also called asparagine-linked glycosylation 13 (ALG13), glycosyltransferase 28 domain-containing protein 1 (GLT28D1), or UDP-N-acetylglucosamine transferase subunit ALG13, is a putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase (EC 2.4.1.141/EC 3.4.19.12). It is a potential member of the Alg7p/Alg13p/Alg14p complex catalyzing the first two initial reactions in the N-glycosylation process. OTUD4, also called HIV-1-induced protein HIN-1, is a phospho-activated K63 deubiquitinase that hydrolyzes the isopeptide bond between the ubiquitin C-terminus and the lysine epsilon-amino group of the target protein. It may negatively regulate inflammatory and pathogen recognition signaling in innate immune response. Members of this family contain one Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1480008125  283 QYEVGDKCQVRLDHNGKFLNADVQGIHSENGPVLV--EELGKKHT--SKNLK 330
Cdd:cd20380      1 QFKPGDKCQVELDSPGKVYEAHIQEISPDKGPVTVfvEELGEKKTvpYENLK 52

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 1480008125   29 LRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEAFIEG--SFEEYLKRLENPQEWVGQVEI 106
Cdd:cd22770      9 LQALGLKLRDIPGDGNCLFRALGDQLEGHSRNHLKHRQETVQYMIEHREDFEPFVEDdvPFDKHVANLSKPGTYAGNDAI 88

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1480008125  107 SALSLMYRKDFIIYrEPNVSPSQVTENNFPEKVLLCFS--NGNHYDIVYPI 155
Cdd:cd22770     89 VAFARLHQVNVVIH-QLNAPLWQIRGTEKSSSRELHISyhNGDHYSSVRKL 138

OTU (ovarian tumor) domain of deubiquitinating enzymes OTU3 and OTU4 from plants, and similar proteins; Deubiquitinating enzyme OTU3 (also called OTU domain-containing protein 3) and deubiquitinating enzyme OTU4 (also called OTU domain-containing protein 4) are deubiquitinases (DUBs) or 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. OTU3 and OTU4 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 1480008125   42 DGSCLFRAVAEQVLHSQ-----SRHVEV------RMACIHYLRENREKFEA---FIEGSFEEYLKRLENPQEWVGQVEIS 107
Cdd:cd22746     10 DGRCLFRAVARGLALATggrplSERRERadadalRKAVVEEIRKRRDELFEgslVIEGDFDAYCQRMSHPDTWGGEPELL 89

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1480008125  108 ALSLMYRKDFIIY----REPNVSPSQVTENNFP--EKVLLCFSNGNHYD 150
Cdd:cd22746     90 MLADVLQRPIAVYlptpGKGGLRKIQEYGEEYLggEPIRLLYNGGNHYD 138

Tudor domain found in Tudor domain-containing protein 13 (TDRD13); TDRD13, also called asparagine-linked glycosylation 13 (ALG13), glycosyltransferase 28 domain-containing protein 1 (GLT28D1), or UDP-N-acetylglucosamine transferase subunit ALG13, is a putative bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase (EC 2.4.1.141/EC 3.4.19.12). It is a potential member of the Alg7p/Alg13p/Alg14p complex catalyzing the first two initial reactions in the N-glycosylation process. It contains one Tudor domain. The Tudor domain binds to proteins with dimethylated arginine or lysine residues, and may also bind methylated histone tails to facilitate protein-protein interactions.

                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1480008125  280 AGLQYEVGDKCQVRLDHNGKFLNADVQ--GIHSENGPVLVEELGKKHTSK--NLK-----APPPeSWNTVSGKK 344
Cdd:cd20447      2 AGRQYYLGDKCQVRLEPGGKYYNAHIQevGQDSNSVTVFIEELAEKHTVPlaNLKpvtqvTPVP-AWNMMPNRK 74

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 1480008125   36 RKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKF-EAFIEGSFEEYLKRLENPQEWVGQVEISALSLMYR 114
Cdd:cd22793      5 RRVIDSDNSCLFNAVGYVMEGSRKKAPELRQVIADAVLSDPFEYnEAFLGKSNKEYCEWILNPNSWGGAIELSILSDHYG 84

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1480008125  115 KDFIIYrepNVSPSQV----TENNFPEKVLLCFsNGNHYD 150
Cdd:cd22793     85 REIAAF---DIQTKRCdvygEGKGYTERVMLIY-DGLHYD 120

OTU (ovarian tumor) domain of ubiquitin thioesterase OTU1 and similar proteins; Ubiquitin thioesterase (EC 3.4.19.12) OTU1 is also called OTU domain-containing protein 1 in yeast, while human OTU1 is also called HIV-1-induced protease 7 (HIN7), DUBA-8, or OTU domain-containing protein 2 (OTUD2). OTU1 is a deubiquitinase (DUB) that catalyzes the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. OTU1 has been implicated in the ER-associated degradation (ERAD) pathway. In yeast, it counteracts the activity of Ufd2 by deubiquitinating Ufd2 substrates; Ufd2 is a E4 ubiquitin ligase that interacts with Cdc48, an AAA ATPase that plays a central role in the ERAD pathway by chaperoning proteins to the proteasome for destruction. OTU1 also functions as a substrate-processing factor of valosin-containing protein (VCP, the mammalian counterpart of yeast Cdc48) that is required for the retrotranslocation of the ERAD pathway. OTU1 has been shown to preferentially hydrolyze polyubiquitin chains with Lys48 linkages. It contains ubiquitin-like (Ubl) domain with a beta-grasp Ubl fold, a C2H2-type zinc finger, and an OTU (ovarian tumor) domain. This model represents the OTU domain that interacts with ubiquitin and possesses catalytic activity. OTU1 belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. This family also contains plant OTU1 and OTU2.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125   34 LYRKLVAKDGSCLFRAVAEQVLHSQSRHV-EVRMACIHYLRENREKF-EAFIEGSFEEYLKRLENPQEWVGQVEISALSL 111
Cdd:cd22745      3 LVRRVVPDDNSCLFTSISYLLEGGLLDSApELREIVADAILSDPDTYnEAILGKPPDEYCAWILKPDSWGGAIELSILSK 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1480008125  112 MYR--------KDFIIYR--EpnvspsqvtENNFPEKVLLCFSnGNHYDIVY 153
Cdd:cd22745     83 HFGveicvvdvQTGRVDRfgE---------DKGYSKRIFLLYS-GIHYDALA 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 1480008125   36 RKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKF-EAFIEG-SFEEYLKRLENPQEWVGQVEISALSLMY 113
Cdd:cd21880     24 IERVPGDGNCFFRSIAELLFDTEDEWRLVKNTIESYARANWDECpEARLYYlSLEEYLRDAMKDGYWGGSLEAEILSKAL 103

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1480008125  114 RKDFIIYRepnVSPSQVTENNF---PEKVL----LCFsNGNHYDIVYPI 155
Cdd:cd21880    104 GITIIIWV---VDDSDWVTAAVrfgDGDVStslnLLH-SGGHFDALRLK 148

Otubain subfamily of ubiquitin thioesterases; The otubain subfamily is composed of otubain-1 (also called ubiquitin thioesterase OTUB1 or OTU domain-containing ubiquitin aldehyde-binding protein 1), otubain-2 (also called ubiquitin thioesterase OTUB2 or OTU domain-containing ubiquitin aldehyde-binding protein 2), and similar proteins. They function as deubiquitylases (DUBs)/ubiquitin thioesterases (EC 3.4.19.12). OTUB1 can specifically remove 'Lys-48'-linked conjugated ubiquitin from protein substrates, while OTUB2 mediates the deubiquitination of 'Lys-11'-,'Lys-48'- and 'Lys-63'-linked polyubiquitin chains, with a preference for 'Lys-63'-linked polyubiquitin chains. The otubain subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. Members of this subfamily are classified as family C65 cysteine proteases by MEROPS.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125   65 RMACIHYLRENREKFEAFIEG--SFEEYLKR-LENPQEWVGQVEISALSLMYRKDF-IIYREpNVSPSQVTENNFPE--- 137
Cdd:cd22749    135 RLLTSAYLKTNADDYEPFLFEgmSVEEFCEReVEPMGKEADHLQITALANALGVPVrVEYLD-RSAGGEVNFHEFPPeds 213

                           90       100
                   ....*....|....*....|
gi 1480008125  138 ----KVLLCFSNGnHYDIVY 153
Cdd:cd22749    214 dslpVITLLYRPG-HYDILY 232

Herpes virus major outer envelope glycoprotein (BLLF1); This family consists of the BLLF1 viral late glycoprotein, also termed gp350/220. It is the most abundantly expressed glycoprotein in the viral envelope of the Herpesviruses and is the major antigen responsible for stimulating the production of neutralising antibodies in vivo.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  528 PEPSTLENITDDKYATVSSPSKSKKLECPSPAEQKPAehvsLSNPAPLLVSPEVHLTPavPSLPATVPAwpsePTTFGPT 607
Cdd:pfam05109  490 PSPSPRDNGTESKAPDMTSPTSAVTTPTPNATSPTPA----VTTPTPNATSPTLGKTS--PTSAVTTPT----PNATSPT 559

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1480008125  608 -GVPAPIPVLSVTQTLTTGPDSAVSqahlTPSPVPVS 643
Cdd:pfam05109  560 pAVTTPTPNATIPTLGKTSPTSAVT----TPTPNATS 592

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1480008125  526 KRPE---PSTLENITD-DKYATVSSPSKSKKLECPSPAEQKPAEHVSLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEP 601
Cdd:PHA03247   355 RRPTwtpPSSLEDLSAgRHHPKRASLPTRKRRSARHAATPFARGPGGDDQTRPAAPVPASVPTPAPTPVPASAPPPPATP 434

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1480008125  602 TTF-------GPTGVPAPIPVLSVTQTLTTGPDSAVSQA 633
Cdd:PHA03247   435 LPSaepgsddGPAPPPERQPPAPATEPAPDDPDDATRKA 473