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 1239937946   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEA-----------------EWVGQV 87
Cdd:cd22794      1 MDEYLRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAfiegpfeqylknlenpkEWAGQV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1239937946   88 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 137
Cdd:cd22794     81 EISALSLMYKRDFIIYQEPGKPPSNVTENGFPDKILLCFSNGNHYDSVYP 130

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 1239937946  512 PSTLENISDDKcariSSPSKSKKLECPPVEQkpAEHVSLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEPTTFGPTGVP 591
Cdd:pfam03154  149 PSPQDNESDSD----SSAQQQILQTQPPVLQ--AQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQ 222

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  592 AQIPVLSVTQTLTT-------GPDSAVSQAHLTPSPVPVSIQAVNQPLM-----PLPQTL----SLYQDPLYP-GFPYNE 654
Cdd:pfam03154  223 STAAPHTLIQQTPTlhpqrlpSPHPPLQPMTQPPPPSQVSPQPLPQPSLhgqmpPMPHSLqtgpSHMQHPVPPqPFPLTP 302

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  655 KGDRAIAPP---YSLCHTGEDLPKDknilrfffnlgvkaySCPMWAPHSYLYPLHQAYLAACRMYPKVSVPVYPPNPwfq 731
Cdd:pfam03154  303 QSSQSQVPPgpsPAAPGQSQQRIHT---------------PPSQSQLQSQQPPREQPLPPAPLSMPHIKPPPTTPIP--- 364

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  732 EAPSAQNEgdctctdaHFPMQTEATVNGQMPqAEIGPPtfssPLVIPPSQVSESHGQLSYQADIESENSGQLLHAEYEES 811
Cdd:pfam03154  365 QLPNPQSH--------KHPPHLSGPSPFQMN-SNLPPP----PALKPLSSLSTHHPPSAHPPPLQLMPQSQQLPPPPAQP 431

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1239937946  812 ---LSGKNMFPQPSFGPNP-FLGPVPIAPPFFPH 841
Cdd:pfam03154  432 pvlTQSQSLPPPAASHPPTsGLHQVPSQSPFPQH 465

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 1239937946   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEA-----------------EWVGQV 87
Cdd:cd22794      1 MDEYLRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAfiegpfeqylknlenpkEWAGQV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1239937946   88 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 137
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 1239937946   42 DGSCLFRAVAEQV-----LHSQSRHVEVRMACIHYLRENREKFE-----------------AEWVGQVEISALSLMYRKD 99
Cdd:pfam02338    3 DGNCLYRSISHQLwgvhdVLRKMLVQELRETLAEYMREHKEEFEpfleddetgdiieieqtGAWGGEIEIFALAHILRRP 82

                   ....*
gi 1239937946  100 FIIYR 104
Cdd:pfam02338   83 IIVYK 87

transcription termination factor Rho; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  886 VSAVDEFQEARGEGTHCLPEASVGKHEGRAEQSSQTPKVDLARPSILPVAEEEAhlPTQILNRERETVPVELEPKRTIPS 965
Cdd:PRK12678    52 IAAIKEARGGGAAAAAATPAAPAAAARRAARAAAAARQAEQPAAEAAAAKAEAA--PAARAAAAAAAEAASAPEAAQARE 129

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  966 LKEKSEK-----VKDPKTAADAVSGANSVESRVQRPKEESSEDENEVsnilRSGRSKQfyNQTYGGRKYKSDWGSSGRGG 1040
Cdd:PRK12678   130 RRERGEAarrgaARKAGEGGEQPATEARADAAERTEEEERDERRRRG----DREDRQA--EAERGERGRREERGRDGDDR 203

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|
gi 1239937946 1041 YQHARGEESWKGQPGRSRDEGyQYHRNVRGRPYRGDRRRSGMGDGHRGQN 1090
Cdd:PRK12678   204 DRRDRREQGDRREERGRRDGG-DRRGRRRRRDRRDARGDDNREDRGDRDG 252

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 1239937946   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEA-----------------EWVGQV 87
Cdd:cd22794      1 MDEYLRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAfiegpfeqylknlenpkEWAGQV 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1239937946   88 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 137
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 1239937946   25 MDAYLRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEA-----------------EWVGQV 87
Cdd:cd22795      1 MDEYLGSLGLYRKLTAKDASCLFRAVSEQLFLCQIHHLEIRKACVSYMRANQCNFESyvegsfekylerledpkESAGQL 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1239937946   88 EISALSLMYRKDFIIYREPNVSPSQVTENNFPEKVLLCFSNGNHYDIVYP 137
Cdd:cd22795     81 EISALSLIYNRDFILYRYPGKPPTYATDNGFEDKILLCCSSNGHYDSVYT 130

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 1239937946   33 GLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFE-------------------AEWVGQVEISALS 93
Cdd:cd22771      1 GLRIRDVEGDGNCLFRALADQLYGDEERHAELRKKVVDYMEAHEEDFEpffeddetfedyvsrmredGTWGGNLELQAAS 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1239937946   94 LMYRKDFIIYREpNVSPSQVTenNFPEK----VLLCFSNGNHYDIV 135
Cdd:cd22771     81 LVYRVNIVVHQL-GQPRWEIE--NFPDKgartIHLSYHDGEHYNSV 123

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 1239937946   33 GLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKF-----------------EAEWVGQVEISALSLM 95
Cdd:cd22752      1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFsqfvtedfeeyinrkrqDGVWGNHIEIQAMSEL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1239937946   96 YRKDFIIY---REP-NVSPSQVTENNFPekVLLCFSNGNHYDIVYP 137
Cdd:cd22752     81 YNRPIEVYaysTEPiNTFHEASSSDNEP--IRLSYHGNSHYNSIVD 124

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 1239937946   42 DGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEA-------------------------EWVGQVEISALSLMY 96
Cdd:cd22756      8 DGNCLFRALSDQLYGDPDRHLEIRAEVVEYMRANPDDFKPfseaatfaeddeafedylarmakdgTYGDNLEIVAFARAY 87

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1239937946   97 RKDFIIYRE---PNVSPSQVTENNFPEKVL-LCFSNGNHYDIV 135
Cdd:cd22756     88 NVDVKVYQPdpvYVISAPEDGSPGPARRVLhIAYHNWEHYSSV 130

OTU (ovarian tumor) domain of Invertebrate iridescent virus putative ubiquitin thioesterase 232R and similar proteins; This subfamily contains putative ubiquitin thioesterases 232R from Invertebrate iridescent virus and L96 from Tipula iridescent virus (TIV), Dictyostelium discoideum OTU domain-containing protein DDB_G0284757, and similar proteins. L96 may be involved in TIV genomic DNA packaging in a manner related to the Gag polyproteins of the mammalian viruses. Proteins in this subfamily contain an OTU domain. OTU domains typically function as deubiquitinases (DUBs)/ubiquitin thiolesterases (EC 3.4.19.12) that catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. These DUBs may play important regulatory roles at the level of protein turnover by preventing degradation. They belong to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946   29 LRKLGLYRKLVAKDGSCLFRAVAEQV--LHSQSRHVEVRMACIHYLRENREKFEA-----------------------EW 83
Cdd:cd22758      1 AKENGFEIRDVPGDGNCFFHAVSDQLygNGIEHSHKELRQQAVNYLRENPELYDGfflsefdeeesweeylnrmskdgTW 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1239937946   84 VGQVEISALSLMYRKDFIIYRE-PNVSPSQVTENNFPEK--VLLCFSNGNHY 132
Cdd:cd22758     81 GDHIILQAAANLFNVRIVIISSdGSDETTIIEPGNSKNGrtIYLGHIGENHY 132

OTU (ovarian tumor) domain of plant deubiquitinating enzyme OTU9 and similar proteins; This subfamily contains Arabidopsis thaliana deubiquitinating enzymes OTU8, OTU9, OTU10, OTU11, and OTU12, and similar proteins from plants and other eukaryotes. OTU8-OTU12 are deubiquitinases (DUBs)/ubiquitin thiolesterases (EC 3.4.19.12) that catalyze the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin, a small regulatory protein that can be conjugated to a large range of target proteins. Protein ubiquitination is a post-translational modification of mostly Lys residues that regulates many cellular processes, including protein degradation, intracellular trafficking, cell signaling, autophagy, transcription, translation, and the DNA damage response. These DUBs may play important regulatory roles at the level of protein turnover by preventing degradation. They belong to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946   29 LRKLGLYRKLVAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENRE---------KFEA---------EW------- 83
Cdd:cd22751      5 LDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPElyyefyvpeEYDEylkkmskdgEWgdeltlq 84

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1239937946   84 ----VGQVEISALSLMYRKDFIIYRepnvsPSQVTEnnfPEKVL-LCFSNGNHYDIVY 136
Cdd:cd22751     85 aaadAFGVKIHVITSFEDNWFLEIE-----PRGLVR---SKRVLfLSYWAEVHYNSIY 134

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 1239937946   42 DGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEA------------------------EWVGQVEISALSLMYR 97
Cdd:cd22757      9 DGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIythdsegnnyksaeeyradmskpgTYGTLCELVAAAELYP 88

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1239937946   98 KDFIIYREPNVsPSQVTENNFPEKVLLC---FSNGnHYDiVY 136
Cdd:cd22757     89 FHFEVYRNGKL-YASFGDPSNPVKRLKFsgdLSNG-HFD-VL 127

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 1239937946   39 VAKDGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKF----------------------EAEWVGQVEISALSLM- 95
Cdd:cd22755      6 IVGDGNCFFRALSYAITGSEKYHRKIRKAIVDFLEKNPDEFrnllrsdyesveeyleksrmryDGTWATDVEIFAAATLl 85

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1239937946   96 ------YRKDF---IIYRePNVSPSQVTENNFPekVLLCFSNGNHYDIV 135
Cdd:cd22755     86 gvdiyvYSKGGykwLLYS-PRFKLGKRNGSREA--IYLKNTNGNHFEPV 131

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 1239937946   42 DGSCLFRAVAEQV-----LHSQSRHVEVRMACIHYLRENREKFE-----------------AEWVGQVEISALSLMYRKD 99
Cdd:pfam02338    3 DGNCLYRSISHQLwgvhdVLRKMLVQELRETLAEYMREHKEEFEpfleddetgdiieieqtGAWGGEIEIFALAHILRRP 82

                   ....*
gi 1239937946  100 FIIYR 104
Cdd:pfam02338   83 IIVYK 87

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 1239937946   29 LRKLGLYRKLVAKDGSCLFRAVAEQ-----VLHSQSRHVEVRMACIHYLRENREKFE----------------------- 80
Cdd:cd22797      5 LAPLGLAIKEIKADGHCLYRAVEDQlqlrgGGAPAPDYQQLRELAADYMRAHPDDFLpflededeggdgdeafeaycrev 84

                           90       100
                   ....*....|....*....|....*.
gi 1239937946   81 ---AEWVGQVEISALSLMYRKDFIIY 103
Cdd:cd22797     85 estAAWGGQLELGALAHALRRHIKVY 110

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 1239937946  512 PSTLENISDDKcariSSPSKSKKLECPPVEQkpAEHVSLSNPAPLLVSPEVHLTPAVPSLPATVPAWPSEPTTFGPTGVP 591
Cdd:pfam03154  149 PSPQDNESDSD----SSAQQQILQTQPPVLQ--AQSGAASPPSPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQ 222

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  592 AQIPVLSVTQTLTT-------GPDSAVSQAHLTPSPVPVSIQAVNQPLM-----PLPQTL----SLYQDPLYP-GFPYNE 654
Cdd:pfam03154  223 STAAPHTLIQQTPTlhpqrlpSPHPPLQPMTQPPPPSQVSPQPLPQPSLhgqmpPMPHSLqtgpSHMQHPVPPqPFPLTP 302

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  655 KGDRAIAPP---YSLCHTGEDLPKDknilrfffnlgvkaySCPMWAPHSYLYPLHQAYLAACRMYPKVSVPVYPPNPwfq 731
Cdd:pfam03154  303 QSSQSQVPPgpsPAAPGQSQQRIHT---------------PPSQSQLQSQQPPREQPLPPAPLSMPHIKPPPTTPIP--- 364

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  732 EAPSAQNEgdctctdaHFPMQTEATVNGQMPqAEIGPPtfssPLVIPPSQVSESHGQLSYQADIESENSGQLLHAEYEES 811
Cdd:pfam03154  365 QLPNPQSH--------KHPPHLSGPSPFQMN-SNLPPP----PALKPLSSLSTHHPPSAHPPPLQLMPQSQQLPPPPAQP 431

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1239937946  812 ---LSGKNMFPQPSFGPNP-FLGPVPIAPPFFPH 841
Cdd:pfam03154  432 pvlTQSQSLPPPAASHPPTsGLHQVPSQSPFPQH 465

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
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1239937946   42 DGSCLFRAVAEQVLHSQSRHVEVRMACIHYLRENREKFEA-------------EWVGQVEISALS 93
Cdd:cd22791      9 DGNCLFRAASLLLFGDESLHLELRLRTVLELVLNSEFYEAiyeaeikatckpgSYSGIWHIYALS 73

large tegument protein UL36; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  525 RISSPSKSKKLECPPveQKPAEHVSLSNPAPLLVSPEVHLTPAVPSlPATVPAWPSEPTTFGPTGVPAQIPVLSVTQTLT 604
Cdd:PHA03247  2666 RARRLGRAAQASSPP--QRPRRRAARPTVGSLTSLADPPPPPPTPE-PAPHALVSATPLPPGPAAARQASPALPAAPAPP 2742

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  605 TGPDSAVSQAHLTPSPVPVSIQAVNQPLMP-LPQTLSLYQDPLYPGFPYNEKGDRAIAPPYSLCHTGEDLPKDknilrff 683
Cdd:PHA03247  2743 AVPAGPATPGGPARPARPPTTAGPPAPAPPaAPAAGPPRRLTRPAVASLSESRESLPSPWDPADPPAAVLAPA------- 2815

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  684 fnlgvkAYSCPMWAPHSYLYPLHQAYLAACRMYPKVSVPVYPPNPW------FQEAPSAQNEGDCTCTDAHFPMQteatv 757
Cdd:PHA03247  2816 ------AALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSvapggdVRRRPPSRSPAAKPAAPARPPVR----- 2884

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1239937946  758 ngQMPQAEIGPPTFSSPLviPPSQVSEshgQLSYQADIESENSGQLLHAEYEESLSGKNMFPQPSFGPNPFLGPVPIAPP 837
Cdd:PHA03247  2885 --RLARPAVSRSTESFAL--PPDQPER---PPQPQAPPPPQPQPQPPPPPQPQPPPPPPPRPQPPLAPTTDPAGAGEPSG 2957

                          330       340       350
                   ....*....|....*....|....*....|....*.
gi 1239937946  838 FFPHVWYGYPFQGFVenPVMRQNIVLPSDEKELDLP 873
Cdd:PHA03247  2958 AVPQPWLGALVPGRV--AVPRFRVPQPAPSREAPAS 2991