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 1173943012 181 QLQLVEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYVVGDmpaFLRYVAHKRQDAVWGDDPELQAL 260
Cdd:cd22752     1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTED---FEEYINRKRQDGVWGNHIEIQAM 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1173943012 261 SELYDRPLQVFVSDAStgaaCLRTFHEASAGRGPPLRLSFYGGGHYDSIIP 311
Cdd:cd22752    78 SELYNRPIEVYAYSTE----PINTFHEASSSDNEPIRLSYHGNSHYNSIVD 124

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 1173943012 181 QLQLVEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYVVGDmpaFLRYVAHKRQDAVWGDDPELQAL 260
Cdd:cd22752     1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTED---FEEYINRKRQDGVWGNHIEIQAM 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1173943012 261 SELYDRPLQVFVSDAStgaaCLRTFHEASAGRGPPLRLSFYGGGHYDSIIP 311
Cdd:cd22752    78 SELYNRPIEVYAYSTE----PINTFHEASSSDNEPIRLSYHGNSHYNSIVD 124

malignant brain tumor (MBT) repeat found in PHD finger protein 20-like protein 1 (PHF20L1) and similar domains; PHF20L1 associates with SOX2, antagonizes SOX2 ubiquitination and the sequential degradation induced by MLL1/WDR5 complexes. It binds both monomethylated Lys-42 and Lys-117 in SOX2 and thereby prevents SOX2 proteolysis. PHF20L1 also reads and controls enzyme levels of methylated DNMT1 in cells, thus representing a novel antagonist of DNMT1 degradation. PHF20L1 contains one MBT (malignant brain tumor) repeat. The MBT repeat is a protein module that recognizes methylated lysine residues on histones. MBT repeats contain a semi-aromatic cage to accommodate methyllysine and show specificity towards the lower methylation states of lysine. This model corresponds to the MBT repeat of PHF20L1 and similar domains that contains the semi-aromatic cage that may bind methylated lysine residues.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1173943012  29 LRVRDSVDVRNVFGNWCAAMILQV--TTSSVRVRFHNMNDKWDAWYPRHSLSLAPAST 84
Cdd:cd20104     1 FKVGDRVDALDGEGKWYEAKIVEVdeEENKVLVHYDGWSSRYDEWIDRDSERLRPLHT 58

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 1173943012 181 QLQLVEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYVVGDmpaFLRYVAHKRQDAVWGDDPELQAL 260
Cdd:cd22752     1 GFIIKEMEEDGNCLFRAVADQVYGDQEMHDVVRKHCMDYMEKNRDYFSQFVTED---FEEYINRKRQDGVWGNHIEIQAM 77

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1173943012 261 SELYDRPLQVFVSDAStgaaCLRTFHEASAGRGPPLRLSFYGGGHYDSIIP 311
Cdd:cd22752    78 SELYNRPIEVYAYSTE----PINTFHEASSSDNEPIRLSYHGNSHYNSIVD 124

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 1173943012 182 LQLVEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYVVGDMPaFLRYVAHKRQDAVWGDDPELQALS 261
Cdd:cd22771     2 LRIRDVEGDGNCLFRALADQLYGDEERHAELRKKVVDYMEAHEEDFEPFFEDDET-FEDYVSRMREDGTWGGNLELQAAS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1173943012 262 ELYDRPLQVFVSDAStgAACLRTFHEASAgrgPPLRLSFYGGGHYDSI 309
Cdd:cd22771    81 LVYRVNIVVHQLGQP--RWEIENFPDKGA---RTIHLSYHDGEHYNSV 123

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 1173943012 177 LQDQQLQLVEVPGDGNCLFRAISHQL---YGDDRFHAV--VRAACMDYMEAEKTYFEPYVV---GDM---PAFLRYVAHK 245
Cdd:cd22748     1 LKPLGLRIKEIPPDGHCLYRAIADQLklrGGSEEPYSYkeLRKLAADYMRAHRDDFLPFLTnddGDLmteEEFEEYCDKI 80

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1173943012 246 RQDAVWGDDPELQALSELYDRPLQVFVSDASTgaaclRTFHEASaGRGPPLRLSF----YG-GGHYDSII 310
Cdd:cd22748    81 ENTAEWGGQLELRALSKALKRPIHVYQAGSPP-----LVIGEEF-DSGEPLRLSYhrhaYGlGEHYNSVV 144

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 1173943012 184 LVEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYV-----VGDMPAFLRYVAHKRQDAVWGDDPELQ 258
Cdd:cd22756     2 AKDITGDGNCLFRALSDQLYGDPDRHLEIRAEVVEYMRANPDDFKPFSeaatfAEDDEAFEDYLARMAKDGTYGDNLEIV 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1173943012 259 ALSELYDRPLQVFVSDAstgaacLRTFHEASAGRGPPLR----LSFYGGGHYDSI 309
Cdd:cd22756    82 AFARAYNVDVKVYQPDP------VYVISAPEDGSPGPARrvlhIAYHNWEHYSSV 130

OTU (ovarian tumor) domain of fungal OTU domain-containing protein 2 and similar proteins; This subfamily includes Schizosaccharomyces pombe and Saccharomyces cerevisiae OTU domain-containing protein 2 (OTU2) and similar proteins. S. pombe OTU2 is a ubiquitin thioesterase/hydrolase (EC 3.4.19.12) that can remove conjugated ubiquitin from protein substrates and may therefore play an important regulatory role at the level of protein turnover by preventing degradation. Fungal OTU2 bbelongs 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 1173943012 177 LQDQQLQLVEVPGDGNCLFRAISHQL----YGDDRFHAVVRAACMDYMEAEKTYFEPYVV---GDMPAFLRYVAHKRQDA 249
Cdd:cd22762     2 LEELGLEEHDIKPDGHCLFAAIADQLqlrgSEINLDYKELRKLAAEYIRKHPDDFEPFLFeetDELEDIDEYCKKIENTA 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1173943012 250 VWGDDPELQALSELYDRPLQVFVSDASTgaaclRTFHEASAGRGPPLRLSFYG-----GGHYDSII 310
Cdd:cd22762    82 EWGGELELLALAKAFGVPIHVVQAEGRV-----IKINEEGDSDKPELWLAYYKhsyglGEHYNSLR 142

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 1173943012 177 LQDQQLQLVEVPGDGNCLFRAISHQLYGDDRFHAV--VRAACMDYMEAEKTYFEPYVV----GDM---PAFLRYVAHKRQ 247
Cdd:cd22761     5 LKERGLKIHEIPSDGDCLYNAIAHQLSLRGIETSVeeLRKQTADYMRENKDDFLPFLTnpdtGDPlteEEFEKYCDDVEN 84

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1173943012 248 DAVWGDDPELQALSELYDRPLQVFVSDASTGaaclrTFHEaSAGRGPPLRLSF----YG-GGHYDSII 310
Cdd:cd22761    85 TGAWGGQLELRALSHVLKRPIEVIQAEGPPI-----IIGE-EFKSGKPLILTYhrhaYGlGEHYNSVE 146

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 1173943012 177 LQDQQLQLVEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYVVGDmpaFLRYVAHKRQDAVWGDDPE 256
Cdd:cd22794     5 LRSLGLYRKQIAKDGSCLFRAVAEQVFHTQSRHLEVRKACVDYLRRNREKFEAFIEGP---FEQYLKNLENPKEWAGQVE 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1173943012 257 LQALSELYDRPLQVFvSDASTGAACLrtfheasAGRGPP--LRLSFYGGGHYDSIIP 311
Cdd:cd22794    82 ISALSLMYKRDFIIY-QEPGKPPSNV-------TENGFPdkILLCFSNGNHYDSVYP 130

OTU (ovarian tumor) domain of bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 and similar proteins; Bifunctional UDP-N-acetylglucosamine transferase and deubiquitinase ALG13 is alco called asparagine-linked glycosylation 13 homolog, glycosyltransferase 28 domain-containing protein 1 (GLT28D1), or UDP-N-acetylglucosamine transferase subunit ALG13 homolog. It displays both glycosyltransferase (EC 2.4.1.141) and deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) activities. With ALG14, it forms a UDP-N-acetylglucosamine transferase that catalyzes the second step of eukaryotic N-linked glycosylation in the endoplasmic reticulum. ALG13 variants cause a form of early infantile epileptic encephalopathy known as EIEE36 refractory seizures, neurodevelopmental impairment, and poor prognosis; given the essential role of ALG13 in glycosylation, it is also considered a congenital disorder of glycosylation (CDG). This subfamily also contains OTU domain-containing protein 4 (OTUD4), also called HIV-1-induced protein HIN-1, a DUB that specifically deubiquitinates 'Lys-63'-polyubiquitinated MYD88 adapter protein upon phosphorylation, triggering down-regulation of NF-kappa-B-dependent transcription of inflammatory mediators. This subfamily belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1173943012 187 VPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYVVGDmpaFLRYVAHKRQDAVWGDDPELQALSELYDR 266
Cdd:cd22753    15 IPRDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEIS---FDDYLERLSDPKEWGGLLELEALSLLYKV 91

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 1173943012 267 PLQVFVSdaSTGAACLRTfheaSAGRGPPLRLSFYGGGHYDSI 309
Cdd:cd22753    92 DFIVYSI--PDQPPSNIT----NNGYPKKIMLCYSGGNHYDSV 128

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 1173943012 181 QLQLVEVPGDGNCLFRAISHQLYGDDRFHAVV-----------RAACMDYMEAEKTYFEP---YVVGDMPAFLRYVAHKR 246
Cdd:cd22746     1 SLRVVPVKGDGRCLFRAVARGLALATGGRPLSerreradadalRKAVVEEIRKRRDELFEgslVIEGDFDAYCQRMSHPD 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1173943012 247 qdaVWGDDPELQALSELYDRPLQVFVSDASTGAACLRTFHEASAGRGPPLRLSFYGGGHYD 307
Cdd:cd22746    81 ---TWGGEPELLMLADVLQRPIAVYLPTPGKGGLRKIQEYGEEYLGGEPIRLLYNGGNHYD 138

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 1173943012 174 RRGLQDQQLQLVEVPGDGNCLFRAISHQL-----YGDDRFHAVVRAACMDYMEAEKTYFEPYVVGDMP------AFLRYV 242
Cdd:cd22797     2 RAKLAPLGLAIKEIKADGHCLYRAVEDQLqlrggGAPAPDYQQLRELAADYMRAHPDDFLPFLEDEDEggdgdeAFEAYC 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1173943012 243 AHKRQDAVWGDDPELQALSELYDRPLQVFvsdaSTGAACLrTFHEASAGRGPPLRLSF----YG-GGHYDSII 310
Cdd:cd22797    82 REVESTAAWGGQLELGALAHALRRHIKVY----SAGMPDV-EMGEEYAGTGPPLRLCYhrhaFGlGEHYNSVV 149

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 1173943012 190 DGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYVVGdmpAFLRYVAHKRQDAVWGDDPELQALSELYDRPLQ 269
Cdd:cd22795    18 DASCLFRAVSEQLFLCQIHHLEIRKACVSYMRANQCNFESYVEG---SFEKYLERLEDPKESAGQLEISALSLIYNRDFI 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 1173943012 270 VFVSDASTGAaclrtfHEASAGRGPPLRLSFYGGGHYDSIIP 311
Cdd:cd22795    95 LYRYPGKPPT------YATDNGFEDKILLCCSSNGHYDSVYT 130

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 1173943012 182 LQLVEVPGDGNCLFRAISHQLYGDDRFHAVV-RAACMDYMEAEK-TYFEpyVVGDMPAFlRYVAHKRQDAVWGDDPELQA 259
Cdd:cd22745     3 LVRRVVPDDNSCLFTSISYLLEGGLLDSAPElREIVADAILSDPdTYNE--AILGKPPD-EYCAWILKPDSWGGAIELSI 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1173943012 260 LSELYDrpLQVFVSDASTGAacLRTFHEasaGRGPPLR-LSFYGGGHYDSII-------PLGAHETLWEA--PGAWEQAR 329
Cdd:cd22745    80 LSKHFG--VEICVVDVQTGR--VDRFGE---DKGYSKRiFLLYSGIHYDALAlnpsldaPEDFDVTVFSVsdDEVLEAAL 152

                  ....
gi 1173943012 330 -LAA 332
Cdd:cd22745   153 eLAK 156

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
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1173943012 185 VEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDYMEAEKTYFEPYvvgdmpaFLRYVAHKRQDAVWGDDPELQALS 261
Cdd:cd22791     4 LRVTGDGNCLFRAASLLLFGDESLHLELRLRTVLELVLNSEFYEAI-------YEAEIKATCKPGSYSGIWHIYALS 73

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 1173943012 185 VEVPGDGNCLFRAISHQLYGDDRFHAVVRAACMDY--------MEAEKTYFEPYVvgdmpaflrYVAHKRQDAVWGDDPE 256
Cdd:cd21880    25 ERVPGDGNCFFRSIAELLFDTEDEWRLVKNTIESYaranwdecPEARLYYLSLEE---------YLRDAMKDGYWGGSLE 95

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1173943012 257 LQALSELYDRPLQVFVSDASTgaaclRTFHEASAGRGPPLRlSF---YGGGHYDSIIPL 312
Cdd:cd21880    96 AEILSKALGITIIIWVVDDSD-----WVTAAVRFGDGDVST-SLnllHSGGHFDALRLK 148