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 45554520  21 DQYLESRGLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEIPGDFDSYMQDMSKPKTYGTMTE 100
Cdd:cd22753   2 DEYLDSLGLYRKHIPRDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKEWGGLLE 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 45554520 101 LRAMSCLYRRNVILYEPYNMGTSVVFNRRYAENFRVFFNNENHFDSVYD 149
Cdd:cd22753  82 LEALSLLYKVDFIVYSIPDQPPSNITNNGYPKKIMLCYSGGNHYDSVYS 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 45554520  21 DQYLESRGLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEIPGDFDSYMQDMSKPKTYGTMTE 100
Cdd:cd22753   2 DEYLDSLGLYRKHIPRDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKEWGGLLE 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 45554520 101 LRAMSCLYRRNVILYEPYNMGTSVVFNRRYAENFRVFFNNENHFDSVYD 149
Cdd:cd22753  82 LEALSLLYKVDFIVYSIPDQPPSNITNNGYPKKIMLCYSGGNHYDSVYS 130

Tudor domain; Domain of unknown function present in several RNA-binding proteins. 10 copies in the Drosophila Tudor protein. Initial proposal that the survival motor neuron gene product contain a Tudor domain are corroborated by more recent database search techniques such as PSI-BLAST (unpublished).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 45554520    335 YNFKVGAKCKVELpNETEMYTCHVQNISKDkNYCHVFVERIGKEIVVPYESLHPLPPD 392
Cdd:smart00333   1 PTFKVGDKVAARW-EDGEWYRARIVKVDGE-QLYEVFFIDYGNEEVVPPSDLRQLPEE 56

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 45554520  21 DQYLESRGLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEIPGDFDSYMQDMSKPKTYGTMTE 100
Cdd:cd22753   2 DEYLDSLGLYRKHIPRDGSCLFRAVSEQLFFTQSYHQQVRQACVEYLEKNREEFEKFSEISFDDYLERLSDPKEWGGLLE 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*....
gi 45554520 101 LRAMSCLYRRNVILYEPYNMGTSVVFNRRYAENFRVFFNNENHFDSVYD 149
Cdd:cd22753  82 LEALSLLYKVDFIVYSIPDQPPSNITNNGYPKKIMLCYSGGNHYDSVYS 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 45554520  21 DQYLESRGLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEIPGDFDSYMQDMSKPKTYGTMTE 100
Cdd:cd22795   2 DEYLGSLGLYRKLTAKDASCLFRAVSEQLFLCQIHHLEIRKACVSYMRANQCNFESYVEGSFEKYLERLEDPKESAGQLE 81

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 45554520 101 LRAMSCLYRRNVILYEPYNMGTSVVFNRRYAENFRVFFNNENHFDSVY 148
Cdd:cd22795  82 ISALSLIYNRDFILYRYPGKPPTYATDNGFEDKILLCCSSNGHYDSVY 129

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 45554520  30 YRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEI------PGDFDSYMQDMSKPKTYGTMTELRA 103
Cdd:cd22744   1 RVVDVPGDGNCLFRALAHALYGDQESHRELRQEVVDYLRENPDLYEPAEladeddGEDFDEYLQRMRKPGTWGGELELQA 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 45554520 104 MSCLYRRNVILYEPYNMGTSV-VFNRRYAENFR---VFFNNENHFDSV 147
Cdd:cd22744  81 LANALNVPIVVYSEDGGFLPVsVFGPGPGPSGRpihLLYTGGNHYDAL 128

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 45554520  28 GLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEIPGD--FDSYMQDMSKPKTYGTMTELRAMS 105
Cdd:cd22771   1 GLRIRDVEGDGNCLFRALADQLYGDEERHAELRKKVVDYMEAHEEDFEPFFEDDetFEDYVSRMREDGTWGGNLELQAAS 80

                        90       100       110       120
                ....*....|....*....|....*....|....*....|...
gi 45554520 106 CLYRRNVILY-EPYNMGTSVVFNRRYAENFRVFFNNENHFDSV 147
Cdd:cd22771  81 LVYRVNIVVHqLGQPRWEIENFPDKGARTIHLSYHDGEHYNSV 123

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 45554520  37 DASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEI---PGDF----DSYMQDMSKPKTYGTMTELRAMSCLYR 109
Cdd:cd22757   9 DGACLFRALSYLLYGTQSRHLEVRKEVVDYVVNNWDEFSIYThdsEGNNyksaEEYRADMSKPGTYGTLCELVAAAELYP 88

                        90
                ....*....|....*
gi 45554520 110 RNVILYEPYNMGTSV 124
Cdd:cd22757  89 FHFEVYRNGKLYASF 103

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 45554520  21 DQYLESRGLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKR-RIFEKEIPGDFDSYMQDMSKPKTYGTMT 99
Cdd:cd22751   2 LRRLDLYGLVERKVEGDGNCQFRALSDQLFGTQDHHAEVRELVVKQLRAHPeLYYEFYVPEEYDEYLKKMSKDGEWGDEL 81

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 45554520 100 ELRAMSCLYRRNVIL-----------YEPYNMgtsvvfnrryAENFRVFF---NNENHFDSVY 148
Cdd:cd22751  82 TLQAAADAFGVKIHVitsfednwfleIEPRGL----------VRSKRVLFlsyWAEVHYNSIY 134

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 45554520  21 DQYLESRGLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEIPGDFDSYMQDMSKPKTYGTMTE 100
Cdd:cd22747  13 DKYLRERNKYRFHIIPDGNCLYRAVSKAVYGDQALHRELREQTVHYIADHLDEFNPIIEGDVGEFLIKAAQDGAWAGYPE 92

                        90
                ....*....|....
gi 45554520 101 LRAMSCLYRRNVIL 114
Cdd:cd22747  93 LLAMGQMLNVNIRL 106

Tudor domain; Domain of unknown function present in several RNA-binding proteins. 10 copies in the Drosophila Tudor protein. Initial proposal that the survival motor neuron gene product contain a Tudor domain are corroborated by more recent database search techniques such as PSI-BLAST (unpublished).

                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 45554520    335 YNFKVGAKCKVELpNETEMYTCHVQNISKDkNYCHVFVERIGKEIVVPYESLHPLPPD 392
Cdd:smart00333   1 PTFKVGDKVAARW-EDGEWYRARIVKVDGE-QLYEVFFIDYGNEEVVPPSDLRQLPEE 56

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 45554520  37 DASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFEKEIPGDFDS---YMQDMSKPK--TYGTMTELRAMSCLYRRN 111
Cdd:cd22755   9 DGNCFFRALSYAITGSEKYHRKIRKAIVDFLEKNPDEFRNLLRSDYESveeYLEKSRMRYdgTWATDVEIFAAATLLGVD 88

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*...
gi 45554520 112 V----------ILYEPYNMGTSVVFNRR--YAENfrvffNNENHFDSV 147
Cdd:cd22755  89 IyvyskggykwLLYSPRFKLGKRNGSREaiYLKN-----TNGNHFEPV 131

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 45554520  24 LESRGLYRKHTARDASSLFRVIAEQMYDTQMLHYEIRLECVRFMTLKRRIFE----KEIPgdFDSYMQDMSKPKTYGTMT 99
Cdd:cd22770   9 LQALGLKLRDIPGDGNCLFRALGDQLEGHSRNHLKHRQETVQYMIEHREDFEpfveDDVP--FDKHVANLSKPGTYAGND 86

                        90
                ....*....|....*..
gi 45554520 100 ELRAMSCLYRRNVILYE 116
Cdd:cd22770  87 AIVAFARLHQVNVVIHQ 103