OTU (ovarian tumor) domain of Ubiquitin thioesterase ZRANB1 and similar proteins; ZRANB1 is also called TRAF-binding domain-containing protein, Trabid, or zinc finger Ran-binding domain-containing protein 1. It is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin; it also cleaves 'Lys-63'-linked chains with less efficiency. ZRANB1 binds, deubiquitinates, and stabilizes EZH2, which is the catalytic component of the Polycomb repressive complex 2 (PRC2) that silences gene transcription by methylating histone H3 at lysine 27 and is mutated or highly expressed in many types of cancer, including lymphoma, melanoma, prostate cancer, ovarian cancer, and breast cancer. Drosophila Trabid interacts with TGF-beta Activating Kinase 1 (TAK1), which triggers both immunity and apoptosis, resulting in reduced immune signaling output and K63-linked ubiquitination. ZRANB1 belongs to the OTU family of cysteine proteases that use a conserved cysteine and histidine, and in most cases an aspartate, as the catalytic triad. ZRANB1 does not contain the conserved aspartate, and uses cysteine and histidine as a catalytic dyad. It is classified as a family C64 cysteine protease by MEROPS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 431 RDVQKELEEESPIINWSLELATRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRWKDW 510
Cdd:cd22767     1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 511 ESWYSQSfgLHFSLREEQWQEDWAFILSLASQPGASLEQTHIFVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLP 590
Cdd:cd22767    81 ESWQAQS--LGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLP 158

                         170       180
                  ....*....|....*....|....*..
gi 1375456854 591 LLWEQSFCWKSPIALGYTRGHFSALVA 617
Cdd:cd22767   159 LLWEQSFCWKSPIALGYTRGHFSALVP 185

Zinc finger domain; Zinc finger domain in Ran-binding proteins (RanBPs), and other proteins. In RanBPs, this domain binds RanGDP.

                           10        20
                   ....*....|....*....|....
gi 1375456854  178 HWTCSVCTYENWAKAKKCVVCDHP 201
Cdd:smart00547   2 DWECPACTFLNFASRSKCFACGAP 25

Zinc finger domain; Zinc finger domain in Ran-binding proteins (RanBPs), and other proteins. In RanBPs, this domain binds RanGDP.

                           10        20
                   ....*....|....*....|...
gi 1375456854   33 KWACEYCTYENWPSAIKCTMCRA 55
Cdd:smart00547   2 DWECPACTFLNFASRSKCFACGA 24

OTU (ovarian tumor) domain of Ubiquitin thioesterase ZRANB1 and similar proteins; ZRANB1 is also called TRAF-binding domain-containing protein, Trabid, or zinc finger Ran-binding domain-containing protein 1. It is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin; it also cleaves 'Lys-63'-linked chains with less efficiency. ZRANB1 binds, deubiquitinates, and stabilizes EZH2, which is the catalytic component of the Polycomb repressive complex 2 (PRC2) that silences gene transcription by methylating histone H3 at lysine 27 and is mutated or highly expressed in many types of cancer, including lymphoma, melanoma, prostate cancer, ovarian cancer, and breast cancer. Drosophila Trabid interacts with TGF-beta Activating Kinase 1 (TAK1), which triggers both immunity and apoptosis, resulting in reduced immune signaling output and K63-linked ubiquitination. ZRANB1 belongs to the OTU family of cysteine proteases that use a conserved cysteine and histidine, and in most cases an aspartate, as the catalytic triad. ZRANB1 does not contain the conserved aspartate, and uses cysteine and histidine as a catalytic dyad. It is classified as a family C64 cysteine protease by MEROPS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 431 RDVQKELEEESPIINWSLELATRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRWKDW 510
Cdd:cd22767     1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 511 ESWYSQSfgLHFSLREEQWQEDWAFILSLASQPGASLEQTHIFVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLP 590
Cdd:cd22767    81 ESWQAQS--LGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLP 158

                         170       180
                  ....*....|....*....|....*..
gi 1375456854 591 LLWEQSFCWKSPIALGYTRGHFSALVA 617
Cdd:cd22767   159 LLWEQSFCWKSPIALGYTRGHFSALVP 185

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 1375456854 464 RTAGDCLLDSVLQATW-----GIYDKDSVLRKALHDSLHDcshwfytrwkdweswysqsfglHFSLREEQWQEDWAFILS 538
Cdd:pfam02338   1 PGDGNCLYRSISHQLWgvhdvLRKMLVQELRETLAEYMRE----------------------HKEEFEPFLEDDETGDII 58

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1375456854 539 LASQPGASLEQTHIFVLAHILRRPIIVYgvkyyKSFRGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHF 612
Cdd:pfam02338  59 EIEQTGAWGGEIEIFALAHILRRPIIVY-----KSEGGEELGGLKEYGIYLPLGWDPSLCLVYPRHLYYLGGHY 127

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 1375456854 175 RTQHWTCSVCTYENWAKAKKCVVCDHPRPN 204
Cdd:pfam00641   1 REGDWDCSKCLVQNFATSTKCVACQAPKPD 30

Zinc finger domain; Zinc finger domain in Ran-binding proteins (RanBPs), and other proteins. In RanBPs, this domain binds RanGDP.

                           10        20
                   ....*....|....*....|...
gi 1375456854   33 KWACEYCTYENWPSAIKCTMCRA 55
Cdd:smart00547   2 DWECPACTFLNFASRSKCFACGA 24

OTU (ovarian tumor) domain of Ubiquitin thioesterase ZRANB1 and similar proteins; ZRANB1 is also called TRAF-binding domain-containing protein, Trabid, or zinc finger Ran-binding domain-containing protein 1. It is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that specifically hydrolyzes 'Lys-29'-linked and 'Lys-33'-linked diubiquitin; it also cleaves 'Lys-63'-linked chains with less efficiency. ZRANB1 binds, deubiquitinates, and stabilizes EZH2, which is the catalytic component of the Polycomb repressive complex 2 (PRC2) that silences gene transcription by methylating histone H3 at lysine 27 and is mutated or highly expressed in many types of cancer, including lymphoma, melanoma, prostate cancer, ovarian cancer, and breast cancer. Drosophila Trabid interacts with TGF-beta Activating Kinase 1 (TAK1), which triggers both immunity and apoptosis, resulting in reduced immune signaling output and K63-linked ubiquitination. ZRANB1 belongs to the OTU family of cysteine proteases that use a conserved cysteine and histidine, and in most cases an aspartate, as the catalytic triad. ZRANB1 does not contain the conserved aspartate, and uses cysteine and histidine as a catalytic dyad. It is classified as a family C64 cysteine protease by MEROPS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 431 RDVQKELEEESPIINWSLELATRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRWKDW 510
Cdd:cd22767     1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 511 ESWYSQSfgLHFSLREEQWQEDWAFILSLASQPGASLEQTHIFVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLP 590
Cdd:cd22767    81 ESWQAQS--LGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLP 158

                         170       180
                  ....*....|....*....|....*..
gi 1375456854 591 LLWEQSFCWKSPIALGYTRGHFSALVA 617
Cdd:cd22767   159 LLWEQSFCWKSPIALGYTRGHFSALVP 185

Ankyrin ubiquitin-binding domain; This is an Ankyrin repeat domain found in TRABID (also known as Ubiquitin thioesterase ZRANB1) (EC:3.4.19.12). In TRABID, the first ankyrin repeat spans residues 260-290 and is connected to the second repeat residues 313-340 by a long linker that packs against what would correspond to the concave surface in an extended ankyrin-repeat structure. Ankyrin-repeat domains mediate protein interactions through a variety of surfaces. The ankyrin domain of TRABID interacts with ubiquitin, hence it is referred to as the ankyrin ubiquitin-binding domain, or AnkUBD.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 272 EVDFKKLKQIKNRMKKTDWLFLNACVGVVEGDLAAIEAYKSSGGDIARQLTADEVRLLNRPSAFDVGYTLVHLAIRFQRQ 351
Cdd:pfam18418   1 EVDFKKLKQIKNRMKKTDWLFLNACVGPIEGDLAAIEAFKLSGGDIAGLLDADEVRLLNRPPAFDVGYTLVHLAIRFQRQ 80

                          90
                  ....*....|....*.
gi 1375456854 352 DMLAILLTEVSQQAAK 367
Cdd:pfam18418  81 DMLAILLTEVSQHAAK 96

OTU (ovarian tumor) domain of OTU domain-containing proteins 7A, 7B, and similar proteins; This subfamily consists of OTU domain-containing protein 7A (OTUD7A), OTUD7B, and similar proteins. OTUD7A and OTUD7B are deubiquitinases (DUBs)/ubiquitin thioesterases (EC 3.4.19.12) that specifically target Lys11-linked polyubiquitin. OTUD7A, also called zinc finger protein Cezanne 2, has been identified as a critical gene for brain function. It localizes to dendritic and spine compartments in cortical neurons, and its reduced levels contributed to dendritic spine and dendrite outgrowth deficits. OTUD7B, also called zinc finger protein Cezanne, functions as a negative regulator of the non-canonical NF-kappaB pathway by mediating the deubiquitination of TRAF3, an inhibitor of the NF-kappaB pathway, resulting in preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappaB. OTUD7 proteins belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. They are classified as family C64 cysteine proteases by MEROPS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 439 EESPIINWSLElaTRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSL--HDCSHWFYTRWKdWESWYS- 515
Cdd:cd22768     8 EQAGRLNWWAK--DGGCQRLLPLATTGDGNCLLHAASLGMWGFHDRLLTLRKALYETLtsSAAKEALKRRWR-WQQTQVn 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 516 QSFGLHFSlrEEQWQEDWAFILSLAS-QP-----------------------GASLEQTHIFVLAHILRRPIIVYGVKYY 571
Cdd:cd22768    85 KEAGLVYS--EEEWEREWKSLLKLAStEPrsqpspssgseleevienssdptYESLEEIHVFVLAHVLRRPIIVVADTML 162

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1375456854 572 KSFRGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVA 617
Cdd:cd22768   163 RDSNGEPLAPIPFGGIYLPLECPPSECHRSPLVLAYDAAHFSALVP 208

OTU (ovarian tumor) domain of OTU domain-containing protein 7B; OTU domain-containing protein 7B (OTUD7B) is also called cellular zinc finger anti-NF-kappa-B protein, zinc finger A20 domain-containing protein 1, or zinc finger protein Cezanne. It is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that specifically targets Lys11-linked polyubiquitin. It functions as a negative regulator of the non-canonical NF-kappaB pathway by mediating the deubiquitination of TRAF3, an inhibitor of the NF-kappaB pathway, resulting in preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappaB. OTUD7B also deubiquitinates ZAP70, and thus, regulates T cell receptor (TCR) signaling. It belongs to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad. It is classified as a family C64 cysteine protease by MEROPS.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 439 EESPIINWSLELATRLdSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSH--WFYTRWKDWESWYSQ 516
Cdd:cd22772     8 EQAGRLNWWVSVDPTC-QRLLPLATTGDGNCLLHAASLGMWGFHDRDLMLRKALYALMEKGVEkeALKRRWRWQQTQQNK 86

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 517 SFGLHFSlrEEQWQEDWAFILSLASQP----------------------GASLEQTHIFVLAHILRRPIIVYGVKYYKSF 574
Cdd:cd22772    87 ESGLVYT--EDEWQKEWNELIKLASSEprmhygtngancggvesseepvYESLEEFHVFVLAHVLRRPIVVVADTMLRDS 164

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 1375456854 575 RGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVA 617
Cdd:cd22772   165 GGEAFAPIPFGGIYLPLEVPASKCHRSPLVLAYDQAHFSALVS 207

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 1375456854 467 GDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRwkdweswysqsfglhfSLREEQWQEDWAFILSLASQPGAS 546
Cdd:cd22744     9 GNCLFRALAHALYGDQESHRELRQEVVDYLRENPDLYEPA----------------ELADEDDGEDFDEYLQRMRKPGTW 72

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 547 LEQTHIFVLAHILRRPIIVYgvkyykSFRGETLGYTRFQGVYLPllweqsfcWKSPIALGYT-RGHFSAL 615
Cdd:cd22744    73 GGELELQALANALNVPIVVY------SEDGGFLPVSVFGPGPGP--------SGRPIHLLYTgGNHYDAL 128

Zn-finger in Ran binding protein and others;

                          10        20        30
                  ....*....|....*....|....*....|
gi 1375456854 175 RTQHWTCSVCTYENWAKAKKCVVCDHPRPN 204
Cdd:pfam00641   1 REGDWDCSKCLVQNFATSTKCVACQAPKPD 30

OTU (ovarian tumor) domain of deubiquitinating protein VCIP135; Deubiquitinating protein VCIP135 is also called valosin-containing protein p97/p47 complex-interacting protein 1, valosin-containing protein p97/p47 complex-interacting protein p135, or VCP/p47 complex-interacting 135-kDa protein. It is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that hydrolyzes 'Lys-11'- and 'Lys-48'-linked polyubiquitin chains. It is necessary for VCP-mediated reassembly of Golgi stacks after mitosis, and may play a role in VCP-mediated formation of transitional endoplasmic reticulum (tER). VCIP135 controls Golgi membrane dynamics in the cell cycle and is required for Golgi and ER assembly. It belongs to the OTU family of cysteine proteases that use a conserved cysteine and histidine, and in most cases an aspartate, as the catalytic triad. Not all members of this subfamily contain the active site. It is closely related to proteins classified as family C64 cysteine protease by MEROPS, such as TNFAIP3, ZRANB1, and OTUD7A/B.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1375456854 521 HFSLREEQWQE---------DWAFILSLA-----SQPGAS--LEQTHIFVLAHILRRPIIVygvkyYKSFRG-ETLG-YT 582
Cdd:cd22769    82 HFKENLDQYKAlfqdfiddsEWPDIIAECdpdfvPPEGEPlgLRNIHIFGLANVLKRPIIL-----LDSLSGmQSSGdYS 156

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 1375456854 583 rfqGVYLPLLWEQSFC------WKSPIALGYT---RGHFSALVA 617
Cdd:cd22769   157 ---AIFLPGLVPPEKCrgkdglLNKPICIAWSssgRNHFIPLVG 197