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 585670591 388 RDVQKELEQESHIINWSMELSERLGSRLYSLWNRTAGDCLLDSVLQATWGIFDQDNTLRRALSESLNEGAARFYVRWKDY 467
Cdd:cd22767    1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 585670591 468 ETIQAENLEYSLDEEQWQQDWAIMLSLASQPGAPLEQTHIFALAHILRRPIIVYGVKFIKSFRGETLGYARFQGVYLPLL 547
Cdd:cd22767   81 ESWQAQSLGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLPLL 160

                        170       180
                 ....*....|....*....|....*
gi 585670591 548 WEPGFCWKSPIALGYTRGHFSALVS 572
Cdd:cd22767  161 WEQSFCWKSPIALGYTRGHFSALVP 185

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

                           10        20
                   ....*....|....*....|...
gi 585670591   131 KWNCSACTYDNWPRSKKCVLCHT 153
Cdd:smart00547   2 DWECPACTFLNFASRSKCFACGA 24

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

                           10        20
                   ....*....|....*....|....
gi 585670591     6 KWTCEYCTYLNWPSAVKCTLCRAP 29
Cdd:smart00547   2 DWECPACTFLNFASRSKCFACGAP 25

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 585670591 388 RDVQKELEQESHIINWSMELSERLGSRLYSLWNRTAGDCLLDSVLQATWGIFDQDNTLRRALSESLNEGAARFYVRWKDY 467
Cdd:cd22767    1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 585670591 468 ETIQAENLEYSLDEEQWQQDWAIMLSLASQPGAPLEQTHIFALAHILRRPIIVYGVKFIKSFRGETLGYARFQGVYLPLL 547
Cdd:cd22767   81 ESWQAQSLGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLPLL 160

                        170       180
                 ....*....|....*....|....*
gi 585670591 548 WEPGFCWKSPIALGYTRGHFSALVS 572
Cdd:cd22767  161 WEQSFCWKSPIALGYTRGHFSALVP 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 585670591  421 RTAGDCLLDSVLQATWGIFDQdntLRRALSESLnegaarfyvRWKDYETIQAENLEYsldEEQWQQDWAIMLSLASQPGA 500
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHDV---LRKMLVQEL---------RETLAEYMREHKEEF---EPFLEDDETGDIIEIEQTGA 65

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 585670591  501 PLEQTHIFALAHILRRPIIVYgvkfiKSFRGETLGYARFQGVYLPLLWEPGFCWKSPIALGYTRGHF 567
Cdd:pfam02338  66 WGGEIEIFALAHILRRPIIVY-----KSEGGEELGGLKEYGIYLPLGWDPSLCLVYPRHLYYLGGHY 127

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

                           10        20
                   ....*....|....*....|...
gi 585670591    73 WSCKSCTYLNWPKAINCMQCHSP 95
Cdd:smart00547   3 WECPACTFLNFASRSKCFACGAP 25

Zn-finger in Ran binding protein and others;

                          10        20
                  ....*....|....*....|....
gi 585670591  132 WNCSACTYDNWPRSKKCVLCHTAR 155
Cdd:pfam00641   5 WDCSKCLVQNFATSTKCVACQAPK 28

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 585670591 388 RDVQKELEQESHIINWSMELSERLGSRLYSLWNRTAGDCLLDSVLQATWGIFDQDNTLRRALSESLNEGAARFYVRWKDY 467
Cdd:cd22767    1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 585670591 468 ETIQAENLEYSLDEEQWQQDWAIMLSLASQPGAPLEQTHIFALAHILRRPIIVYGVKFIKSFRGETLGYARFQGVYLPLL 547
Cdd:cd22767   81 ESWQAQSLGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLPLL 160

                        170       180
                 ....*....|....*....|....*
gi 585670591 548 WEPGFCWKSPIALGYTRGHFSALVS 572
Cdd:cd22767  161 WEQSFCWKSPIALGYTRGHFSALVP 185

OTU (ovarian tumor) domain of tumor necrosis factor alpha induced protein 3; Tumor necrosis factor (TNF) alpha-induced protein 3 (TNFAIP3) is also called OTU domain-containing protein 7C (OTUD7C), DNA-binding protein A20, or zinc finger protein A20. It is a ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) activities. It antagonizes IKK [IkappaB (inhibitor of kappaB) kinase] activation by modulating Lys63-linked polyubiquitination of cytokine-receptor-associated factors including TRAF2/6 (tumour-necrosis-factor-receptor-associated factor 2/6) and RIP1 (receptor-interacting protein 1). It can also inhibit IKK through a non-catalytic mechanism which involves polyubiquitin. In vitro, TNFAIP3 is able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. TNFAIP3 contains several A20-type zinc fingers that mediate the ubiquitin ligase activity and an OTU (ovarian tumor) domain that contains the DUB activity. 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 585670591 363 TFTLPvEIEDFPLPVRNQLFDEILDRDVQKELEQEShIINWSMELSerlgsRLYSLwnRTAGD--CLLDSVLQATWGIFD 440
Cdd:cd22766    7 TLQLP-RLCQFPPDFREFLQKALIDRNIQRTLEEAK-KLNWCREVR-----KLVPL--KTTGDgnCLLHAVSLYMWGVQD 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 585670591 441 QDNTLRRALSESLNEGAAR-FYVRW-----KDYETIqAENLEYslDEEQWQQDWAIMLSLAS------QPGAP---LEQT 505
Cdd:cd22766   78 TDLVLRKALYEALVETDTRnFKLRWqrerlKSQEFV-GTGLRY--DTREWEEEWDNVVKMASpeskpaAGGLPynsLEEI 154

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 585670591 506 HIFALAHILRRPIIVYGVKFIKSFRGETLGYARFQGVYLPLLWEPGFCWKSPIALGYTRGHFSALV 571
Cdd:cd22766  155 HIFVLANILRRPIIVIADDMLRSLEGSSLAPLNFGGIYLPLHWPPQECYKYPIVLGYDSQHFTPLV 220

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 585670591  236 KLRKRMRKSDWLFLNACIGVVDNDIQAVEAYLTSGGDPGRQLTQDEINLLNRTSAFDVGFTLVHLAIRFQREDLLSVLLT 315
Cdd:pfam18418   9 QIKNRMKKTDWLFLNACVGPIEGDLAAIEAFKLSGGDIAGLLDADEVRLLNRPPAFDVGYTLVHLAIRFQRQDMLAILLT 88

                  ....*....
gi 585670591  316 pDVASHALK 324
Cdd:pfam18418  89 -EVSQHAAK 96

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 585670591 394 LEQESHIiNWSMELSERLgSRLYSLWNRTAGDCLLDSVLQATWGIFDQDNTLRRALSESLNEGAAR--FYVRWKDYETIQ 471
Cdd:cd22772    7 LEQAGRL-NWWVSVDPTC-QRLLPLATTGDGNCLLHAASLGMWGFHDRDLMLRKALYALMEKGVEKeaLKRRWRWQQTQQ 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 585670591 472 AENLEYSLDEEQWQQDWAIMLSLASQP----------------------GAPLEQTHIFALAHILRRPIIVYGVKFIKSF 529
Cdd:cd22772   85 NKESGLVYTEDEWQKEWNELIKLASSEprmhygtngancggvesseepvYESLEEFHVFVLAHVLRRPIVVVADTMLRDS 164

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 585670591 530 RGETLGYARFQGVYLPLLWEPGFCWKSPIALGYTRGHFSALVS 572
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 585670591 424 GDCLLDSVLQATWGIFDQDNTLRRALSESLNEgaarfyvRWKDYEtiqaenlEYSLDEEQWQQDWAIMLSLASQPGAPLE 503
Cdd:cd22744    9 GNCLFRALAHALYGDQESHRELRQEVVDYLRE-------NPDLYE-------PAELADEDDGEDFDEYLQRMRKPGTWGG 74

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 585670591 504 QTHIFALAHILRRPIIVYgvkfikSFRGETLGYARFQGvylpllwePGFCWKSPIALGYT-RGHFSAL 570
Cdd:cd22744   75 ELELQALANALNVPIVVY------SEDGGFLPVSVFGP--------GPGPSGRPIHLLYTgGNHYDAL 128

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

                           10        20
                   ....*....|....*....|...
gi 585670591   131 KWNCSACTYDNWPRSKKCVLCHT 153
Cdd:smart00547   2 DWECPACTFLNFASRSKCFACGA 24

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

                           10        20
                   ....*....|....*....|....
gi 585670591     6 KWTCEYCTYLNWPSAVKCTLCRAP 29
Cdd:smart00547   2 DWECPACTFLNFASRSKCFACGAP 25

Zn-finger in Ran binding protein and others;

                          10        20
                  ....*....|....*....|....*....
gi 585670591    4 SRKWTCEYCTYLNWPSAVKCTLCRAPKPL 32
Cdd:pfam00641   2 EGDWDCSKCLVQNFATSTKCVACQAPKPD 30