UBA-like domain found in OTU domain-containing proteins OTU7A, OTU7B and similar proteins; OTU7A, also called zinc finger protein Cezanne 2, belongs to a family of proteins that have been characterized as highly specific ubiquitin iso-peptidases removing ubiquitin from proteins. OTU7B, also called cellular zinc finger anti-NF-kappaB protein, zinc finger A20 domain-containing protein 1, or zinc finger protein Cezanne, is a novel deubiquitinating enzyme that acts as a negative regulator of NF-kappaB and may play a role in the control of the inflammatory process. Both OTU7A and OTU7B contain an N-terminal ubiquitin-associated (UBA)-like domain, followed by an ovarian tumor (OTU) domain and a ubiquitin binding domain, A20-like zinc finger. In addition, they both display proteolytic activity.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 71043957   4 DMDAVLSDFVRSTGAEPGLARDLLEGKNWDVSAALSDFEQLRQ 46
Cdd:cd14347   1 DMDAVLSDFVRSTGAEPGLARDLLEGKNWDLTAALSDYEQLRQ 43

UBA-like domain found in OTU domain-containing proteins OTU7A, OTU7B and similar proteins; OTU7A, also called zinc finger protein Cezanne 2, belongs to a family of proteins that have been characterized as highly specific ubiquitin iso-peptidases removing ubiquitin from proteins. OTU7B, also called cellular zinc finger anti-NF-kappaB protein, zinc finger A20 domain-containing protein 1, or zinc finger protein Cezanne, is a novel deubiquitinating enzyme that acts as a negative regulator of NF-kappaB and may play a role in the control of the inflammatory process. Both OTU7A and OTU7B contain an N-terminal ubiquitin-associated (UBA)-like domain, followed by an ovarian tumor (OTU) domain and a ubiquitin binding domain, A20-like zinc finger. In addition, they both display proteolytic activity.

                        10        20        30        40
                ....*....|....*....|....*....|....*....|...
gi 71043957   4 DMDAVLSDFVRSTGAEPGLARDLLEGKNWDVSAALSDFEQLRQ 46
Cdd:cd14347   1 DMDAVLSDFVRSTGAEPGLARDLLEGKNWDLTAALSDYEQLRQ 43

A20-like zinc finger; The A20 Zn-finger of bovine/human Rabex5/rabGEF1 is a Ubiquitin Binding Domain. The zinc finger mediates self-association in A20. These fingers also mediate IL-1-induced NF-kappa B activation.

                          10        20
                  ....*....|....*....|...
gi 71043957   798 KCKQpNCSFYGHPETNNLCSCCY 820
Cdd:pfam01754   2 LCRN-GCGFYGSPATNGLCSKCY 23

UBA-like domain;

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 71043957     6 DAVLSDFVRSTGAEPGLARDLLEGKNWDVSAALSDF 41
Cdd:pfam14555   1 DELIAQFQAITGADEEVARQYLEAHNWDLEAAVNAF 36

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 71043957 158 QSMLVALEQAGRLNWWVSmDSTCQRLLPLATTGDGNCLLHAASLGMWGFHDRDLVLRKALYALMEKGVEKEALRRRWRWQ 237
Cdd:cd22768   1 TSTLVSLEQAGRLNWWAK-DGGCQRLLPLATTGDGNCLLHAASLGMWGFHDRLLTLRKALYETLTSSAAKEALKRRWRWQ 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043957 238 QTQQNKESGLVYTEDEWQKEWNELIKLASSEPRMH--LGSNGASGGGVESSEEPVYESLEEFHVFVLAHVLKRPIVVVAD 315
Cdd:cd22768  80 QTQVNKEAGLVYSEEEWEREWKSLLKLASTEPRSQpsPSSGSELEEVIENSSDPTYESLEEIHVFVLAHVLRRPIIVVAD 159

                       170       180       190       200
                ....*....|....*....|....*....|....*....|....*....
gi 71043957 316 TMLRDSGGEAFAPIPFGGIYLPLEVPASQCHRSPLVLAYDQAHFSALVS 364
Cdd:cd22768 160 TMLRDSNGEPLAPIPFGGIYLPLECPPSECHRSPLVLAYDAAHFSALVP 208

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 71043957 128 LEMPICAFQLPDLTVYKEDFRSFIERDLIEQSMLVALEQAGRLNWWvsmdSTCQRLLPLATTGDGNCLLHAASLGMWGFH 207
Cdd:cd22766   1 LTMHRYTLQLPRLCQFPPDFREFLQKALIDRNIQRTLEEAKKLNWC----REVRKLVPLKTTGDGNCLLHAVSLYMWGVQ 76

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043957 208 DRDLVLRKALYALMEKGvEKEALRRRWR--WQQTQQNKESGLVYTEDEWQKEWNELIKLASSEPRMHLGSngasgggves 285
Cdd:cd22766  77 DTDLVLRKALYEALVET-DTRNFKLRWQreRLKSQEFVGTGLRYDTREWEEEWDNVVKMASPESKPAAGG---------- 145

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 71043957 286 seePVYESLEEFHVFVLAHVLKRPIVVVADTMLRDSGGEAFAPIPFGGIYLPLEVPASQCHRSPLVLAYDQAHFSALV 363
Cdd:cd22766 146 ---LPYNSLEEIHIFVLANILRRPIIVIADDMLRSLEGSSLAPLNFGGIYLPLHWPPQECYKYPIVLGYDSQHFTPLV 220

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 71043957 164 LEQAGR-LNWWVSMDSTCQ-RLLPLATTGDGNCLLHAASLGMWGFHDRDLVLRKALYALMEKGVEKeaLRRRWRWQQTQQ 241
Cdd:cd22767   7 LEEESPiINWSLELTDRLGsRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHW--FYSRWKEYESWQ 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043957 242 NKESGLVYTEDEWQKEWNELIKLASSePRMhlgsngasgggvesseepvyeSLEEFHVFVLAHVLKRPIVVVADTMLRDS 321
Cdd:cd22767  85 AQSLGYSLEEEQWQKDWAFLLSLASQ-PGA---------------------SLEQTHIFALAHILRRPIIVYGVKYVKSF 142

                       170       180       190       200
                ....*....|....*....|....*....|....*....|...
gi 71043957 322 GGEAFAPIPFGGIYLPLEVPASQCHRSPLVLAYDQAHFSALVS 364
Cdd:cd22767 143 RGETLGYARFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVP 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 71043957   189 TGDGNCLLHAASLGMWGFHDRDlvlrkalyalmekgveKEALRRRWRWQQT---QQNKESGLVYTEDEWQKEWNELIKla 265
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHDVL----------------RKMLVQELRETLAeymREHKEEFEPFLEDDETGDIIEIEQ-- 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043957   266 sseprmhlgsNGASGGgvesseepvyesleEFHVFVLAHVLKRPIVVvadtmLRDSGGEAFAPIPFGGIYLPLEVPASQC 345
Cdd:pfam02338  63 ----------TGAWGG--------------EIEIFALAHILRRPIIV-----YKSEGGEELGGLKEYGIYLPLGWDPSLC 113

                         170
                  ....*....|....
gi 71043957   346 HRSPLVLAYDQAHF 359
Cdd:pfam02338 114 LVYPRHLYYLGGHY 127

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 71043957 181 QRLLPLATTGDGNCLLHAASlgmwgfhdRDLVLRKALY-ALmekgveKEALRRRWRWQQTQ-QNKESGLVYTEdewqkEW 258
Cdd:cd22769  43 ERLIPIHADGDGHCLVHAVS--------RALVGRELFWhAL------RENLKQHFKENLDQyKALFQDFIDDS-----EW 103

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 71043957 259 NELIklASSEPRMHLGSNGASGggvesseepvyesLEEFHVFVLAHVLKRPIVVVaDTM--LRDSGGeafapipFGGIYL 336
Cdd:cd22769 104 PDII--AECDPDFVPPEGEPLG-------------LRNIHIFGLANVLKRPIILL-DSLsgMQSSGD-------YSAIFL 160

                       170       180       190
                ....*....|....*....|....*....|....*.
gi 71043957 337 PLEVPASQCH------RSPLVLAYDQA---HFSALV 363
Cdd:cd22769 161 PGLVPPEKCRgkdgllNKPICIAWSSSgrnHFIPLV 196

A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger mediates self-association in A20. These fingers also mediate IL-1-induced NF-kappaB activation.

                           10        20
                   ....*....|....*....|...
gi 71043957    798 KCKQPNCSFYGHPETNNLCSCCY 820
Cdd:smart00259   3 KCRRPGCGFFGNPATEGLCSKCF 25

UBA-like domain found in the NXF family of mRNA nuclear export factors and similar proteins; This family includes nuclear RNA export factors (NXF1/NXF2), FAS-associated factors (FAF1/2), tyrosyl-DNA phosphodiesterase 2 (TDP2), OTU domain-containing proteins (OTU7A/OTU7B), NSFL1 cofactor p47, defective in cullin neddylation protein 1 (DCN1)-like protein (DCNL1/DCNL2), yeast defective in cullin neddylation protein 1 (DCN1) and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. FAF1 is an apoptotic signaling molecule that acts downstream in the Fas signal transduction pathway. It interacts with the cytoplasmic domain of Fas, but not to a Fas mutant that is deficient in signal transduction. FAF2 is the translation product of a highly expressed gene in the T-cells and eosinophils of atopic dermatitis patients compared with those of normal individuals. Its biological function remains unclear. TDP2 is a 5'-Tyr-DNA phosphodiesterase required for the efficient repair of topoisomerase II-induced DNA double strand breaks. OTU7A and OTU7B are zinc finger proteins that function as deubiquitinating enzymes. p47 is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. DCNL1 plays an essential role in the neddylation E3 complex and participates in the release of inhibitory effects of CAND1 on cullin-RING ligase E3 complex assembly and activity. The biological function of DCNL2 remains unclear. Yeast DCN1 is a scaffold-type E3 ligase for cullin neddylation. It can bind directly to cullins and the ubiquitin-like protein Nedd8-specific E2 (Ubc12), and regulate cullin neddylation and thus display ubiquitin ligase activity.

                        10        20        30
                ....*....|....*....|....*....|
gi 71043957  12 FVRSTGAEPGLARDLLEGKNWDVSAALSDF 41
Cdd:cd14273   1 FMEITGADPETARQYLESNNWDLEAAINLY 30

UBA-like domain found in NSFL1 cofactor p47 and similar proteins; p47, also called UBX domain-containing protein 2C, is a major cofactor of the cytosolic AAA ATPase p97. It is required for the p97-regulated membrane reassembly of the endoplasmic reticulum (ER), the nuclear envelope and the Golgi apparatus. p47, together with p97, forms the p97-p47 complex that plays an important role in regulation of membrane fusion events. p47 contains an N-terminal ubiquitin-associated (UBA)-like domain, a central SEP (named after shp1, eyc and p47) domain, and a ubiquitin-like (UBX) domain. UBA-like domain is responsible for forming a highly stable complex with ubiquitin. SEP domain and UBX domain may involve in p47 trimerization or forms a stable complex with the p97 N-terminal domain.

                        10        20        30
                ....*....|....*....|....*....|....*.
gi 71043957   6 DAVLSDFVRSTGAEPGLARDLLEGKNWDVSAALSDF 41
Cdd:cd14348   1 DELIAQFVSVTGADEDRAKFFLESAGWDLEAALSSF 36