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 767909928   4 DMDAVLSDFVRSTGAEPGLARDLLEGKNWDVNAALSDFEQLRQ 46
Cdd:cd14347    1 DMDAVLSDFVRSTGAEPGLARDLLEGKNWDLTAALSDYEQLRQ 43

No apical meristem-associated C-terminal domain; This domain is found in a number of different types of plant proteins including NAM-like proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767909928  432 KWIPLSSDAQVKTSPTSTLAPLAQPESPTASAGDEPRSTPES-GDSDKESVGSSSTSNEG----GRRKEKSKR-----DR 501
Cdd:pfam14303  16 KWKDYCRDIKRNKKPSSTASSSPAPTSLASTDPDTDSSDSSSaGSNESNSDDSSPSSKSPtrpiGRKKAKEKRqeeldAA 95

                  ....*...
gi 767909928  502 EKDKKRAD 509
Cdd:pfam14303  96 KEEKKQND 103

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 767909928   4 DMDAVLSDFVRSTGAEPGLARDLLEGKNWDVNAALSDFEQLRQ 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 767909928  810 KCKQpNCSFYGHPETNNFCSCCY 832
Cdd:pfam01754   2 LCRN-GCGFYGSPATNGLCSKCY 23

UBA-like domain;

                          10        20        30
                  ....*....|....*....|....*....|....*.
gi 767909928    6 DAVLSDFVRSTGAEPGLARDLLEGKNWDVNAALSDF 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 767909928 158 QSMLVALEQAGRLNWWVSvDPTSQRLLPLATTGDGNCLLHAASLGMWGFHDRDLMLRKALYALMEKGVEKEALKRRWRWQ 237
Cdd:cd22768    1 TSTLVSLEQAGRLNWWAK-DGGCQRLLPLATTGDGNCLLHAASLGMWGFHDRLLTLRKALYETLTSSAAKEALKRRWRWQ 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767909928 238 QTQQNKESGLVYTEDEWQKEWNELIKLASSEPRMHLGTNGANC--GGVESSEEPVYESLEEFHVFVLAHVLRRPIVVVAD 315
Cdd:cd22768   80 QTQVNKEAGLVYSEEEWEREWKSLLKLASTEPRSQPSPSSGSEleEVIENSSDPTYESLEEIHVFVLAHVLRRPIIVVAD 159

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 767909928 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 767909928 128 LEMPICAFQLPDLTVYNEDFRSFIERDLIEQSMLVALEQAGRLNWWvsvdPTSQRLLPLATTGDGNCLLHAASLGMWGFH 207
Cdd:cd22766    1 LTMHRYTLQLPRLCQFPPDFREFLQKALIDRNIQRTLEEAKKLNWC----REVRKLVPLKTTGDGNCLLHAVSLYMWGVQ 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767909928 208 DRDLMLRKALYALMEKGvEKEALKRRWRWQ--QTQQNKESGLVYTEDEWQKEWNELIKLASSEPrmHLGTNGancggves 285
Cdd:cd22766   77 DTDLVLRKALYEALVET-DTRNFKLRWQRErlKSQEFVGTGLRYDTREWEEEWDNVVKMASPES--KPAAGG-------- 145

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767909928 286 seePVYESLEEFHVFVLAHVLRRPIVVVADTMLRDSGGEAFAPIPFGGIYLPLEVPASQCHRSPLVLAYDQAHFSALV 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 767909928 164 LEQAGRLNWWvSVDPTSQ---RLLPLATTGDGNCLLHAASLGMWGFHDRDLMLRKALYALMEKGVEKeaLKRRWRWQQTQ 240
Cdd:cd22767    7 LEEESPIINW-SLELTDRlgsRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHW--FYSRWKEYESW 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767909928 241 QNKESGLVYTEDEWQKEWNELIKLASSePRMhlgtngancggvesseepvyeSLEEFHVFVLAHVLRRPIVVVADTMLRD 320
Cdd:cd22767   84 QAQSLGYSLEEEQWQKDWAFLLSLASQ-PGA---------------------SLEQTHIFALAHILRRPIIVYGVKYVKS 141

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 767909928 321 SGGEAFAPIPFGGIYLPLEVPASQCHRSPLVLAYDQAHFSALVS 364
Cdd:cd22767  142 FRGETLGYARFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVP 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 767909928  189 TGDGNCLLHAASLGMWGFHDrdlMLRKALY-ALMEKGVEkealkrrwrwqQTQQNKESGLVYTEDEWQKEWNELIKLASS 267
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHD---VLRKMLVqELRETLAE-----------YMREHKEEFEPFLEDDETGDIIEIEQTGAW 66

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767909928  268 EprmhlgtngancggvesseepvyeslEEFHVFVLAHVLRRPIVVvadtmLRDSGGEAFAPIPFGGIYLPLEVPASQCHR 347
Cdd:pfam02338  67 G--------------------------GEIEIFALAHILRRPIIV-----YKSEGGEELGGLKEYGIYLPLGWDPSLCLV 115

                         170
                  ....*....|..
gi 767909928  348 SPLVLAYDQAHF 359
Cdd:pfam02338 116 YPRHLYYLGGHY 127

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 767909928 188 TTGDGNCLLHAASLGMWGFHDRDLMLRKALYALMEKgvekealkrrwrwqqtQQNKESGLVYTEDEWQKEWNELIKlass 267
Cdd:cd22744    5 VPGDGNCLFRALAHALYGDQESHRELRQEVVDYLRE----------------NPDLYEPAELADEDDGEDFDEYLQ---- 64

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767909928 268 eprmHLGTNGAnCGGvesseepvyesleEFHVFVLAHVLRRPIVVVadtmlrDSGGEAFAPIPFGgiylplevPASQCHR 347
Cdd:cd22744   65 ----RMRKPGT-WGG-------------ELELQALANALNVPIVVY------SEDGGFLPVSVFG--------PGPGPSG 112

                        170
                 ....*....|....*.
gi 767909928 348 SPLVLAYDQA-HFSAL 362
Cdd:cd22744  113 RPIHLLYTGGnHYDAL 128

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
                 ....*....|....*....|....*....|..
gi 767909928 183 LLPLATTGDGNCLLHAASLGMWGFHDRDLMLR 214
Cdd:cd22791    1 LEPLRVTGDGNCLFRAASLLLFGDESLHLELR 32

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 767909928  12 FVRSTGAEPGLARDLLEGKNWDVNAALSDF 41
Cdd:cd14273    1 FMEITGADPETARQYLESNNWDLEAAINLY 30

No apical meristem-associated C-terminal domain; This domain is found in a number of different types of plant proteins including NAM-like proteins.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767909928  432 KWIPLSSDAQVKTSPTSTLAPLAQPESPTASAGDEPRSTPES-GDSDKESVGSSSTSNEG----GRRKEKSKR-----DR 501
Cdd:pfam14303  16 KWKDYCRDIKRNKKPSSTASSSPAPTSLASTDPDTDSSDSSSaGSNESNSDDSSPSSKSPtrpiGRKKAKEKRqeeldAA 95

                  ....*...
gi 767909928  502 EKDKKRAD 509
Cdd:pfam14303  96 KEEKKQND 103

UBA-like domain found in nuclear RNA export factor NXF1, NXF2 and similar proteins; The NXF family of mRNA nuclear export factors including vertebrate NXF1 (also called tip-associated protein or mRNA export factor TAP), NXF2 (also called cancer/testis antigen CT39 or TAP-like protein TAPL-2), Caenorhabditis elegans NXF1 (ceNXF1), Saccharomyces cerevisiae mRNA nuclear export factor Mex67p and similar proteins. NXF proteins can stimulate nuclear export of mRNAs and facilitate the export of unspliced viral mRNA containing the constitutive transport element. It is a multi-domain protein with a nuclear localization sequence (NLS), a non-canonical mRNA-binding domain, and four leucine-rich repeats (LLR) at the N-terminal region. Its C-terminal part contains a NTF2-like domain and a ubiquitin-associated (UBA)-like domain, joined by flexible Pro-rich linker. Caenorhabditis elegans NXF1 are essential for the nuclear export of poly(A)+mRNA. In budding yeast, Mex67p binds mRNAs through its adaptor Yra1/REF. It also interacts directly with Nab2, an essential shuttling mRNA-binding protein required for export. Moreover, Mex67p associates with both nuclear pore protein (nucleoporin) FG repeats and Hpr1, a component of the TREX/THO complex linking transcription and export.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|...
gi 767909928  12 FVRSTGAEPGLARDLLEGKNWDVNAALSDFEQLRQvhAGNLPP 54
Cdd:cd14342    8 LSAQTGMNLEWSQKCLEDNGWDYEKALANFEELKA--QGKIPP 48