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Conserved domains on  [gi|568950912|ref|XP_006508032|]
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ubiquitin thioesterase Zranb1 isoform X2 [Mus musculus]

Protein Classification

OTU family ubiquitin thioesterase( domain architecture ID 17785049)

OTU family ubiquitin thioesterase catalyzes the thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin

EC:  3.4.19.12
MEROPS:  C65
PubMed:  10664582|23827681|31884527|12704427
SCOP:  4004307

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
OTU_ZRANB1 cd22767
OTU (ovarian tumor) domain of Ubiquitin thioesterase ZRANB1 and similar proteins; ZRANB1 is ...
 79-265 9.62e-137

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.


:

Pssm-ID: 438604  Cd Length: 185  Bit Score: 387.42  E-value: 9.62e-137
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  79 RDVQKELEEESPIINWSLELATRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRWKDW 158
Cdd:cd22767    1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 159 ESWYSQSfgLHFSLREEQWQEDWAFILSLASQPGASLEQTHIFVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLP 238
Cdd:cd22767   81 ESWQAQS--LGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLP 158

                        170       180
                 ....*....|....*....|....*..
gi 568950912 239 LLWEQSFCWKSPIALGYTRGHFSALVA 265
Cdd:cd22767  159 LLWEQSFCWKSPIALGYTRGHFSALVP 185
 
Name Accession Description Interval E-value
OTU_ZRANB1 cd22767
OTU (ovarian tumor) domain of Ubiquitin thioesterase ZRANB1 and similar proteins; ZRANB1 is ...
 79-265 9.62e-137

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.


Pssm-ID: 438604  Cd Length: 185  Bit Score: 387.42  E-value: 9.62e-137
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  79 RDVQKELEEESPIINWSLELATRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRWKDW 158
Cdd:cd22767    1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 159 ESWYSQSfgLHFSLREEQWQEDWAFILSLASQPGASLEQTHIFVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLP 238
Cdd:cd22767   81 ESWQAQS--LGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLP 158

                        170       180
                 ....*....|....*....|....*..
gi 568950912 239 LLWEQSFCWKSPIALGYTRGHFSALVA 265
Cdd:cd22767  159 LLWEQSFCWKSPIALGYTRGHFSALVP 185
OTU pfam02338
OTU-like cysteine protease; This family is comprised of a group of predicted cysteine ...
 112-260 2.88e-39

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.


Pssm-ID: 426728 [Multi-domain]  Cd Length: 127  Bit Score: 136.43  E-value: 2.88e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  112 RTAGDCLLDSVLQATW-----GIYDKDSVLRKALHDSLHDcshwfytrwkdweswysqsfglHFSLREEQWQEDWAFILS 186
Cdd:pfam02338   1 PGDGNCLYRSISHQLWgvhdvLRKMLVQELRETLAEYMRE----------------------HKEEFEPFLEDDETGDII 58

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568950912  187 LASQPGASLEQTHIFVLAHILRRPIIVYgvkyyKSFRGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHF 260
Cdd:pfam02338  59 EIEQTGAWGGEIEIFALAHILRRPIIVY-----KSEGGEELGGLKEYGIYLPLGWDPSLCLVYPRHLYYLGGHY 127
 
Name Accession Description Interval E-value
OTU_ZRANB1 cd22767
OTU (ovarian tumor) domain of Ubiquitin thioesterase ZRANB1 and similar proteins; ZRANB1 is ...
 79-265 9.62e-137

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.


Pssm-ID: 438604  Cd Length: 185  Bit Score: 387.42  E-value: 9.62e-137
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  79 RDVQKELEEESPIINWSLELATRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRWKDW 158
Cdd:cd22767    1 RDVQKELEEESPIINWSLELTDRLGSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHWFYSRWKEY 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 159 ESWYSQSfgLHFSLREEQWQEDWAFILSLASQPGASLEQTHIFVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLP 238
Cdd:cd22767   81 ESWQAQS--LGYSLEEEQWQKDWAFLLSLASQPGASLEQTHIFALAHILRRPIIVYGVKYVKSFRGETLGYARFQGVYLP 158

                        170       180
                 ....*....|....*....|....*..
gi 568950912 239 LLWEQSFCWKSPIALGYTRGHFSALVA 265
Cdd:cd22767  159 LLWEQSFCWKSPIALGYTRGHFSALVP 185
OTU_C64 cd22750
OTU (ovarian tumor) domain of family C64 cysteine proteases; This group includes proteins ...
 79-264 1.77e-73

OTU (ovarian tumor) domain of family C64 cysteine proteases; This group includes proteins classified as family C64 cysteine protease by MEROPS, such as tumor necrosis factor (TNF) alpha-induced protein 3 (TNFAIP3), ZRANB1, OTU domain-containing protein 7A (OTUD7A), and OTUD7B. It also includes VCIP135. These proteins are deubiquitinases (DUBs)/ubiquitin thioesterases (EC 3.4.19.12) that mediates the deubiquitination of protein substrates. TNFAIP3 also contains ubiquitin ligase activity. 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). 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. OTUD7A has been identified as a critical gene for brain function, while OTUD7B 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. VCIP135 controls Golgi membrane dynamics in the cell cycle and is required for Golgi and ER assembly. This group 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.


Pssm-ID: 438587  Cd Length: 185  Bit Score: 226.84  E-value: 1.77e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  79 RDVQKELEEEsPIINWslelaTRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDC-SHWFYTRWKD 157
Cdd:cd22750    1 RDLKDDLESE-KVINW-----CRGVSRLVPLHTRGDGNCLLHAVSLALWGVEDRDLLLRSALHETLQNDqERRFRARWRR 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 158 WESWYSQSFGLhfSLREEQWQEDWAFILSLASQ------PGASLEQTHIFVLAHILRRPIIVYGVKYYKSFRGETLGYTR 231
Cdd:cd22750   75 QQLKSGQELGL--SLDEEALQAEWEEILKAAETptvpagPGSYLEEIHIFVLANVLRRPIIVLADDSARSLEGSALQDNG 152

                        170       180       190
                 ....*....|....*....|....*....|...
gi 568950912 232 FQGVYLPLLWEQSFCWKSPIALGYTRGHFSALV 264
Cdd:cd22750  153 MSGIYLPLLWPPSECSRSPLALGYSNGHFSPLV 185
OTU_TNFAIP3 cd22766
OTU (ovarian tumor) domain of tumor necrosis factor alpha induced protein 3; Tumor necrosis ...
 54-264 1.32e-48

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.


Pssm-ID: 438603  Cd Length: 220  Bit Score: 163.97  E-value: 1.32e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  54 TFTLPaDIEDLPPTVQEKLFDEVLDRDVQKELEEESpIINWSLELatrldSRLYALwnRTAGD--CLLDSVLQATWGIYD 131
Cdd:cd22766    7 TLQLP-RLCQFPPDFREFLQKALIDRNIQRTLEEAK-KLNWCREV-----RKLVPL--KTTGDgnCLLHAVSLYMWGVQD 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 132 KDSVLRKALHDSL-HDCSHWFYTRWKDwESWYSQSF-GLHFSLREEQWQEDWAFILSLASQ---------PGASLEQTHI 200
Cdd:cd22766   78 TDLVLRKALYEALvETDTRNFKLRWQR-ERLKSQEFvGTGLRYDTREWEEEWDNVVKMASPeskpaagglPYNSLEEIHI 156

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568950912 201 FVLAHILRRPIIVYGVKYYKSFRGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALV 264
Cdd:cd22766  157 FVLANILRRPIIVIADDMLRSLEGSSLAPLNFGGIYLPLHWPPQECYKYPIVLGYDSQHFTPLV 220
OTU_OTUD7 cd22768
OTU (ovarian tumor) domain of OTU domain-containing proteins 7A, 7B, and similar proteins; ...
 87-265 1.74e-42

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.


Pssm-ID: 438605  Cd Length: 208  Bit Score: 147.45  E-value: 1.74e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  87 EESPIINWSLElaTRLDSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSL--HDCSHWFYTRWKdWESWYS- 163
Cdd:cd22768    8 EQAGRLNWWAK--DGGCQRLLPLATTGDGNCLLHAASLGMWGFHDRLLTLRKALYETLtsSAAKEALKRRWR-WQQTQVn 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 164 QSFGLHFSlrEEQWQEDWAFILSLAS-QP-----------------------GASLEQTHIFVLAHILRRPIIVYGVKYY 219
Cdd:cd22768   85 KEAGLVYS--EEEWEREWKSLLKLAStEPrsqpspssgseleevienssdptYESLEEIHVFVLAHVLRRPIIVVADTML 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 568950912 220 KSFRGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVA 265
Cdd:cd22768  163 RDSNGEPLAPIPFGGIYLPLECPPSECHRSPLVLAYDAAHFSALVP 208
OTU pfam02338
OTU-like cysteine protease; This family is comprised of a group of predicted cysteine ...
 112-260 2.88e-39

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.


Pssm-ID: 426728 [Multi-domain]  Cd Length: 127  Bit Score: 136.43  E-value: 2.88e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  112 RTAGDCLLDSVLQATW-----GIYDKDSVLRKALHDSLHDcshwfytrwkdweswysqsfglHFSLREEQWQEDWAFILS 186
Cdd:pfam02338   1 PGDGNCLYRSISHQLWgvhdvLRKMLVQELRETLAEYMRE----------------------HKEEFEPFLEDDETGDII 58

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568950912  187 LASQPGASLEQTHIFVLAHILRRPIIVYgvkyyKSFRGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHF 260
Cdd:pfam02338  59 EIEQTGAWGGEIEIFALAHILRRPIIVY-----KSEGGEELGGLKEYGIYLPLGWDPSLCLVYPRHLYYLGGHY 127
OTU_OTUD7B cd22772
OTU (ovarian tumor) domain of OTU domain-containing protein 7B; OTU domain-containing protein ...
 87-265 6.50e-30

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.


Pssm-ID: 438609  Cd Length: 207  Bit Score: 114.36  E-value: 6.50e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  87 EESPIINWSLELATRLdSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSH--WFYTRWKDWESWYSQ 164
Cdd:cd22772    8 EQAGRLNWWVSVDPTC-QRLLPLATTGDGNCLLHAASLGMWGFHDRDLMLRKALYALMEKGVEkeALKRRWRWQQTQQNK 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 165 SFGLHFSlrEEQWQEDWAFILSLASQP----------------------GASLEQTHIFVLAHILRRPIIVYGVKYYKSF 222
Cdd:cd22772   87 ESGLVYT--EDEWQKEWNELIKLASSEprmhygtngancggvesseepvYESLEEFHVFVLAHVLRRPIVVVADTMLRDS 164

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 568950912 223 RGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVA 265
Cdd:cd22772  165 GGEAFAPIPFGGIYLPLEVPASKCHRSPLVLAYDQAHFSALVS 207
OTU_OTUD7A cd22773
OTU (ovarian tumor) domain of OTU domain-containing protein 7A; OTU domain-containing protein ...
 87-265 9.19e-26

OTU (ovarian tumor) domain of OTU domain-containing protein 7A; OTU domain-containing protein 7A (OTUD7A), also called zinc finger protein Cezanne 2, is a deubiquitinase (DUB)/ubiquitin thioesterase (EC 3.4.19.12) that specifically targets Lys11-linked polyubiquitin. OTUD7A 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. A homozygous OTUD7A missense variant located within the OTU catalytic domain is linked to early-onset epileptic encephalopathy and proteasome dysfunction. OTUD7A 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.


Pssm-ID: 438610  Cd Length: 207  Bit Score: 103.22  E-value: 9.19e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912  87 EESPIINWSLELATRLdSRLYALWNRTAGDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSH--WFYTRWKDWESWYSQ 164
Cdd:cd22773    8 EQAGRLNWWSTVCTSC-KRLLPLATTGDGNCLLHAASLGMWGFHDRDLVLRKALYTMMKSGAEreALKRRWRWQQTQQNK 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 165 SFGLHFSlrEEQWQEDWAFILSLAS---------QPGA-------------SLEQTHIFVLAHILRRPIIVYGVKYYKSF 222
Cdd:cd22773   87 ESGLVYT--EEEWEREWNELLKLASseprthfskNGGTgggvdnsedpvyeSLEEFHVFVLAHILRRPIVVVADTMLRDS 164

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 568950912 223 RGETLGYTRFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALVA 265
Cdd:cd22773  165 GGEAFAPIPFGGIYLPLEVPPNRCHCSPLVLAYDQAHFSALVS 207
OTU cd22744
OTU (ovarian tumor) domain family; The OTU family of cysteine proteases use a conserved ...
 115-263 8.36e-09

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.


Pssm-ID: 438581 [Multi-domain]  Cd Length: 128  Bit Score: 53.59  E-value: 8.36e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 115 GDCLLDSVLQATWGIYDKDSVLRKALHDSLHDCSHWFYTRwkdweswysqsfglhfSLREEQWQEDWAFILSLASQPGAS 194
Cdd:cd22744    9 GNCLFRALAHALYGDQESHRELRQEVVDYLRENPDLYEPA----------------ELADEDDGEDFDEYLQRMRKPGTW 72

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 195 LEQTHIFVLAHILRRPIIVYgvkyykSFRGETLGYTRFQGVYLPllweqsfcWKSPIALGYT-RGHFSAL 263
Cdd:cd22744   73 GGELELQALANALNVPIVVY------SEDGGFLPVSVFGPGPGP--------SGRPIHLLYTgGNHYDAL 128
OTU_VCIP135 cd22769
OTU (ovarian tumor) domain of deubiquitinating protein VCIP135; Deubiquitinating protein ...
 169-265 3.17e-04

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.


Pssm-ID: 438606  Cd Length: 197  Bit Score: 41.51  E-value: 3.17e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568950912 169 HFSLREEQWQE---------DWAFILSLA-----SQPGAS--LEQTHIFVLAHILRRPIIVygvkyYKSFRG-ETLG-YT 230
Cdd:cd22769   82 HFKENLDQYKAlfqdfiddsEWPDIIAECdpdfvPPEGEPlgLRNIHIFGLANVLKRPIIL-----LDSLSGmQSSGdYS 156

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 568950912 231 rfqGVYLPLLWEQSFC------WKSPIALGYT---RGHFSALVA 265
Cdd:cd22769  157 ---AIFLPGLVPPEKCrgkdglLNKPICIAWSssgRNHFIPLVG 197
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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