NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|767943502|ref|XP_011534397|]
View 

tumor necrosis factor alpha-induced protein 3 isoform X2 [Homo sapiens]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
OTU_TNFAIP3 cd22766
OTU (ovarian tumor) domain of tumor necrosis factor alpha induced protein 3; Tumor necrosis ...
 41-261 2.45e-145

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: 425.52  E-value: 2.45e-145
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  41 KTMHRYTLEMFRTCQFCPQFREIIHKALIDRNIQATLESQKKLNWCREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDL 120
Cdd:cd22766    1 LTMHRYTLQLPRLCQFPPDFREFLQKALIDRNIQRTLEEAKKLNWCREVRKLVPLKTTGDGNCLLHAVSLYMWGVQDTDL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 121 VLRKALFSTLKETDTRNFKFRWQLESLKSQEFVETGLCYDTRNWNDEWDNLIKMASTDTPMARSGLQYNSLEEIHIFVLC 200
Cdd:cd22766   81 VLRKALYEALVETDTRNFKLRWQRERLKSQEFVGTGLRYDTREWEEEWDNVVKMASPESKPAAGGLPYNSLEEIHIFVLA 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767943502 201 NILRRPIIVISDKMLRSLEsGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLV 261
Cdd:cd22766  161 NILRRPIIVIADDMLRSLE-GSSLAPLNFGGIYLPLHWPPQECYKYPIVLGYDSQHFTPLV 220
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 759-784 1.41e-05

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.


:

Pssm-ID: 128555  Cd Length: 26  Bit Score: 42.19  E-value: 1.41e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   759 KQRCRAPACDHFGNAKCNGYCNECFQ 784
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 475-500 1.84e-05

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.


:

Pssm-ID: 128555  Cd Length: 26  Bit Score: 41.80  E-value: 1.84e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   475 AMKCRSPGCPFTLNVQHNGFCERCHN 500
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 604-629 6.96e-05

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.


:

Pssm-ID: 128555  Cd Length: 26  Bit Score: 40.26  E-value: 6.96e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   604 TSKCRKAGCVYFGTPENKGFCTLCFI 629
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 654-679 2.75e-04

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.


:

Pssm-ID: 128555  Cd Length: 26  Bit Score: 38.72  E-value: 2.75e-04
                           10        20
                   ....*....|....*....|....*.
gi 767943502   654 TIPCLGRECGTLGSTMFEGYCQKCFI 679
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 384-409 4.36e-04

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.


:

Pssm-ID: 128555  Cd Length: 26  Bit Score: 37.95  E-value: 4.36e-04
                           10        20
                   ....*....|....*....|....*.
gi 767943502   384 DVKCETPNCPFFMSVNTQPLCHECSE 409
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 713-738 2.10e-03

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.


:

Pssm-ID: 128555  Cd Length: 26  Bit Score: 36.02  E-value: 2.10e-03
                           10        20
                   ....*....|....*....|....*.
gi 767943502   713 RPKCARASCKNILACRSEELCMECQH 738
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
 
Name Accession Description Interval E-value
OTU_TNFAIP3 cd22766
OTU (ovarian tumor) domain of tumor necrosis factor alpha induced protein 3; Tumor necrosis ...
 41-261 2.45e-145

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: 425.52  E-value: 2.45e-145
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  41 KTMHRYTLEMFRTCQFCPQFREIIHKALIDRNIQATLESQKKLNWCREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDL 120
Cdd:cd22766    1 LTMHRYTLQLPRLCQFPPDFREFLQKALIDRNIQRTLEEAKKLNWCREVRKLVPLKTTGDGNCLLHAVSLYMWGVQDTDL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 121 VLRKALFSTLKETDTRNFKFRWQLESLKSQEFVETGLCYDTRNWNDEWDNLIKMASTDTPMARSGLQYNSLEEIHIFVLC 200
Cdd:cd22766   81 VLRKALYEALVETDTRNFKLRWQRERLKSQEFVGTGLRYDTREWEEEWDNVVKMASPESKPAAGGLPYNSLEEIHIFVLA 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767943502 201 NILRRPIIVISDKMLRSLEsGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLV 261
Cdd:cd22766  161 NILRRPIIVIADDMLRSLE-GSSLAPLNFGGIYLPLHWPPQECYKYPIVLGYDSQHFTPLV 220
OTU pfam02338
OTU-like cysteine protease; This family is comprised of a group of predicted cysteine ...
 98-257 4.17e-34

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: 126.80  E-value: 4.17e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502   98 NGDGNCLMHATSQYMWGVQDtdlVLRKALFSTLKETDTRNFKfrwqleslksQEFVETGLCYDtrnwNDEWDNLIKMAST 177
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHD---VLRKMLVQELRETLAEYMR----------EHKEEFEPFLE----DDETGDIIEIEQT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  178 dtpmarsglqYNSLEEIHIFVLCNILRRPIIVISDkmlrslESGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHF 257
Cdd:pfam02338  64 ----------GAWGGEIEIFALAHILRRPIIVYKS------EGGEELGGLKEYGIYLPLGWDPSLCLVYPRHLYYLGGHY 127
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 759-784 1.41e-05

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 42.19  E-value: 1.41e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   759 KQRCRAPACDHFGNAKCNGYCNECFQ 784
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 475-500 1.84e-05

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 41.80  E-value: 1.84e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   475 AMKCRSPGCPFTLNVQHNGFCERCHN 500
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 604-629 6.96e-05

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 40.26  E-value: 6.96e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   604 TSKCRKAGCVYFGTPENKGFCTLCFI 629
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 654-679 2.75e-04

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 38.72  E-value: 2.75e-04
                           10        20
                   ....*....|....*....|....*.
gi 767943502   654 TIPCLGRECGTLGSTMFEGYCQKCFI 679
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 384-409 4.36e-04

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 37.95  E-value: 4.36e-04
                           10        20
                   ....*....|....*....|....*.
gi 767943502   384 DVKCETPNCPFFMSVNTQPLCHECSE 409
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
zf-A20 pfam01754
A20-like zinc finger; The A20 Zn-finger of bovine/human Rabex5/rabGEF1 is a Ubiquitin Binding ...
 760-784 7.23e-04

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.


Pssm-ID: 460313  Cd Length: 24  Bit Score: 37.48  E-value: 7.23e-04
                          10        20
                  ....*....|....*....|....*
gi 767943502  760 QRCRAPaCDHFGNAKCNGYCNECFQ 784
Cdd:pfam01754   1 LLCRNG-CGFYGSPATNGLCSKCYK 24
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 713-738 2.10e-03

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 36.02  E-value: 2.10e-03
                           10        20
                   ....*....|....*....|....*.
gi 767943502   713 RPKCARASCKNILACRSEELCMECQH 738
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
 
Name Accession Description Interval E-value
OTU_TNFAIP3 cd22766
OTU (ovarian tumor) domain of tumor necrosis factor alpha induced protein 3; Tumor necrosis ...
 41-261 2.45e-145

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: 425.52  E-value: 2.45e-145
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  41 KTMHRYTLEMFRTCQFCPQFREIIHKALIDRNIQATLESQKKLNWCREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDL 120
Cdd:cd22766    1 LTMHRYTLQLPRLCQFPPDFREFLQKALIDRNIQRTLEEAKKLNWCREVRKLVPLKTTGDGNCLLHAVSLYMWGVQDTDL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 121 VLRKALFSTLKETDTRNFKFRWQLESLKSQEFVETGLCYDTRNWNDEWDNLIKMASTDTPMARSGLQYNSLEEIHIFVLC 200
Cdd:cd22766   81 VLRKALYEALVETDTRNFKLRWQRERLKSQEFVGTGLRYDTREWEEEWDNVVKMASPESKPAAGGLPYNSLEEIHIFVLA 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767943502 201 NILRRPIIVISDKMLRSLEsGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLV 261
Cdd:cd22766  161 NILRRPIIVIADDMLRSLE-GSSLAPLNFGGIYLPLHWPPQECYKYPIVLGYDSQHFTPLV 220
OTU_C64 cd22750
OTU (ovarian tumor) domain of family C64 cysteine proteases; This group includes proteins ...
 71-261 9.30e-83

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: 261.89  E-value: 9.30e-83
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  71 RNIQATLESQKKLNWCREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDLVLRKALFSTLKETDTRNFKFRWQLESLKSQ 150
Cdd:cd22750    1 RDLKDDLESEKVINWCRGVSRLVPLHTRGDGNCLLHAVSLALWGVEDRDLLLRSALHETLQNDQERRFRARWRRQQLKSG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 151 EfvETGLCYDTRNWNDEWDNLIKMASTDTPMARSGlqyNSLEEIHIFVLCNILRRPIIVISDKMLRSLEsGSNFAPLKVG 230
Cdd:cd22750   81 Q--ELGLSLDEEALQAEWEEILKAAETPTVPAGPG---SYLEEIHIFVLANVLRRPIIVLADDSARSLE-GSALQDNGMS 154

                        170       180       190
                 ....*....|....*....|....*....|.
gi 767943502 231 GIYLPLHWPAQECYRYPIVLGYDSHHFVPLV 261
Cdd:cd22750  155 GIYLPLLWPPSECSRSPLALGYSNGHFSPLV 185
OTU_OTUD7 cd22768
OTU (ovarian tumor) domain of OTU domain-containing proteins 7A, 7B, and similar proteins; ...
 76-261 4.07e-65

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: 215.63  E-value: 4.07e-65
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  76 TLESQKKLNWCREVR---KLVALKTNGDGNCLMHATSQYMWGVQDTDLVLRKALFSTLKETDTRN-FKFRW---QLESLK 148
Cdd:cd22768    6 SLEQAGRLNWWAKDGgcqRLLPLATTGDGNCLLHAASLGMWGFHDRLLTLRKALYETLTSSAAKEaLKRRWrwqQTQVNK 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 149 sqefvETGLCYDTRNWNDEWDNLIKMASTDTPMARSG---------------LQYNSLEEIHIFVLCNILRRPIIVISDK 213
Cdd:cd22768   86 -----EAGLVYSEEEWEREWKSLLKLASTEPRSQPSPssgseleevienssdPTYESLEEIHVFVLAHVLRRPIIVVADT 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*...
gi 767943502 214 MLRSLeSGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLV 261
Cdd:cd22768  161 MLRDS-NGEPLAPIPFGGIYLPLECPPSECHRSPLVLAYDAAHFSALV 207
OTU_OTUD7B cd22772
OTU (ovarian tumor) domain of OTU domain-containing protein 7B; OTU domain-containing protein ...
 77-262 3.94e-55

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: 188.71  E-value: 3.94e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  77 LESQKKLNWCREV----RKLVALKTNGDGNCLMHATSQYMWGVQDTDLVLRKALFSTLK---ETDTRNFKFRWQleslKS 149
Cdd:cd22772    7 LEQAGRLNWWVSVdptcQRLLPLATTGDGNCLLHAASLGMWGFHDRDLMLRKALYALMEkgvEKEALKRRWRWQ----QT 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 150 QEFVETGLCYDTRNWNDEWDNLIKMASTDTPM-------ARSGLQ------YNSLEEIHIFVLCNILRRPIIVISDKMLR 216
Cdd:cd22772   83 QQNKESGLVYTEDEWQKEWNELIKLASSEPRMhygtngaNCGGVEsseepvYESLEEFHVFVLAHVLRRPIVVVADTMLR 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 767943502 217 SlESGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLVT 262
Cdd:cd22772  163 D-SGGEAFAPIPFGGIYLPLEVPASKCHRSPLVLAYDQAHFSALVS 207
OTU_OTUD7A cd22773
OTU (ovarian tumor) domain of OTU domain-containing protein 7A; OTU domain-containing protein ...
 77-262 2.04e-49

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: 172.94  E-value: 2.04e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  77 LESQKKLNW----CREVRKLVALKTNGDGNCLMHATSQYMWGVQDTDLVLRKALFSTLK---ETDTRNFKFRWQleslKS 149
Cdd:cd22773    7 LEQAGRLNWwstvCTSCKRLLPLATTGDGNCLLHAASLGMWGFHDRDLVLRKALYTMMKsgaEREALKRRWRWQ----QT 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 150 QEFVETGLCYDTRNWNDEWDNLIKMASTD--TPMARSGLQ-----------YNSLEEIHIFVLCNILRRPIIVISDKMLR 216
Cdd:cd22773   83 QQNKESGLVYTEEEWEREWNELLKLASSEprTHFSKNGGTgggvdnsedpvYESLEEFHVFVLAHILRRPIVVVADTMLR 162

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 767943502 217 SlESGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLVT 262
Cdd:cd22773  163 D-SGGEAFAPIPFGGIYLPLEVPPNRCHCSPLVLAYDQAHFSALVS 207
OTU_ZRANB1 cd22767
OTU (ovarian tumor) domain of Ubiquitin thioesterase ZRANB1 and similar proteins; ZRANB1 is ...
 71-261 2.49e-41

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: 149.37  E-value: 2.49e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  71 RNIQATLESQ-KKLNWCREV-----RKLVALKTNGDGNCLMHATSQYMWGVQDTDLVLRKALFSTLKETDTRnFKFRWQ- 143
Cdd:cd22767    1 RDVQKELEEEsPIINWSLELtdrlgSRLYALWNRTAGDCLLDSVLQATWGVFDRDNVLRRALADSLHDCAHW-FYSRWKe 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 144 LESLKSQEFvetGLCYDTRNWNDEWDNLIKMASTdtPMArsglqynSLEEIHIFVLCNILRRPIIVISDKMLRSLEsGSN 223
Cdd:cd22767   80 YESWQAQSL---GYSLEEEQWQKDWAFLLSLASQ--PGA-------SLEQTHIFALAHILRRPIIVYGVKYVKSFR-GET 146

                        170       180       190
                 ....*....|....*....|....*....|....*...
gi 767943502 224 FAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHFVPLV 261
Cdd:cd22767  147 LGYARFQGVYLPLLWEQSFCWKSPIALGYTRGHFSALV 184
OTU pfam02338
OTU-like cysteine protease; This family is comprised of a group of predicted cysteine ...
 98-257 4.17e-34

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: 126.80  E-value: 4.17e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502   98 NGDGNCLMHATSQYMWGVQDtdlVLRKALFSTLKETDTRNFKfrwqleslksQEFVETGLCYDtrnwNDEWDNLIKMAST 177
Cdd:pfam02338   1 PGDGNCLYRSISHQLWGVHD---VLRKMLVQELRETLAEYMR----------EHKEEFEPFLE----DDETGDIIEIEQT 63

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  178 dtpmarsglqYNSLEEIHIFVLCNILRRPIIVISDkmlrslESGSNFAPLKVGGIYLPLHWPAQECYRYPIVLGYDSHHF 257
Cdd:pfam02338  64 ----------GAWGGEIEIFALAHILRRPIIVYKS------EGGEELGGLKEYGIYLPLGWDPSLCLVYPRHLYYLGGHY 127
OTU_VCIP135 cd22769
OTU (ovarian tumor) domain of deubiquitinating protein VCIP135; Deubiquitinating protein ...
 73-261 2.41e-16

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: 78.11  E-value: 2.41e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  73 IQATLESQKKLNWCREVrkLVALKTNGDGNCLMHATSQymwgvqdtDLVLRKALFSTLKEtdtrNFK--FRWQLESLKS- 149
Cdd:cd22769   28 LHDTLEEIKKANDNEER--LIPIHADGDGHCLVHAVSR--------ALVGRELFWHALRE----NLKqhFKENLDQYKAl 93

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 150 -QEFVETglcydtrnwnDEWDNLIKMASTD-TPMARSGLqynSLEEIHIFVLCNILRRPIIVISDkmLRSLESGSNFApl 227
Cdd:cd22769   94 fQDFIDD----------SEWPDIIAECDPDfVPPEGEPL---GLRNIHIFGLANVLKRPIILLDS--LSGMQSSGDYS-- 156

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 767943502 228 kvgGIYLPLHWPAQEC------YRYPIVLGYDS---HHFVPLV 261
Cdd:cd22769  157 ---AIFLPGLVPPEKCrgkdglLNKPICIAWSSsgrNHFIPLV 196
OTU cd22744
OTU (ovarian tumor) domain family; The OTU family of cysteine proteases use a conserved ...
 99-260 7.34e-10

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: 57.45  E-value: 7.34e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  99 GDGNCLMHATSQYMWGVQDTDLVLRKALFSTLKEtdtrnfkfRWQLESlksqefvetGLCYDTRNWNDEWDNLIKMastd 178
Cdd:cd22744    7 GDGNCLFRALAHALYGDQESHRELRQEVVDYLRE--------NPDLYE---------PAELADEDDGEDFDEYLQR---- 65

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 179 tpMARSGlqyNSLEEIHIFVLCNILRRPIIVISDkmlrslesgsnfaplkvGGIYLPLHW--PAQECYRYPIVLGYDSH- 255
Cdd:cd22744   66 --MRKPG---TWGGELELQALANALNVPIVVYSE-----------------DGGFLPVSVfgPGPGPSGRPIHLLYTGGn 123


                 ....*
gi 767943502 256 HFVPL 260
Cdd:cd22744  124 HYDAL 128
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 759-784 1.41e-05

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 42.19  E-value: 1.41e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   759 KQRCRAPACDHFGNAKCNGYCNECFQ 784
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 475-500 1.84e-05

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 41.80  E-value: 1.84e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   475 AMKCRSPGCPFTLNVQHNGFCERCHN 500
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 604-629 6.96e-05

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 40.26  E-value: 6.96e-05
                           10        20
                   ....*....|....*....|....*.
gi 767943502   604 TSKCRKAGCVYFGTPENKGFCTLCFI 629
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
OTU_232R-like cd22758
OTU (ovarian tumor) domain of Invertebrate iridescent virus putative ubiquitin thioesterase ...
 99-260 2.00e-04

OTU (ovarian tumor) domain of Invertebrate iridescent virus putative ubiquitin thioesterase 232R and similar proteins; This subfamily contains putative ubiquitin thioesterases 232R from Invertebrate iridescent virus and L96 from Tipula iridescent virus (TIV), Dictyostelium discoideum OTU domain-containing protein DDB_G0284757, and similar proteins. L96 may be involved in TIV genomic DNA packaging in a manner related to the Gag polyproteins of the mammalian viruses. Proteins in this subfamily contain an OTU domain. 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. They belong to the OTU family of cysteine proteases that use a conserved cysteine, histidine, and an aspartate, as the catalytic triad.


Pssm-ID: 438595 [Multi-domain]  Cd Length: 135  Bit Score: 41.87  E-value: 2.00e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502  99 GDGNCLMHATSQ--YMWGVQDTDLVLRKALFSTLKETdtrnfkfrwqleslkSQEFVETGLCYDTRnwNDEWDNLIKMas 176
Cdd:cd22758   13 GDGNCFFHAVSDqlYGNGIEHSHKELRQQAVNYLREN---------------PELYDGFFLSEFDE--EESWEEYLNR-- 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767943502 177 tdtpMARSGlQYNslEEIHIFVLCNILRRPIIVISdkmlrSLESGSNFaplkvggIYLPLHWPAQEcyryPIVLGY-DSH 255
Cdd:cd22758   74 ----MSKDG-TWG--DHIILQAAANLFNVRIVIIS-----SDGSDETT-------IIEPGNSKNGR----TIYLGHiGEN 130


                 ....*
gi 767943502 256 HFVPL 260
Cdd:cd22758  131 HYVSL 135
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 654-679 2.75e-04

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 38.72  E-value: 2.75e-04
                           10        20
                   ....*....|....*....|....*.
gi 767943502   654 TIPCLGRECGTLGSTMFEGYCQKCFI 679
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 384-409 4.36e-04

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 37.95  E-value: 4.36e-04
                           10        20
                   ....*....|....*....|....*.
gi 767943502   384 DVKCETPNCPFFMSVNTQPLCHECSE 409
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
zf-A20 pfam01754
A20-like zinc finger; The A20 Zn-finger of bovine/human Rabex5/rabGEF1 is a Ubiquitin Binding ...
 760-784 7.23e-04

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.


Pssm-ID: 460313  Cd Length: 24  Bit Score: 37.48  E-value: 7.23e-04
                          10        20
                  ....*....|....*....|....*
gi 767943502  760 QRCRAPaCDHFGNAKCNGYCNECFQ 784
Cdd:pfam01754   1 LLCRNG-CGFYGSPATNGLCSKCYK 24
ZnF_A20 smart00259
A20-like zinc fingers; A20- (an inhibitor of cell death)-like zinc fingers. The zinc finger ...
 713-738 2.10e-03

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.


Pssm-ID: 128555  Cd Length: 26  Bit Score: 36.02  E-value: 2.10e-03
                           10        20
                   ....*....|....*....|....*.
gi 767943502   713 RPKCARASCKNILACRSEELCMECQH 738
Cdd:smart00259   1 PIKCRRPGCGFFGNPATEGLCSKCFK 26
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH