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Protein

OTU domain-containing protein 7B

Gene

OTUD7B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Negative regulator of the non-canonical NF-kappa-B pathway that acts by mediating deubiquitination of TRAF3, an inhibitor of the NF-kappa-B pathway, thereby acting as a negative regulator of B-cell responses. In response to non-canonical NF-kappa-B stimuli, deubiquitinates 'Lys-48'-linked polyubiquitin chains of TRAF3, preventing TRAF3 proteolysis and over-activation of non-canonical NF-kappa-B. Negatively regulates mucosal immunity against infections (By similarity). Deubiquitinates ZAP70, and thereby regulates T cell receptor (TCR) signaling that leads to the activation of NF-kappa-B (PubMed:26903241). Plays a role in T cell homeostasis and is required for normal T cell responses, including production of IFNG and IL2 (By similarity). Mediates deubiquitination of EGFR (PubMed:22179831). Has deubiquitinating activity toward 'Lys-11', 'Lys-48' and 'Lys-63'-linked polyubiquitin chains (PubMed:27732584). Has a much higher catalytic rate with 'Lys-11'-linked polyubiquitin chains (in vitro); however the physiological significance of these data are unsure (PubMed:27732584). Hydrolyzes both linear and branched forms of polyubiquitin.By similarity7 Publications

Catalytic activityi

Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal).6 Publications

Activity regulationi

Deubiquitinase activity is inhibited following interaction with PARK7.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei191By similarity1
Active sitei194Nucleophile4 Publications1
Sitei197Stabilizes the conformation of the regulatory loop1 Publication1
Active sitei358Proton acceptor1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri796 – 831A20-typePROSITE-ProRule annotationAdd BLAST36

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Thiol protease
Biological processAdaptive immunity, Immunity, Ubl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5689896 Ovarian tumor domain proteases
SignaLinkiQ6GQQ9

Protein family/group databases

MEROPSiC64.001

Names & Taxonomyi

Protein namesi
Recommended name:
OTU domain-containing protein 7B (EC:3.4.19.126 Publications)
Alternative name(s):
Cellular zinc finger anti-NF-kappa-B protein1 Publication
Short name:
Cezanne3 Publications
Zinc finger A20 domain-containing protein 1
Zinc finger protein CezanneCurated
Gene namesi
Name:OTUD7B
Synonyms:ZA20D1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000264522.5
HGNCiHGNC:16683 OTUD7B
MIMi611748 gene
neXtProtiNX_Q6GQQ9

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi155 – 156LI → GG: Reduces deubiquitinating activity. 1 Publication2
Mutagenesisi157E → K: Reduces deubiquitinating activity with 'Lys-11'-linked ubiquitin chains; no effect on cleavage of 'Lys-48'-linked and 'Lys-63'-linked ubiquitin chains. 1 Publication1
Mutagenesisi193N → L or M: Loss of deubiquitinating activity due to stabilization of the autoinhibited conformation. 1 Publication1
Mutagenesisi194C → A: Loss of deubiquitinating activity. Increased ability to interact with polyubiquitin. 4 Publications1
Mutagenesisi194C → S: Loss of deubiquitinating activity. 3 Publications1
Mutagenesisi194C → S: Loss of deubiquitinating activity; when associated with N-358. 1 Publication1
Mutagenesisi197H → A or E: Strongly reduces deubiquitinating activity. 1 Publication1
Mutagenesisi197H → D or N: Reduces deubiquitinating activity. 1 Publication1
Mutagenesisi210D → A: Reduces deubiquitinating activity. 1 Publication1
Mutagenesisi295E → K: Loss of deubiquitinating activity. 1 Publication1
Mutagenesisi358H → A: Loss of deubiquitinating activity. 1 Publication1
Mutagenesisi358H → N: Loss of deubiquitinating activity; when associated with S-194. 1 Publication1
Mutagenesisi809F → A: Does not affect interaction with EGFR. 1 Publication1
Mutagenesisi810Y → A: Impairs interaction with EGFR. 1 Publication1

Organism-specific databases

DisGeNETi56957
OpenTargetsiENSG00000264522
PharmGKBiPA134873802

Polymorphism and mutation databases

DMDMi51701318

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001887881 – 843OTU domain-containing protein 7BAdd BLAST843

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei100PhosphoserineCombined sources1
Modified residuei464PhosphoserineBy similarity1
Modified residuei467PhosphoserineCombined sources1
Modified residuei471PhosphoserineBy similarity1
Modified residuei729PhosphothreonineBy similarity1

Post-translational modificationi

Phosphorylated by EGFR.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ6GQQ9
MaxQBiQ6GQQ9
PaxDbiQ6GQQ9
PeptideAtlasiQ6GQQ9
PRIDEiQ6GQQ9
ProteomicsDBi66318

PTM databases

iPTMnetiQ6GQQ9
PhosphoSitePlusiQ6GQQ9

Expressioni

Tissue specificityi

Widely expressed. Abundant in kidney, heart and fetal liver. Expressed differentially among B-cells at distinct developmental stages. Higher expression seen in primary immature B-cells as compared to the mature cells.2 Publications

Inductioni

By TNF-alpha.1 Publication

Gene expression databases

BgeeiENSG00000264522 Expressed in 203 organ(s), highest expression level in brain
CleanExiHS_OTUD7B
ExpressionAtlasiQ6GQQ9 baseline and differential
GenevisibleiQ6GQQ9 HS

Organism-specific databases

HPAiHPA027045

Interactioni

Subunit structurei

Interacts with ZAP70 in activated T cells, but not in resting T cells (PubMed:26903241). Interacts with TRAF3 (By similarity). Interacts with TRAF6 (PubMed:11463333). Interacts with PARK7, leading to inhibit deubiquitinase activity (PubMed:21097510). Interacts with EGFR, ITCH and NEDD4 (PubMed:22179831).By similarity4 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121281, 20 interactors
DIPiDIP-33805N
IntActiQ6GQQ9, 24 interactors
STRINGi9606.ENSP00000358131

Structurei

Secondary structure

1843
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ6GQQ9
SMRiQ6GQQ9
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini183 – 365OTUPROSITE-ProRule annotationAdd BLAST183

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni152 – 401TRAF-bindingAdd BLAST250
Regioni167 – 440CatalyticAdd BLAST274
Regioni187 – 193Regulatory loop1 Publication7

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi483 – 498Nuclear localization signalSequence analysisAdd BLAST16

Domaini

The protein undergoes a significant conformation change upon binding to ubiquitinated substrates. The loop that precedes the active site is in an autoinhibitory conformation in the apoprotein. Ubiquitin binding leads to a conformation change; the loop is stabilized in a catalytically competent conformation with the result that the active site Cys can form the reaction state intermediate.1 Publication

Sequence similaritiesi

Belongs to the peptidase C64 family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri796 – 831A20-typePROSITE-ProRule annotationAdd BLAST36

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4345 Eukaryota
ENOG410XT8E LUCA
GeneTreeiENSGT00530000062989
HOGENOMiHOG000048103
HOVERGENiHBG050904
InParanoidiQ6GQQ9
KOiK11860
OMAiYATFPRQ
OrthoDBiEOG091G03R0
PhylomeDBiQ6GQQ9
TreeFamiTF323312

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR002653 Znf_A20
PfamiView protein in Pfam
PF02338 OTU, 1 hit
PF01754 zf-A20, 1 hit
SMARTiView protein in SMART
SM00259 ZnF_A20, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit
PS51036 ZF_A20, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q6GQQ9-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide
        10         20         30         40         50
MTLDMDAVLS DFVRSTGAEP GLARDLLEGK NWDVNAALSD FEQLRQVHAG
60 70 80 90 100
NLPPSFSEGS GGSRTPEKGF SDREPTRPPR PILQRQDDIV QEKRLSRGIS
110 120 130 140 150
HASSSIVSLA RSHVSSNGGG GGSNEHPLEM PICAFQLPDL TVYNEDFRSF
160 170 180 190 200
IERDLIEQSM LVALEQAGRL NWWVSVDPTS QRLLPLATTG DGNCLLHAAS
210 220 230 240 250
LGMWGFHDRD LMLRKALYAL MEKGVEKEAL KRRWRWQQTQ QNKESGLVYT
260 270 280 290 300
EDEWQKEWNE LIKLASSEPR MHLGTNGANC GGVESSEEPV YESLEEFHVF
310 320 330 340 350
VLAHVLRRPI VVVADTMLRD SGGEAFAPIP FGGIYLPLEV PASQCHRSPL
360 370 380 390 400
VLAYDQAHFS ALVSMEQKEN TKEQAVIPLT DSEYKLLPLH FAVDPGKGWE
410 420 430 440 450
WGKDDSDNVR LASVILSLEV KLHLLHSYMN VKWIPLSSDA QAPLAQPESP
460 470 480 490 500
TASAGDEPRS TPESGDSDKE SVGSSSTSNE GGRRKEKSKR DREKDKKRAD
510 520 530 540 550
SVANKLGSFG KTLGSKLKKN MGGLMHSKGS KPGGVGTGLG GSSGTETLEK
560 570 580 590 600
KKKNSLKSWK GGKEEAAGDG PVSEKPPAES VGNGGSKYSQ EVMQSLSILR
610 620 630 640 650
TAMQGEGKFI FVGTLKMGHR HQYQEEMIQR YLSDAEERFL AEQKQKEAER
660 670 680 690 700
KIMNGGIGGG PPPAKKPEPD AREEQPTGPP AESRAMAFST GYPGDFTIPR
710 720 730 740 750
PSGGGVHCQE PRRQLAGGPC VGGLPPYATF PRQCPPGRPY PHQDSIPSLE
760 770 780 790 800
PGSHSKDGLH RGALLPPPYR VADSYSNGYR EPPEPDGWAG GLRGLPPTQT
810 820 830 840
KCKQPNCSFY GHPETNNFCS CCYREELRRR EREPDGELLV HRF
Length:843
Mass (Da):92,526
Last modified:July 19, 2004 - v1
Checksum:i6D386C864B12EE57
GO
Isoform 2 (identifier: Q6GQQ9-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     805-833: Missing.

Show »
Length:814
Mass (Da):88,947
Checksum:i26C3BFE215BEC0D3
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
Q5SZ59Q5SZ59_HUMAN
OTU domain containing 7B
OTUD7B RP11-212K13.2-003
427Annotation score:

Sequence cautioni

The sequence CAB97494 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti243K → E in AAH20622 (PubMed:15489334).Curated1
Sequence conflicti421K → R in AAH20622 (PubMed:15489334).Curated1
Sequence conflicti791G → S in BAH13129 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046015805 – 833Missing in isoform 2. 1 PublicationAdd BLAST29

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ293573 mRNA Translation: CAB97494.1 Different initiation.
AK299790 mRNA Translation: BAH13129.1
AL590487 Genomic DNA Translation: CAI12651.1
CH471121 Genomic DNA Translation: EAW53586.1
CH471121 Genomic DNA Translation: EAW53587.1
BC020622 mRNA Translation: AAH20622.1
BC072681 mRNA Translation: AAH72681.1
AL122102 mRNA Translation: CAB59268.1
CCDSiCCDS72903.1 [Q6GQQ9-1]
PIRiT34535
RefSeqiNP_064590.2, NM_020205.3 [Q6GQQ9-1]
UniGeneiHs.98322

Genome annotation databases

EnsembliENST00000581312; ENSP00000462729; ENSG00000264522 [Q6GQQ9-1]
GeneIDi56957
KEGGihsa:56957
UCSCiuc001etn.5 human [Q6GQQ9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ293573 mRNA Translation: CAB97494.1 Different initiation.
AK299790 mRNA Translation: BAH13129.1
AL590487 Genomic DNA Translation: CAI12651.1
CH471121 Genomic DNA Translation: EAW53586.1
CH471121 Genomic DNA Translation: EAW53587.1
BC020622 mRNA Translation: AAH20622.1
BC072681 mRNA Translation: AAH72681.1
AL122102 mRNA Translation: CAB59268.1
CCDSiCCDS72903.1 [Q6GQQ9-1]
PIRiT34535
RefSeqiNP_064590.2, NM_020205.3 [Q6GQQ9-1]
UniGeneiHs.98322

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5LRUX-ray2.20A129-438[»]
5LRVX-ray2.80A129-438[»]
5LRWX-ray2.00A/C129-266[»]
A/C292-438[»]
ProteinModelPortaliQ6GQQ9
SMRiQ6GQQ9
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121281, 20 interactors
DIPiDIP-33805N
IntActiQ6GQQ9, 24 interactors
STRINGi9606.ENSP00000358131

Protein family/group databases

MEROPSiC64.001

PTM databases

iPTMnetiQ6GQQ9
PhosphoSitePlusiQ6GQQ9

Polymorphism and mutation databases

DMDMi51701318

Proteomic databases

EPDiQ6GQQ9
MaxQBiQ6GQQ9
PaxDbiQ6GQQ9
PeptideAtlasiQ6GQQ9
PRIDEiQ6GQQ9
ProteomicsDBi66318

Protocols and materials databases

DNASUi56957
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000581312; ENSP00000462729; ENSG00000264522 [Q6GQQ9-1]
GeneIDi56957
KEGGihsa:56957
UCSCiuc001etn.5 human [Q6GQQ9-1]

Organism-specific databases

CTDi56957
DisGeNETi56957
EuPathDBiHostDB:ENSG00000264522.5
GeneCardsiOTUD7B
HGNCiHGNC:16683 OTUD7B
HPAiHPA027045
MIMi611748 gene
neXtProtiNX_Q6GQQ9
OpenTargetsiENSG00000264522
PharmGKBiPA134873802
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4345 Eukaryota
ENOG410XT8E LUCA
GeneTreeiENSGT00530000062989
HOGENOMiHOG000048103
HOVERGENiHBG050904
InParanoidiQ6GQQ9
KOiK11860
OMAiYATFPRQ
OrthoDBiEOG091G03R0
PhylomeDBiQ6GQQ9
TreeFamiTF323312

Enzyme and pathway databases

ReactomeiR-HSA-5357786 TNFR1-induced proapoptotic signaling
R-HSA-5357905 Regulation of TNFR1 signaling
R-HSA-5357956 TNFR1-induced NFkappaB signaling pathway
R-HSA-5689896 Ovarian tumor domain proteases
SignaLinkiQ6GQQ9

Miscellaneous databases

ChiTaRSiOTUD7B human
GeneWikiiOTUD7B
GenomeRNAii56957
PROiPR:Q6GQQ9
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000264522 Expressed in 203 organ(s), highest expression level in brain
CleanExiHS_OTUD7B
ExpressionAtlasiQ6GQQ9 baseline and differential
GenevisibleiQ6GQQ9 HS

Family and domain databases

InterProiView protein in InterPro
IPR003323 OTU_dom
IPR002653 Znf_A20
PfamiView protein in Pfam
PF02338 OTU, 1 hit
PF01754 zf-A20, 1 hit
SMARTiView protein in SMART
SM00259 ZnF_A20, 1 hit
PROSITEiView protein in PROSITE
PS50802 OTU, 1 hit
PS51036 ZF_A20, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiOTU7B_HUMAN
AccessioniPrimary (citable) accession number: Q6GQQ9
Secondary accession number(s): B7Z643
, D3DUZ8, Q5SZ60, Q8WWA7, Q9NQ53, Q9UFF4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: July 19, 2004
Last modified: November 7, 2018
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
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Main funding by: National Institutes of Health

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