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Protein

OTU domain-containing protein 7B

Gene

OTUD7B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Mediates deubiquitination of EGFR. Has deubiquitinating activity toward 'Lys-11', 'Lys-48' or 'Lys-63'-linked polyubiquitin chains. In vitro, has preference for 'Lys-11'-linked polyubiquitin chains; however such data are unsure in vivo. Hydrolyzes both linear and branched forms of polyubiquitin.6 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).1 Publication

Enzyme regulationi

Deubiquitinase activity is inhibited following interaction with PARK7.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei191By similarity1
Active sitei194NucleophileCurated1
Active sitei358Proton acceptorBy similarity1

Regions

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Immunity, Ubl conjugation pathway

Keywords - Ligandi

Metal-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:3.4.19.12)
Alternative name(s):
Cellular zinc finger anti-NF-kappa-B protein
Zinc finger A20 domain-containing protein 1
Zinc finger protein Cezanne
Gene namesi
Name:OTUD7B
Synonyms:ZA20D1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:16683. OTUD7B.

Subcellular locationi

  • Cytoplasm
  • Nucleus

  • Note: Shuttles be cytoplasm and the nucleus in a XPO1/CRM1-dependent manner.

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • nucleus Source: HGNC
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi194C → A: Increased ability to interact with polyubiquitin. 3 Publications1
Mutagenesisi194C → S: Loss of deubiquitinating activity. 3 Publications1
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.

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

BgeeiENSG00000163113.
CleanExiHS_OTUD7B.
ExpressionAtlasiQ6GQQ9. baseline and differential.
GenevisibleiQ6GQQ9. HS.

Organism-specific databases

HPAiHPA027045.

Interactioni

Subunit structurei

Interacts with TRAF3 and TRAF6. Interacts with PARK7, leading to inhibit deubiquitinase activity. Interacts with EGFR, ITCH and NEDD4.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
CCDC50Q8IVM05EBI-527784,EBI-723996
PARK7Q994973EBI-527784,EBI-1164361
PIK3R3Q925693EBI-527784,EBI-79893

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121281. 18 interactors.
DIPiDIP-33805N.
IntActiQ6GQQ9. 14 interactors.
STRINGi9606.ENSP00000358131.

Structurei

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...

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

Motif

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

Sequence similaritiesi

Belongs to the peptidase C64 family.Curated
Contains 1 A20-type zinc finger.PROSITE-ProRule annotation
Contains 1 OTU domain.PROSITE-ProRule annotation

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.
OMAiYPHQDSI.
OrthoDBiEOG091G03R0.
PhylomeDBiQ6GQQ9.
TreeFamiTF323312.

Family and domain databases

InterProiIPR033477. Cezanne-2.
IPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PANTHERiPTHR13367:SF9. PTHR13367:SF9. 1 hit.
PfamiPF02338. OTU. 1 hit.
PF01754. zf-A20. 1 hit.
[Graphical view]
SMARTiSM00259. ZnF_A20. 1 hit.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

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. 18 interactors.
DIPiDIP-33805N.
IntActiQ6GQQ9. 14 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.

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.
GeneCardsiOTUD7B.
HGNCiHGNC:16683. OTUD7B.
HPAiHPA027045.
MIMi611748. gene.
neXtProtiNX_Q6GQQ9.
OpenTargetsiENSG00000264522.
PharmGKBiPA134873802.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4345. Eukaryota.
ENOG410XT8E. LUCA.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000048103.
HOVERGENiHBG050904.
InParanoidiQ6GQQ9.
KOiK11860.
OMAiYPHQDSI.
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.
PROiQ6GQQ9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000163113.
CleanExiHS_OTUD7B.
ExpressionAtlasiQ6GQQ9. baseline and differential.
GenevisibleiQ6GQQ9. HS.

Family and domain databases

InterProiIPR033477. Cezanne-2.
IPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PANTHERiPTHR13367:SF9. PTHR13367:SF9. 1 hit.
PfamiPF02338. OTU. 1 hit.
PF01754. zf-A20. 1 hit.
[Graphical view]
SMARTiSM00259. ZnF_A20. 1 hit.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiOTU7B_HUMAN
AccessioniPrimary (citable) accession number: Q6GQQ9
Secondary accession number(s): B7Z643
, D3DUZ8, Q5SZ60, Q8WWA7, Q9NQ53, Q9UFF4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 31, 2004
Last sequence update: July 19, 2004
Last modified: November 30, 2016
This is version 135 of the entry and version 1 of the sequence. [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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Peptidase families
    Classification of peptidase families and list of entries
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.