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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 (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

Enzyme 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

  • adaptive immune response Source: UniProtKB-KW
  • immune response Source: GO_Central
  • mucosal immune response Source: UniProtKB
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: HGNC
  • negative regulation of interleukin-8 production Source: ParkinsonsUK-UCL
  • negative regulation of protein localization to nucleus Source: ParkinsonsUK-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: ParkinsonsUK-UCL
  • protein deubiquitination Source: Reactome
  • protein deubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein K11-linked deubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: ParkinsonsUK-UCL
  • protein K63-linked deubiquitination Source: UniProtKB

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

HGNCiHGNC:16683. OTUD7B.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HGNC
  • cytosol Source: Reactome
  • nucleus Source: HGNC

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.

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 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

Show more details

GO - Molecular functioni

Protein-protein interaction databases

BioGridi121281. 19 interactors.
DIPiDIP-33805N.
IntActiQ6GQQ9. 22 interactors.
STRINGi9606.ENSP00000358131.

Structurei

Secondary structure

1843
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi129 – 135Combined sources7
Beta strandi141 – 143Combined sources3
Helixi144 – 152Combined sources9
Helixi158 – 166Combined sources9
Beta strandi169 – 171Combined sources3
Helixi173 – 176Combined sources4
Beta strandi177 – 179Combined sources3
Beta strandi183 – 186Combined sources4
Beta strandi190 – 192Combined sources3
Helixi194 – 199Combined sources6
Helixi200 – 203Combined sources4
Turni206 – 208Combined sources3
Helixi209 – 222Combined sources14
Helixi227 – 243Combined sources17
Turni244 – 246Combined sources3
Helixi251 – 266Combined sources16
Helixi294 – 304Combined sources11
Beta strandi308 – 311Combined sources4
Beta strandi314 – 317Combined sources4
Beta strandi323 – 326Combined sources4
Beta strandi331 – 333Combined sources3
Helixi340 – 342Combined sources3
Beta strandi348 – 353Combined sources6
Beta strandi356 – 362Combined sources7
Helixi363 – 366Combined sources4
Beta strandi373 – 378Combined sources6
Helixi393 – 395Combined sources3
Helixi401 – 406Combined sources6
Helixi410 – 426Combined sources17
Beta strandi430 – 433Combined sources4

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
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

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

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.

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: July 5, 2017
This is version 141 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. 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