Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Tumor necrosis factor alpha-induced protein 3

Gene

Tnfaip3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Ubiquitin-editing enzyme that contains both ubiquitin ligase and deubiquitinase activities. Involved in immune and inflammatory responses signaled by cytokines, such as TNF-alpha and IL-1 beta, or pathogens via Toll-like receptors (TLRs) through terminating NF-kappa-B activity. Essential component of a ubiquitin-editing protein complex, comprising also RNF11, ITCH and TAX1BP1, that ensures the transient nature of inflammatory signaling pathways. In cooperation with TAX1BP1 promotes disassembly of E2-E3 ubiquitin protein ligase complexes in IL-1R and TNFR-1 pathways; affected are at least E3 ligases TRAF6, TRAF2 and BIRC2, and E2 ubiquitin-conjugating enzymes UBE2N and UBE2D3. In cooperation with TAX1BP1 promotes ubiquitination of UBE2N and proteasomal degradation of UBE2N and UBE2D3. Upon TNF stimulation, deubiquitinates 'Lys-63'-polyubiquitin chains on RIPK1 and catalyzes the formation of 'Lys-48'-polyubiquitin chains. This leads to RIPK1 proteasomal degradation and consequently termination of the TNF- or LPS-mediated activation of NF-kappa-B. Deubiquitinates TRAF6 probably acting on 'Lys-63'-linked polyubiquitin. Upon T-cell receptor (TCR)-mediated T-cell activation, deubiquitinates 'Lys-63'-polyubiquitin chains on MALT1 thereby mediating disassociation of the CBM (CARD11:BCL10:MALT1) and IKK complexes and preventing sustained IKK activation. Deubiquitinates NEMO/IKBKG; the function is facilitated by TNIP1 and leads to inhibition of NF-kappa-B activation. Upon stimulation by bacterial peptidoglycans, probably deubiquitinates RIPK2. Can also inhibit I-kappa-B-kinase (IKK) through a non-catalytic mechanism which involves polyubiquitin; polyubiquitin promotes association with IKBKG and prevents IKK MAP3K7-mediated phosphorylation. Targets TRAF2 for lysosomal degradation. In vitro able to deubiquitinate 'Lys-11'-, 'Lys-48'- and 'Lys-63' polyubiquitin chains. Inhibitor of programmed cell death. Has a role in the function of the lymphoid system. Required for LPS-induced production of proinflammatory cytokines and IFN beta in LPS-tolerized macrophages.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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei100By similarity1
Active sitei103NucleophileBy similarity1
Active sitei256Proton acceptorBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri381 – 416A20-type 1PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri464 – 499A20-type 2PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri500 – 533A20-type 3PROSITE-ProRule annotationAdd BLAST34
Zinc fingeri586 – 621A20-type 4PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri636 – 671A20-type 5PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri695 – 730A20-type 6PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri741 – 775A20-type 7PROSITE-ProRule annotationAdd BLAST35

GO - Molecular functioni

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • B-1 B cell homeostasis Source: BHF-UCL
  • cellular response to hydrogen peroxide Source: UniProtKB
  • cellular response to lipopolysaccharide Source: BHF-UCL
  • establishment of protein localization to vacuole Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • marginal zone B cell differentiation Source: BHF-UCL
  • negative regulation of autophagy Source: BHF-UCL
  • negative regulation of B cell activation Source: BHF-UCL
  • negative regulation of CD40 signaling pathway Source: BHF-UCL
  • negative regulation of cell death Source: BHF-UCL
  • negative regulation of chronic inflammatory response Source: BHF-UCL
  • negative regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCL
  • negative regulation of endothelial cell apoptotic process Source: MGI
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: BHF-UCL
  • negative regulation of granuloma formation Source: BHF-UCL
  • negative regulation of heterotypic cell-cell adhesion Source: BHF-UCL
  • negative regulation of I-kappaB kinase/NF-kappaB signaling Source: UniProtKB
  • negative regulation of inflammatory response Source: UniProtKB
  • negative regulation of innate immune response Source: UniProtKB
  • negative regulation of interleukin-1 beta production Source: BHF-UCL
  • negative regulation of interleukin-2 production Source: MGI
  • negative regulation of interleukin-6 production Source: BHF-UCL
  • negative regulation of NF-kappaB transcription factor activity Source: MGI
  • negative regulation of nucleotide-binding oligomerization domain containing 1 signaling pathway Source: BHF-UCL
  • negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway Source: BHF-UCL
  • negative regulation of protein ubiquitination Source: MGI
  • negative regulation of smooth muscle cell proliferation Source: BHF-UCL
  • negative regulation of toll-like receptor 3 signaling pathway Source: MGI
  • negative regulation of toll-like receptor 5 signaling pathway Source: BHF-UCL
  • negative regulation of tumor necrosis factor production Source: BHF-UCL
  • positive regulation of cellular protein catabolic process Source: MGI
  • positive regulation of hepatocyte proliferation Source: BHF-UCL
  • positive regulation of protein catabolic process Source: BHF-UCL
  • protein deubiquitination Source: BHF-UCL
  • protein deubiquitination involved in ubiquitin-dependent protein catabolic process Source: GO_Central
  • protein K11-linked deubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: UniProtKB
  • protein K48-linked ubiquitination Source: UniProtKB
  • protein K63-linked deubiquitination Source: UniProtKB
  • regulation of germinal center formation Source: BHF-UCL
  • regulation of immunoglobulin production Source: BHF-UCL
  • regulation of innate immune response Source: BHF-UCL
  • response to molecule of bacterial origin Source: BHF-UCL
  • response to muramyl dipeptide Source: BHF-UCL
  • response to wounding Source: BHF-UCL
  • tolerance induction to lipopolysaccharide Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Ligase, Protease, Thiol protease

Keywords - Biological processi

Apoptosis, Inflammatory response, Ubl conjugation pathway

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
R-MMU-5357786. TNFR1-induced proapoptotic signaling.
R-MMU-5357905. Regulation of TNFR1 signaling.
R-MMU-5357956. TNFR1-induced NFkappaB signaling pathway.
R-MMU-5689896. Ovarian tumor domain proteases.
R-MMU-936440. Negative regulators of RIG-I/MDA5 signaling.

Names & Taxonomyi

Protein namesi
Recommended name:
Tumor necrosis factor alpha-induced protein 3 (EC:3.4.19.12, EC:6.3.2.-)
Short name:
TNF alpha-induced protein 3
Alternative name(s):
Putative DNA-binding protein A20
Zinc finger protein A20
Gene namesi
Name:Tnfaip3
Synonyms:Tnfip3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 10

Organism-specific databases

MGIiMGI:1196377. Tnfaip3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: MGI
  • extracellular exosome Source: MGI
  • lysosome Source: UniProtKB-SubCell
  • nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Lysosome, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi100D → A: Loss of deubiquitinating activity. 1 Publication1
Mutagenesisi103C → A: Loss of deubiquitinating activity, does not disassemble TRAF6:UBE2N ubiquitin ligase complex, abolioshes TAX1BP1 interaction with UBE2N. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00001887932 – 775Tumor necrosis factor alpha-induced protein 3Add BLAST774

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineBy similarity1
Modified residuei451PhosphoserineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ60769.
MaxQBiQ60769.
PaxDbiQ60769.
PRIDEiQ60769.

PTM databases

iPTMnetiQ60769.
PhosphoSitePlusiQ60769.

Expressioni

Tissue specificityi

Found in most tissues during development. Strikingly high levels are found in lymphoid organs, including the thymus, spleen, and gut-associated lymphoid tissue. Constitutively expressed in immature and mature thymocyte subpopulations as well as in resting peripheral T-cells; activation of these leads to down-regulation.

Inductioni

By cytokines. TNF-alpha may regulate expression in the thymus. Up-regulated in presence of reactive oxygen species (ROS), like H2O2, in LPS-tolerized macrophages.1 Publication

Gene expression databases

BgeeiENSMUSG00000019850.
CleanExiMM_TNFAIP3.
ExpressionAtlasiQ60769. baseline and differential.
GenevisibleiQ60769. MM.

Interactioni

Subunit structurei

Homodimer. Interacts with TNIP1, TAX1BP1 and TRAF2. Interacts with RNF11, ITCH and TAX1BP1 only after TNF stimulation; these interaction are transient and they are lost after 1 hour of stimulation with TNF (By similarity). Interacts with YWHAZ and YWHAH. Interacts with IKBKG; the interaction is induced by TNF stimulation and by polyubiquitin. Interacts with RIPK1. Interacts with UBE2N; the interaction requires TAX1BP1. Interacts with TRAF6 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Tnip1Q9WUU83EBI-646595,EBI-6126152
Traf2P394293EBI-646595,EBI-520016

GO - Molecular functioni

Protein-protein interaction databases

BioGridi204243. 18 interactors.
DIPiDIP-41120N.
IntActiQ60769. 6 interactors.
MINTiMINT-97373.
STRINGi10090.ENSMUSP00000019997.

Structurei

Secondary structure

1775
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni10 – 14Combined sources5
Helixi15 – 24Combined sources10
Helixi26 – 28Combined sources3
Beta strandi39 – 42Combined sources4
Helixi43 – 45Combined sources3
Helixi58 – 68Combined sources11
Helixi71 – 78Combined sources8
Turni79 – 81Combined sources3
Beta strandi93 – 95Combined sources3
Helixi103 – 113Combined sources11
Helixi121 – 132Combined sources12
Helixi136 – 145Combined sources10
Turni146 – 150Combined sources5
Turni164 – 166Combined sources3
Helixi167 – 174Combined sources8
Beta strandi183 – 185Combined sources3
Helixi193 – 203Combined sources11
Beta strandi207 – 209Combined sources3
Beta strandi231 – 233Combined sources3
Helixi240 – 242Combined sources3
Beta strandi248 – 255Combined sources8
Beta strandi257 – 261Combined sources5
Beta strandi272 – 279Combined sources8
Beta strandi282 – 285Combined sources4
Helixi293 – 297Combined sources5
Helixi299 – 302Combined sources4
Beta strandi305 – 307Combined sources3
Beta strandi312 – 315Combined sources4
Beta strandi322 – 325Combined sources4
Beta strandi327 – 329Combined sources3
Turni337 – 339Combined sources3
Helixi342 – 356Combined sources15

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DQ6X-ray2.80A/B1-360[»]
ProteinModelPortaliQ60769.
SMRiQ60769.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini92 – 263OTUPROSITE-ProRule annotationAdd BLAST172
Repeati286 – 3171Add BLAST32
Repeati324 – 3562Add BLAST33

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni58 – 300TRAF-bindingBy similarityAdd BLAST243
Regioni157 – 159Interaction with ubiquitinBy similarity3
Regioni190 – 192Interaction with ubiquitinBy similarity3
Regioni224 – 227Interaction with ubiquitinBy similarity4
Regioni286 – 3562 X approximate repeatsAdd BLAST71
Regioni369 – 775Interaction with TNIP11 PublicationAdd BLAST407
Regioni386 – 445Interaction with RIPK1By similarityAdd BLAST60
Regioni590 – 640Required for proteosomal degradation of UBE2N and UBE2D3, TRAF6 deubiquitination, and TAX1BP1 interaction with UBE2N1 PublicationAdd BLAST51
Regioni591 – 775Sufficient for inhibitory activity of TNF-induced NF-kappa-B activityAdd BLAST185
Regioni682 – 775Required for lysosomal localization and for TRAF2 lysosomal degradationBy similarityAdd BLAST94

Domaini

The A20-type zinc fingers mediate the ubiquitin ligase activity. The A20-type zinc finger 4 selectively recognizes 'Lys-63'-linked polyubiquitin. The A20-type zinc finger 4-7 are sufficient to bind polyubiquitin (By similarity).By similarity
The OTU domain mediates the deubiquitinase activity.By similarity

Sequence similaritiesi

Belongs to the peptidase C64 family.Curated
Contains 7 A20-type zinc fingers.PROSITE-ProRule annotation
Contains 1 OTU domain.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri381 – 416A20-type 1PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri464 – 499A20-type 2PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri500 – 533A20-type 3PROSITE-ProRule annotationAdd BLAST34
Zinc fingeri586 – 621A20-type 4PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri636 – 671A20-type 5PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri695 – 730A20-type 6PROSITE-ProRule annotationAdd BLAST36
Zinc fingeri741 – 775A20-type 7PROSITE-ProRule annotationAdd BLAST35

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410IQZK. Eukaryota.
ENOG41117NJ. LUCA.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000133004.
HOVERGENiHBG059260.
InParanoidiQ60769.
KOiK11859.
OMAiETTAMKC.
OrthoDBiEOG091G01QE.
TreeFamiTF323312.

Family and domain databases

InterProiIPR033478. A20.
IPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PANTHERiPTHR13367:SF3. PTHR13367:SF3. 1 hit.
PfamiPF02338. OTU. 1 hit.
PF01754. zf-A20. 4 hits.
[Graphical view]
SMARTiSM00259. ZnF_A20. 7 hits.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 7 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q60769-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAEQLLPQAL YLSNMRKAVK IRERTPEDIF KPTNGIIYHF KTMHRYTLEM
60 70 80 90 100
FRTCQFCPQF REIIHKALID RSVQASLESQ KKLNWCREVR KLVALKTNGD
110 120 130 140 150
GNCLMHAACQ YMWGVQDTDL VLRKALCSTL KETDTRNFKF RWQLESLKSQ
160 170 180 190 200
EFVETGLCYD TRNWNDEWDN LVKMASADTP AARSGLQYNS LEEIHIFVLS
210 220 230 240 250
NILRRPIIVI SDKMLRSLES GSNFAPLKVG GIYLPLHWPA QECYRYPIVL
260 270 280 290 300
GYDSQHFVPL VTLKDSGPEL RAVPLVNRDR GRFEDLKVHF LTDPENEMKE
310 320 330 340 350
KLLKEYLIVM EIPVQGWDHG TTHLINAAKL DEANLPKEIN LVDDYFELVQ
360 370 380 390 400
HEYKKWQENS DQARRAAHAQ NPLEPSTPQL SLMDIKCETP NCPFFMSVNT
410 420 430 440 450
QPLCHECSER RQKNQSKLPK LNSKLGPEGL PGVGLGSSNW SPEETAGGPH
460 470 480 490 500
SAPPTAPSLF LFSETTAMKC RSPGCPFTLN VQHNGFCERC HARQINASHT
510 520 530 540 550
ADPGKCQACL QDVTRTFNGI CSTCFKRTTA EPSSSLTSSI PASCHQRSKS
560 570 580 590 600
DPSQLIQSLT PHSCHRTGNV SPSGCLSQAA RTPGDRAGTS KCRKAGCMYF
610 620 630 640 650
GTPENKGFCT LCFIEYRENK QSVTASEKAG SPAPRFQNNV PCLGRECGTL
660 670 680 690 700
GSTMFEGYCQ KCFIEAQNQR FHEARRTEEQ LRSSQHRDMP RTTQVASRLK
710 720 730 740 750
CARASCKNIL ACRSEELCME CQHLSQRVGS VAHRGEPTPE EPPKQRCRAP
760 770
ACDHFGNAKC NGYCNECYQF KQMYG
Length:775
Mass (Da):87,654
Last modified:July 27, 2011 - v2
Checksum:i32349928908B3185
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti627E → A in AAC52153 (PubMed:7836754).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19463 mRNA. Translation: AAC52153.1.
AK151921 mRNA. Translation: BAE30799.1.
CCDSiCCDS23715.1.
PIRiI49237.
RefSeqiNP_033423.3. NM_009397.3.
XP_006512765.1. XM_006512702.2.
UniGeneiMm.116683.

Genome annotation databases

EnsembliENSMUST00000019997; ENSMUSP00000019997; ENSMUSG00000019850.
ENSMUST00000105527; ENSMUSP00000101167; ENSMUSG00000019850.
GeneIDi21929.
KEGGimmu:21929.
UCSCiuc007ena.3. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U19463 mRNA. Translation: AAC52153.1.
AK151921 mRNA. Translation: BAE30799.1.
CCDSiCCDS23715.1.
PIRiI49237.
RefSeqiNP_033423.3. NM_009397.3.
XP_006512765.1. XM_006512702.2.
UniGeneiMm.116683.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DQ6X-ray2.80A/B1-360[»]
ProteinModelPortaliQ60769.
SMRiQ60769.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204243. 18 interactors.
DIPiDIP-41120N.
IntActiQ60769. 6 interactors.
MINTiMINT-97373.
STRINGi10090.ENSMUSP00000019997.

PTM databases

iPTMnetiQ60769.
PhosphoSitePlusiQ60769.

Proteomic databases

EPDiQ60769.
MaxQBiQ60769.
PaxDbiQ60769.
PRIDEiQ60769.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000019997; ENSMUSP00000019997; ENSMUSG00000019850.
ENSMUST00000105527; ENSMUSP00000101167; ENSMUSG00000019850.
GeneIDi21929.
KEGGimmu:21929.
UCSCiuc007ena.3. mouse.

Organism-specific databases

CTDi7128.
MGIiMGI:1196377. Tnfaip3.

Phylogenomic databases

eggNOGiENOG410IQZK. Eukaryota.
ENOG41117NJ. LUCA.
GeneTreeiENSGT00530000062989.
HOGENOMiHOG000133004.
HOVERGENiHBG059260.
InParanoidiQ60769.
KOiK11859.
OMAiETTAMKC.
OrthoDBiEOG091G01QE.
TreeFamiTF323312.

Enzyme and pathway databases

ReactomeiR-MMU-168638. NOD1/2 Signaling Pathway.
R-MMU-5357786. TNFR1-induced proapoptotic signaling.
R-MMU-5357905. Regulation of TNFR1 signaling.
R-MMU-5357956. TNFR1-induced NFkappaB signaling pathway.
R-MMU-5689896. Ovarian tumor domain proteases.
R-MMU-936440. Negative regulators of RIG-I/MDA5 signaling.

Miscellaneous databases

PROiQ60769.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000019850.
CleanExiMM_TNFAIP3.
ExpressionAtlasiQ60769. baseline and differential.
GenevisibleiQ60769. MM.

Family and domain databases

InterProiIPR033478. A20.
IPR003323. OTU_dom.
IPR002653. Znf_A20.
[Graphical view]
PANTHERiPTHR13367:SF3. PTHR13367:SF3. 1 hit.
PfamiPF02338. OTU. 1 hit.
PF01754. zf-A20. 4 hits.
[Graphical view]
SMARTiSM00259. ZnF_A20. 7 hits.
[Graphical view]
PROSITEiPS50802. OTU. 1 hit.
PS51036. ZF_A20. 7 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTNAP3_MOUSE
AccessioniPrimary (citable) accession number: Q60769
Secondary accession number(s): Q3U968
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 27, 2011
Last modified: November 2, 2016
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Peptidase families
    Classification of peptidase families and list of entries
  4. 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.