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Protein

Ubiquitin thioesterase OTUB1

Gene

OTUB1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Hydrolase that can specifically remove 'Lys-48'-linked conjugated ubiquitin from proteins and plays an important regulatory role at the level of protein turnover by preventing degradation. Regulator of T-cell anergy, a phenomenon that occurs when T-cells are rendered unresponsive to antigen rechallenge and no longer respond to their cognate antigen. Acts via its interaction with RNF128/GRAIL, a crucial inductor of CD4 T-cell anergy. Isoform 1 destabilizes RNF128, leading to prevent anergy. In contrast, isoform 2 stabilizes RNF128 and promotes anergy. Surprisingly, it regulates RNF128-mediated ubiquitination, but does not deubiquitinate polyubiquitinated RNF128. Deubiquitinates estrogen receptor alpha (ESR1). Mediates deubiquitination of 'Lys-48'-linked polyubiquitin chains, but not 'Lys-63'-linked polyubiquitin chains. Not able to cleave di-ubiquitin. Also capable of removing NEDD8 from NEDD8 conjugates, but with a much lower preference compared to 'Lys-48'-linked ubiquitin.
Plays a key non-catalytic role in DNA repair regulation by inhibiting activity of RNF168, an E3 ubiquitin-protein ligase that promotes accumulation of 'Lys-63'-linked histone H2A and H2AX at DNA damage sites. Inhibits RNF168 independently of ubiquitin thioesterase activity by binding and inhibiting UBE2N/UBC13, the E2 partner of RNF168, thereby limiting spreading of 'Lys-63'-linked histone H2A and H2AX marks. Inhibition occurs by binding to free ubiquitin: free ubiquitin acts as an allosteric regulator that increases affinity for UBE2N/UBC13 and disrupts interaction with UBE2V1. The OTUB1-UBE2N/UBC13-free ubiquitin complex adopts a configuration that mimics a cleaved 'Lys48'-linked di-ubiquitin chain.

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

By free ubiquitin: binding of free ubiquitin triggers conformational changes in the OTU domain and formation of a ubiquitin-binding helix in the N-terminus, promoting binding of the conjugated donor ubiquitin in UBE2N/UBC13 to OTUB1.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei23Required for proximal ubiquitin-binding1 Publication1
Active sitei88Combined sources1 Publication1
Active sitei91Nucleophile1 Publication1 Publication1
Binding sitei221Free ubiquitin1 Publication1
Binding sitei235Free ubiquitin1 Publication1
Binding sitei237Free ubiquitin1 Publication1
Binding sitei261Free ubiquitin1 Publication1
Active sitei2651 Publication1 Publication1
Binding sitei266Free ubiquitinCombined sources2 Publications1

GO - Molecular functioni

  • NEDD8-specific protease activity Source: UniProtKB
  • thiol-dependent ubiquitin-specific protease activity Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

  • adaptive immune response Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • cellular response to interleukin-1 Source: Ensembl
  • DNA repair Source: UniProtKB-KW
  • negative regulation of double-strand break repair Source: UniProtKB
  • negative regulation of histone H2A K63-linked ubiquitination Source: UniProtKB
  • protein K48-linked deubiquitination Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Adaptive immunity, DNA damage, DNA repair, Immunity, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
SIGNORiQ96FW1.

Protein family/group databases

MEROPSiC65.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Ubiquitin thioesterase OTUB1 (EC:3.4.19.121 Publication)
Alternative name(s):
Deubiquitinating enzyme OTUB1
OTU domain-containing ubiquitin aldehyde-binding protein 1
Otubain-1
Short name:
hOTU1
Ubiquitin-specific-processing protease OTUB1
Gene namesi
Name:OTUB1
Synonyms:OTB1, OTU1
ORF Names:HSPC263
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:23077. OTUB1.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23C → A: Abolishes only ubiquitin-vinylsulfone adduct formation. 1 Publication1
Mutagenesisi33Q → R: Impairs inhibition of UBE2N/UBC13. 1 Publication1
Mutagenesisi37I → T: Impairs inhibition of UBE2N/UBC13. 1 Publication1
Mutagenesisi39Q → L: Does not affect activity in DNA repair and ability to inhibit UBE2N/UBC13. 1 Publication1
Mutagenesisi87P → G: Slightly improves ability to cleave 'K63'-linked ubiquitin. 1 Publication1
Mutagenesisi88D → E: Abolishes hydrolase activity in vitro. Abolishes ability to inhibit RNF168; when associated with S-91 and A-265. 2 Publications1
Mutagenesisi91C → A: Prevents RNF128 autoubiquitination, and stabilizes RNF128 in vivo. Abolishes both ubiquitin-binding and adduct formation with ubiquitin-vinylsulfone. 7 Publications1
Mutagenesisi91C → S: Abolishes hydrolase activity in vitro. Does not affect ability to inhibit RNF168. Abolishes ability to inhibit RNF168; when associated with A-88 and A-265. 7 Publications1
Mutagenesisi116A → T: Does not affect ability to inhibit UBE2N/UBC13. 1 Publication1
Mutagenesisi134T → R: Impairs inhibition of UBE2N/UBC13. 1 Publication1
Mutagenesisi137D → G: Impairs inhibition of UBE2N/UBC13. 1 Publication1
Mutagenesisi176R → L: No effect on RNF128. 1 Publication1
Mutagenesisi190F → S: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. 1 Publication1
Mutagenesisi212C → A: No effect on RNF128. 2 Publications1
Mutagenesisi261Y → H: Impairs inhibition of UBE2N/UBC13. 1 Publication1
Mutagenesisi263P → L: Fails to inhibit ubiquitin conjugation by UBE2N/UBC13. 1 Publication1
Mutagenesisi265H → A: Abolishes ability to inhibit RNF168; when associated with A-88 and S-91. 2 Publications1
Mutagenesisi265H → R: Abolishes hydrolase activity in vitro. 2 Publications1

Organism-specific databases

DisGeNETi55611.
OpenTargetsiENSG00000167770.
PharmGKBiPA134988141.

Polymorphism and mutation databases

BioMutaiOTUB1.
DMDMi44888286.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002210082 – 271Ubiquitin thioesterase OTUB1Add BLAST270

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei16PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96FW1.
MaxQBiQ96FW1.
PaxDbiQ96FW1.
PeptideAtlasiQ96FW1.
PRIDEiQ96FW1.

PTM databases

iPTMnetiQ96FW1.
PhosphoSitePlusiQ96FW1.
SwissPalmiQ96FW1.

Expressioni

Tissue specificityi

Isoform 1 is ubiquitous. Isoform 2 is expressed only in lymphoid tissues such as tonsils, lymph nodes and spleen, as well as peripheral blood mononuclear cells.2 Publications

Gene expression databases

BgeeiENSG00000167770.
CleanExiHS_OTUB1.
ExpressionAtlasiQ96FW1. baseline and differential.
GenevisibleiQ96FW1. HS.

Organism-specific databases

HPAiCAB072836.
HPA039176.

Interactioni

Subunit structurei

Isoform 1 and isoform 2 interact with RNF128. Isoform 1 forms a ternary complex with RNF128 and USP8. Isoform 1 interacts with the C-terminal UCH catalytic domain of USP8. Isoform 2 does not associate with USP8. Interacts with FUS, ESR1 and RACK1. Interacts with UBE2N/UBC13.6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BIRC2Q134903EBI-1058491,EBI-514538
HIF1ANQ9NWT64EBI-1058491,EBI-745632
MDM2Q009875EBI-1058491,EBI-389668
TP53P046378EBI-1058491,EBI-366083
UBE2D1P516688EBI-1058491,EBI-743540
UBE2D2P628379EBI-1058491,EBI-347677
UBE2D3P610779EBI-1058491,EBI-348268
UBE2D4Q9Y2X83EBI-1058491,EBI-745527
UBE2E1P519653EBI-1058491,EBI-348546
ypkAQ569215EBI-1058491,EBI-8022937From a different organism.
ypkAQ9RI123EBI-1058491,EBI-2849107From a different organism.

GO - Molecular functioni

  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi120751. 207 interactors.
DIPiDIP-41158N.
IntActiQ96FW1. 328 interactors.
MINTiMINT-5001867.
STRINGi9606.ENSP00000402551.

Structurei

Secondary structure

1271
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi24 – 44Combined sources21
Beta strandi47 – 53Combined sources7
Helixi54 – 60Combined sources7
Helixi66 – 75Combined sources10
Turni76 – 78Combined sources3
Beta strandi81 – 83Combined sources3
Beta strandi87 – 89Combined sources3
Helixi91 – 104Combined sources14
Helixi108 – 127Combined sources20
Helixi132 – 150Combined sources19
Helixi155 – 162Combined sources8
Helixi165 – 185Combined sources21
Helixi187 – 190Combined sources4
Helixi191 – 193Combined sources3
Beta strandi194 – 197Combined sources4
Helixi200 – 207Combined sources8
Helixi217 – 227Combined sources11
Beta strandi231 – 235Combined sources5
Beta strandi240 – 242Combined sources3
Beta strandi245 – 250Combined sources6
Beta strandi256 – 262Combined sources7
Beta strandi265 – 270Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZFYX-ray1.69A40-271[»]
3VONX-ray3.15A/H/O/V/c/j45-271[»]
4DDGX-ray3.30A/B/C/J/K/L25-271[»]
4DDIX-ray3.80A/B/C25-271[»]
4DHZX-ray3.11A1-45[»]
4I6LX-ray2.49A45-271[»]
4LDTX-ray1.90A1-45[»]
ProteinModelPortaliQ96FW1.
SMRiQ96FW1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96FW1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini80 – 271OTUPROSITE-ProRule annotationAdd BLAST192

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni130 – 138Ubiquitin-conjugating enzyme E2 binding1 Publication9
Regioni169 – 177Ubiquitin-conjugating enzyme E2 binding1 Publication9
Regioni189 – 195Free ubiquitin bindingCombined sources2 Publications7
Regioni206 – 213Ubiquitin-conjugating enzyme E2 bindingCombined sources2 Publications8
Regioni214 – 221Free ubiquitin bindingCombined sources2 Publications8
Regioni245 – 251Free ubiquitin bindingCombined sources2 Publications7

Domaini

In addition to ubiquitin-binding at the Cys-91 active site, a proximal ubiquitin-binding site is also present at Cys-23 Occupancy of the active site is needed to enable tight binding to the second site. Distinct binding sites for the ubiquitins may allow to discriminate among different isopeptide linkages (i.e. 'Lys-48'-, 'Lys-63'-linked polyubiquitin) in polyubiquitin substrates and achieve linkage-specific deubiquitination.1 Publication

Sequence similaritiesi

Belongs to the peptidase C65 family.Curated
Contains 1 OTU domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG3991. Eukaryota.
ENOG410ZMN7. LUCA.
GeneTreeiENSGT00390000006979.
HOVERGENiHBG053383.
InParanoidiQ96FW1.
KOiK09602.
PhylomeDBiQ96FW1.
TreeFamiTF314145.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030298. OTUB1.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF19. PTHR12931:SF19. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Isoform 1 (identifier: Q96FW1-1) [UniParc]FASTAAdd to basket
Also known as: Otubain-1

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
MAAEEPQQQK QEPLGSDSEG VNCLAYDEAI MAQQDRIQQE IAVQNPLVSE
60 70 80 90 100
RLELSVLYKE YAEDDNIYQQ KIKDLHKKYS YIRKTRPDGN CFYRAFGFSH
110 120 130 140 150
LEALLDDSKE LQRFKAVSAK SKEDLVSQGF TEFTIEDFHN TFMDLIEQVE
160 170 180 190 200
KQTSVADLLA SFNDQSTSDY LVVYLRLLTS GYLQRESKFF EHFIEGGRTV
210 220 230 240 250
KEFCQQEVEP MCKESDHIHI IALAQALSVS IQVEYMDRGE GGTTNPHIFP
260 270
EGSEPKVYLL YRPGHYDILY K
Length:271
Mass (Da):31,284
Last modified:March 1, 2004 - v2
Checksum:i63188EE1DC5FD66F
GO
Isoform 2 (identifier: Q96FW1-2) [UniParc]FASTAAdd to basket
Also known as: ARF-1

The sequence of this isoform differs from the canonical sequence as follows:
     1-112: MAAEEPQQQK...ALLDDSKELQ → MMKPSWLSRT...MLGPPFHPTP

Note: Lacks the catalytic sites for protease activity.
Show »
Length:315
Mass (Da):35,285
Checksum:i3B37EB8F1B3B2404
GO

Sequence cautioni

The sequence AAF28941 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti61Y → C in AAH10368 (PubMed:15489334).Curated1
Sequence conflicti151K → R in BAA90956 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0094641 – 112MAAEE…SKELQ → MMKPSWLSRTEFSKRLLCRT LWCQSGWSSRSYTRSMLKMT TSINRRSRTSTKSTRTSARP GLTATVSIGLSDSPTWRHCW MTARSCSGEKGGHWAPRQVG VYLLPGRVGCVSSRVSPSFP GDGLDSGLARRGSAVSALAS GLVEEPMLGPPFHPTP in isoform 2. 1 PublicationAdd BLAST112

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY177200 mRNA. Translation: AAO27702.1.
AF161381 mRNA. Translation: AAF28941.1. Different initiation.
AK000120 mRNA. Translation: BAA90956.1.
AP000721 Genomic DNA. No translation available.
BC007519 mRNA. Translation: AAH07519.1.
BC010368 mRNA. Translation: AAH10368.1.
BC107701 mRNA. Translation: AAI07702.1.
CCDSiCCDS8055.1. [Q96FW1-1]
RefSeqiNP_060140.2. NM_017670.2. [Q96FW1-1]
UniGeneiHs.473788.

Genome annotation databases

EnsembliENST00000428192; ENSP00000402551; ENSG00000167770. [Q96FW1-1]
ENST00000538426; ENSP00000444357; ENSG00000167770. [Q96FW1-1]
GeneIDi55611.
KEGGihsa:55611.
UCSCiuc001nyf.2. human. [Q96FW1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY177200 mRNA. Translation: AAO27702.1.
AF161381 mRNA. Translation: AAF28941.1. Different initiation.
AK000120 mRNA. Translation: BAA90956.1.
AP000721 Genomic DNA. No translation available.
BC007519 mRNA. Translation: AAH07519.1.
BC010368 mRNA. Translation: AAH10368.1.
BC107701 mRNA. Translation: AAI07702.1.
CCDSiCCDS8055.1. [Q96FW1-1]
RefSeqiNP_060140.2. NM_017670.2. [Q96FW1-1]
UniGeneiHs.473788.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2ZFYX-ray1.69A40-271[»]
3VONX-ray3.15A/H/O/V/c/j45-271[»]
4DDGX-ray3.30A/B/C/J/K/L25-271[»]
4DDIX-ray3.80A/B/C25-271[»]
4DHZX-ray3.11A1-45[»]
4I6LX-ray2.49A45-271[»]
4LDTX-ray1.90A1-45[»]
ProteinModelPortaliQ96FW1.
SMRiQ96FW1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120751. 207 interactors.
DIPiDIP-41158N.
IntActiQ96FW1. 328 interactors.
MINTiMINT-5001867.
STRINGi9606.ENSP00000402551.

Protein family/group databases

MEROPSiC65.001.

PTM databases

iPTMnetiQ96FW1.
PhosphoSitePlusiQ96FW1.
SwissPalmiQ96FW1.

Polymorphism and mutation databases

BioMutaiOTUB1.
DMDMi44888286.

Proteomic databases

EPDiQ96FW1.
MaxQBiQ96FW1.
PaxDbiQ96FW1.
PeptideAtlasiQ96FW1.
PRIDEiQ96FW1.

Protocols and materials databases

DNASUi55611.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000428192; ENSP00000402551; ENSG00000167770. [Q96FW1-1]
ENST00000538426; ENSP00000444357; ENSG00000167770. [Q96FW1-1]
GeneIDi55611.
KEGGihsa:55611.
UCSCiuc001nyf.2. human. [Q96FW1-1]

Organism-specific databases

CTDi55611.
DisGeNETi55611.
GeneCardsiOTUB1.
HGNCiHGNC:23077. OTUB1.
HPAiCAB072836.
HPA039176.
MIMi608337. gene.
neXtProtiNX_Q96FW1.
OpenTargetsiENSG00000167770.
PharmGKBiPA134988141.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3991. Eukaryota.
ENOG410ZMN7. LUCA.
GeneTreeiENSGT00390000006979.
HOVERGENiHBG053383.
InParanoidiQ96FW1.
KOiK09602.
PhylomeDBiQ96FW1.
TreeFamiTF314145.

Enzyme and pathway databases

ReactomeiR-HSA-5689880. Ub-specific processing proteases.
R-HSA-5689896. Ovarian tumor domain proteases.
SIGNORiQ96FW1.

Miscellaneous databases

ChiTaRSiOTUB1. human.
EvolutionaryTraceiQ96FW1.
GeneWikiiOTUB1.
GenomeRNAii55611.
PROiQ96FW1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000167770.
CleanExiHS_OTUB1.
ExpressionAtlasiQ96FW1. baseline and differential.
GenevisibleiQ96FW1. HS.

Family and domain databases

InterProiIPR003323. OTU_dom.
IPR030298. OTUB1.
IPR016615. Otubain.
IPR019400. Peptidase_C65_otubain.
[Graphical view]
PANTHERiPTHR12931:SF19. PTHR12931:SF19. 1 hit.
PfamiPF10275. Peptidase_C65. 1 hit.
[Graphical view]
PIRSFiPIRSF013503. Ubiquitin_thioesterase_Otubain. 1 hit.
PROSITEiPS50802. OTU. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiOTUB1_HUMAN
AccessioniPrimary (citable) accession number: Q96FW1
Secondary accession number(s): Q32Q78
, Q96II3, Q9NXQ4, Q9P0B8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 2004
Last sequence update: March 1, 2004
Last modified: November 30, 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
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

Miscellaneous

In the structure described by PubMed:18954305, the His-265 active site of the catalytic triad is located too far to interact directly with the active site Cys-91. A possible explanation is that OTUB1 is in inactive conformation in absence of ubiquitin and a conformation change may move His-265 in the proximity of Cys-91 in presence of ubiquitin substrate.

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: 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.