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Protein

mRNA interferase RelE

Gene

relE

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Toxic component of a type II toxin-antitoxin (TA) module (PubMed:9767574). A sequence-specific, ribosome-dependent mRNA endoribonuclease that inhibits translation during amino acid starvation (the stringent response). In vitro acts by cleaving mRNA with high codon specificity in the ribosomal A site between positions 2 and 3. The stop codon UAG is cleaved at a fast rate while UAA and UGA are cleaved with intermediate and slow rates. In vitro mRNA cleavage can also occur in the ribosomal E site after peptide release from peptidyl-tRNA in the P site as well as on free 30S subunits (PubMed:12526800). In vivo cuts frequently in the first 100 codons, most frequently after the second and third base and rarely near the stop codon (PubMed:21324908). Overexpression of RelE results in the inhibition of bacterial growth and a sharp decrease in colony-forming ability which is neutralized by the labile cognate antitoxin RelB. Overexpression also sharply increases persisters (cells that neither grow nor die in the presence of bactericidal agents and are largely responsible for high levels of biofilm tolerance to antimicrobials) (PubMed:15576765). Plays a role in dormancy when expressed in high-density cells in the absence of antitoxin RelB; amino acid starvation and an unidentified extracellular factor promote dormancy, while expression of antitoxin RelB restores cell culturability (PubMed:22210768). Acts with RelB as a corepressor of relBE transcription, considerably increasing the repression of RelB alone. 2 RelB dimers bind to 2 operator sequences; DNA-binding and repression is stronger when complexed with toxin/corepressor RelE by conditional cooperativity (PubMed:9767574, PubMed:19747491, PubMed:18501926, PubMed:22981948).14 Publications
Seems to be a principal mediator of cell death in liquid media (PubMed:19707553). Implicated in hydroxy radical-mediated cell death induced by hydroxyurea treatment (PubMed:20005847).2 Publications
Cross-talk can occur between different TA modules. Ectopic expression of this toxin induces transcription of 7 tested TA modules (dinJ/yafQ, hicAB, mazEF, mqsRA, prlF(sohA)/yhaV, relBEF and yefM/yoeB) with specific cleavage of the relBEF mRNA produced immediately upstream and within the relB coding sequence. The cleaved mRNA can be translated into RelE, leading to a positive feedback cycle of RelE expression. The relBEF operon is required for transcription of the mazEF TA module operon during amino acid starvation.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei52 – 521Proton acceptor1 Publication
Sitei54 – 541Transition state stabilizer1 Publication
Sitei61 – 611Transition state stabilizer1 Publication
Active sitei81 – 811Proton donor1 Publication

GO - Molecular functioni

  • endoribonuclease activity Source: EcoCyc
  • ribosome binding Source: EcoCyc
  • rRNA binding Source: UniProtKB-KW

GO - Biological processi

  • cellular response to amino acid starvation Source: EcoCyc
  • mRNA catabolic process Source: EcoCyc
  • negative regulation of translation Source: EcoCyc
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • response to antibiotic Source: EcoCyc
  • RNA phosphodiester bond hydrolysis, endonucleolytic Source: GOC
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Endonuclease, Hydrolase, Nuclease, Repressor, Toxin

Keywords - Biological processi

Antibiotic resistance, Stress response, Transcription, Transcription regulation

Keywords - Ligandi

RNA-binding, rRNA-binding

Enzyme and pathway databases

BioCyciEcoCyc:EG11131-MONOMER.
ECOL316407:JW1555-MONOMER.
MetaCyc:EG11131-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
mRNA interferase RelE (EC:3.1.-.-)
Alternative name(s):
Endoribonuclease RelE
Toxin RelE
Gene namesi
Name:relE
Ordered Locus Names:b1563, JW1555
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG11131. relE.

Pathology & Biotechi

Disruption phenotypei

Cells missing relBE have a higher steady-state level of translation during amino acid starvation than wild-type cells. They survive antibiotic treatment in log phase better than wild-type cells. Cells missing mazE-mazF survive hydroxyurea treatment better than wild-type; further disruption of relE-relB and tonB yields even better survival (PubMed:20005847).3 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi52 – 521K → A: Reduces mRNA cleavage rate constant 2100-fold. Reduces mRNA cleavage rate constant 1000000-fold; when associated with F-87. 1 Publication
Mutagenesisi54 – 541K → A: Reduces mRNA cleavage rate constant 2700-fold. 1 Publication
Mutagenesisi61 – 611R → A: Reduces mRNA cleavage rate constant 2700000-fold. 2 Publications
Mutagenesisi81 – 833RER → AEA: Significant reduction in endonuclease activity, still binds RelB. 1 Publication
Mutagenesisi81 – 811R → A: Reduces mRNA cleavage rate constant 60000-fold, significantly less translation inhibition which is countered by RelB. Almost complete loss of mRNA cleavage; when associated with F-87. 3 Publications
Mutagenesisi87 – 871Y → A: Reduces mRNA cleavage rate constant 180000-fold. 2 Publications
Mutagenesisi87 – 871Y → F: Reduces mRNA cleavage rate constant 130-fold. Almost complete loss of mRNA cleavage; when associated with A-81 (Ref.20). Reduces mRNA cleavage rate constant 1000000-fold; when associated with A-52 (Ref.18). 2 Publications
Mutagenesisi90 – 956AVKRIL → VTVTVT: Does not inhibit translation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 9595mRNA interferase RelEPRO_0000097245Add
BLAST

Proteomic databases

PaxDbiP0C077.
PRIDEiP0C077.

Expressioni

Inductioni

By amino acid starvation, by glucose starvation and by chloramphenicol; induction is independent of ppGpp. Autorepressed by RelB, RelE acts as a corepressor (PubMed:9767574, PubMed:19747491, PubMed:18501926, PubMed:22981948). Member of the relBEF operon (PubMed:2990907). Operon induced by ectopic expression of toxins HicA, HipA, MazF, MqsR and itself, but not by YafQ (PubMed:23432955).8 Publications

Interactioni

Subunit structurei

Forms an RelB(2)-RelE2 heterotetramer (PubMed:18501926, PubMed:22981948). Also forms an RelB(2)-RelE heterotrimer (PubMed:18532983, PubMed:19747491). The RelB(2)-RelE complex is probably the one that binds DNA and represses transcription, possibly as 2 heterotrimers, 1 bound to each of 2 operators (PubMed:22981948, PubMed:19747491). RelE occupies the A site of the 70S ribosome, making extensive contacts with the 16S rRNA. Its presence blocks access of tRNAs and translation factors. RelB bound to RelE prevents RelE from entering the ribosomal A site and thus inhibits its endonuclease activity (PubMed:19297318).6 Publications

Protein-protein interaction databases

DIPiDIP-35978N.
IntActiP0C077. 11 interactions.
MINTiMINT-1282331.
STRINGi511145.b1563.

Structurei

Secondary structure

1
95
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi4 – 74Combined sources
Helixi9 – 179Combined sources
Helixi20 – 3516Combined sources
Helixi40 – 423Combined sources
Beta strandi45 – 473Combined sources
Beta strandi50 – 545Combined sources
Turni56 – 594Combined sources
Beta strandi60 – 678Combined sources
Helixi68 – 703Combined sources
Beta strandi72 – 809Combined sources
Helixi82 – 843Combined sources
Helixi85 – 9410Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KC8NMR-A1-95[»]
2KC9NMR-A1-95[»]
4FXEX-ray2.75D/E/F1-95[»]
4FXHX-ray2.40A/B1-95[»]
4FXIX-ray1.80A/B/C1-95[»]
4V7JX-ray3.30Ay/By1-95[»]
4V7KX-ray3.60Ay/By1-95[»]
ProteinModelPortaliP0C077.
SMRiP0C077. Positions 2-80.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0C077.

Family & Domainsi

Sequence similaritiesi

Belongs to the RelE toxin family.Curated

Phylogenomic databases

eggNOGiCOG2026.
HOGENOMiHOG000219994.
InParanoidiP0C077.
KOiK06218.
OMAiPRVEANR.
OrthoDBiEOG6S52Q2.

Family and domain databases

InterProiIPR007712. RelE/ParE_toxin.
[Graphical view]
PfamiPF05016. Plasmid_stabil. 1 hit.
[Graphical view]
TIGRFAMsiTIGR02385. RelE_StbE. 1 hit.

Sequencei

Sequence statusi: Complete.

P0C077-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAYFLDFDER ALKEWRKLGS TVREQLKKKL VEVLESPRIE ANKLRGMPDC
60 70 80 90
YKIKLRSSGY RLVYQVIDEK VVVFVISVGK RERSEVYSEA VKRIL
Length:95
Mass (Da):11,225
Last modified:April 1, 1988 - v1
Checksum:iF516B2E7A437CCEC
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02405 Genomic DNA. Translation: CAA26251.1.
U00096 Genomic DNA. Translation: AAC74636.1.
AP009048 Genomic DNA. Translation: BAA15262.1.
PIRiB22830. QQECR1.
RefSeqiNP_416081.1. NC_000913.3.
WP_000323025.1. NZ_CP010445.1.

Genome annotation databases

EnsemblBacteriaiAAC74636; AAC74636; b1563.
BAA15262; BAA15262; BAA15262.
GeneIDi947549.
KEGGieco:b1563.
PATRICi32118432. VBIEscCol129921_1636.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X02405 Genomic DNA. Translation: CAA26251.1.
U00096 Genomic DNA. Translation: AAC74636.1.
AP009048 Genomic DNA. Translation: BAA15262.1.
PIRiB22830. QQECR1.
RefSeqiNP_416081.1. NC_000913.3.
WP_000323025.1. NZ_CP010445.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KC8NMR-A1-95[»]
2KC9NMR-A1-95[»]
4FXEX-ray2.75D/E/F1-95[»]
4FXHX-ray2.40A/B1-95[»]
4FXIX-ray1.80A/B/C1-95[»]
4V7JX-ray3.30Ay/By1-95[»]
4V7KX-ray3.60Ay/By1-95[»]
ProteinModelPortaliP0C077.
SMRiP0C077. Positions 2-80.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-35978N.
IntActiP0C077. 11 interactions.
MINTiMINT-1282331.
STRINGi511145.b1563.

Proteomic databases

PaxDbiP0C077.
PRIDEiP0C077.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC74636; AAC74636; b1563.
BAA15262; BAA15262; BAA15262.
GeneIDi947549.
KEGGieco:b1563.
PATRICi32118432. VBIEscCol129921_1636.

Organism-specific databases

EchoBASEiEB1121.
EcoGeneiEG11131. relE.

Phylogenomic databases

eggNOGiCOG2026.
HOGENOMiHOG000219994.
InParanoidiP0C077.
KOiK06218.
OMAiPRVEANR.
OrthoDBiEOG6S52Q2.

Enzyme and pathway databases

BioCyciEcoCyc:EG11131-MONOMER.
ECOL316407:JW1555-MONOMER.
MetaCyc:EG11131-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP0C077.
PROiP0C077.

Family and domain databases

InterProiIPR007712. RelE/ParE_toxin.
[Graphical view]
PfamiPF05016. Plasmid_stabil. 1 hit.
[Graphical view]
TIGRFAMsiTIGR02385. RelE_StbE. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Sequence of the relB transcription unit from Escherichia coli and identification of the relB gene."
    Bech F.W., Joergensen S.T., Diderichsen B., Karlstroem O.H.
    EMBO J. 4:1059-1066(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    Strain: K12 / CS520.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
    Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
    Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  5. "The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family."
    Gotfredsen M., Gerdes K.
    Mol. Microbiol. 29:1065-1076(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A TOXIN, FUNCTION AS A TRANSCRIPTIONAL COREPRESSOR, INDUCTION.
  6. "Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes."
    Galvani C., Terry J., Ishiguro E.E.
    J. Bacteriol. 183:2700-2703(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, RIBOSOME-BINDING.
  7. "RelE, a global inhibitor of translation, is activated during nutritional stress."
    Christensen S.K., Mikkelsen M., Pedersen K., Gerdes K.
    Proc. Natl. Acad. Sci. U.S.A. 98:14328-14333(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A TRANSLATION INHIBITOR, INDUCTION, DISRUPTION PHENOTYPE.
  8. "Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins."
    Pedersen K., Christensen S.K., Gerdes K.
    Mol. Microbiol. 45:501-510(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS A TOXIN, MUTAGENESIS OF ARG-81 AND 90-ALA--LEU-95.
    Strain: K12.
  9. "The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site."
    Pedersen K., Zavialov A.V., Pavlov M.Y., Elf J., Gerdes K., Ehrenberg M.
    Cell 112:131-140(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION AS AN ENDORIBONUCLEASE ON THE RIBOSOME, SUBSTRATE SPECIFICITY.
  10. "Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli."
    Keren I., Shah D., Spoering A., Kaldalu N., Lewis K.
    J. Bacteriol. 186:8172-8180(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: RELATION WITH PERSISTERS.
  11. "A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation."
    Kolodkin-Gal I., Verdiger R., Shlosberg-Fedida A., Engelberg-Kulka H.
    PLoS ONE 4:E6785-E6785(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CELL DEATH, DISRUPTION PHENOTYPE, ANTIBIOTIC RESISTANCE.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
  12. "Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module."
    Li G.Y., Zhang Y., Inouye M., Ikura M.
    J. Mol. Biol. 380:107-119(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, INDUCTION.
  13. "Messenger RNA interferase RelE controls relBE transcription by conditional cooperativity."
    Overgaard M., Borch J., Joergensen M.G., Gerdes K.
    Mol. Microbiol. 69:841-857(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, INDUCTION.
    Strain: K12.
  14. "RelB and RelE of Escherichia coli form a tight complex that represses transcription via the ribbon-helix-helix motif in RelB."
    Overgaard M., Borch J., Gerdes K.
    J. Mol. Biol. 394:183-196(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, INDUCTION.
    Strain: K12.
  15. "Hydroxyurea induces hydroxyl radical-mediated cell death in Escherichia coli."
    Davies B.W., Kohanski M.A., Simmons L.A., Winkler J.A., Collins J.J., Walker G.C.
    Mol. Cell 36:845-860(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.
    Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
  16. "Bacterial toxin RelE mediates frequent codon-independent mRNA cleavage from the 5' end of coding regions in vivo."
    Hurley J.M., Cruz J.W., Ouyang M., Woychik N.A.
    J. Biol. Chem. 286:14770-14778(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBSTRATE SPECIFICITY.
    Strain: K12 / BW25113.
  17. "RelE-mediated dormancy is enhanced at high cell density in Escherichia coli."
    Tashiro Y., Kawata K., Taniuchi A., Kakinuma K., May T., Okabe S.
    J. Bacteriol. 194:1169-1176(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN DORMANCY, ANTIBIOTIC RESISTANCE.
    Strain: K12 / MG1655 / ATCC 47076.
  18. "Transcriptional cross-activation between toxin-antitoxin systems of Escherichia coli."
    Kasari V., Mets T., Tenson T., Kaldalu N.
    BMC Microbiol. 13:45-45(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION BY OTHER TA MODULES.
    Strain: K12 / BW25113.
  19. "Bacterial toxin RelE: a highly efficient ribonuclease with exquisite substrate specificity using atypical catalytic residues."
    Griffin M.A., Davis J.H., Strobel S.A.
    Biochemistry 52:8633-8642(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROBABLE ACTIVE SITE, MUTAGENESIS OF LYS-52; LYS-54; ARG-61; ARG-81 AND TYR-87.
    Strain: K12 / MG1655 / ATCC 47076.
  20. "mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems."
    Yamaguchi Y., Inouye M.
    Prog. Mol. Biol. Transl. Sci. 85:467-500(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  21. "The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE."
    Neubauer C., Gao Y.G., Andersen K.R., Dunham C.M., Kelley A.C., Hentschel J., Gerdes K., Ramakrishnan V., Brodersen D.E.
    Cell 139:1084-1095(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN ISOLATION AND BOUND TO RIBOSOMES BEFORE AND AFTER MRNA CLEAVAGE, FUNCTION, RIBOSOME-BINDING, RRNA-BINDING, MECHANISM OF RNA CLEAVAGE, MUTAGENESIS OF ARG-61; ARG-81 AND TYR-87.
  22. "Inhibitory mechanism of Escherichia coli RelE-RelB toxin-antitoxin module involves a helix displacement near an mRNA interferase active site."
    Li G.Y., Zhang Y., Inouye M., Ikura M.
    J. Biol. Chem. 284:14628-14636(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF MUTANT 81-ARG--ARG-83 IN COMPLEX WITH RELB FRAGMENT, SUBUNIT.
  23. "The crystal structure of the intact E. coli RelBE toxin-antitoxin complex provides the structural basis for conditional cooperativity."
    Boggild A., Sofos N., Andersen K.R., Feddersen A., Easter A.D., Passmore L.A., Brodersen D.E.
    Structure 20:1641-1648(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) AND X-RAY CRYSTALLOGRAPHY (2.75 ANGSTROMS) IN COMPLEX WITH RELE, FUNCTION, SUBUNIT, INDUCTION.

Entry informationi

Entry nameiRELE_ECOLI
AccessioniPrimary (citable) accession number: P0C077
Secondary accession number(s): P07008
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 1, 1988
Last sequence update: April 1, 1988
Last modified: July 22, 2015
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

There are estimated to be 550-1100 RelB and 50-100 RelE molecules in rapidly growing cells of MG1655; as they have quite high affinity for each other (dissociation constant of 0.33 nM) there is probably less than 1 free RelE molecule per cell. The RelB(2)-RelE complex has a half-life of over 70 minutes.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.