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Protein

3'-5' exoribonuclease 1

Gene

ERI1

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

Functioni

RNA exonuclease that binds to the 3'-end of histone mRNAs and degrades them, suggesting that it plays an essential role in histone mRNA decay after replication. A 2' and 3'-hydroxyl groups at the last nucleotide of the histone 3'-end is required for efficient degradation of RNA substrates. Also able to degrade the 3'-overhangs of short interfering RNAs (siRNAs) in vitro, suggesting a possible role as regulator of RNA interference (RNAi). Requires for binding the 5'-ACCCA-3' sequence present in stem-loop structure. Able to bind other mRNAs. Required for 5.8S rRNA 3'-end processing. Also binds to 5.8s ribosomal RNA. Binds with high affinity to the stem-loop structure of replication-dependent histone pre-mRNAs.2 Publications

Cofactori

Mg2+Note: Binds 2 magnesium ions per subunit.

Enzyme regulationi

Although it can bind simultaneously with SLBP to the 3'-end of histone mRNA, the presence of SLBP prevents the exonuclease activity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi134 – 1341Magnesium 1
Metal bindingi134 – 1341Magnesium 2
Active sitei136 – 1361Proton acceptorSequence Analysis
Metal bindingi136 – 1361Magnesium 1
Binding sitei136 – 1361AMP1 Publication
Binding sitei137 – 1371AMP; via amide nitrogen and carbonyl oxygen1 Publication
Metal bindingi234 – 2341Magnesium 2
Active sitei293 – 2931Proton acceptorSequence Analysis
Binding sitei293 – 2931AMP1 Publication
Metal bindingi298 – 2981Magnesium 1

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Exonuclease, Hydrolase, Nuclease

Keywords - Biological processi

RNA-mediated gene silencing, rRNA processing

Keywords - Ligandi

Magnesium, Metal-binding, RNA-binding

Names & Taxonomyi

Protein namesi
Recommended name:
3'-5' exoribonuclease 1 (EC:3.1.-.-)
Alternative name(s):
3'-5' exonuclease ERI1
Eri-1 homolog
Histone mRNA 3'-end-specific exoribonuclease
Histone mRNA 3'-exonuclease 1
Protein 3'hExo
Short name:
HEXO
Gene namesi
Name:ERI1
Synonyms:3'EXO, THEX1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:23994. ERI1.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Nucleus 1 Publication
  • Nucleusnucleolus 1 Publication

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • histone pre-mRNA 3'end processing complex Source: UniProtKB
  • nucleolus Source: UniProtKB
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi92 – 921K → A: Does not inhibit RNA-binding to the stem-loop structure. Does not inhibit RNA-binding to the stem-loop structure, when associated with A-104. 1 Publication
Mutagenesisi96 – 961R → A: Does not inhibit RNA-binding to the stem-loop structure. 1 Publication
Mutagenesisi99 – 991K → A: Reduces slightly RNA-binding to the stem-loop structure. 1 Publication
Mutagenesisi104 – 1041K → A: Does not inhibit RNA-binding to the stem-loop structure. Does not inhibit RNA-binding to the stem-loop structure, when associated with A-92. 1 Publication
Mutagenesisi105 – 1051R → A: Inhibits RNA-binding to the stem-loop structure. 1 Publication
Mutagenesisi109 – 1091Y → A: Reduces slightly RNA-binding to the stem-loop structure; when associated with A-110. 1 Publication
Mutagenesisi110 – 1101Y → A: Reduces slightly RNA-binding to the stem-loop structure; when associated with A-109. 1 Publication
Mutagenesisi111 – 1111K → A: Reduces RNA-binding to the stem-loop structure but not 3'-end histone mRNA exonuclease activity; when associated with A-112. 1 Publication
Mutagenesisi112 – 1121K → A: Reduces RNA-binding to the stem-loop structure but not 3'-end histone mRNA exonuclease activity; when associated with A-111. 1 Publication
Mutagenesisi234 – 2341D → A: Inhibits 3'-end histone mRNA exonuclease activity. 1 Publication
Mutagenesisi235 – 2351M → A: Inhibits RNA-binding to the stem-loop structure and 3'-end histone mRNA exonuclease activity. 1 Publication
Mutagenesisi298 – 2981D → A: Inhibits 3'-end histone mRNA exonuclease activity. 1 Publication

Organism-specific databases

PharmGKBiPA164719226.

Polymorphism and mutation databases

BioMutaiERI1.
DMDMi45476938.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methioninei1 – 11Removed1 Publication
Chaini2 – 3493483'-5' exoribonuclease 1PRO_0000187007Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei62 – 621Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8IV48.
PaxDbiQ8IV48.
PeptideAtlasiQ8IV48.
PRIDEiQ8IV48.

PTM databases

PhosphoSiteiQ8IV48.

Expressioni

Gene expression databases

BgeeiQ8IV48.
CleanExiHS_ERI1.
ExpressionAtlasiQ8IV48. baseline and differential.
GenevisibleiQ8IV48. HS.

Organism-specific databases

HPAiCAB033838.
HPA055548.
HPA056074.

Interactioni

Subunit structurei

Identified in a histone pre-mRNA complex, at least composed of ERI1, LSM11, SLBP, SNRPB, SYNCRIP and YBX1. Interacts in a cooperative manner with SLBP to the mature 3'-end of histone mRNAs (By similarity). Binds to 40S and 60S ribosomal subunits and to 80S assembled ribosomes. Found in a ternary complex with SLBP and the stem-loop structure of the 3'-end of histone mRNAs.By similarity2 Publications

Protein-protein interaction databases

BioGridi124718. 5 interactions.
STRINGi9606.ENSP00000250263.

Structurei

Secondary structure

1
349
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi47 – 493Combined sources
Turni50 – 523Combined sources
Beta strandi53 – 575Combined sources
Helixi64 – 7714Combined sources
Helixi81 – 9010Combined sources
Helixi99 – 11416Combined sources
Beta strandi115 – 1195Combined sources
Beta strandi126 – 1327Combined sources
Beta strandi151 – 16010Combined sources
Turni161 – 1633Combined sources
Beta strandi165 – 17410Combined sources
Beta strandi177 – 1793Combined sources
Helixi184 – 1907Combined sources
Helixi194 – 1985Combined sources
Beta strandi200 – 2023Combined sources
Helixi203 – 21614Combined sources
Turni220 – 2223Combined sources
Beta strandi225 – 2317Combined sources
Turni232 – 2354Combined sources
Helixi236 – 24611Combined sources
Helixi252 – 2543Combined sources
Beta strandi255 – 2595Combined sources
Helixi260 – 2689Combined sources
Helixi272 – 2743Combined sources
Helixi277 – 2837Combined sources
Helixi295 – 31117Combined sources
Beta strandi320 – 3234Combined sources
Beta strandi326 – 3294Combined sources
Beta strandi332 – 3343Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1W0HX-ray1.59A123-322[»]
1ZBHX-ray3.00A/B/C/D51-349[»]
1ZBUX-ray3.00A/B/C/D1-349[»]
4L8RX-ray2.60B/E55-349[»]
4QOZX-ray2.30B/E55-349[»]
ProteinModelPortaliQ8IV48.
SMRiQ8IV48. Positions 60-349.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8IV48.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini76 – 11035SAPPROSITE-ProRule annotationAdd
BLAST
Domaini130 – 306177ExonucleaseAdd
BLAST

Domaini

The SAP domain is necessary for binding to the stem-loop structure of histone mRNAs and to form the ternary complex with SLBP, but not for 3'-end histone mRNA exonuclease activity.

Sequence similaritiesi

Contains 1 exonuclease domain.Curated
Contains 1 SAP domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiCOG5018.
GeneTreeiENSGT00530000063205.
HOGENOMiHOG000006635.
HOVERGENiHBG048925.
KOiK18416.
OMAiFLNIQCR.
OrthoDBiEOG7BGHM2.
PhylomeDBiQ8IV48.
TreeFamiTF313449.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR012337. RNaseH-like_dom.
IPR003034. SAP_dom.
[Graphical view]
PfamiPF00929. RNase_T. 1 hit.
PF02037. SAP. 1 hit.
[Graphical view]
SMARTiSM00479. EXOIII. 1 hit.
SM00513. SAP. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS50800. SAP. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q8IV48-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEDPQSKEPA GEAVALALLE SPRPEGGEEP PRPSPEETQQ CKFDGQETKG
60 70 80 90 100
SKFITSSASD FSDPVYKEIA ITNGCINRMS KEELRAKLSE FKLETRGVKD
110 120 130 140 150
VLKKRLKNYY KKQKLMLKES NFADSYYDYI CIIDFEATCE EGNPPEFVHE
160 170 180 190 200
IIEFPVVLLN THTLEIEDTF QQYVRPEINT QLSDFCISLT GITQDQVDRA
210 220 230 240 250
DTFPQVLKKV IDWMKLKELG TKYKYSLLTD GSWDMSKFLN IQCQLSRLKY
260 270 280 290 300
PPFAKKWINI RKSYGNFYKV PRSQTKLTIM LEKLGMDYDG RPHCGLDDSK
310 320 330 340
NIARIAVRML QDGCELRINE KMHAGQLMSV SSSLPIEGTP PPQMPHFRK
Length:349
Mass (Da):40,064
Last modified:January 23, 2007 - v3
Checksum:iD5837AA05F09410C
GO

Sequence cautioni

The sequence CAB70871.2 differs from that shown. Reason: Frameshift at position 117. Curated
The sequence CAB70871.2 differs from that shown. Reason: Erroneous termination at position 159. Translated as Leu.Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti16 – 161L → P.1 Publication
Corresponds to variant rs2288672 [ dbSNP | Ensembl ].
VAR_018107

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY310909 mRNA. Translation: AAQ21219.1.
AK291062 mRNA. Translation: BAF83751.1.
AL137679 mRNA. Translation: CAB70871.2. Sequence problems.
BC035279 mRNA. Translation: AAH35279.1.
CCDSiCCDS5972.1.
PIRiT46432.
RefSeqiNP_699163.2. NM_153332.3.
UniGeneiHs.20000.

Genome annotation databases

EnsembliENST00000250263; ENSP00000250263; ENSG00000104626.
ENST00000519292; ENSP00000430190; ENSG00000104626.
ENST00000523898; ENSP00000429615; ENSG00000104626.
GeneIDi90459.
KEGGihsa:90459.
UCSCiuc003wsk.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY310909 mRNA. Translation: AAQ21219.1.
AK291062 mRNA. Translation: BAF83751.1.
AL137679 mRNA. Translation: CAB70871.2. Sequence problems.
BC035279 mRNA. Translation: AAH35279.1.
CCDSiCCDS5972.1.
PIRiT46432.
RefSeqiNP_699163.2. NM_153332.3.
UniGeneiHs.20000.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1W0HX-ray1.59A123-322[»]
1ZBHX-ray3.00A/B/C/D51-349[»]
1ZBUX-ray3.00A/B/C/D1-349[»]
4L8RX-ray2.60B/E55-349[»]
4QOZX-ray2.30B/E55-349[»]
ProteinModelPortaliQ8IV48.
SMRiQ8IV48. Positions 60-349.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124718. 5 interactions.
STRINGi9606.ENSP00000250263.

PTM databases

PhosphoSiteiQ8IV48.

Polymorphism and mutation databases

BioMutaiERI1.
DMDMi45476938.

Proteomic databases

MaxQBiQ8IV48.
PaxDbiQ8IV48.
PeptideAtlasiQ8IV48.
PRIDEiQ8IV48.

Protocols and materials databases

DNASUi90459.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250263; ENSP00000250263; ENSG00000104626.
ENST00000519292; ENSP00000430190; ENSG00000104626.
ENST00000523898; ENSP00000429615; ENSG00000104626.
GeneIDi90459.
KEGGihsa:90459.
UCSCiuc003wsk.2. human.

Organism-specific databases

CTDi90459.
GeneCardsiGC08P008900.
HGNCiHGNC:23994. ERI1.
HPAiCAB033838.
HPA055548.
HPA056074.
MIMi608739. gene.
neXtProtiNX_Q8IV48.
PharmGKBiPA164719226.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG5018.
GeneTreeiENSGT00530000063205.
HOGENOMiHOG000006635.
HOVERGENiHBG048925.
KOiK18416.
OMAiFLNIQCR.
OrthoDBiEOG7BGHM2.
PhylomeDBiQ8IV48.
TreeFamiTF313449.

Miscellaneous databases

EvolutionaryTraceiQ8IV48.
GenomeRNAii90459.
NextBioi76770.
PROiQ8IV48.
SOURCEiSearch...

Gene expression databases

BgeeiQ8IV48.
CleanExiHS_ERI1.
ExpressionAtlasiQ8IV48. baseline and differential.
GenevisibleiQ8IV48. HS.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
InterProiIPR006055. Exonuclease.
IPR013520. Exonuclease_RNaseT/DNA_pol3.
IPR012337. RNaseH-like_dom.
IPR003034. SAP_dom.
[Graphical view]
PfamiPF00929. RNase_T. 1 hit.
PF02037. SAP. 1 hit.
[Graphical view]
SMARTiSM00479. EXOIII. 1 hit.
SM00513. SAP. 1 hit.
[Graphical view]
SUPFAMiSSF53098. SSF53098. 1 hit.
PROSITEiPS50800. SAP. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A 3' exonuclease that specifically interacts with the 3' end of histone mRNA."
    Dominski Z., Yang X.-C., Kaygun H., Dadlez M., Marzluff W.F.
    Mol. Cell 12:295-305(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 2-23; 43-48; 53-67; 161-172; 200-208; 225-237; 263-269 AND 284-291, FUNCTION, ENZYME REGULATION, ENZYME ACTIVITY, RNA-BINDING.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PRO-16.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Testis.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  5. "A conserved siRNA-degrading RNase negatively regulates RNA interference in C. elegans."
    Kennedy S., Wang D., Ruvkun G.
    Nature 427:645-649(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME ACTIVITY IN VITRO.
  6. "Characterization of 3'hExo, a 3' exonuclease specifically interacting with the 3' end of histone mRNA."
    Yang X.-C., Purdy M., Marzluff W.F., Dominski Z.
    J. Biol. Chem. 281:30447-30454(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, IDENTIFICATION IN A TERNARY COMPLEX, ENZYME ACTIVITY, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-92; ARG-96; LYS-99; LYS-104; ARG-105; THY-109; THY-110; LYS-111; LYS-112; ASP-234; MET-235 AND ASP-298, RNA-BINDING.
  7. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-62, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  8. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. "Crystallographic structure of the nuclease domain of 3'hExo, a DEDDh family member, bound to rAMP."
    Cheng Y., Patel D.J.
    J. Mol. Biol. 343:305-312(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 123-322 IN COMPLEX WITH MAGNESIUM IONS AND AMP.

Entry informationi

Entry nameiERI1_HUMAN
AccessioniPrimary (citable) accession number: Q8IV48
Secondary accession number(s): A8K4U7, Q9NSX3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2004
Last sequence update: January 23, 2007
Last modified: June 24, 2015
This is version 131 of the entry and version 3 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.