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Protein

E3 ubiquitin-protein ligase Topors

Gene

TOPORS

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

Functioni

Functions as an E3 ubiquitin-protein ligase and as an E3 SUMO1-protein ligase. Probable tumor suppressor involved in cell growth, cell proliferation and apoptosis that regulates p53/TP53 stability through ubiquitin-dependent degradation. May regulate chromatin modification through sumoylation of several chromatin modification-associated proteins. May be involved in DNA damage-induced cell death through IKBKE sumoylation.7 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri103 – 142RING-typePROSITE-ProRule annotationAdd BLAST40

GO - Molecular functioni

  • antigen binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • DNA topoisomerase binding Source: UniProtKB
  • ligase activity Source: UniProtKB-KW
  • SUMO transferase activity Source: UniProtKB
  • ubiquitin protein ligase activity Source: BHF-UCL
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: InterPro

GO - Biological processi

  • cellular response to DNA damage stimulus Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: Ensembl
  • maintenance of protein location in nucleus Source: UniProtKB
  • negative regulation of apoptotic process Source: BHF-UCL
  • photoreceptor cell outer segment organization Source: BHF-UCL
  • positive regulation of transcription, DNA-templated Source: Ensembl
  • positive regulation of ubiquitin-protein transferase activity Source: BHF-UCL
  • proteasome-mediated ubiquitin-dependent protein catabolic process Source: UniProtKB
  • protein K48-linked ubiquitination Source: BHF-UCL
  • protein localization to nucleus Source: UniProtKB
  • protein monoubiquitination Source: BHF-UCL
  • protein polyubiquitination Source: BHF-UCL
  • protein sumoylation Source: UniProtKB
  • regulation of cell proliferation Source: Ensembl
  • retina layer formation Source: BHF-UCL
  • retinal cone cell development Source: BHF-UCL
  • retinal rod cell development Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB
  • ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

DNA damage, Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

SIGNORiQ9NS56.

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase Topors (EC:6.3.2.-)
Alternative name(s):
SUMO1-protein E3 ligase Topors
Topoisomerase I-binding RING finger protein
Topoisomerase I-binding arginine/serine-rich protein
Tumor suppressor p53-binding protein 3
Short name:
p53-binding protein 3
Short name:
p53BP3
Gene namesi
Name:TOPORS
Synonyms:LUN, TP53BPL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:21653. TOPORS.

Subcellular locationi

  • Nucleus
  • NucleusPML body

  • Note: Localizes to discrete nuclear foci which partly overlap with PML nuclear bodies. Targeted to PML nuclear bodies upon DNA damage.

GO - Cellular componenti

  • centriole Source: BHF-UCL
  • ciliary basal body Source: BHF-UCL
  • gamma-tubulin complex Source: BHF-UCL
  • midbody Source: BHF-UCL
  • nuclear speck Source: UniProtKB
  • nucleus Source: UniProtKB
  • photoreceptor connecting cilium Source: BHF-UCL
  • PML body Source: UniProtKB
  • spindle pole Source: BHF-UCL
  • ubiquitin ligase complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Retinitis pigmentosa 31 (RP31)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA retinal dystrophy belonging to the group of pigmentary retinopathies. Retinitis pigmentosa is characterized by retinal pigment deposits visible on fundus examination and primary loss of rod photoreceptor cells followed by secondary loss of cone photoreceptors. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well.
See also OMIM:609923

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi76K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi98S → A: Loss of phosphorylation but no effect on E3 ubiquitin-protein ligase activity. 1 Publication1
Mutagenesisi98S → D: Increase in E3 ubiquitin-protein ligase activity and increased binding to UBE2D1. No effect on SUMO1-protein ligase activity. 1 Publication1
Mutagenesisi131W → A: Abrogates E3 ubiquitin-protein ligase activity. 1 Publication1
Mutagenesisi301K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi485K → R: No effect on sumoylation. 1 Publication1
Mutagenesisi560K → R: Strongly reduces sumoylation. 1 Publication1
Mutagenesisi718S → A: Loss of phosphorylation by PLK1 and increases in p53/TP53 stability. 1 Publication1
Mutagenesisi921K → R: No effect on sumoylation. 1 Publication1

Keywords - Diseasei

Retinitis pigmentosa

Organism-specific databases

DisGeNETi10210.
MalaCardsiTOPORS.
MIMi609923. phenotype.
OpenTargetsiENSG00000197579.
Orphaneti791. Retinitis pigmentosa.
PharmGKBiPA134979531.

Polymorphism and mutation databases

BioMutaiTOPORS.
DMDMi74752935.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002326261 – 1045E3 ubiquitin-protein ligase ToporsAdd BLAST1045

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki76Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki83Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei98PhosphoserineCombined sources1 Publication1
Modified residuei194PhosphoserineCombined sources1
Cross-linki249Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei499Phosphoserine1 Publication1
Cross-linki560Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO)
Modified residuei585PhosphoserineCombined sources1 Publication1
Cross-linki701Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei718Phosphoserine; by PLK11 Publication1
Modified residuei734PhosphoserineCombined sources1
Modified residuei864PhosphoserineCombined sources1
Modified residuei866PhosphoserineCombined sources1 Publication1
Modified residuei912PhosphoserineBy similarity1
Modified residuei914PhosphoserineBy similarity1
Modified residuei1028PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-98 regulates the E3 ubiquitin-protein ligase activity but not the SUMO1-protein ligase activity. Phosphorylation at Ser-718 increases the E3 ubiquitin-protein ligase activity versus the SUMO1-protein ligase activity resulting in increased p53/TP53 ubiquitination and degradation.2 Publications
Sumoylated.2 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9NS56.
MaxQBiQ9NS56.
PaxDbiQ9NS56.
PeptideAtlasiQ9NS56.
PRIDEiQ9NS56.

PTM databases

iPTMnetiQ9NS56.
PhosphoSitePlusiQ9NS56.

Expressioni

Tissue specificityi

Expressed at highest levels in testis and at lower levels in adrenal gland, bone marrow, brain, colon, heart, kidney, liver, muscle, ovary, pancreas, placenta, prostate, skeletal muscle, skin, small intestine, spleen, stomach, testis, thymus, thyroid and uterus. Expressed in the alveolar epithelium of the lung. Expression is commonly decreased in colon adenocarcinomas and lung cancers.3 Publications

Inductioni

By genotoxic agents such as cisplatin and camptothecin.1 Publication

Gene expression databases

BgeeiENSG00000197579.
CleanExiHS_TOPORS.
GenevisibleiQ9NS56. HS.

Organism-specific databases

HPAiHPA065661.

Interactioni

Subunit structurei

Interacts with PARK7/DJ-1 (By similarity). Interacts with TOP1. Interacts with p53/TP53; can both ubiquitinate and sumoylate p53/TP53. Interacts with the SUMO1 conjugating enzyme UBE2I. Interacts with SUMO1. Interacts with NKX3-1; polyubiquitinates NKX3-1 and induces its proteasomal degradation. Interacts with SIN3A; sumoylates SIN3A. Interacts with IKBKE; induced by DNA damage.By similarity7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Rep68P031323EBI-1996473,EBI-7387242From a different organism.

GO - Molecular functioni

  • DNA topoisomerase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi115505. 64 interactors.
IntActiQ9NS56. 19 interactors.
MINTiMINT-94004.
STRINGi9606.ENSP00000353735.

Structurei

3D structure databases

ProteinModelPortaliQ9NS56.
SMRiQ9NS56.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 195E3 ubiquitin-protein ligase activityAdd BLAST195
Regioni51 – 374Required for DNA-bindingAdd BLAST324
Regioni437 – 654Interaction with SUMO11 PublicationAdd BLAST218
Regioni437 – 574Required for sumoylation and localization to discrete nuclear fociAdd BLAST138
Regioni456 – 882Interaction with TOP11 PublicationAdd BLAST427
Regioni456 – 731Interaction with p53/TP531 PublicationAdd BLAST276
Regioni854 – 917Interaction with UBE2I1 PublicationAdd BLAST64

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi579 – 788Arg-richAdd BLAST210
Compositional biasi854 – 895Lys-richAdd BLAST42

Sequence similaritiesi

Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri103 – 142RING-typePROSITE-ProRule annotationAdd BLAST40

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG4430. Eukaryota.
ENOG410XQZR. LUCA.
GeneTreeiENSGT00530000064170.
HOGENOMiHOG000231723.
HOVERGENiHBG080410.
InParanoidiQ9NS56.
KOiK10631.
OMAiDIINFRR.
OrthoDBiEOG091G089U.
PhylomeDBiQ9NS56.
TreeFamiTF339497.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9NS56-1) [UniParc]FASTAAdd to basket
Also known as: LUN-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
MGSQPPLGSP LSREEGEAPP PAPASEGRRR SRRVRLRGSC RHRPSFLGCR
60 70 80 90 100
ELAASAPARP APASSEIMAS AAKEFKMDNF SPKAGTSKLQ QTVPADASPD
110 120 130 140 150
SKCPICLDRF DNVSYLDRCL HKFCFRCVQE WSKNKAECPL CKQPFDSIFH
160 170 180 190 200
SVRAEDDFKE YVLRPSYNGS FVTPDRRFRY RTTLTRERNA SVYSPSGPVN
210 220 230 240 250
RRTTTPPDSG VLFEGLGIST RPRDVEIPQF MRQIAVRRPT TADERSLRKI
260 270 280 290 300
QEQDIINFRR TLYRAGARVR NIEDGGRYRD ISAEFFRRNP ACLHRLVPWL
310 320 330 340 350
KRELTVLFGA HGSLVNIVQH IIMSNVTRYD LESQAFVSDL RPFLLNRTEH
360 370 380 390 400
FIHEFISFAR SPFNMAAFDQ HANYDCPAPS YEEGSHSDSS VITISPDEAE
410 420 430 440 450
TQELDINVAT VSQAPWDDET PGPSYSSSEQ VHVTMSSLLN TSDSSDEELV
460 470 480 490 500
TGGATSQIQG VQTNDDLNND SDDSSDNCVI VGFVKPLAER TPELVELSSD
510 520 530 540 550
SEDLGSYEKM ETVKTQEQEQ SYSSGDSDVS RCSSPHSVLG KDEQINKGHC
560 570 580 590 600
DSSTRIKSKK EEKRSTSLSS PRNLNSSVRG DRVYSPYNHR HRKRGRSRSS
610 620 630 640 650
DSRSQSRSGH DQKNHRKHHG KKRMKSKRSR SRESSRPRGR RDKKRSRTRD
660 670 680 690 700
SSWSRRSQTL SLSSESTSRS RSRSSDHGKR RSRSRNRDRY YLRNNYGSRY
710 720 730 740 750
KWEYTYYSRN KDRDGYESSY RRRTLSRAHY SRQSSSPEFR VQSFSERTNA
760 770 780 790 800
RKKNNHSERK YYYYERHRSR SLSSNRSRTA STGTDRVRNE KPGGKRKYKT
810 820 830 840 850
RHLEGTNEVA QPSREFASKA KDSHYQKSSS KLDGNYKNES DTFSDSRSSD
860 870 880 890 900
RETKHKRRKR KTRSLSVEIV YEGKATDTTK HHKKKKKKHK KKHKKHHGDN
910 920 930 940 950
ASRSPVVITI DSDSDKDSEV KEDTECDNSG PQDPLQNEFL APSLEPFETK
960 970 980 990 1000
DVVTIEAEFG VLDKECDIAT LSNNLNNANK TVDNIPPLAA SVEQTLDVRE
1010 1020 1030 1040
ESTFVSDLEN QPSNIVSLQT EPSRQLPSPR TSLMSVCLGR DCDMS
Length:1,045
Mass (Da):119,198
Last modified:October 1, 2000 - v1
Checksum:i3DA635FDB5C83B77
GO
Isoform 2 (identifier: Q9NS56-2) [UniParc]FASTAAdd to basket
Also known as: LUN-2

The sequence of this isoform differs from the canonical sequence as follows:
     1-65: Missing.
     66-66: E → M

Show »
Length:980
Mass (Da):112,344
Checksum:i85E2A39A2978B20E
GO

Sequence cautioni

The sequence AAC98530 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti124 – 125CF → K in AAC98530 (PubMed:10415337).Curated2
Sequence conflicti257N → S in AAD23379 (PubMed:10352183).Curated1
Sequence conflicti308F → S in AAD23379 (PubMed:10352183).Curated1
Sequence conflicti922E → G in AAD23379 (PubMed:10352183).Curated1
Sequence conflicti1040R → K in AAD23379 (PubMed:10352183).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_037629154A → T.1 PublicationCorresponds to variant rs17855104dbSNPEnsembl.1
Natural variantiVAR_037630517E → K.1 PublicationCorresponds to variant rs17855103dbSNPEnsembl.1
Natural variantiVAR_037631749N → D.1 PublicationCorresponds to variant rs17857515dbSNPEnsembl.1
Natural variantiVAR_037632812P → R.Corresponds to variant rs36034138dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0179161 – 65Missing in isoform 2. 1 PublicationAdd BLAST65
Alternative sequenceiVSP_01791766E → M in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF098300 mRNA. Translation: AAD23379.1.
AB045732 mRNA. Translation: BAB03714.1.
AB045733 mRNA. Translation: BAB03715.1.
AL353671 Genomic DNA. Translation: CAH71253.1.
AL353671 Genomic DNA. Translation: CAH71254.1.
BC060884 mRNA. Translation: AAH60884.1.
U82939 mRNA. Translation: AAC98530.1. Different initiation.
CCDSiCCDS56566.1. [Q9NS56-2]
CCDS6527.1. [Q9NS56-1]
RefSeqiNP_001182551.1. NM_001195622.1. [Q9NS56-2]
NP_005793.2. NM_005802.4. [Q9NS56-1]
UniGeneiHs.589962.

Genome annotation databases

EnsembliENST00000360538; ENSP00000353735; ENSG00000197579. [Q9NS56-1]
ENST00000379858; ENSP00000369187; ENSG00000197579. [Q9NS56-2]
GeneIDi10210.
KEGGihsa:10210.
UCSCiuc003zrb.4. human. [Q9NS56-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF098300 mRNA. Translation: AAD23379.1.
AB045732 mRNA. Translation: BAB03714.1.
AB045733 mRNA. Translation: BAB03715.1.
AL353671 Genomic DNA. Translation: CAH71253.1.
AL353671 Genomic DNA. Translation: CAH71254.1.
BC060884 mRNA. Translation: AAH60884.1.
U82939 mRNA. Translation: AAC98530.1. Different initiation.
CCDSiCCDS56566.1. [Q9NS56-2]
CCDS6527.1. [Q9NS56-1]
RefSeqiNP_001182551.1. NM_001195622.1. [Q9NS56-2]
NP_005793.2. NM_005802.4. [Q9NS56-1]
UniGeneiHs.589962.

3D structure databases

ProteinModelPortaliQ9NS56.
SMRiQ9NS56.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115505. 64 interactors.
IntActiQ9NS56. 19 interactors.
MINTiMINT-94004.
STRINGi9606.ENSP00000353735.

PTM databases

iPTMnetiQ9NS56.
PhosphoSitePlusiQ9NS56.

Polymorphism and mutation databases

BioMutaiTOPORS.
DMDMi74752935.

Proteomic databases

EPDiQ9NS56.
MaxQBiQ9NS56.
PaxDbiQ9NS56.
PeptideAtlasiQ9NS56.
PRIDEiQ9NS56.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000360538; ENSP00000353735; ENSG00000197579. [Q9NS56-1]
ENST00000379858; ENSP00000369187; ENSG00000197579. [Q9NS56-2]
GeneIDi10210.
KEGGihsa:10210.
UCSCiuc003zrb.4. human. [Q9NS56-1]

Organism-specific databases

CTDi10210.
DisGeNETi10210.
GeneCardsiTOPORS.
GeneReviewsiTOPORS.
HGNCiHGNC:21653. TOPORS.
HPAiHPA065661.
MalaCardsiTOPORS.
MIMi609507. gene.
609923. phenotype.
neXtProtiNX_Q9NS56.
OpenTargetsiENSG00000197579.
Orphaneti791. Retinitis pigmentosa.
PharmGKBiPA134979531.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4430. Eukaryota.
ENOG410XQZR. LUCA.
GeneTreeiENSGT00530000064170.
HOGENOMiHOG000231723.
HOVERGENiHBG080410.
InParanoidiQ9NS56.
KOiK10631.
OMAiDIINFRR.
OrthoDBiEOG091G089U.
PhylomeDBiQ9NS56.
TreeFamiTF339497.

Enzyme and pathway databases

SIGNORiQ9NS56.

Miscellaneous databases

ChiTaRSiTOPORS. human.
GeneWikiiTOPORS.
GenomeRNAii10210.
PROiQ9NS56.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000197579.
CleanExiHS_TOPORS.
GenevisibleiQ9NS56. HS.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
SMARTiSM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTOPRS_HUMAN
AccessioniPrimary (citable) accession number: Q9NS56
Secondary accession number(s): O43273
, Q6P987, Q9NS55, Q9UNR9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 18, 2006
Last sequence update: October 1, 2000
Last modified: November 2, 2016
This is version 137 of the entry and version 1 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

Caution

Was originally thought to bind to the palindromic consensus sequence 5'-TCCCAGCACTTTGGGA-3' and to regulate the transcription of numerous genes in the lung.1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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. 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.