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Protein

Probable ubiquitin carboxyl-terminal hydrolase FAF-Y

Gene

USP9Y

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

Functioni

May function as a ubiquitin-protein or polyubiquitin hydrolase involved both in the processing of ubiquitin precursors and of ubiquitinated proteins. May therefore play an important regulatory role at the level of protein turnover by preventing degradation of proteins through the removal of conjugated ubiquitin. Essential component of TGF-beta/BMP signaling cascade. Deubiquitinates monoubiquitinated SMAD4, opposing the activity of E3 ubiquitin-protein ligase TRIM33. Monoubiquitination of SMAD4 hampers its ability to form a stable complex with activated SMAD2/3 resulting in inhibition of TGF-beta/BMP signaling cascade. Deubiqitination of SMAD4 by USP9X re-empowers its competence to mediate TGF-beta signaling (By similarity).By similarity

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).

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1568NucleophilePROSITE-ProRule annotation1
Active sitei1881Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • co-SMAD binding Source: BHF-UCL
  • cysteine-type peptidase activity Source: ProtInc
  • thiol-dependent ubiquitin-specific protease activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease, Thiol protease

Keywords - Biological processi

Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:HS03762-MONOMER.

Protein family/group databases

MEROPSiC19.028.

Names & Taxonomyi

Protein namesi
Recommended name:
Probable ubiquitin carboxyl-terminal hydrolase FAF-Y (EC:3.4.19.12)
Alternative name(s):
Deubiquitinating enzyme FAF-Y
Fat facets protein-related, Y-linked
Ubiquitin thioesterase FAF-Y
Ubiquitin-specific protease 9, Y chromosome
Ubiquitin-specific-processing protease FAF-Y
Gene namesi
Name:USP9Y
Synonyms:DFFRY
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome Y

Organism-specific databases

HGNCiHGNC:12633. USP9Y.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

USP9Y is located in the 'azoospermia factor a' (AZFa) region on chromosome Y which is deleted in Sertoli cell-only syndrome. This is an infertility disorder in which no germ cells are visible in seminiferous tubules leading to azoospermia. However, AZFa deletions resulting in complete loss of USP9Y have also been found in normospermic men (PubMed:19246359).

Spermatogenic failure Y-linked 2 (SPGFY2)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry. The role of USP9Y in spermatogenesis failure is uncertain (PubMed:19246359). A 4-bp deletion in a splice-donor site, causing exon skipping and protein truncation has been observed in non-obstructive azoospermia (PubMed:10581029). However, complete USP9Y deletion has been detected in individuals with no spermatogenic defects (PubMed:19246359).2 Publications
Disease descriptionA disorder resulting in the absence (azoospermia) or reduction (oligozoospermia) of sperm in the semen, leading to male infertility.
See also OMIM:415000

Organism-specific databases

DisGeNETi8287.
MalaCardsiUSP9Y.
MIMi415000. phenotype.
OpenTargetsiENSG00000114374.
Orphaneti1646. Partial chromosome Y deletion.
PharmGKBiPA37258.

Polymorphism and mutation databases

BioMutaiUSP9Y.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000806901 – 2555Probable ubiquitin carboxyl-terminal hydrolase FAF-YAdd BLAST2555

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei589PhosphoserineBy similarity1
Modified residuei591PhosphothreonineBy similarity1
Modified residuei2444PhosphoserineBy similarity1
Modified residuei2541PhosphotyrosineBy similarity1
Modified residuei2548PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO00507.
MaxQBiO00507.
PaxDbiO00507.
PeptideAtlasiO00507.
PRIDEiO00507.

PTM databases

iPTMnetiO00507.
PhosphoSitePlusiO00507.

Expressioni

Tissue specificityi

Widely expressed in embryonic and adult tissues.

Gene expression databases

BgeeiENSG00000114374.
CleanExiHS_USP10.
HS_USP9Y.
ExpressionAtlasiO00507. baseline and differential.
GenevisibleiO00507. HS.

Interactioni

Subunit structurei

Interacts with SMAD4.By similarity

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113892. 13 interactors.
IntActiO00507. 6 interactors.
MINTiMINT-7230431.
STRINGi9606.ENSP00000342812.

Structurei

3D structure databases

ProteinModelPortaliO00507.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1559 – 1958USPAdd BLAST400

Sequence similaritiesi

Belongs to the peptidase C19 family.Curated
Contains 1 USP domain.Curated

Phylogenomic databases

eggNOGiKOG1866. Eukaryota.
COG5077. LUCA.
GeneTreeiENSGT00760000119158.
HOGENOMiHOG000231283.
HOVERGENiHBG073749.
InParanoidiO00507.
KOiK11840.
OMAiNSINCAR.
OrthoDBiEOG091G0069.
PhylomeDBiO00507.
TreeFamiTF323966.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Note: Additional isoforms seem to exist.
Isoform Long (identifier: O00507-1) [UniParc]FASTAAdd to basket

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
MTAITHGSPV GGNDSQGQVL DGQSQHLFQQ NQTSSPDSSN ENSVATPPPE
60 70 80 90 100
EQGQGDAPPQ HEDEEPAFPH TELANLDDMI NRPRWVVPVL PKGELEVLLE
110 120 130 140 150
AAIDLSVKGL DVKSEACQRF FRDGLTISFT KILMDEAVSG WKFEIHRCII
160 170 180 190 200
NNTHRLVELC VAKLSQDWFP LLELLAMALN PHCKFHIYNG TRPCELISSN
210 220 230 240 250
AQLPEDELFA RSSDPRSPKG WLVDLINKFG TLNGFQILHD RFFNGSALNI
260 270 280 290 300
QIIAALIKPF GQCYEFLSQH TLKKYFIPVI EIVPHLLENL TDEELKKEAK
310 320 330 340 350
NEAKNDALSM IIKSLKNLAS RISGQDETIK NLEIFRLKMI LRLLQISSFN
360 370 380 390 400
GKMNALNEIN KVISSVSYYT HRHSNPEEEE WLTAERMAEW IQQNNILSIV
410 420 430 440 450
LQDSLHQPQY VEKLEKILRF VIKEKALTLQ DLDNIWAAQA GKHEAIVKNV
460 470 480 490 500
HDLLAKLAWD FSPGQLDHLF DCFKASWTNA SKKQREKLLE LIRRLAEDDK
510 520 530 540 550
DGVMAHKVLN LLWNLAQSDD VPVDIMDLAL SAHIKILDYS CSQDRDAQKI
560 570 580 590 600
QWIDHFIEEL RTNDKWVIPA LKQIREICSL FGEASQNLSQ TQRSPHIFYR
610 620 630 640 650
HDLINQLQQN HALVTLVAEN LATYMNSIRL YAGDHEDYDP QTVRLGSRYS
660 670 680 690 700
HVQEVQERLN FLRFLLKDGQ LWLCAPQAKQ IWKCLAENAV YLCDREACFK
710 720 730 740 750
WYSKLMGDEP DLDPDINKDF FESNVLQLDP SLLTENGMKC FERFFKAVNC
760 770 780 790 800
RERKLIAKRR SYMMDDLELI GLDYLWRVVI QSSDEIANRA IDLLKEIYTN
810 820 830 840 850
LGPRLKANQV VIHEDFIQSC FDRLKASYDT LCVFDGDKNS INCARQEAIR
860 870 880 890 900
MVRVLTVIKE YINECDSDYH KERMILPMSR AFRGKHLSLI VRFPNQGRQV
910 920 930 940 950
DELDIWSHTN DTIGSVRRCI VNRIKANVAH KKIELFVGGE LIDSEDDRKL
960 970 980 990 1000
IGQLNLKDKS LITAKLTQIN FNMPSSPDSS SDSSTASPGN HRNHYNDGPN
1010 1020 1030 1040 1050
LEVESCLPGV IMSVHPRYIS FLWQVADLGS NLNMPPLRDG ARVLMKLMPP
1060 1070 1080 1090 1100
DRTAVEKLRA VCLDHAKLGE GKLSPPLDSL FFGPSASQVL YLTEVVYALL
1110 1120 1130 1140 1150
MPAGVPLTDG SSDFQVHFLK SGGLPLVLSM LIRNNFLPNT DMETRRGAYL
1160 1170 1180 1190 1200
NALKIAKLLL TAIGYGHVRA VAEACQPVVD GTDPITQINQ VTHDQAVVLQ
1210 1220 1230 1240 1250
SALQSIPNPS SECVLRNESI LLAQEISNEA SRYMPDICVI RAIQKIIWAS
1260 1270 1280 1290 1300
ACGALGLVFS PNEEITKIYQ MTTNGSNKLE VEDEQVCCEA LEVMTLCFAL
1310 1320 1330 1340 1350
LPTALDALSK EKAWQTFIID LLLHCPSKTV RQLAQEQFFL MCTRCCMGHR
1360 1370 1380 1390 1400
PLLFFITLLF TILGSTAREK GKYSGDYFTL LRHLLNYAYN GNINIPNAEV
1410 1420 1430 1440 1450
LLVSEIDWLK RIRDNVKNTG ETGVEEPILE GHLGVTKELL AFQTSEKKYH
1460 1470 1480 1490 1500
FGCEKGGANL IKELIDDFIF PASKVYLQYL RSGELPAEQA IPVCSSPVTI
1510 1520 1530 1540 1550
NAGFELLVAL AIGCVRNLKQ IVDCLTEMYY MGTAITTCEA LTEWEYLPPV
1560 1570 1580 1590 1600
GPRPPKGFVG LKNAGATCYM NSVIQQLYMI PSIRNSILAI EGTGSDLHDD
1610 1620 1630 1640 1650
MFGDEKQDSE SNVDPRDDVF GYPHQFEDKP ALSKTEDRKE YNIGVLRHLQ
1660 1670 1680 1690 1700
VIFGHLAASQ LQYYVPRGFW KQFRLWGEPV NLREQHDALE FFNSLVDSLD
1710 1720 1730 1740 1750
EALKALGHPA ILSKVLGGSF ADQKICQGCP HRYECEESFT TLNVDIRNHQ
1760 1770 1780 1790 1800
NLLDSLEQYI KGDLLEGANA YHCEKCDKKV DTVKRLLIKK LPRVLAIQLK
1810 1820 1830 1840 1850
RFDYDWEREC AIKFNDYFEF PRELDMGPYT VAGVANLERD NVNSENELIE
1860 1870 1880 1890 1900
QKEQSDNETA GGTKYRLVGV LVHSGQASGG HYYSYIIQRN GKDDQTDHWY
1910 1920 1930 1940 1950
KFDDGDVTEC KMDDDEEMKN QCFGGEYMGE VFDHMMKRMS YRRQKRWWNA
1960 1970 1980 1990 2000
YILFYEQMDM IDEDDEMIRY ISELTIARPH QIIMSPAIER SVRKQNVKFM
2010 2020 2030 2040 2050
HNRLQYSLEY FQFVKKLLTC NGVYLNPAPG QDYLLPEAEE ITMISIQLAA
2060 2070 2080 2090 2100
RFLFTTGFHT KKIVRGPASD WYDALCVLLR HSKNVRFWFT HNVLFNVSNR
2110 2120 2130 2140 2150
FSEYLLECPS AEVRGAFAKL IVFIAHFSLQ DGSCPSPFAS PGPSSQACDN
2160 2170 2180 2190 2200
LSLSDHLLRA TLNLLRREVS EHGHHLQQYF NLFVMYANLG VAEKTQLLKL
2210 2220 2230 2240 2250
NVPATFMLVS LDEGPGPPIK YQYAELGKLY SVVSQLIRCC NVSSTMQSSI
2260 2270 2280 2290 2300
NGNPPLPNPF GDLNLSQPIM PIQQNVLDIL FVRTSYVKKI IEDCSNSEDT
2310 2320 2330 2340 2350
IKLLRFCSWE NPQFSSTVLS ELLWQVAYSY TYELRPYLDL LFQILLIEDS
2360 2370 2380 2390 2400
WQTHRIHNAL KGIPDDRDGL FDTIQRSKNH YQKRAYQCIK CMVALFSSCP
2410 2420 2430 2440 2450
VAYQILQGNG DLKRKWTWAV EWLGDELERR PYTGNPQYSY NNWSPPVQSN
2460 2470 2480 2490 2500
ETANGYFLER SHSARMTLAK ACELCPEEEP DDQDAPDEHE PSPSEDAPLY
2510 2520 2530 2540 2550
PHSPASQYQQ NNHVHGQPYT GPAAHHLNNP QKTGQRTQEN YEGNEEVSSP

QMKDQ
Length:2,555
Mass (Da):291,077
Last modified:May 5, 2009 - v2
Checksum:i421D47D5899F4415
GO
Isoform Short (identifier: O00507-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     2071-2555: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.
Show »
Length:2,070
Mass (Da):235,723
Checksum:i70219CB0CCD269C5
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti206D → E in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti206D → E in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti282I → M in AAC51833 (PubMed:9381176).Curated1
Sequence conflicti524D → Y in AAC51833 (PubMed:9381176).Curated1
Sequence conflicti542S → A in AAC51833 (PubMed:9381176).Curated1
Sequence conflicti666L → V in AAC51833 (PubMed:9381176).Curated1
Sequence conflicti883R → C in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti883R → C in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti907S → F in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti907S → F in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti946D → N in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti946D → N in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti1002E → K in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti1002E → K in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti1017R → K in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti1017R → K in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti1025 – 1027VAD → FAN in CAA73940 (PubMed:9384609).Curated3
Sequence conflicti1025 – 1027VAD → FAN in CAA73941 (PubMed:9384609).Curated3
Sequence conflicti1038 – 1039RD → KN in CAA73940 (PubMed:9384609).Curated2
Sequence conflicti1038 – 1039RD → KN in CAA73941 (PubMed:9384609).Curated2
Sequence conflicti1067K → N in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti1067K → N in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti1258V → F in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti1258V → F in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti1733Y → F in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti1733Y → F in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti1953L → P in CAA73940 (PubMed:9384609).Curated1
Sequence conflicti1953L → P in CAA73941 (PubMed:9384609).Curated1
Sequence conflicti2086R → G in AAC51833 (PubMed:9381176).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05535065E → D.Corresponds to variant rs7067496dbSNPEnsembl.1
Natural variantiVAR_055351211R → C.Corresponds to variant rs2032596dbSNPEnsembl.1
Natural variantiVAR_0293281035P → S.Corresponds to variant rs20319dbSNPEnsembl.1
Natural variantiVAR_0161941060A → T.1 PublicationCorresponds to variant rs20320dbSNPEnsembl.1
Natural variantiVAR_0553521705A → S.Corresponds to variant rs2032606dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0052722071 – 2555Missing in isoform Short. CuratedAdd BLAST485

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000986 mRNA. Translation: AAC51833.1.
Y13618 mRNA. Translation: CAA73940.1.
Y13619 mRNA. Translation: CAA73941.1.
AC002531 Genomic DNA. No translation available.
CCDSiCCDS14781.1. [O00507-1]
RefSeqiNP_004645.2. NM_004654.3. [O00507-1]
UniGeneiHs.598540.

Genome annotation databases

EnsembliENST00000338981; ENSP00000342812; ENSG00000114374. [O00507-1]
GeneIDi8287.
KEGGihsa:8287.
UCSCiuc004fst.2. human. [O00507-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF000986 mRNA. Translation: AAC51833.1.
Y13618 mRNA. Translation: CAA73940.1.
Y13619 mRNA. Translation: CAA73941.1.
AC002531 Genomic DNA. No translation available.
CCDSiCCDS14781.1. [O00507-1]
RefSeqiNP_004645.2. NM_004654.3. [O00507-1]
UniGeneiHs.598540.

3D structure databases

ProteinModelPortaliO00507.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113892. 13 interactors.
IntActiO00507. 6 interactors.
MINTiMINT-7230431.
STRINGi9606.ENSP00000342812.

Protein family/group databases

MEROPSiC19.028.

PTM databases

iPTMnetiO00507.
PhosphoSitePlusiO00507.

Polymorphism and mutation databases

BioMutaiUSP9Y.

Proteomic databases

EPDiO00507.
MaxQBiO00507.
PaxDbiO00507.
PeptideAtlasiO00507.
PRIDEiO00507.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338981; ENSP00000342812; ENSG00000114374. [O00507-1]
GeneIDi8287.
KEGGihsa:8287.
UCSCiuc004fst.2. human. [O00507-1]

Organism-specific databases

CTDi8287.
DisGeNETi8287.
GeneCardsiUSP9Y.
GeneReviewsiUSP9Y.
HGNCiHGNC:12633. USP9Y.
MalaCardsiUSP9Y.
MIMi400005. gene.
415000. phenotype.
neXtProtiNX_O00507.
OpenTargetsiENSG00000114374.
Orphaneti1646. Partial chromosome Y deletion.
PharmGKBiPA37258.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1866. Eukaryota.
COG5077. LUCA.
GeneTreeiENSGT00760000119158.
HOGENOMiHOG000231283.
HOVERGENiHBG073749.
InParanoidiO00507.
KOiK11840.
OMAiNSINCAR.
OrthoDBiEOG091G0069.
PhylomeDBiO00507.
TreeFamiTF323966.

Enzyme and pathway databases

BioCyciZFISH:HS03762-MONOMER.

Miscellaneous databases

GeneWikiiUSP9Y.
GenomeRNAii8287.
PROiO00507.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000114374.
CleanExiHS_USP10.
HS_USP9Y.
ExpressionAtlasiO00507. baseline and differential.
GenevisibleiO00507. HS.

Family and domain databases

InterProiIPR016024. ARM-type_fold.
IPR001394. Peptidase_C19_UCH.
IPR018200. USP_CS.
IPR028889. USP_dom.
[Graphical view]
PfamiPF00443. UCH. 1 hit.
[Graphical view]
SUPFAMiSSF48371. SSF48371. 3 hits.
PROSITEiPS00972. USP_1. 1 hit.
PS00973. USP_2. 1 hit.
PS50235. USP_3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiUSP9Y_HUMAN
AccessioniPrimary (citable) accession number: O00507
Secondary accession number(s): O14601
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 5, 2009
Last modified: November 2, 2016
This is version 161 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome Y
    Human chromosome Y: 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. Peptidase families
    Classification of peptidase families and list of entries
  6. 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.