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Protein

Cardiac phospholamban

Gene

PLN

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

Functioni

Reversibly inhibits the activity of ATP2A2 in cardiac sarcoplasmic reticulum by decreasing the apparent affinity of the ATPase for Ca2+. Modulates the contractility of the heart muscle in response to physiological stimuli via its effects on ATP2A2. Modulates calcium re-uptake during muscle relaxation and plays an important role in calcium homeostasis in the heart muscle. The degree of ATP2A2 inhibition depends on the oligomeric state of PLN. ATP2A2 inhibition is alleviated by PLN phosphorylation.2 Publications

GO - Molecular functioni

  1. ATPase binding Source: BHF-UCL
  2. ATPase inhibitor activity Source: BHF-UCL
  3. calcium channel regulator activity Source: InterPro
  4. enzyme inhibitor activity Source: BHF-UCL
  5. identical protein binding Source: BHF-UCL

GO - Biological processi

  1. adrenergic receptor signaling pathway involved in heart process Source: Ensembl
  2. blood circulation Source: ProtInc
  3. calcium ion transport Source: InterPro
  4. cardiac muscle tissue development Source: Ensembl
  5. cytosolic calcium ion homeostasis Source: BHF-UCL
  6. negative regulation of ATPase activity Source: BHF-UCL
  7. negative regulation of calcium ion binding Source: BHF-UCL
  8. negative regulation of calcium ion import Source: BHF-UCL
  9. negative regulation of calcium ion import into sarcoplasmic reticulum Source: BHF-UCL
  10. negative regulation of calcium ion transmembrane transporter activity Source: BHF-UCL
  11. negative regulation of calcium ion transport Source: BHF-UCL
  12. negative regulation of calcium-transporting ATPase activity Source: BHF-UCL
  13. negative regulation of catalytic activity Source: BHF-UCL
  14. negative regulation of heart rate Source: BHF-UCL
  15. protein homooligomerization Source: Ensembl
  16. regulation of calcium ion transport Source: UniProtKB
  17. regulation of calcium-transporting ATPase activity Source: UniProtKB
  18. regulation of cardiac muscle cell contraction Source: BHF-UCL
  19. regulation of cardiac muscle cell membrane potential Source: BHF-UCL
  20. regulation of cardiac muscle contraction by regulation of the release of sequestered calcium ion Source: Ensembl
  21. regulation of heart contraction Source: BHF-UCL
  22. regulation of relaxation of cardiac muscle Source: BHF-UCL
  23. regulation of ryanodine-sensitive calcium-release channel activity Source: Ensembl
  24. regulation of the force of heart contraction Source: BHF-UCL
  25. regulation of the force of heart contraction by cardiac conduction Source: Ensembl
  26. relaxation of cardiac muscle Source: BHF-UCL
  27. response to insulin Source: Ensembl
  28. response to testosterone Source: Ensembl
  29. response to zinc ion Source: Ensembl
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_25149. Ion transport by P-type ATPases.

Protein family/group databases

TCDBi1.A.50.1.1. the phospholamban (ca(2+)-channel and ca(2+)-atpase regulator) (plb) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Cardiac phospholamban
Short name:
PLB
Gene namesi
Name:PLN
Synonyms:PLB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:9080. PLN.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3131CytoplasmicCuratedAdd
BLAST
Transmembranei32 – 5221HelicalCuratedAdd
BLAST

GO - Cellular componenti

  1. calcium ion-transporting ATPase complex Source: BHF-UCL
  2. endoplasmic reticulum Source: BHF-UCL
  3. membrane Source: BHF-UCL
  4. mitochondrial membrane Source: UniProtKB-SubCell
  5. mitochondrion Source: UniProtKB
  6. perinuclear region of cytoplasm Source: BHF-UCL
  7. sarcoplasmic reticulum membrane Source: UniProtKB-SubCell
  8. vesicle Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Mitochondrion, Sarcoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Cardiomyopathy, dilated 1P (CMD1P)2 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.

See also OMIM:609909
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti9 – 91R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025989
Natural varianti14 – 141Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025990
Cardiomyopathy, familial hypertrophic 18 (CMH18)1 Publication

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionA hereditary heart disorder characterized by ventricular hypertrophy, which is usually asymmetric and often involves the interventricular septum. The symptoms include dyspnea, syncope, collapse, palpitations, and chest pain. They can be readily provoked by exercise. The disorder has inter- and intrafamilial variability ranging from benign to malignant forms with high risk of cardiac failure and sudden cardiac death.

See also OMIM:613874

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi9 – 91R → H or L: Impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 1 Publication
Mutagenesisi13 – 131R → A: Abolishes phosphorylation by PKA. 1 Publication
Mutagenesisi14 – 141R → A: Abolishes phosphorylation by PKA. 1 Publication
Mutagenesisi16 – 161S → A: Abolishes phosphorylation by PKA. 1 Publication
Mutagenesisi17 – 171T → A: No effect on phosphorylation by PKA. 1 Publication

Keywords - Diseasei

Cardiomyopathy, Disease mutation

Organism-specific databases

MIMi609909. phenotype.
613874. phenotype.
Orphaneti154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA272.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 5252Cardiac phospholambanPRO_0000191244Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei16 – 161Phosphoserine; by PKA and DMPK2 Publications
Modified residuei17 – 171Phosphothreonine; by CaMK21 Publication

Post-translational modificationi

Phosphorylation by PKA abolishes the inhibition of ATP2A2-mediated calcium uptake. Phosphorylated at Thr-17 by CaMK2, and in response to beta-adrenergic stimulation. Phosphorylation by DMPK may stimulate sarcoplasmic reticulum calcium uptake in cardiomyocytes.3 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiP26678.
PaxDbiP26678.
PRIDEiP26678.

PTM databases

PhosphoSiteiP26678.

Expressioni

Tissue specificityi

Heart muscle (at protein level).1 Publication

Gene expression databases

BgeeiP26678.
CleanExiHS_PLN.
ExpressionAtlasiP26678. baseline and differential.
GenevestigatoriP26678.

Organism-specific databases

HPAiCAB005597.
HPA026900.

Interactioni

Subunit structurei

Homopentamer. Interacts with HAX1 and ATP2A2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
DMPKQ090134EBI-692836,EBI-692774

Protein-protein interaction databases

BioGridi111365. 8 interactions.
IntActiP26678. 2 interactions.
STRINGi9606.ENSP00000350132.

Structurei

Secondary structure

1
52
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi4 – 1411Combined sources
Beta strandi18 – 203Combined sources
Helixi23 – 5028Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1K9Nmodel-A/B/C/D/E35-52[»]
1KCHmodel-A/B/C/D/E35-52[»]
1PLNmodel-A/B/C/D/E35-52[»]
1PLPNMR-A1-24[»]
1PSLmodel-A/B/C/D/E1-52[»]
1ZLLNMR-A/B/C/D/E1-52[»]
2HYNNMR-A/B/C/D/E1-52[»]
ProteinModelPortaliP26678.
SMRiP26678. Positions 1-35.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP26678.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni16 – 227Involved in HAX1 binding

Sequence similaritiesi

Belongs to the phospholamban family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG44917.
HOGENOMiHOG000115660.
HOVERGENiHBG108280.
InParanoidiP26678.
KOiK05852.
OMAiQHARQNL.
PhylomeDBiP26678.
TreeFamiTF330750.

Family and domain databases

InterProiIPR005984. P_lamban.
[Graphical view]
PANTHERiPTHR21194. PTHR21194. 1 hit.
PfamiPF04272. Phospholamban. 1 hit.
[Graphical view]
PIRSFiPIRSF001665. PLB. 1 hit.
ProDomiPD014689. P_lamban. 1 hit.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsiTIGR01294. P_lamban. 1 hit.

Sequencei

Sequence statusi: Complete.

P26678-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEKVQYLTRS AIRRASTIEM PQQARQKLQN LFINFCLILI CLLLICIIVM

LL
Length:52
Mass (Da):6,109
Last modified:July 31, 1992 - v1
Checksum:i0766304A76A854D3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti9 – 91R → C in CMD1P; impairs phosphorylation by PKA and inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025989
Natural varianti14 – 141Missing in CMD1P; impairs phosphorylation by PKA, destabilizes the homopentamer and mildly reduces inhibition of ATP2A1-mediated calcium uptake. 3 Publications
VAR_025990

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63603 mRNA. Translation: AAA60083.1.
M60411 mRNA. Translation: AAA60109.1.
AF177764 Genomic DNA. Translation: AAD55950.1.
BC005269 mRNA. Translation: AAH05269.1.
CCDSiCCDS5120.1.
PIRiA40424.
RefSeqiNP_002658.1. NM_002667.3.
UniGeneiHs.170839.

Genome annotation databases

EnsembliENST00000357525; ENSP00000350132; ENSG00000198523.
GeneIDi5350.
KEGGihsa:5350.
UCSCiuc003pye.3. human.

Polymorphism databases

DMDMi130774.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M63603 mRNA. Translation: AAA60083.1.
M60411 mRNA. Translation: AAA60109.1.
AF177764 Genomic DNA. Translation: AAD55950.1.
BC005269 mRNA. Translation: AAH05269.1.
CCDSiCCDS5120.1.
PIRiA40424.
RefSeqiNP_002658.1. NM_002667.3.
UniGeneiHs.170839.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1K9Nmodel-A/B/C/D/E35-52[»]
1KCHmodel-A/B/C/D/E35-52[»]
1PLNmodel-A/B/C/D/E35-52[»]
1PLPNMR-A1-24[»]
1PSLmodel-A/B/C/D/E1-52[»]
1ZLLNMR-A/B/C/D/E1-52[»]
2HYNNMR-A/B/C/D/E1-52[»]
ProteinModelPortaliP26678.
SMRiP26678. Positions 1-35.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111365. 8 interactions.
IntActiP26678. 2 interactions.
STRINGi9606.ENSP00000350132.

Protein family/group databases

TCDBi1.A.50.1.1. the phospholamban (ca(2+)-channel and ca(2+)-atpase regulator) (plb) family.

PTM databases

PhosphoSiteiP26678.

Polymorphism databases

DMDMi130774.

Proteomic databases

MaxQBiP26678.
PaxDbiP26678.
PRIDEiP26678.

Protocols and materials databases

DNASUi5350.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357525; ENSP00000350132; ENSG00000198523.
GeneIDi5350.
KEGGihsa:5350.
UCSCiuc003pye.3. human.

Organism-specific databases

CTDi5350.
GeneCardsiGC06P118869.
GeneReviewsiPLN.
HGNCiHGNC:9080. PLN.
HPAiCAB005597.
HPA026900.
MIMi172405. gene.
609909. phenotype.
613874. phenotype.
neXtProtiNX_P26678.
Orphaneti154. Familial isolated dilated cardiomyopathy.
155. Familial isolated hypertrophic cardiomyopathy.
PharmGKBiPA272.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG44917.
HOGENOMiHOG000115660.
HOVERGENiHBG108280.
InParanoidiP26678.
KOiK05852.
OMAiQHARQNL.
PhylomeDBiP26678.
TreeFamiTF330750.

Enzyme and pathway databases

ReactomeiREACT_25149. Ion transport by P-type ATPases.

Miscellaneous databases

EvolutionaryTraceiP26678.
GeneWikiiPhospholamban.
GenomeRNAii5350.
NextBioi20738.
PROiP26678.
SOURCEiSearch...

Gene expression databases

BgeeiP26678.
CleanExiHS_PLN.
ExpressionAtlasiP26678. baseline and differential.
GenevestigatoriP26678.

Family and domain databases

InterProiIPR005984. P_lamban.
[Graphical view]
PANTHERiPTHR21194. PTHR21194. 1 hit.
PfamiPF04272. Phospholamban. 1 hit.
[Graphical view]
PIRSFiPIRSF001665. PLB. 1 hit.
ProDomiPD014689. P_lamban. 1 hit.
[Graphical view] [Entries sharing at least one domain]
TIGRFAMsiTIGR01294. P_lamban. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Structure of the rabbit phospholamban gene, cloning of the human cDNA, and assignment of the gene to human chromosome 6."
    Fujii J., Zarain-Herzberg A., Willard H.F., Tada M., Maclennan D.H.
    J. Biol. Chem. 266:11669-11675(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  2. "Cloning of human cardiac phospholamban."
    Salvatore C.A., Jacobson M.A.
    Submitted (FEB-1991) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  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(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Liver.
  5. "Mutation of the phospholamban promoter associated with hypertrophic cardiomyopathy."
    Minamisawa S., Sato Y., Tatsuguchi Y., Fujino T., Imamura S., Uetsuka Y., Nakazawa M., Matsuoka R.
    Biochem. Biophys. Res. Commun. 304:1-4(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CMH18.
  6. "Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum."
    Kaliman P., Catalucci D., Lam J.T., Kondo R., Gutierrez J.C., Reddy S., Palacin M., Zorzano A., Chien K.R., Ruiz-Lozano P.
    J. Biol. Chem. 280:8016-8021(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-16 BY DMPK.
  7. "Ca2+-calmodulin-dependent protein kinase expression and signalling in skeletal muscle during exercise."
    Rose A.J., Kiens B., Richter E.A.
    J. Physiol. (Lond.) 574:889-903(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-17 BY CAMK2.
  8. "Phospholamban interacts with HAX-1, a mitochondrial protein with anti-apoptotic function."
    Vafiadaki E., Sanoudou D., Arvanitis D.A., Catino D.H., Kranias E.G., Kontrogianni-Konstantopoulos A.
    J. Mol. Biol. 367:65-79(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH HAX1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  9. "Lethal, hereditary mutants of phospholamban elude phosphorylation by protein kinase A."
    Ceholski D.K., Trieber C.A., Holmes C.F., Young H.S.
    J. Biol. Chem. 287:26596-26605(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, CHARACTERIZATION OF VARIANTS CMD1P CYS-9 AND ARG-14 DEL, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-16, MUTAGENESIS OF ARG-9; ARG-13; ARG-14; SER-16 AND THR-17.
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. "Solution structure of the cytoplasmic domain of phospholamban: phosphorylation leads to a local perturbation in secondary structure."
    Mortishire-Smith R.J., Pitzenberger S.M., Burke C.J., Middaugh C.R., Garsky V.M., Johnson R.G.
    Biochemistry 34:7603-7613(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 1-25.
  12. "Computational searching and mutagenesis suggest a structure for the pentameric transmembrane domain of phospholamban."
    Adams P.D., Arkin I.T., Engelman D.M., Bruenger A.T.
    Nat. Struct. Biol. 2:154-162(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.
  13. "Using experimental information to produce a model of the transmembrane domain of the ion channel phospholamban."
    Herzyk P., Hubbard R.E.
    Biophys. J. 74:1203-1214(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: 3D-STRUCTURE MODELING.
  14. "The structure of phospholamban pentamer reveals a channel-like architecture in membranes."
    Oxenoid K., Chou J.J.
    Proc. Natl. Acad. Sci. U.S.A. 102:10870-10875(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR, SUBCELLULAR LOCATION, SUBUNIT.
  15. "Structure determination of symmetric homo-oligomers by a complete search of symmetry configuration space, using NMR restraints and van der Waals packing."
    Potluri S., Yan A.K., Chou J.J., Donald B.R., Bailey-Kellogg C.
    Proteins 65:203-219(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR, SUBUNIT.
  16. "Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban."
    Schmitt J.P., Kamisago M., Asahi M., Li G.H., Ahmad F., Mende U., Kranias E.G., MacLennan D.H., Seidman J.G., Seidman C.E.
    Science 299:1410-1413(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CMD1P CYS-9, CHARACTERIZATION OF VARIANT CMD1P CYS-9.
  17. Cited for: VARIANT CMD1P ARG-14 DEL, CHARACTERIZATION OF VARIANT CMD1P ARG-14 DEL.
  18. "Hydrophobic imbalance in the cytoplasmic domain of phospholamban is a determinant for lethal dilated cardiomyopathy."
    Ceholski D.K., Trieber C.A., Young H.S.
    J. Biol. Chem. 287:16521-16529(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: CHARACTERIZATION OF VARIANTS CMD1P CYS-9 AND ARG-14 DEL, FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiPPLA_HUMAN
AccessioniPrimary (citable) accession number: P26678
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 31, 1992
Last sequence update: July 31, 1992
Last modified: March 3, 2015
This is version 149 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

Miscellaneous

For practical reasons, PLN activity is most often studied with ATP2A1 instead of ATP2A2.

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: 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.