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Protein

Polycystic kidney disease 2-like 1 protein

Gene

PKD2L1

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

Functioni

Pore-forming subunit of a ciliary calcium channel that controls calcium concentration within primary cilia without affecting cytoplasmic calcium concentration. Forms a heterodimer with PKD1L1 in primary cilia and forms a calcium-permeant ciliary channel that regulates sonic hedgehog/SHH signaling and GLI2 transcription. May act as a sour taste receptor by forming a calcium channel with PKD1L3 in gustatory cells; however, its contribution to sour taste perception is unclear in vivo and may be indirect.4 Publications

Enzyme regulationi

The calcium channel is gated following an off-response property by acid: gated open after the removal of acid stimulus, but not during acid application.3 Publications

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Calcium bindingi646 – 657Sequence analysisAdd BLAST12

GO - Molecular functioni

  • alpha-actinin binding Source: BHF-UCL
  • calcium activated cation channel activity Source: BHF-UCL
  • calcium-activated potassium channel activity Source: BHF-UCL
  • calcium channel activity Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • cation channel activity Source: BHF-UCL
  • cytoskeletal protein binding Source: UniProtKB
  • identical protein binding Source: BHF-UCL
  • muscle alpha-actinin binding Source: BHF-UCL
  • sodium channel activity Source: BHF-UCL
  • sour taste receptor activity Source: Ensembl

GO - Biological processi

  • cation transport Source: BHF-UCL
  • cellular response to acidic pH Source: BHF-UCL
  • detection of chemical stimulus involved in sensory perception of sour taste Source: BHF-UCL
  • detection of mechanical stimulus Source: GO_Central
  • potassium ion transmembrane transport Source: BHF-UCL
  • protein homotrimerization Source: UniProtKB
  • sensory perception of sour taste Source: UniProtKB
  • smoothened signaling pathway Source: UniProtKB
  • sodium ion transmembrane transport Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Calcium channel, Ion channel

Keywords - Biological processi

Calcium transport, Ion transport, Transport

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000107593-MONOMER.

Protein family/group databases

TCDBi1.A.5.1.3. the polycystin cation channel (pcc) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Polycystic kidney disease 2-like 1 protein
Alternative name(s):
Polycystin-2 homolog
Polycystin-2L1
Polycystin-L
Polycystin-L1
Gene namesi
Name:PKD2L1
Synonyms:PKD2L, PKDL, TRPP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:9011. PKD2L1.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 103CytoplasmicSequence analysisAdd BLAST103
Transmembranei104 – 124HelicalSequence analysisAdd BLAST21
Topological domaini125 – 313ExtracellularSequence analysisAdd BLAST189
Transmembranei314 – 334HelicalSequence analysisAdd BLAST21
Topological domaini335 – 347CytoplasmicSequence analysisAdd BLAST13
Transmembranei348 – 368HelicalSequence analysisAdd BLAST21
Topological domaini369 – 384ExtracellularSequence analysisAdd BLAST16
Transmembranei385 – 405HelicalSequence analysisAdd BLAST21
Topological domaini406 – 476CytoplasmicSequence analysisAdd BLAST71
Transmembranei477 – 497HelicalSequence analysisAdd BLAST21
Topological domaini498 – 539ExtracellularSequence analysisAdd BLAST42
Transmembranei540 – 560HelicalSequence analysisAdd BLAST21
Topological domaini561 – 805CytoplasmicSequence analysisAdd BLAST245

GO - Cellular componenti

  • calcium channel complex Source: UniProtKB
  • cell surface Source: Ensembl
  • ciliary membrane Source: UniProtKB-SubCell
  • endoplasmic reticulum Source: BHF-UCL
  • integral component of membrane Source: UniProtKB
  • intracellular membrane-bounded organelle Source: BHF-UCL
  • membrane Source: UniProtKB
  • non-motile cilium Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • receptor complex Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cilium, Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi523 – 525DFD → AFA: Abolishes ion channel activity. 1 Publication3
Mutagenesisi523D → Q: Increased permeability of dimethylamine and trimethylamine and decreased permeability of magnesium. 1 Publication1
Mutagenesisi525D → K: Increased permeability of dimethylamine and trimethylamine and decreased permeability of magnesium. 1 Publication1
Mutagenesisi530D → A: Does not affect ion channel activity. 1
Mutagenesisi710L → A: Abolishes homotrimer formation; when associated with A-714; A-717; A-728; A-731 and A-735. 1 Publication1
Mutagenesisi714V → A: Abolishes homotrimer formation; when associated with A-710; A-717; A-728; A-731 and A-735. 1 Publication1
Mutagenesisi717L → A: Abolishes homotrimer formation; when associated with A-710; A-714; A-728; A-731 and A-735. 1 Publication1
Mutagenesisi728I → A: Abolishes homotrimer formation; when associated with A-710; A-714; A-717; A-731 and A-735. 1 Publication1
Mutagenesisi731V → A: Abolishes homotrimer formation; when associated with A-710; A-714; A-717; A-728 and A-735. 1 Publication1
Mutagenesisi735L → A: Abolishes homotrimer formation; when associated with A-710; A-714; A-717; A-728 and A-731. 1 Publication1

Organism-specific databases

DisGeNETi9033.
OpenTargetsiENSG00000107593.
PharmGKBiPA33344.

Chemistry databases

GuidetoPHARMACOLOGYi505.

Polymorphism and mutation databases

BioMutaiPKD2L1.
DMDMi23821938.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001643601 – 805Polycystic kidney disease 2-like 1 proteinAdd BLAST805

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi177N-linked (GlcNAc...)Sequence analysis1
Glycosylationi207N-linked (GlcNAc...)Sequence analysis1
Glycosylationi241N-linked (GlcNAc...)Sequence analysis1
Glycosylationi505N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiQ9P0L9.
PeptideAtlasiQ9P0L9.
PRIDEiQ9P0L9.

PTM databases

iPTMnetiQ9P0L9.
PhosphoSitePlusiQ9P0L9.

Expressioni

Tissue specificityi

Expressed in adult heart, skeletal muscle, brain, spleen, testis, retina and liver. According to PubMed:9748274, expressed at high levels in fetal tissues, including kidney and liver, and down-regulated in adult tissues. According to PubMed:10602361, expressed in fetal brain, but not expressed in fetal lung, liver or kidney. Isoform 4 appears to be expressed only in transformed lymphoblasts.2 Publications

Gene expression databases

BgeeiENSG00000107593.
CleanExiHS_PKD2L1.
ExpressionAtlasiQ9P0L9. baseline and differential.
GenevisibleiQ9P0L9. HS.

Organism-specific databases

HPAiCAB022621.

Interactioni

Subunit structurei

Homotrimer; trimerization is independent of calcium-binding. Calcium channels are probably composed of 3 subunit of PKD2L1 and 1 subunit of some PKD1 protein (PKD1, PKD1L1, PKD1L2 or PKDL3). Interacts with PKD1. Interacts with PKD1L1; to form ciliary calcium channel. Interacts with PKD1L3, to form putative sour taste receptor. Interacts with RACK1; inhibits the channel activity possibly by impairing localization to the cell membrane.6 Publications

GO - Molecular functioni

  • alpha-actinin binding Source: BHF-UCL
  • cytoskeletal protein binding Source: UniProtKB
  • identical protein binding Source: BHF-UCL
  • muscle alpha-actinin binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi114499. 2 interactors.
IntActiQ9P0L9. 1 interactor.
MINTiMINT-3973148.
STRINGi9606.ENSP00000325296.

Structurei

Secondary structure

1805
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi704 – 731Combined sources28
Helixi734 – 741Combined sources8

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TE3X-ray2.69A/B/C/D/E/F699-737[»]
4GIFX-ray2.80A699-743[»]
ProteinModelPortaliQ9P0L9.
SMRiQ9P0L9.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini633 – 668EF-handAdd BLAST36

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni704 – 763Required for protein homotrimerizationAdd BLAST60

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili650 – 686Sequence analysisAdd BLAST37

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi195 – 207Polycystin motifAdd BLAST13

Domaini

The EF-hand domain probably mediates calcium-binding. It is not required for channel activation (PubMed:11959145).1 Publication

Sequence similaritiesi

Belongs to the polycystin family.Curated
Contains 1 EF-hand domain.Curated

Keywords - Domaini

Coiled coil, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3599. Eukaryota.
ENOG410XTGE. LUCA.
GeneTreeiENSGT00700000104221.
HOGENOMiHOG000230858.
HOVERGENiHBG014945.
InParanoidiQ9P0L9.
KOiK04990.
OMAiFIYYENM.
OrthoDBiEOG091G034F.
PhylomeDBiQ9P0L9.
TreeFamiTF316484.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR013122. PKD1_2_channel.
IPR003915. PKD_2.
[Graphical view]
PfamiPF08016. PKD_channel. 1 hit.
[Graphical view]
PRINTSiPR01433. POLYCYSTIN2.

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9P0L9-1) [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
MNAVGSPEGQ ELQKLGSGAW DNPAYSGPPS PHGTLRVCTI SSTGPLQPQP
60 70 80 90 100
KKPEDEPQET AYRTQVSSCC LHICQGIRGL WGTTLTENTA ENRELYIKTT
110 120 130 140 150
LRELLVYIVF LVDICLLTYG MTSSSAYYYT KVMSELFLHT PSDTGVSFQA
160 170 180 190 200
ISSMADFWDF AQGPLLDSLY WTKWYNNQSL GHGSHSFIYY ENMLLGVPRL
210 220 230 240 250
RQLKVRNDSC VVHEDFREDI LSCYDVYSPD KEEQLPFGPF NGTAWTYHSQ
260 270 280 290 300
DELGGFSHWG RLTSYSGGGY YLDLPGSRQG SAEALRALQE GLWLDRGTRV
310 320 330 340 350
VFIDFSVYNA NINLFCVLRL VVEFPATGGA IPSWQIRTVK LIRYVSNWDF
360 370 380 390 400
FIVGCEVIFC VFIFYYVVEE ILELHIHRLR YLSSIWNILD LVVILLSIVA
410 420 430 440 450
VGFHIFRTLE VNRLMGKLLQ QPNTYADFEF LAFWQTQYNN MNAVNLFFAW
460 470 480 490 500
IKIFKYISFN KTMTQLSSTL ARCAKDILGF AVMFFIVFFA YAQLGYLLFG
510 520 530 540 550
TQVENFSTFI KCIFTQFRII LGDFDYNAID NANRILGPAY FVTYVFFVFF
560 570 580 590 600
VLLNMFLAII NDTYSEVKEE LAGQKDELQL SDLLKQGYNK TLLRLRLRKE
610 620 630 640 650
RVSDVQKVLQ GGEQEIQFED FTNTLRELGH AEHEITELTA TFTKFDRDGN
660 670 680 690 700
RILDEKEQEK MRQDLEEERV ALNTEIEKLG RSIVSSPQGK SGPEAARAGG
710 720 730 740 750
WVSGEEFYML TRRVLQLETV LEGVVSQIDA VGSKLKMLER KGWLAPSPGV
760 770 780 790 800
KEQAIWKHPQ PAPAVTPDPW GVQGGQESEV PYKREEEALE ERRLSRGEIP

TLQRS
Length:805
Mass (Da):91,982
Last modified:October 1, 2000 - v1
Checksum:i3714C07F4B71F9C6
GO
Isoform 2 (identifier: Q9P0L9-2) [UniParc]FASTAAdd to basket
Also known as: PKDLdel15, PCL-TS, Testis isoform

The sequence of this isoform differs from the canonical sequence as follows:
     751-760: KEQAIWKHPQ → RFPIKEKRKP
     761-805: Missing.

Show »
Length:760
Mass (Da):86,988
Checksum:i203D20F881C40055
GO
Isoform 3 (identifier: Q9P0L9-3) [UniParc]FASTAAdd to basket
Also known as: PKDLdel5

The sequence of this isoform differs from the canonical sequence as follows:
     245-319: Missing.

Show »
Length:730
Mass (Da):83,511
Checksum:i02ABA835A71B32AD
GO
Isoform 4 (identifier: Q9P0L9-4) [UniParc]FASTAAdd to basket
Also known as: PKDLdel456

The sequence of this isoform differs from the canonical sequence as follows:
     225-344: Missing.

Note: Unusual intron exon spliced junction.
Show »
Length:685
Mass (Da):78,520
Checksum:iE805D32F37E6F54E
GO
Isoform 5 (identifier: Q9P0L9-5) [UniParc]FASTAAdd to basket
Also known as: PCL-LV, Liver isoform

The sequence of this isoform differs from the canonical sequence as follows:
     638-666: Missing.

Show »
Length:776
Mass (Da):88,472
Checksum:i2EC2917E99DFF104
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13Q → H in AAD41638 (PubMed:9748274).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050555278R → Q.Corresponds to variant rs17112895dbSNPEnsembl.1
Natural variantiVAR_050556378R → W.Corresponds to variant rs7909153dbSNPEnsembl.1
Natural variantiVAR_024569393V → I.1 PublicationCorresponds to variant rs2278842dbSNPEnsembl.1
Natural variantiVAR_024570681R → L.Corresponds to variant rs6584356dbSNPEnsembl.1
Natural variantiVAR_050557788A → D.Corresponds to variant rs12782963dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_004728225 – 344Missing in isoform 4. 1 PublicationAdd BLAST120
Alternative sequenceiVSP_004729245 – 319Missing in isoform 3. CuratedAdd BLAST75
Alternative sequenceiVSP_053718638 – 666Missing in isoform 5. CuratedAdd BLAST29
Alternative sequenceiVSP_004730751 – 760KEQAIWKHPQ → RFPIKEKRKP in isoform 2. Curated10
Alternative sequenceiVSP_004731761 – 805Missing in isoform 2. CuratedAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF073481 mRNA. Translation: AAD41638.1.
AF153474
, AF153459, AF153460, AF153461, AF153462, AF153463, AF153464, AF153465, AF153466, AF153467, AF153468, AF153469, AF153470, AF153471, AF153472, AF153473 Genomic DNA. Translation: AAF28108.1.
AL139819 Genomic DNA. Translation: CAH72822.1.
CH471066 Genomic DNA. Translation: EAW49833.1.
BC025665 mRNA. Translation: AAH25665.1.
AF094827 mRNA. Translation: AAD08695.1.
AF053316 mRNA. Translation: AAD51859.1.
CCDSiCCDS7492.1. [Q9P0L9-1]
RefSeqiNP_001240766.1. NM_001253837.1.
NP_057196.2. NM_016112.2. [Q9P0L9-1]
UniGeneiHs.159241.

Genome annotation databases

EnsembliENST00000318222; ENSP00000325296; ENSG00000107593. [Q9P0L9-1]
GeneIDi9033.
KEGGihsa:9033.
UCSCiuc001kqx.2. human. [Q9P0L9-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF073481 mRNA. Translation: AAD41638.1.
AF153474
, AF153459, AF153460, AF153461, AF153462, AF153463, AF153464, AF153465, AF153466, AF153467, AF153468, AF153469, AF153470, AF153471, AF153472, AF153473 Genomic DNA. Translation: AAF28108.1.
AL139819 Genomic DNA. Translation: CAH72822.1.
CH471066 Genomic DNA. Translation: EAW49833.1.
BC025665 mRNA. Translation: AAH25665.1.
AF094827 mRNA. Translation: AAD08695.1.
AF053316 mRNA. Translation: AAD51859.1.
CCDSiCCDS7492.1. [Q9P0L9-1]
RefSeqiNP_001240766.1. NM_001253837.1.
NP_057196.2. NM_016112.2. [Q9P0L9-1]
UniGeneiHs.159241.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3TE3X-ray2.69A/B/C/D/E/F699-737[»]
4GIFX-ray2.80A699-743[»]
ProteinModelPortaliQ9P0L9.
SMRiQ9P0L9.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114499. 2 interactors.
IntActiQ9P0L9. 1 interactor.
MINTiMINT-3973148.
STRINGi9606.ENSP00000325296.

Chemistry databases

GuidetoPHARMACOLOGYi505.

Protein family/group databases

TCDBi1.A.5.1.3. the polycystin cation channel (pcc) family.

PTM databases

iPTMnetiQ9P0L9.
PhosphoSitePlusiQ9P0L9.

Polymorphism and mutation databases

BioMutaiPKD2L1.
DMDMi23821938.

Proteomic databases

PaxDbiQ9P0L9.
PeptideAtlasiQ9P0L9.
PRIDEiQ9P0L9.

Protocols and materials databases

DNASUi9033.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318222; ENSP00000325296; ENSG00000107593. [Q9P0L9-1]
GeneIDi9033.
KEGGihsa:9033.
UCSCiuc001kqx.2. human. [Q9P0L9-1]

Organism-specific databases

CTDi9033.
DisGeNETi9033.
GeneCardsiPKD2L1.
HGNCiHGNC:9011. PKD2L1.
HPAiCAB022621.
MIMi604532. gene.
neXtProtiNX_Q9P0L9.
OpenTargetsiENSG00000107593.
PharmGKBiPA33344.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3599. Eukaryota.
ENOG410XTGE. LUCA.
GeneTreeiENSGT00700000104221.
HOGENOMiHOG000230858.
HOVERGENiHBG014945.
InParanoidiQ9P0L9.
KOiK04990.
OMAiFIYYENM.
OrthoDBiEOG091G034F.
PhylomeDBiQ9P0L9.
TreeFamiTF316484.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000107593-MONOMER.

Miscellaneous databases

GeneWikiiPKD2L1.
GenomeRNAii9033.
PROiQ9P0L9.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000107593.
CleanExiHS_PKD2L1.
ExpressionAtlasiQ9P0L9. baseline and differential.
GenevisibleiQ9P0L9. HS.

Family and domain databases

Gene3Di1.10.238.10. 1 hit.
InterProiIPR011992. EF-hand-dom_pair.
IPR013122. PKD1_2_channel.
IPR003915. PKD_2.
[Graphical view]
PfamiPF08016. PKD_channel. 1 hit.
[Graphical view]
PRINTSiPR01433. POLYCYSTIN2.
ProtoNetiSearch...

Entry informationi

Entry nameiPK2L1_HUMAN
AccessioniPrimary (citable) accession number: Q9P0L9
Secondary accession number(s): O75972
, Q5W039, Q9UP35, Q9UPA2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2002
Last sequence update: October 1, 2000
Last modified: November 30, 2016
This is version 144 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

PKD1L3 and PKD2L1 have been defined as sour taste receptor in gustatory cells based on a number of indirect evidences in mouse. Some data confirm this hypothesis in human: in 2 patients with sour ageusia that are unresponsive to sour stimuli, but show normal responses to bitter, sweet, and salty stimuli, expression of PKD1L3 and PKD2L1 is absent in the anterior part of the tongue (PubMed:19812697). However, a number of experiments have recently shown that the sour taste receptor activity is probably indirect.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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

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.