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Protein

Transmembrane protein 165

Gene

TMEM165

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

Functioni

May function as a calcium/proton transporter involved in calcium and in lysosomal pH homeostasis. Therefore, it may play an indirect role in protein glycosylation.2 Publications

GO - Biological processi

  • cellular calcium ion homeostasis Source: UniProtKB
  • Golgi calcium ion transport Source: UniProtKB
  • protein N-linked glycosylation Source: UniProtKB
  • regulation of lysosomal lumen pH Source: UniProtKB
Complete GO annotation...

Protein family/group databases

TCDBi2.A.106.2.2. the ca(2+):h(+) antiporter-2 (caca2) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Transmembrane protein 165
Alternative name(s):
Transmembrane protein PT27
Transmembrane protein TPARL
Gene namesi
Name:TMEM165
Synonyms:TPARL
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:30760. TMEM165.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini34 – 8956LumenalSequence analysisAdd
BLAST
Transmembranei90 – 11021HelicalSequence analysisAdd
BLAST
Topological domaini111 – 12616CytoplasmicSequence analysisAdd
BLAST
Transmembranei127 – 14721HelicalSequence analysisAdd
BLAST
Topological domaini148 – 1514LumenalSequence analysis
Transmembranei152 – 17221HelicalSequence analysisAdd
BLAST
Topological domaini173 – 22856CytoplasmicSequence analysisAdd
BLAST
Transmembranei229 – 24921HelicalSequence analysisAdd
BLAST
Topological domaini250 – 26718LumenalSequence analysisAdd
BLAST
Transmembranei268 – 28821HelicalSequence analysisAdd
BLAST
Topological domaini289 – 29911CytoplasmicSequence analysisAdd
BLAST
Transmembranei300 – 32021HelicalSequence analysisAdd
BLAST
Topological domaini321 – 3244LumenalSequence analysis

GO - Cellular componenti

  • early endosome membrane Source: UniProtKB-SubCell
  • endosome membrane Source: UniProtKB
  • Golgi apparatus Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • intracellular membrane-bounded organelle Source: HPA
  • late endosome membrane Source: UniProtKB-SubCell
  • lysosomal membrane Source: UniProtKB
  • trans-Golgi network membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Golgi apparatus, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Congenital disorder of glycosylation 2K (CDG2K)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder with a variable phenotype. Affected individuals show psychomotor retardation and growth retardation, and most have short stature. Other features include dysmorphism, hypotonia, eye abnormalities, acquired microcephaly, hepatomegaly, and skeletal dysplasia. Congenital disorders of glycosylation are caused by a defect in glycoprotein biosynthesis and characterized by under-glycosylated serum glycoproteins and a wide variety of clinical features. The broad spectrum of features reflects the critical role of N-glycoproteins during embryonic development, differentiation, and maintenance of cell functions.
See also OMIM:614727
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti126 – 1261R → C in CDG2K; alters subcellular location. 2 Publications
VAR_068446
Natural varianti126 – 1261R → H in CDG2K; alters subcellular location. 2 Publications
VAR_068447
Natural varianti304 – 3041G → R in CDG2K; accumulates in Golgi compartment. 2 Publications
VAR_068448

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi124 – 1241Y → S: Alters subcellular location. 1 Publication
Mutagenesisi127 – 1271L → G: No effect on subcellular location. 1 Publication
Mutagenesisi209 – 2102LL → GG: No effect on subcellular location. 1 Publication

Keywords - Diseasei

Congenital disorder of glycosylation, Disease mutation

Organism-specific databases

MalaCardsiTMEM165.
MIMi614727. phenotype.
Orphaneti314667. TMEM165-CDG.
PharmGKBiPA147357214.

Polymorphism and mutation databases

DMDMi74718825.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3333Sequence analysisAdd
BLAST
Chaini34 – 324291Transmembrane protein 165PRO_0000247334Add
BLAST

Proteomic databases

EPDiQ9HC07.
MaxQBiQ9HC07.
PaxDbiQ9HC07.
PeptideAtlasiQ9HC07.
PRIDEiQ9HC07.

PTM databases

iPTMnetiQ9HC07.
PhosphoSiteiQ9HC07.
SwissPalmiQ9HC07.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiQ9HC07.
CleanExiHS_TMEM165.
ExpressionAtlasiQ9HC07. baseline and differential.
GenevisibleiQ9HC07. HS.

Organism-specific databases

HPAiHPA038299.

Interactioni

Protein-protein interaction databases

BioGridi120960. 20 interactions.
IntActiQ9HC07. 16 interactions.
STRINGi9606.ENSP00000370736.

Structurei

3D structure databases

ProteinModelPortaliQ9HC07.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili184 – 21128Sequence analysisAdd
BLAST

Sequence similaritiesi

Belongs to the GDT1 family.Curated

Keywords - Domaini

Coiled coil, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG2881. Eukaryota.
COG2119. LUCA.
GeneTreeiENSGT00390000005261.
HOGENOMiHOG000224541.
HOVERGENiHBG002358.
InParanoidiQ9HC07.
OMAiPIFVQAF.
PhylomeDBiQ9HC07.
TreeFamiTF105960.

Family and domain databases

InterProiIPR001727. Gdt1.
[Graphical view]
PANTHERiPTHR12608. PTHR12608. 1 hit.
PfamiPF01169. UPF0016. 2 hits.
[Graphical view]
PROSITEiPS01214. UPF0016. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

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

Isoform 1 (identifier: Q9HC07-1) [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
MAAAAPGNGR ASAPRLLLLF LVPLLWAPAA VRAGPDEDLS HRNKEPPAPA
60 70 80 90 100
QQLQPQPVAV QGPEPARVEK IFTPAAPVHT NKEDPATQTN LGFIHAFVAA
110 120 130 140 150
ISVIIVSELG DKTFFIAAIM AMRYNRLTVL AGAMLALGLM TCLSVLFGYA
160 170 180 190 200
TTVIPRVYTY YVSTVLFAIF GIRMLREGLK MSPDEGQEEL EEVQAELKKK
210 220 230 240 250
DEEFQRTKLL NGPGDVETGT SITVPQKKWL HFISPIFVQA LTLTFLAEWG
260 270 280 290 300
DRSQLTTIVL AAREDPYGVA VGGTVGHCLC TGLAVIGGRM IAQKISVRTV
310 320
TIIGGIVFLA FAFSALFISP DSGF
Length:324
Mass (Da):34,906
Last modified:March 1, 2001 - v1
Checksum:iA0E6C8BBFF189D72
GO
Isoform 2 (identifier: Q9HC07-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: MAAAAPGNGRASAPRLLLLFLVPLLWAPAAVRAGPDEDLSHRNKEPPAPAQQLQPQPVAVQGPEPARVE → MEIPMQ

Note: No experimental confirmation available.
Show »
Length:261
Mass (Da):28,432
Checksum:i16F4AA6268D395EF
GO

Sequence cautioni

The sequence AAF67653.1 differs from that shown. Reason: Frameshift at positions 2 and 7. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti126 – 1261R → C in CDG2K; alters subcellular location. 2 Publications
VAR_068446
Natural varianti126 – 1261R → H in CDG2K; alters subcellular location. 2 Publications
VAR_068447
Natural varianti304 – 3041G → R in CDG2K; accumulates in Golgi compartment. 2 Publications
VAR_068448

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 6969MAAAA…PARVE → MEIPMQ in isoform 2. 1 PublicationVSP_056691Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132746 mRNA. Translation: AAL75947.1.
AF183409 mRNA. Translation: AAG09678.1.
AF220188 mRNA. Translation: AAF67653.1. Frameshift.
AK290663 mRNA. Translation: BAF83352.1.
AK295289 mRNA. Translation: BAG58273.1.
AC069200 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX05467.1.
BC003545 mRNA. Translation: AAH03545.2.
BC104980 mRNA. Translation: AAI04981.1.
BC104978 mRNA. Translation: AAI04979.1.
BC107582 mRNA. Translation: AAI07583.1.
CCDSiCCDS3499.1. [Q9HC07-1]
RefSeqiNP_060945.2. NM_018475.4. [Q9HC07-1]
UniGeneiHs.479766.

Genome annotation databases

EnsembliENST00000381334; ENSP00000370736; ENSG00000134851. [Q9HC07-1]
GeneIDi55858.
KEGGihsa:55858.
UCSCiuc003hax.4. human. [Q9HC07-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF132746 mRNA. Translation: AAL75947.1.
AF183409 mRNA. Translation: AAG09678.1.
AF220188 mRNA. Translation: AAF67653.1. Frameshift.
AK290663 mRNA. Translation: BAF83352.1.
AK295289 mRNA. Translation: BAG58273.1.
AC069200 Genomic DNA. No translation available.
CH471057 Genomic DNA. Translation: EAX05467.1.
BC003545 mRNA. Translation: AAH03545.2.
BC104980 mRNA. Translation: AAI04981.1.
BC104978 mRNA. Translation: AAI04979.1.
BC107582 mRNA. Translation: AAI07583.1.
CCDSiCCDS3499.1. [Q9HC07-1]
RefSeqiNP_060945.2. NM_018475.4. [Q9HC07-1]
UniGeneiHs.479766.

3D structure databases

ProteinModelPortaliQ9HC07.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120960. 20 interactions.
IntActiQ9HC07. 16 interactions.
STRINGi9606.ENSP00000370736.

Protein family/group databases

TCDBi2.A.106.2.2. the ca(2+):h(+) antiporter-2 (caca2) family.

PTM databases

iPTMnetiQ9HC07.
PhosphoSiteiQ9HC07.
SwissPalmiQ9HC07.

Polymorphism and mutation databases

DMDMi74718825.

Proteomic databases

EPDiQ9HC07.
MaxQBiQ9HC07.
PaxDbiQ9HC07.
PeptideAtlasiQ9HC07.
PRIDEiQ9HC07.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381334; ENSP00000370736; ENSG00000134851. [Q9HC07-1]
GeneIDi55858.
KEGGihsa:55858.
UCSCiuc003hax.4. human. [Q9HC07-1]

Organism-specific databases

CTDi55858.
GeneCardsiTMEM165.
GeneReviewsiTMEM165.
H-InvDBHIX0004223.
HGNCiHGNC:30760. TMEM165.
HPAiHPA038299.
MalaCardsiTMEM165.
MIMi614726. gene.
614727. phenotype.
neXtProtiNX_Q9HC07.
Orphaneti314667. TMEM165-CDG.
PharmGKBiPA147357214.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2881. Eukaryota.
COG2119. LUCA.
GeneTreeiENSGT00390000005261.
HOGENOMiHOG000224541.
HOVERGENiHBG002358.
InParanoidiQ9HC07.
OMAiPIFVQAF.
PhylomeDBiQ9HC07.
TreeFamiTF105960.

Miscellaneous databases

ChiTaRSiTMEM165. human.
GenomeRNAii55858.
PROiQ9HC07.
SOURCEiSearch...

Gene expression databases

BgeeiQ9HC07.
CleanExiHS_TMEM165.
ExpressionAtlasiQ9HC07. baseline and differential.
GenevisibleiQ9HC07. HS.

Family and domain databases

InterProiIPR001727. Gdt1.
[Graphical view]
PANTHERiPTHR12608. PTHR12608. 1 hit.
PfamiPF01169. UPF0016. 2 hits.
[Graphical view]
PROSITEiPS01214. UPF0016. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning of a new human cDNA homologous to Mus musculus transmembrane protein."
    Yue P., Yu L., Zhao S.Y.
    Submitted (MAR-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Hypothalamus.
  3. "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] (ISOFORMS 1 AND 2).
    Tissue: Caudate nucleus.
  4. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "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] (ISOFORM 1).
    Tissue: Brain, Lung and Uterus.
  7. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  8. "Impact of disease-causing mutations on TMEM165 subcellular localization, a recently identified protein involved in CDG-II."
    Rosnoblet C., Legrand D., Demaegd D., Hacine-Gherbi H., de Bettignies G., Bammens R., Borrego C., Duvet S., Morsomme P., Matthijs G., Foulquier F.
    Hum. Mol. Genet. 22:2914-2928(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-124; LEU-127 AND 209-LEU-LEU-210, CHARACTERIZATION OF VARIANTS CDG2K HIS-126; CYS-126 AND ARG-304, TOPOLOGY.
  9. "Bone dysplasia as a key feature in three patients with a novel congenital disorder of glycosylation (CDG) type II due to a deep intronic splice mutation in TMEM165."
    Zeevaert R., de Zegher F., Sturiale L., Garozzo D., Smet M., Moens M., Matthijs G., Jaeken J.
    JIMD Rep. 8:145-152(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN CDG2K.
  10. "Newly characterized Golgi-localized family of proteins is involved in calcium and pH homeostasis in yeast and human cells."
    Demaegd D., Foulquier F., Colinet A.S., Gremillon L., Legrand D., Mariot P., Peiter E., Van Schaftingen E., Matthijs G., Morsomme P.
    Proc. Natl. Acad. Sci. U.S.A. 110:6859-6864(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN CALCIUM AND PH HOMEOSTASIS.
  11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  12. Cited for: VARIANTS CDG2K HIS-126; CYS-126 AND ARG-304, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

Entry informationi

Entry nameiTM165_HUMAN
AccessioniPrimary (citable) accession number: Q9HC07
Secondary accession number(s): A8K3P8
, B4DHW1, Q9BTN9, Q9NZ34
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: March 1, 2001
Last modified: June 8, 2016
This is version 106 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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.