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Protein

Fibroblast growth factor 5

Gene

FGF5

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

Functioni

Plays an important role in the regulation of cell proliferation and cell differentiation. Required for normal regulation of the hair growth cycle. Functions as an inhibitor of hair elongation by promoting progression from anagen, the growth phase of the hair follicle, into catagen the apoptosis-induced regression phase (By similarity).By similarity

GO - Molecular functioni

  1. fibroblast growth factor receptor binding Source: MGI

GO - Biological processi

  1. cell-cell signaling Source: ProtInc
  2. cell proliferation Source: ProtInc
  3. epidermal growth factor receptor signaling pathway Source: Reactome
  4. Fc-epsilon receptor signaling pathway Source: Reactome
  5. fibroblast growth factor receptor signaling pathway Source: MGI
  6. glial cell differentiation Source: Ensembl
  7. innate immune response Source: Reactome
  8. insulin receptor signaling pathway Source: Reactome
  9. nervous system development Source: ProtInc
  10. neurotrophin TRK receptor signaling pathway Source: Reactome
  11. phosphatidylinositol-mediated signaling Source: Reactome
  12. positive regulation of cell division Source: UniProtKB-KW
  13. positive regulation of cell proliferation Source: MGI
  14. signal transduction involved in regulation of gene expression Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

Enzyme and pathway databases

ReactomeiREACT_111184. Negative regulation of FGFR signaling.
REACT_120863. Activated point mutants of FGFR2.
REACT_121153. Signaling by activated point mutants of FGFR1.
REACT_121249. Signaling by FGFR3 mutants.
REACT_121337. Signaling by activated point mutants of FGFR3.
REACT_121398. Signaling by FGFR mutants.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_21247. FRS2-mediated cascade.
REACT_21270. PI-3K cascade.
REACT_21310. Phospholipase C-mediated cascade.
REACT_21374. SHC-mediated cascade.
REACT_75829. PIP3 activates AKT signaling.
REACT_9413. FGFR2c ligand binding and activation.
REACT_9510. FGFR3c ligand binding and activation.
REACT_9515. FGFR1c ligand binding and activation.
REACT_976. PI3K Cascade.

Names & Taxonomyi

Protein namesi
Recommended name:
Fibroblast growth factor 5
Short name:
FGF-5
Alternative name(s):
Heparin-binding growth factor 5
Short name:
HBGF-5
Smag-82
Gene namesi
Name:FGF5
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:3683. FGF5.

Subcellular locationi

Secreted Curated

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Trichomegaly1 Publication

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

Disease descriptionA morphologic trait characterized by unusually long eyelashes and mild hypertrichosis of eyebrows. It can be observed in association with corneal irritation, cataracts, and hereditary spherocytosis.

See also OMIM:190330
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti174 – 1741Y → H in TCMGLY. 1 Publication
VAR_072566

Keywords - Diseasei

Disease mutation, Proto-oncogene

Organism-specific databases

MIMi190330. phenotype.
Orphaneti411788. Familial isolated trichomegaly.
PharmGKBiPA28122.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020Sequence AnalysisAdd
BLAST
Chaini21 – 268248Fibroblast growth factor 5PRO_0000008958Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi110 – 1101N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Glycoprotein

Proteomic databases

PaxDbiP12034.
PRIDEiP12034.

PTM databases

PhosphoSiteiP12034.

Expressioni

Tissue specificityi

Expressed in neonatal brain.

Developmental stagei

Can transform NIH 3T3 cells.

Gene expression databases

BgeeiP12034.
CleanExiHS_FGF5.
ExpressionAtlasiP12034. baseline and differential.
GenevestigatoriP12034.

Organism-specific databases

HPAiCAB010313.
HPA042442.

Interactioni

Subunit structurei

Interacts with FGFR1 and FGFR2. Affinity between fibroblast growth factors (FGFs) and their receptors is increased by heparan sulfate glycosaminoglycans that function as coreceptors.1 Publication

Protein-protein interaction databases

DIPiDIP-4018N.
IntActiP12034. 4 interactions.
STRINGi9606.ENSP00000311697.

Structurei

3D structure databases

ProteinModelPortaliP12034.
SMRiP12034. Positions 87-227.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi49 – 524Poly-Ser
Compositional biasi55 – 628Poly-Ser

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG247419.
GeneTreeiENSGT00760000118859.
HOGENOMiHOG000236341.
HOVERGENiHBG007580.
InParanoidiP12034.
KOiK04358.
OMAiGLEQSSF.
OrthoDBiEOG7992S1.
PhylomeDBiP12034.
TreeFamiTF317805.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR028240. FGF5.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF23. PTHR11486:SF23. 1 hit.
PRINTSiPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
PROSITEiPS00247. HBGF_FGF. 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 Long (identifier: P12034-1) [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
MSLSFLLLLF FSHLILSAWA HGEKRLAPKG QPGPAATDRN PRGSSSRQSS
60 70 80 90 100
SSAMSSSSAS SSPAASLGSQ GSGLEQSSFQ WSPSGRRTGS LYCRVGIGFH
110 120 130 140 150
LQIYPDGKVN GSHEANMLSV LEIFAVSQGI VGIRGVFSNK FLAMSKKGKL
160 170 180 190 200
HASAKFTDDC KFRERFQENS YNTYASAIHR TEKTGREWYV ALNKRGKAKR
210 220 230 240 250
GCSPRVKPQH ISTHFLPRFK QSEQPELSFT VTVPEKKKPP SPIKPKIPLS
260
APRKNTNSVK YRLKFRFG
Length:268
Mass (Da):29,551
Last modified:January 24, 2006 - v4
Checksum:i28B7268B26781BCF
GO
Isoform Short (identifier: P12034-2) [UniParc]FASTAAdd to basket

Also known as: FGF-5S

The sequence of this isoform differs from the canonical sequence as follows:
     120-123: VLEI → QVHR
     124-268: Missing.

Note: Seems to have an antagonistic effect compared to that of the isoform Long.

Show »
Length:123
Mass (Da):13,006
Checksum:iE77B31D2CECE1096
GO

Sequence cautioni

The sequence AAB60698.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti42 – 421R → I in AAB06463 (PubMed:1700424).Curated
Sequence conflicti83 – 864PSGR → LGA in AAB60699 (PubMed:3211147).Curated
Sequence conflicti224 – 2241Q → QQ in AAZ67914 (Ref. 6) Curated
Sequence conflicti238 – 2381K → N in AAB06463 (PubMed:1700424).Curated
Sequence conflicti238 – 2381K → N in AAB60699 (PubMed:3211147).Curated
Sequence conflicti245 – 2451P → S in AAB06463 (PubMed:1700424).Curated
Sequence conflicti245 – 2451P → S in AAB60699 (PubMed:3211147).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti54 – 541M → V.1 Publication
Corresponds to variant rs33950145 [ dbSNP | Ensembl ].
VAR_025174
Natural varianti174 – 1741Y → H in TCMGLY. 1 Publication
VAR_072566

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei120 – 1234VLEI → QVHR in isoform Short. 3 PublicationsVSP_001518
Alternative sequencei124 – 268145Missing in isoform Short. 3 PublicationsVSP_001519Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M37825 mRNA. Translation: AAB06463.1.
M23536, M23534, M23535 Genomic DNA. Translation: AAB60699.1.
M23534 Genomic DNA. Translation: AAB60698.1. Sequence problems.
AB016517 mRNA. Translation: BAA33738.1.
AF171928 mRNA. Translation: AAF89742.1.
AF535149 mRNA. Translation: AAN04097.1.
DQ151636 Genomic DNA. Translation: AAZ67914.1.
AK291962 mRNA. Translation: BAF84651.1.
AK312065 mRNA. Translation: BAG35001.1.
CH471057 Genomic DNA. Translation: EAX05859.1.
CH471057 Genomic DNA. Translation: EAX05860.1.
BC074858 mRNA. Translation: AAH74858.1.
BC074859 mRNA. Translation: AAH74859.1.
BC131502 mRNA. Translation: AAI31503.1.
CCDSiCCDS34021.1. [P12034-1]
CCDS3586.1. [P12034-2]
PIRiA31194. TVHUF5.
B31194.
RefSeqiNP_004455.2. NM_004464.3. [P12034-1]
NP_149134.1. NM_033143.2. [P12034-2]
UniGeneiHs.37055.

Genome annotation databases

EnsembliENST00000312465; ENSP00000311697; ENSG00000138675. [P12034-1]
ENST00000456523; ENSP00000398353; ENSG00000138675. [P12034-2]
GeneIDi2250.
KEGGihsa:2250.
UCSCiuc003hmd.3. human. [P12034-1]
uc003hme.3. human. [P12034-2]

Polymorphism databases

DMDMi85700417.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M37825 mRNA. Translation: AAB06463.1.
M23536, M23534, M23535 Genomic DNA. Translation: AAB60699.1.
M23534 Genomic DNA. Translation: AAB60698.1. Sequence problems.
AB016517 mRNA. Translation: BAA33738.1.
AF171928 mRNA. Translation: AAF89742.1.
AF535149 mRNA. Translation: AAN04097.1.
DQ151636 Genomic DNA. Translation: AAZ67914.1.
AK291962 mRNA. Translation: BAF84651.1.
AK312065 mRNA. Translation: BAG35001.1.
CH471057 Genomic DNA. Translation: EAX05859.1.
CH471057 Genomic DNA. Translation: EAX05860.1.
BC074858 mRNA. Translation: AAH74858.1.
BC074859 mRNA. Translation: AAH74859.1.
BC131502 mRNA. Translation: AAI31503.1.
CCDSiCCDS34021.1. [P12034-1]
CCDS3586.1. [P12034-2]
PIRiA31194. TVHUF5.
B31194.
RefSeqiNP_004455.2. NM_004464.3. [P12034-1]
NP_149134.1. NM_033143.2. [P12034-2]
UniGeneiHs.37055.

3D structure databases

ProteinModelPortaliP12034.
SMRiP12034. Positions 87-227.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-4018N.
IntActiP12034. 4 interactions.
STRINGi9606.ENSP00000311697.

PTM databases

PhosphoSiteiP12034.

Polymorphism databases

DMDMi85700417.

Proteomic databases

PaxDbiP12034.
PRIDEiP12034.

Protocols and materials databases

DNASUi2250.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000312465; ENSP00000311697; ENSG00000138675. [P12034-1]
ENST00000456523; ENSP00000398353; ENSG00000138675. [P12034-2]
GeneIDi2250.
KEGGihsa:2250.
UCSCiuc003hmd.3. human. [P12034-1]
uc003hme.3. human. [P12034-2]

Organism-specific databases

CTDi2250.
GeneCardsiGC04P081187.
HGNCiHGNC:3683. FGF5.
HPAiCAB010313.
HPA042442.
MIMi165190. gene.
190330. phenotype.
neXtProtiNX_P12034.
Orphaneti411788. Familial isolated trichomegaly.
PharmGKBiPA28122.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG247419.
GeneTreeiENSGT00760000118859.
HOGENOMiHOG000236341.
HOVERGENiHBG007580.
InParanoidiP12034.
KOiK04358.
OMAiGLEQSSF.
OrthoDBiEOG7992S1.
PhylomeDBiP12034.
TreeFamiTF317805.

Enzyme and pathway databases

ReactomeiREACT_111184. Negative regulation of FGFR signaling.
REACT_120863. Activated point mutants of FGFR2.
REACT_121153. Signaling by activated point mutants of FGFR1.
REACT_121249. Signaling by FGFR3 mutants.
REACT_121337. Signaling by activated point mutants of FGFR3.
REACT_121398. Signaling by FGFR mutants.
REACT_147727. Constitutive PI3K/AKT Signaling in Cancer.
REACT_21247. FRS2-mediated cascade.
REACT_21270. PI-3K cascade.
REACT_21310. Phospholipase C-mediated cascade.
REACT_21374. SHC-mediated cascade.
REACT_75829. PIP3 activates AKT signaling.
REACT_9413. FGFR2c ligand binding and activation.
REACT_9510. FGFR3c ligand binding and activation.
REACT_9515. FGFR1c ligand binding and activation.
REACT_976. PI3K Cascade.

Miscellaneous databases

GeneWikiiFGF5.
GenomeRNAii2250.
NextBioi9107.
PROiP12034.
SOURCEiSearch...

Gene expression databases

BgeeiP12034.
CleanExiHS_FGF5.
ExpressionAtlasiP12034. baseline and differential.
GenevestigatoriP12034.

Family and domain databases

InterProiIPR008996. Cytokine_IL1-like.
IPR028240. FGF5.
IPR002209. Fibroblast_GF_fam.
IPR028142. IL-1_fam/FGF_fam.
[Graphical view]
PANTHERiPTHR11486. PTHR11486. 1 hit.
PTHR11486:SF23. PTHR11486:SF23. 1 hit.
PRINTSiPR00263. HBGFFGF.
PR00262. IL1HBGF.
SMARTiSM00442. FGF. 1 hit.
[Graphical view]
SUPFAMiSSF50353. SSF50353. 1 hit.
PROSITEiPS00247. HBGF_FGF. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Expression of the murine fibroblast growth factor 5 gene in the adult central nervous system."
    Haub O., Drucker B., Goldfarb M.
    Proc. Natl. Acad. Sci. U.S.A. 87:8022-8026(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
    Tissue: Brain stem.
  2. "The human FGF-5 oncogene encodes a novel protein related to fibroblast growth factors."
    Zhan X., Bates B., Hu X., Goldfarb M.
    Mol. Cell. Biol. 8:3487-3495(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  3. "An alternatively-spliced FGF-5 mRNA is abundant in brain and translates into a partial agonist/antagonist for FGF-5 neurotrophic activity."
    Ozawa K., Suzuki S., Asada M., Tomooka Y., Li A., Yoneda A., Komi A., Imamura T.
    Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
  4. "Differential display identification of 40 genes with altered expression in activated human smooth muscle cells. Local expression in atherosclerotic lesions of smags, smooth muscle activation-specific genes."
    de Vries C.J.M., van Achterberg T.A.E., Horrevoets A.J.G., ten Cate J.W., Pannekoek H.
    J. Biol. Chem. 275:23939-23947(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT).
    Tissue: Umbilical artery.
  5. "Identification of fibroblast growth factor-5 as an overexpressed antigen in multiple human adenocarcinomas."
    Hanada K.-I., Perry-Lalley D.M., Ohnmacht G.A., Bettinotti M.P., Yang J.C.
    Cancer Res. 61:5511-5516(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM LONG).
  6. NIEHS SNPs program
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT VAL-54.
  7. "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 SHORT AND LONG).
    Tissue: Cerebellum.
  8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  9. "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 LONG).
    Tissue: Lung.
  10. Cited for: INTERACTION WITH FGFR1 AND FGFR2, FUNCTION IN CELL PROLIFERATION.
  11. "Fibroblast growth factor signalling: from development to cancer."
    Turner N., Grose R.
    Nat. Rev. Cancer 10:116-129(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  12. Cited for: INVOLVEMENT IN TCMGLY, VARIANT TCMGLY HIS-174.

Entry informationi

Entry nameiFGF5_HUMAN
AccessioniPrimary (citable) accession number: P12034
Secondary accession number(s): B2R554
, O75846, Q3Y8M3, Q8NF90
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1989
Last sequence update: January 24, 2006
Last modified: March 4, 2015
This is version 143 of the entry and version 4 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

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.