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Protein

Hydroperoxide isomerase ALOXE3

Gene

ALOXE3

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

Functioni

Non-heme iron-containing lipoxygenase which is atypical in that it displays a prominent hydroperoxide isomerase activity and a reduced dioxygenase activity compared to other lipoxygenases. The hydroperoxide isomerase activity catalyzes the isomerization of hydroperoxides, derived from arachidonic and linoleic acid by ALOX12B, into hepoxilin-type epoxyalcohols. The dioxygenase activity requires a step of activation of the enzyme by molecular oxygen. In presence of oxygen, oxygenates polyunsaturated fatty acids, including arachidonic acid, to produce fatty acid hydroperoxides. In the skin, acts downstream of ALOX12B on the linoleate moiety of esterified omega-hydroxyacyl-sphingosine (EOS) ceramides to produce an epoxy-ketone derivative, a crucial step in the conjugation of omega-hydroxyceramide to membrane proteins. Therefore plays a crucial role in the synthesis of corneocytes lipid envelope and the establishment of the skin barrier to water loss. In parallel, it may have a signaling function in barrier formation through the production of hepoxilins metabolites. Plays also a role in adipocyte differentiation through hepoxilin A3 and hepoxilin B3 production which in turn activate PPARG. Through the production of hepoxilins in the spinal cord, it may regulate inflammatory tactile allodynia.5 Publications

Catalytic activityi

A hydroperoxy icosatetraenoate = a hydroxy epoxy icosatrienoate.5 Publications
A hydroperoxy icosatetraenoate = an oxoicosatetraenoate + H2O.5 Publications

Cofactori

Fe cationPROSITE-ProRule annotationNote: Binds 1 Fe cation per subunit.PROSITE-ProRule annotation

Kineticsi

Has a 5 to 10 fold higher activity toward (12R)-HPETE (hydroperoxyeicosatetraenoic acid) compared to (12S)-HPETE and (15S)-HPETE. From (12R)-HPETE produces a stereoisomer of hepoxilin A3. More active on hydroperoxides with an R configuration than an S one.

  1. KM=46 µM for (12R)-HPETE3 Publications
  2. KM=28 µM for (12S)-HPETE3 Publications
  3. KM=32 µM for (15S)-HPETE3 Publications
  4. KM=50 µM for synthetic fatty acid 9E,11Z,14Z-20:3omega6 (at pH 7.5)3 Publications
  1. Vmax=3.256 µmol/min/mg enzyme for (12R)-HPETE (at pH 7.5)3 Publications
  2. Vmax=0.858 µmol/min/mg enzyme for (12S)-HPETE (at pH 7.5)3 Publications
  3. Vmax=0.484 µmol/min/mg enzyme for (15S)-HPETE (at pH 7.5)3 Publications

Pathwayi: hydroperoxy eicosatetraenoic acid biosynthesis

This protein is involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway hydroperoxy eicosatetraenoic acid biosynthesis and in Lipid metabolism.

Pathwayi: sphingolipid metabolism

This protein is involved in the pathway sphingolipid metabolism, which is part of Lipid metabolism.
View all proteins of this organism that are known to be involved in the pathway sphingolipid metabolism and in Lipid metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi408Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi413Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi588Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi592Iron; catalyticPROSITE-ProRule annotation1
Metal bindingi711Iron; via carboxylate; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

GO - Biological processi

  • arachidonic acid metabolic process Source: UniProtKB
  • ceramide biosynthetic process Source: UniProtKB
  • establishment of skin barrier Source: UniProtKB
  • fat cell differentiation Source: UniProtKB
  • hepoxilin biosynthetic process Source: UniProtKB
  • linoleic acid metabolic process Source: UniProtKB
  • lipoxygenase pathway Source: UniProtKB
  • peroxisome proliferator activated receptor signaling pathway Source: UniProtKB
  • sensory perception of pain Source: UniProtKB
  • sphingolipid metabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Dioxygenase, Isomerase, Lyase, Oxidoreductase

Keywords - Biological processi

Fatty acid metabolism, Lipid metabolism

Keywords - Ligandi

Iron, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000179148-MONOMER.
UniPathwayiUPA00222.
UPA00881.

Chemistry databases

SwissLipidsiSLP:000000656.

Names & Taxonomyi

Protein namesi
Recommended name:
Hydroperoxide isomerase ALOXE3 (EC:5.4.4.75 Publications)
Alternative name(s):
Epidermis-type lipoxygenase 31 Publication
Short name:
Epidermal LOX-3
Short name:
e-LOX-3
Short name:
eLOX-3
Hydroperoxy icosatetraenoate dehydratase (EC:4.2.1.1525 Publications)
Gene namesi
Name:ALOXE3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:13743. ALOXE3.

Subcellular locationi

  • Cytoplasm PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Ichthyosis, congenital, autosomal recessive 3 (ARCI3)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.
See also OMIM:606545
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069561237L → M in ARCI3; no effect on enzyme activity. 2 PublicationsCorresponds to variant rs121434235dbSNPEnsembl.1
Natural variantiVAR_069562281G → V in ARCI3; complete loss of the enzyme activity. 1 PublicationCorresponds to variant rs786205120dbSNPEnsembl.1
Natural variantiVAR_069563344 – 347QYVA → P in ARCI3; complete loss of the enzyme activity. 1 Publication4
Natural variantiVAR_015175396R → S in ARCI3; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs121434234dbSNPEnsembl.1
Natural variantiVAR_069564427L → P in ARCI3. 1 Publication1
Natural variantiVAR_015176500V → F in ARCI3; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs121434232dbSNPEnsembl.1
Natural variantiVAR_069565630P → L in ARCI3; complete loss of the enzyme activity. 3 PublicationsCorresponds to variant rs147149459dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi451A → G: Increases the O2-dependent dioxygenase activity. 2 Publications1

Keywords - Diseasei

Disease mutation, Ichthyosis

Organism-specific databases

DisGeNETi59344.
MalaCardsiALOXE3.
MIMi606545. phenotype.
OpenTargetsiENSG00000179148.
Orphaneti79394. Congenital non-bullous ichthyosiform erythroderma.
281122. Self-healing collodion baby.
PharmGKBiPA24727.

Polymorphism and mutation databases

BioMutaiALOXE3.
DMDMi27923803.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206911 – 711Hydroperoxide isomerase ALOXE3Add BLAST711

Proteomic databases

PaxDbiQ9BYJ1.
PeptideAtlasiQ9BYJ1.
PRIDEiQ9BYJ1.

PTM databases

iPTMnetiQ9BYJ1.
PhosphoSitePlusiQ9BYJ1.

Expressioni

Tissue specificityi

Predominantly expressed in skin.

Gene expression databases

BgeeiENSG00000179148.
CleanExiHS_ALOXE3.
ExpressionAtlasiQ9BYJ1. baseline and differential.
GenevisibleiQ9BYJ1. HS.

Organism-specific databases

HPAiHPA023120.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ALOX12BO753422EBI-6925949,EBI-6925925

Protein-protein interaction databases

BioGridi121886. 22 interactors.
IntActiQ9BYJ1. 2 interactors.
STRINGi9606.ENSP00000314879.

Structurei

3D structure databases

ProteinModelPortaliQ9BYJ1.
SMRiQ9BYJ1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 119PLATPROSITE-ProRule annotationAdd BLAST118
Domaini120 – 711LipoxygenasePROSITE-ProRule annotationAdd BLAST592

Sequence similaritiesi

Belongs to the lipoxygenase family.Curated
Contains 1 lipoxygenase domain.PROSITE-ProRule annotation
Contains 1 PLAT domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IF0U. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiQ9BYJ1.
KOiK18684.
PhylomeDBiQ9BYJ1.
TreeFamiTF105320.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001885. LipOase_mml.
IPR001024. PLAT/LH2_dom.
[Graphical view]
PANTHERiPTHR11771. PTHR11771. 1 hit.
PfamiPF00305. Lipoxygenase. 1 hit.
PF01477. PLAT. 1 hit.
[Graphical view]
PRINTSiPR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.
SMARTiSM00308. LH2. 1 hit.
[Graphical view]
SUPFAMiSSF48484. SSF48484. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEiPS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9BYJ1-1) [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
MAVYRLCVTT GPYLRAGTLD NISVTLVGTC GESPKQRLDR MGRDFAPGSV
60 70 80 90 100
QKYKVRCTAE LGELLLLRVH KERYAFFRKD SWYCSRICVT EPDGSVSHFP
110 120 130 140 150
CYQWIEGYCT VELRPGTART ICQDSLPLLL DHRTRELRAR QECYRWKIYA
160 170 180 190 200
PGFPCMVDVN SFQEMESDKK FALTKTTTCV DQGDSSGNRY LPGFPMKIDI
210 220 230 240 250
PSLMYMEPNV RYSATKTISL LFNAIPASLG MKLRGLLDRK GSWKKLDDMQ
260 270 280 290 300
NIFWCHKTFT TKYVTEHWCE DHFFGYQYLN GVNPVMLHCI SSLPSKLPVT
310 320 330 340 350
NDMVAPLLGQ DTCLQTELER GNIFLADYWI LAEAPTHCLN GRQQYVAAPL
360 370 380 390 400
CLLWLSPQGA LVPLAIQLSQ TPGPDSPIFL PTDSEWDWLL AKTWVRNSEF
410 420 430 440 450
LVHENNTHFL CTHLLCEAFA MATLRQLPLC HPIYKLLLPH TRYTLQVNTI
460 470 480 490 500
ARATLLNPEG LVDQVTSIGR QGLIYLMSTG LAHFTYTNFC LPDSLRARGV
510 520 530 540 550
LAIPNYHYRD DGLKIWAAIE SFVSEIVGYY YPSDASVQQD SELQAWTGEI
560 570 580 590 600
FAQAFLGRES SGFPSRLCTP GEMVKFLTAI IFNCSAQHAA VNSGQHDFGA
610 620 630 640 650
WMPNAPSSMR QPPPQTKGTT TLKTYLDTLP EVNISCNNLL LFWLVSQEPK
660 670 680 690 700
DQRPLGTYPD EHFTEEAPRR SIAAFQSRLA QISRDIQERN QGLALPYTYL
710
DPPLIENSVS I
Length:711
Mass (Da):80,543
Last modified:June 1, 2001 - v1
Checksum:iBDED1E4ED5CF6783
GO
Isoform 2 (identifier: Q9BYJ1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MPRGAFRPCL...PGHPFLLPIM

Note: No experimental confirmation available.
Show »
Length:843
Mass (Da):95,186
Checksum:i75C69C336513F82C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti155C → R in CAC12843 (PubMed:11350124).Curated1
Sequence conflicti194F → L in AAG16899 (PubMed:12881489).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069561237L → M in ARCI3; no effect on enzyme activity. 2 PublicationsCorresponds to variant rs121434235dbSNPEnsembl.1
Natural variantiVAR_069562281G → V in ARCI3; complete loss of the enzyme activity. 1 PublicationCorresponds to variant rs786205120dbSNPEnsembl.1
Natural variantiVAR_069563344 – 347QYVA → P in ARCI3; complete loss of the enzyme activity. 1 Publication4
Natural variantiVAR_015175396R → S in ARCI3; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs121434234dbSNPEnsembl.1
Natural variantiVAR_069564427L → P in ARCI3. 1 Publication1
Natural variantiVAR_015176500V → F in ARCI3; complete loss of the enzyme activity. 2 PublicationsCorresponds to variant rs121434232dbSNPEnsembl.1
Natural variantiVAR_069565630P → L in ARCI3; complete loss of the enzyme activity. 3 PublicationsCorresponds to variant rs147149459dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0432871M → MPRGAFRPCLPALYFAFLTC PTPEQRMSGTQAPDIHLGEP ARGTGCVRGKQTSIRVQDCG RREEARAASRELRREKAQEH PRESWAHPQPYPAPQPLALR PETQPCPACRSSPPGRLLLR PALPGHPFLLPIM in isoform 2. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ269499 mRNA. Translation: CAC12843.1.
AJ305020
, AJ305021, AJ305023, AJ305025 Genomic DNA. Translation: CAC34518.1.
AF182218 mRNA. Translation: AAG16899.1.
AK296416 mRNA. Translation: BAH12346.1.
AK313677 mRNA. Translation: BAG36428.1.
CH471108 Genomic DNA. Translation: EAW90094.1.
BC101938 mRNA. Translation: AAI01939.1.
BC101939 mRNA. Translation: AAI01940.1.
BC103508 mRNA. Translation: AAI03509.1.
BC104724 mRNA. Translation: AAI04725.1.
CCDSiCCDS11130.1. [Q9BYJ1-1]
CCDS54084.1. [Q9BYJ1-2]
RefSeqiNP_001159432.1. NM_001165960.1. [Q9BYJ1-2]
NP_067641.2. NM_021628.2. [Q9BYJ1-1]
UniGeneiHs.232770.

Genome annotation databases

EnsembliENST00000318227; ENSP00000314879; ENSG00000179148. [Q9BYJ1-2]
ENST00000448843; ENSP00000400581; ENSG00000179148. [Q9BYJ1-1]
GeneIDi59344.
KEGGihsa:59344.
UCSCiuc010cnr.4. human. [Q9BYJ1-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Protein Spotlight

about water - Issue 153 of September 2013

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ269499 mRNA. Translation: CAC12843.1.
AJ305020
, AJ305021, AJ305023, AJ305025 Genomic DNA. Translation: CAC34518.1.
AF182218 mRNA. Translation: AAG16899.1.
AK296416 mRNA. Translation: BAH12346.1.
AK313677 mRNA. Translation: BAG36428.1.
CH471108 Genomic DNA. Translation: EAW90094.1.
BC101938 mRNA. Translation: AAI01939.1.
BC101939 mRNA. Translation: AAI01940.1.
BC103508 mRNA. Translation: AAI03509.1.
BC104724 mRNA. Translation: AAI04725.1.
CCDSiCCDS11130.1. [Q9BYJ1-1]
CCDS54084.1. [Q9BYJ1-2]
RefSeqiNP_001159432.1. NM_001165960.1. [Q9BYJ1-2]
NP_067641.2. NM_021628.2. [Q9BYJ1-1]
UniGeneiHs.232770.

3D structure databases

ProteinModelPortaliQ9BYJ1.
SMRiQ9BYJ1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi121886. 22 interactors.
IntActiQ9BYJ1. 2 interactors.
STRINGi9606.ENSP00000314879.

Chemistry databases

SwissLipidsiSLP:000000656.

PTM databases

iPTMnetiQ9BYJ1.
PhosphoSitePlusiQ9BYJ1.

Polymorphism and mutation databases

BioMutaiALOXE3.
DMDMi27923803.

Proteomic databases

PaxDbiQ9BYJ1.
PeptideAtlasiQ9BYJ1.
PRIDEiQ9BYJ1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000318227; ENSP00000314879; ENSG00000179148. [Q9BYJ1-2]
ENST00000448843; ENSP00000400581; ENSG00000179148. [Q9BYJ1-1]
GeneIDi59344.
KEGGihsa:59344.
UCSCiuc010cnr.4. human. [Q9BYJ1-1]

Organism-specific databases

CTDi59344.
DisGeNETi59344.
GeneCardsiALOXE3.
GeneReviewsiALOXE3.
HGNCiHGNC:13743. ALOXE3.
HPAiHPA023120.
MalaCardsiALOXE3.
MIMi606545. phenotype.
607206. gene.
neXtProtiNX_Q9BYJ1.
OpenTargetsiENSG00000179148.
Orphaneti79394. Congenital non-bullous ichthyosiform erythroderma.
281122. Self-healing collodion baby.
PharmGKBiPA24727.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF0U. Eukaryota.
ENOG410YN4N. LUCA.
GeneTreeiENSGT00550000074415.
HOGENOMiHOG000234358.
HOVERGENiHBG005150.
InParanoidiQ9BYJ1.
KOiK18684.
PhylomeDBiQ9BYJ1.
TreeFamiTF105320.

Enzyme and pathway databases

UniPathwayiUPA00222.
UPA00881.
BioCyciZFISH:ENSG00000179148-MONOMER.

Miscellaneous databases

ChiTaRSiALOXE3. human.
GeneWikiiALOXE3.
GenomeRNAii59344.
PROiQ9BYJ1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000179148.
CleanExiHS_ALOXE3.
ExpressionAtlasiQ9BYJ1. baseline and differential.
GenevisibleiQ9BYJ1. HS.

Family and domain databases

Gene3Di2.60.60.20. 1 hit.
InterProiIPR000907. LipOase.
IPR013819. LipOase_C.
IPR020834. LipOase_CS.
IPR020833. LipOase_Fe_BS.
IPR001885. LipOase_mml.
IPR001024. PLAT/LH2_dom.
[Graphical view]
PANTHERiPTHR11771. PTHR11771. 1 hit.
PfamiPF00305. Lipoxygenase. 1 hit.
PF01477. PLAT. 1 hit.
[Graphical view]
PRINTSiPR00087. LIPOXYGENASE.
PR00467. MAMLPOXGNASE.
SMARTiSM00308. LH2. 1 hit.
[Graphical view]
SUPFAMiSSF48484. SSF48484. 1 hit.
SSF49723. SSF49723. 1 hit.
PROSITEiPS00711. LIPOXYGENASE_1. 1 hit.
PS00081. LIPOXYGENASE_2. 1 hit.
PS51393. LIPOXYGENASE_3. 1 hit.
PS50095. PLAT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiLOXE3_HUMAN
AccessioniPrimary (citable) accession number: Q9BYJ1
Secondary accession number(s): B2R981
, B7Z3W0, Q3ZB74, Q9H4F2, Q9HC22
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 27, 2003
Last sequence update: June 1, 2001
Last modified: November 2, 2016
This is version 138 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 17
    Human chromosome 17: 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. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  7. 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.