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Protein

Huntingtin-interacting protein 1

Gene

Hip1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a role in clathrin-mediated endocytosis and trafficking. Involved in regulating AMPA receptor trafficking in the central nervous system in an NMDA-dependent manner. Enhances androgen receptor (AR)-mediated transcription. May act as a proapoptotic protein that induces cell death by acting through the intrinsic apoptosis pathway. Binds 3-phosphoinositides (via ENTH domain). May act through the ENTH domain to promote cell survival by stabilizing receptor tyrosine kinases following ligand-induced endocytosis. May play a functional role in the cell filament networks. May be required for differentiation, proliferation, and/or survival of somatic and germline progenitors.By similarity6 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Apoptosis, Differentiation, Endocytosis, Transcription, Transcription regulation

Keywords - Ligandi

Actin-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Huntingtin-interacting protein 1By similarity
Short name:
HIP-1
Alternative name(s):
Huntingtin-interacting protein I
Short name:
HIP-IBy similarity
Gene namesi
Name:Hip1Imported
Synonyms:Kiaa4113Imported
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1099804. Hip1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Membrane, Nucleus

Pathology & Biotechi

Disruption phenotypei

Mice develop a neurological phenotype by 3 months of age, characterized by wasting, tremor and a gait ataxia secondary to a rigid thoracolumbar kyphosis. They also display micro-ophthalmia with nuclear cataracts. Mutant male mice are mostly infertile and exhibit testicular degeneration with increased apoptosis of postmeiotic spermatids. In comparison, Hip1 and Hip1r double-knockout mice are dwarfed, afflicted with severe vertebral defects and die in early adulthood.5 Publications

Keywords - Diseasei

Neurodegeneration

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 10291029Huntingtin-interacting protein 1PRO_0000361654Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei338 – 3381PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8VD75.
MaxQBiQ8VD75.
PaxDbiQ8VD75.
PRIDEiQ8VD75.

PTM databases

iPTMnetiQ8VD75.
PhosphoSiteiQ8VD75.

Expressioni

Tissue specificityi

Most abundantly expressed in brain. In brain, expressed in cortical tissue, hippocampus, the molecular layer of the cerebellum and olfactory bulb. Also expressed in spinal cord and bone marrow (at protein level). Expressed in reproductive tissues.5 Publications

Gene expression databases

BgeeiQ8VD75.
ExpressionAtlasiQ8VD75. baseline and differential.
GenevisibleiQ8VD75. MM.

Interactioni

Subunit structurei

Homodimer. Binds actin. Binds HTT (via N-terminus). This interaction is restricted to the brain. Binds to IFT57. In normal conditions, it poorly interacts with IFT57, HIP1 being strongly associated with HTT. However, in mutant HTT proteins with a long poly-Gln region, interaction between HTT and HIP1 is inhibited, promoting the interaction between HIP1 and IFT57. Interacts with CLTB (via N-terminus). Interacts (via coiled coil domain) with AR. Interacts with AP2A1, AP2A2, CLTC and HIP1R (By similarity). Interacts with GRIA1, GRIN2A AND GRIN2B.By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi229599. 1 interaction.
STRINGi10090.ENSMUSP00000059033.

Structurei

3D structure databases

ProteinModelPortaliQ8VD75.
SMRiQ8VD75. Positions 371-472, 481-572, 765-958.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini32 – 160129ENTHPROSITE-ProRule annotationAdd
BLAST
Domaini763 – 1004242I/LWEQPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni410 – 49182pDEDAdd
BLAST
Regioni859 – 91658Important for actin bindingBy similarityAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili375 – 636262Sequence analysisAdd
BLAST

Domaini

The pseudo DED region (pDED) mediates the interaction with IFT57.By similarity
Binds F-actin via the talin-like I/LWEQ domain.By similarity

Sequence similaritiesi

Belongs to the SLA2 family.Sequence analysis
Contains 1 ENTH (epsin N-terminal homology) domain.PROSITE-ProRule annotation
Contains 1 I/LWEQ domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0980. Eukaryota.
ENOG410XRXQ. LUCA.
GeneTreeiENSGT00550000074542.
HOGENOMiHOG000020612.
HOVERGENiHBG005968.
InParanoidiQ8VD75.
KOiK04559.
OMAiWEEGTEA.
OrthoDBiEOG72JWFF.
PhylomeDBiQ8VD75.
TreeFamiTF316860.

Family and domain databases

Gene3Di1.20.1410.10. 1 hit.
1.25.40.90. 1 hit.
InterProiIPR011417. ANTH_dom.
IPR013809. ENTH.
IPR008942. ENTH_VHS.
IPR030554. HIP1.
IPR032422. HIP1_clath-bd.
IPR002558. ILWEQ_dom.
IPR030224. Sla2_fam.
[Graphical view]
PANTHERiPTHR10407. PTHR10407. 1 hit.
PTHR10407:SF14. PTHR10407:SF14. 1 hit.
PfamiPF07651. ANTH. 1 hit.
PF16515. HIP1_clath_bdg. 1 hit.
PF01608. I_LWEQ. 1 hit.
[Graphical view]
ProDomiPD011820. ILWEQ. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00273. ENTH. 1 hit.
SM00307. ILWEQ. 1 hit.
[Graphical view]
SUPFAMiSSF109885. SSF109885. 1 hit.
SSF48464. SSF48464. 1 hit.
PROSITEiPS50942. ENTH. 1 hit.
PS50945. I_LWEQ. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8VD75-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MDRMASSMKQ VSNPLPKVLS RRGVGAGMEA AERESFERTQ TVSVNKAINT
60 70 80 90 100
QEVAVKEKHA RTCILGTHHE KGAQTFWSVV NRLPLSSNAM LCWKFCHVFH
110 120 130 140 150
KLLRDGHPNV LKDSLRYKNE LSDMSRMWGH LSEGYGQLCS IYLKLLRTRM
160 170 180 190 200
EYHTKNPRFP GNLQMSDRQL DEAGESDVNN FFQLTVEMFD YLECELNLFQ
210 220 230 240 250
TVFNSLDMSR SVSVTTAGQC RLAPLIQVIL DCSHLYDYTV KLLFKLHSCL
260 270 280 290 300
PADTLQGHRD RFMEQFTKLK DLFQRSSNLQ YFKRLIQIPQ LPENPPNFLR
310 320 330 340 350
ASALSEHISP VVVIPAEVSS PDSEPVLEKD DLMDMDASQQ TLFDNKFDDV
360 370 380 390 400
FGSSLSSDPF NFNNQNGVNK DEKDHLIERL YREISGLTGQ LDNMKIESQR
410 420 430 440 450
AMLQLKGRVS ELEAELAEQQ HLGRQAMDDC EFLRTELDEL KRQREDTEKA
460 470 480 490 500
QRSLTEIERK AQANEQRYSK LKEKYSELVQ NHADLLRKNA EVTKQVSVAR
510 520 530 540 550
QAQVDLEREK KELADSFART QEQQDVLENL KHELATSRQE LQVLHSNLET
560 570 580 590 600
SAQSEAKWLT QIAELEKEQG SLATVAAQRE EELSALRDQL ESTQIKLAGA
610 620 630 640 650
QESMCQQVKD QRKTLLAGIR KAAEREIQEA LSQLEEPTLI SCAGSTDHLL
660 670 680 690 700
SKVSSVSSCL EQLEKNGSQY LACPEDISEL LHSITLLAHL TGDTIIQGSA
710 720 730 740 750
TSLRAPPEPA DSLTEACRQY GRETLAYLSS LEEEGTMENA DVTALRNCLS
760 770 780 790 800
RVKTLGEELL PRGLDIKQEE LGDLVDKEMA ATSAAIEAAT TRIEEILSKS
810 820 830 840 850
RAGDTGVKLE VNERILGSCT SLMQAIKVLV VASKDLQKEI VESGRGTASP
860 870 880 890 900
KEFYAKNSRW TEGLISASKA VGWGATIMVD AADLVVQGKG KFEELMVCSR
910 920 930 940 950
EIAASTAQLV AASKVKANKG SLNLTQLQQA SRGVNQATAA VVASTISGKS
960 970 980 990 1000
QIEETDSMDF SSMTLTQIKR QEMDSQVRVL ELENDLQKER QKLGELRKKH
1010 1020
YELAGVAEGW EEGTEASPST VQEAIPDKE
Length:1,029
Mass (Da):115,202
Last modified:January 20, 2009 - v2
Checksum:iD17B9EED8555450C
GO

Sequence cautioni

The sequence AAH17516.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti402 – 4021M → V in BAE38720 (PubMed:16141072).Curated
Sequence conflicti427 – 4271M → T in BAE38720 (PubMed:16141072).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC017516 mRNA. Translation: AAH17516.1. Different initiation.
AK166346 mRNA. Translation: BAE38720.1.
AK220182 mRNA. Translation: BAD90367.1.
CCDSiCCDS51663.1.
RefSeqiNP_666113.2. NM_146001.2.
XP_011239180.1. XM_011240878.1.
UniGeneiMm.280805.

Genome annotation databases

EnsembliENSMUST00000060311; ENSMUSP00000059033; ENSMUSG00000039959.
GeneIDi215114.
KEGGimmu:215114.
UCSCiuc008zyj.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC017516 mRNA. Translation: AAH17516.1. Different initiation.
AK166346 mRNA. Translation: BAE38720.1.
AK220182 mRNA. Translation: BAD90367.1.
CCDSiCCDS51663.1.
RefSeqiNP_666113.2. NM_146001.2.
XP_011239180.1. XM_011240878.1.
UniGeneiMm.280805.

3D structure databases

ProteinModelPortaliQ8VD75.
SMRiQ8VD75. Positions 371-472, 481-572, 765-958.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi229599. 1 interaction.
STRINGi10090.ENSMUSP00000059033.

PTM databases

iPTMnetiQ8VD75.
PhosphoSiteiQ8VD75.

Proteomic databases

EPDiQ8VD75.
MaxQBiQ8VD75.
PaxDbiQ8VD75.
PRIDEiQ8VD75.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000060311; ENSMUSP00000059033; ENSMUSG00000039959.
GeneIDi215114.
KEGGimmu:215114.
UCSCiuc008zyj.2. mouse.

Organism-specific databases

CTDi3092.
MGIiMGI:1099804. Hip1.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG0980. Eukaryota.
ENOG410XRXQ. LUCA.
GeneTreeiENSGT00550000074542.
HOGENOMiHOG000020612.
HOVERGENiHBG005968.
InParanoidiQ8VD75.
KOiK04559.
OMAiWEEGTEA.
OrthoDBiEOG72JWFF.
PhylomeDBiQ8VD75.
TreeFamiTF316860.

Miscellaneous databases

ChiTaRSiHip1. mouse.
NextBioi374616.
PROiQ8VD75.
SOURCEiSearch...

Gene expression databases

BgeeiQ8VD75.
ExpressionAtlasiQ8VD75. baseline and differential.
GenevisibleiQ8VD75. MM.

Family and domain databases

Gene3Di1.20.1410.10. 1 hit.
1.25.40.90. 1 hit.
InterProiIPR011417. ANTH_dom.
IPR013809. ENTH.
IPR008942. ENTH_VHS.
IPR030554. HIP1.
IPR032422. HIP1_clath-bd.
IPR002558. ILWEQ_dom.
IPR030224. Sla2_fam.
[Graphical view]
PANTHERiPTHR10407. PTHR10407. 1 hit.
PTHR10407:SF14. PTHR10407:SF14. 1 hit.
PfamiPF07651. ANTH. 1 hit.
PF16515. HIP1_clath_bdg. 1 hit.
PF01608. I_LWEQ. 1 hit.
[Graphical view]
ProDomiPD011820. ILWEQ. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00273. ENTH. 1 hit.
SM00307. ILWEQ. 1 hit.
[Graphical view]
SUPFAMiSSF109885. SSF109885. 1 hit.
SSF48464. SSF48464. 1 hit.
PROSITEiPS50942. ENTH. 1 hit.
PS50945. I_LWEQ. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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].
    Strain: C57BL/6JImported.
    Tissue: RetinaImported.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-506.
    Tissue: Mammary glandImported.
  3. "Prediction of the coding sequences of mouse homologues of KIAA gene. The complete nucleotide sequences of mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R.F., Ohara R., Inamoto S., Nagase T., Ohara O., Koga H.
    Submitted (FEB-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 412-1029.
    Tissue: Embryonic tailImported.
  4. "HIP1, a human homologue of S. cerevisiae Sla2p, interacts with membrane-associated huntingtin in the brain."
    Kalchman M.A., Koide H.B., McCutcheon K., Graham R.K., Nichol K., Nishiyama K., Kazemi-Esfarjani P., Lynn F.C., Wellington C., Metzler M., Goldberg Y.P., Kanazawa I., Geitz R.D., Hayden M.R.
    Nat. Genet. 16:44-53(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  5. "Clathrin- and AP-2-binding sites in HIP1 uncover a general assembly role for endocytic accessory proteins."
    Mishra S.K., Agostinelli N.R., Brett T.J., Mizukami I., Ross T.S., Traub L.M.
    J. Biol. Chem. 276:46230-46236(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  6. "Huntingtin interacting protein 1 is a clathrin coat binding protein required for differentiation of late spermatogenic progenitors."
    Rao D.S., Chang J.C., Kumar P.D., Mizukami I., Smithson G.M., Bradley S.V., Parlow A.F., Ross T.S.
    Mol. Cell. Biol. 21:7796-7806(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  7. Cited for: FUNCTION, INTERACTION WITH GRIA1, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  8. "Huntingtin interacting protein 1 mutations lead to abnormal hematopoiesis, spinal defects and cataracts."
    Oravecz-Wilson K.I., Kiel M.J., Li L., Rao D.S., Saint-Dic D., Kumar P.D., Provot M.M., Hankenson K.D., Reddy V.N., Lieberman A.P., Morrison S.J., Ross T.S.
    Hum. Mol. Genet. 13:851-867(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  9. "Degenerative phenotypes caused by the combined deficiency of murine HIP1 and HIP1r are rescued by human HIP1."
    Bradley S.V., Hyun T.S., Oravecz-Wilson K.I., Li L., Waldorff E.I., Ermilov A.N., Goldstein S.A., Zhang C.X., Drubin D.G., Varela K., Parlow A., Dlugosz A.A., Ross T.S.
    Hum. Mol. Genet. 16:1279-1292(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
  10. "NMDA receptor function and NMDA receptor-dependent phosphorylation of huntingtin is altered by the endocytic protein HIP1."
    Metzler M., Gan L., Wong T.P., Liu L., Helm J., Liu L., Georgiou J., Wang Y., Bissada N., Cheng K., Roder J.C., Wang Y.T., Hayden M.R.
    J. Neurosci. 27:2298-2308(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GRIN2A AND GRIN2B.
  11. "Structural abnormalities in spermatids together with reduced sperm counts and motility underlie the reproductive defect in HIP1-/-mice."
    Khatchadourian K., Smith C.E., Metzler M., Gregory M., Hayden M.R., Cyr D.G., Hermo L.
    Mol. Reprod. Dev. 74:341-359(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  12. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Brown adipose tissue, Heart, Lung, Spleen and Testis.

Entry informationi

Entry nameiHIP1_MOUSE
AccessioniPrimary (citable) accession number: Q8VD75
Secondary accession number(s): Q3TLS2, Q571K7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 20, 2009
Last sequence update: January 20, 2009
Last modified: May 11, 2016
This is version 104 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.