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Protein

Telomeric repeat-binding factor 2

Gene

Terf2

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

Functioni

Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and plays a central role in telomere maintenance and protection against end-to-end fusion of chromosomes. In addition to its telomeric DNA-binding role, required to recruit a number of factors and enzymes required for telomere protection, including the shelterin complex, TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection. Shelterin associates with arrays of double-stranded 5'-TTAGGG-3' repeats added by telomerase and protects chromosome ends; without its protective activity, telomeres are no longer hidden from the DNA damage surveillance and chromosome ends are inappropriately processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a key role in telomeric loop (T loop) formation by generating 3' single-stranded overhang at the leading end telomeres: T loops have been proposed to protect chromosome ends from degradation and repair. Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo. Preferentially binds to positive supercoiled DNA. Together with DCLRE1B/Apollo, required to control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed for telomere replication during fork passage and prevent aberrant telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length.3 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi511 – 53626H-T-H motifPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

  • double-stranded telomeric DNA binding Source: BHF-UCL
  • G-rich strand telomeric DNA binding Source: MGI
  • macromolecular complex binding Source: MGI
  • protein C-terminus binding Source: MGI
  • protein homodimerization activity Source: BHF-UCL
  • telomeric DNA binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

ReactomeiR-MMU-1221632. Meiotic synapsis.
R-MMU-1221633. Meiotic Synapsis.
R-MMU-2559586. DNA Damage/Telomere Stress Induced Senescence.

Names & Taxonomyi

Protein namesi
Recommended name:
Telomeric repeat-binding factor 2
Alternative name(s):
TTAGGG repeat-binding factor 2
Telomeric DNA-binding protein
Gene namesi
Name:Terf2
Synonyms:Trf2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 8

Organism-specific databases

MGIiMGI:1195972. Terf2.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation1 Publication
  • Chromosometelomere 1 Publication

  • Note: Colocalizes with telomeric DNA in interphase cells and is located at chromosome ends during metaphase.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi165 – 1651F → A: Abolishes interaction with DCLRE1B/Apollo, leading to activate the ATM signaling pathway. 1 Publication
Mutagenesisi335 – 3362AF → SS: Abolishes interaction with TERF2IP/RAP1 but does not affect protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 541541Telomeric repeat-binding factor 2PRO_0000197132Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei62 – 621Asymmetric dimethylarginine; by PRMT1By similarity
Modified residuei63 – 631Omega-N-methylarginineBy similarity
Modified residuei233 – 2331Phosphothreonine; by ATMBy similarity
Modified residuei364 – 3641PhosphoserineCombined sources
Modified residuei366 – 3661PhosphoserineCombined sources
Modified residuei367 – 3671PhosphoserineCombined sources

Post-translational modificationi

Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites (By similarity).By similarity
Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres (By similarity).By similarity

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiO35144.
MaxQBiO35144.
PaxDbiO35144.
PeptideAtlasiO35144.
PRIDEiO35144.

PTM databases

iPTMnetiO35144.
PhosphoSiteiO35144.

Expressioni

Gene expression databases

BgeeiO35144.
CleanExiMM_TERF2.
ExpressionAtlasiO35144. baseline and differential.
GenevisibleiO35144. MM.

Interactioni

Subunit structurei

Homodimer. Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP/RAP1, ACD and POT1. Interacts with TERF2IP. Interacts with NBN. Interacts with SLX4/BTBD12. Interacts with DCLRE1B/Apollo; the interaction is direct (By similarity). Interacts with TERF2IP/RAP1; the interaction is direct.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dna2Q6ZQJ54EBI-6919263,EBI-6919222

GO - Molecular functioni

  • protein C-terminus binding Source: MGI
  • protein homodimerization activity Source: BHF-UCL

Protein-protein interaction databases

BioGridi204117. 8 interactions.
IntActiO35144. 8 interactions.
MINTiMINT-4137455.
STRINGi10090.ENSMUSP00000118759.

Structurei

3D structure databases

ProteinModelPortaliO35144.
SMRiO35144. Positions 88-294, 326-359, 487-541.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini483 – 54058HTH myb-typePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni87 – 290204TRFH dimerizationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi373 – 3775Nuclear localization signalSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi58 – 7518Arg-rich (basic)Add
BLAST

Domaini

The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2.By similarity
The HTH domain is an independent structural unit and mediates binding to telomeric DNA.By similarity

Sequence similaritiesi

Contains 1 HTH myb-type DNA-binding domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IJXM. Eukaryota.
ENOG4111KJ3. LUCA.
GeneTreeiENSGT00530000063796.
HOGENOMiHOG000154547.
HOVERGENiHBG108560.
InParanoidiO35144.
KOiK11111.
OMAiITKKQKW.
OrthoDBiEOG7DFXCF.
PhylomeDBiO35144.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
1.25.40.210. 1 hit.
InterProiIPR009057. Homeodomain-like.
IPR017930. Myb_dom.
IPR001005. SANT/Myb.
IPR013867. Telomere_rpt-bd_fac_dimer_dom.
IPR030657. TERF2.
IPR031902. TERF2_RBM.
[Graphical view]
PANTHERiPTHR21717:SF13. PTHR21717:SF13. 1 hit.
PfamiPF00249. Myb_DNA-binding. 1 hit.
PF16772. TERF2_RBM. 1 hit.
PF08558. TRF. 1 hit.
[Graphical view]
ProDomiPD014243. Telomere_repeat-bd_fac_dimer. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00717. SANT. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
SSF63600. SSF63600. 1 hit.
PROSITEiPS51294. HTH_MYB. 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: O35144-1) [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
MAAGAGTAGP ASGPGVVRDP MASQPRKRPS REGGEGGEGE RRSNTMAGGG
60 70 80 90 100
GSSDSSGRAA SRRASRSGGR ARRGRHEPGL GGAAERGAGE ARLEEAVNRW
110 120 130 140 150
VLKFYFHEAL RAFRSSRYRD FRQIRDIMQA LLVRPLGKEH TVSRLLRVMQ
160 170 180 190 200
CLSRIEEGEN LDCSFDMEAE LTPLESAINV LEMIKTEFTL TDSMVESSRK
210 220 230 240 250
LVKEAAVIIC IKNKEFEKAS KILKKYMSKD PTTQKLRTDL LNIIREKNLA
260 270 280 290 300
HPVIQNFSYE VFQQKMLRFL ESHLDDTEPY LLTMAKKALK SESAASSTMR
310 320 330 340 350
EEKHPEPVEK PLREPPSRQP QNPPATIGIR TLKAAFKALS TAQDSEAAFA
360 370 380 390 400
KLDQKDLVLA NLASPSSPAH KHKRPRKDEH ESAAPAEGEG GSDRQPRNSP
410 420 430 440 450
MTISRLLLEE DSQSTEPSPG LNSSHKAMSA SKPRALNQPH PGEKKPKASK
460 470 480 490 500
DKWNSPNGLE EKEVWLEEDQ LFEVQAPGED RSSSLTRKQK WTIEESEWVK
510 520 530 540
DGVRKYGEGN WAAISKSYPF VNRTAVMIKD RWRTMKKLGM N
Length:541
Mass (Da):60,263
Last modified:July 27, 2011 - v3
Checksum:i2788F7322506182C
GO
Isoform 2 (identifier: O35144-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     448-541: ASKDKWNSPN...WRTMKKLGMN → YEDLLCRSLGAGWRAWLGLVLLP

Show »
Length:470
Mass (Da):51,828
Checksum:i803C8DD1B0DDFCB0
GO

Sequence cautioni

The sequence AAB81136.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAC33784.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti317 – 3171Missing in AAB81136 (PubMed:9326950).Curated
Sequence conflicti393 – 3931D → S in AAB81136 (PubMed:9326950).Curated
Sequence conflicti426 – 4261K → E in AAH46284 (PubMed:15489334).Curated
Sequence conflicti426 – 4261K → E in AAB81136 (PubMed:9326950).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei448 – 54194ASKDK…KLGMN → YEDLLCRSLGAGWRAWLGLV LLP in isoform 2. 2 PublicationsVSP_027086Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK049507 mRNA. Translation: BAC33784.1. Different initiation.
AC123868 Genomic DNA. No translation available.
BC046284 mRNA. Translation: AAH46284.1.
AF003000 mRNA. Translation: AAB81136.1. Different initiation.
CCDSiCCDS52666.1. [O35144-2]
RefSeqiNP_001076587.1. NM_001083118.2. [O35144-2]
NP_001273129.1. NM_001286200.1.
XP_006530899.1. XM_006530836.2. [O35144-1]
UniGeneiMm.6402.

Genome annotation databases

EnsembliENSMUST00000068421; ENSMUSP00000068948; ENSMUSG00000031921. [O35144-1]
ENSMUST00000116425; ENSMUSP00000112126; ENSMUSG00000031921. [O35144-2]
GeneIDi21750.
KEGGimmu:21750.
UCSCiuc009nhf.2. mouse. [O35144-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK049507 mRNA. Translation: BAC33784.1. Different initiation.
AC123868 Genomic DNA. No translation available.
BC046284 mRNA. Translation: AAH46284.1.
AF003000 mRNA. Translation: AAB81136.1. Different initiation.
CCDSiCCDS52666.1. [O35144-2]
RefSeqiNP_001076587.1. NM_001083118.2. [O35144-2]
NP_001273129.1. NM_001286200.1.
XP_006530899.1. XM_006530836.2. [O35144-1]
UniGeneiMm.6402.

3D structure databases

ProteinModelPortaliO35144.
SMRiO35144. Positions 88-294, 326-359, 487-541.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi204117. 8 interactions.
IntActiO35144. 8 interactions.
MINTiMINT-4137455.
STRINGi10090.ENSMUSP00000118759.

PTM databases

iPTMnetiO35144.
PhosphoSiteiO35144.

Proteomic databases

EPDiO35144.
MaxQBiO35144.
PaxDbiO35144.
PeptideAtlasiO35144.
PRIDEiO35144.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000068421; ENSMUSP00000068948; ENSMUSG00000031921. [O35144-1]
ENSMUST00000116425; ENSMUSP00000112126; ENSMUSG00000031921. [O35144-2]
GeneIDi21750.
KEGGimmu:21750.
UCSCiuc009nhf.2. mouse. [O35144-2]

Organism-specific databases

CTDi7014.
MGIiMGI:1195972. Terf2.

Phylogenomic databases

eggNOGiENOG410IJXM. Eukaryota.
ENOG4111KJ3. LUCA.
GeneTreeiENSGT00530000063796.
HOGENOMiHOG000154547.
HOVERGENiHBG108560.
InParanoidiO35144.
KOiK11111.
OMAiITKKQKW.
OrthoDBiEOG7DFXCF.
PhylomeDBiO35144.

Enzyme and pathway databases

ReactomeiR-MMU-1221632. Meiotic synapsis.
R-MMU-1221633. Meiotic Synapsis.
R-MMU-2559586. DNA Damage/Telomere Stress Induced Senescence.

Miscellaneous databases

ChiTaRSiTerf2. mouse.
PROiO35144.
SOURCEiSearch...

Gene expression databases

BgeeiO35144.
CleanExiMM_TERF2.
ExpressionAtlasiO35144. baseline and differential.
GenevisibleiO35144. MM.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
1.25.40.210. 1 hit.
InterProiIPR009057. Homeodomain-like.
IPR017930. Myb_dom.
IPR001005. SANT/Myb.
IPR013867. Telomere_rpt-bd_fac_dimer_dom.
IPR030657. TERF2.
IPR031902. TERF2_RBM.
[Graphical view]
PANTHERiPTHR21717:SF13. PTHR21717:SF13. 1 hit.
PfamiPF00249. Myb_DNA-binding. 1 hit.
PF16772. TERF2_RBM. 1 hit.
PF08558. TRF. 1 hit.
[Graphical view]
ProDomiPD014243. Telomere_repeat-bd_fac_dimer. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SMARTiSM00717. SANT. 1 hit.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
SSF63600. SSF63600. 1 hit.
PROSITEiPS51294. HTH_MYB. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "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] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Embryo.
  2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  3. "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 2).
    Strain: FVB/N-3.
    Tissue: Mammary tumor.
  4. "Human telomeres contain two distinct Myb-related proteins, TRF1 and TRF2."
    Broccoli D., Smogorzewska A., Chong L., de Lange T.
    Nat. Genet. 17:231-235(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-540 (ISOFORM 1).
    Tissue: Brain.
  5. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  6. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-366, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-364 AND SER-367, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Brain, Lung, Spleen and Testis.
  8. "Apollo contributes to G overhang maintenance and protects leading-end telomeres."
    Wu P., van Overbeek M., Rooney S., de Lange T.
    Mol. Cell 39:606-617(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH DCLRE1B, MUTAGENESIS OF PHE-165.
  9. Cited for: FUNCTION, INTERACTION WITH TERF2IP.
  10. "Loss of Rap1 induces telomere recombination in the absence of NHEJ or a DNA damage signal."
    Sfeir A., Kabir S., van Overbeek M., Celli G.B., de Lange T.
    Science 327:1657-1661(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TERF2IP, MUTAGENESIS OF 335-ALA-PHE-336, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiTERF2_MOUSE
AccessioniPrimary (citable) accession number: O35144
Secondary accession number(s): D3YVG5, Q80VE2, Q8BQJ9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: July 27, 2011
Last modified: July 6, 2016
This is version 145 of the entry and version 3 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.