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Protein

Telomeric repeat-binding factor 2

Gene

TERF2

Organism
Homo sapiens (Human)
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)DescriptionActionsGraphical viewLength
DNA bindingi512 – 537H-T-H motifPROSITE-ProRule annotationAdd BLAST26

GO - Molecular functioni

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

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cellular senescence Source: BHF-UCL
  • negative regulation of beta-galactosidase activity Source: BHF-UCL
  • negative regulation of cellular senescence Source: BHF-UCL
  • negative regulation of gene expression Source: BHF-UCL
  • negative regulation of t-circle formation Source: BHF-UCL
  • negative regulation of telomere capping Source: BHF-UCL
  • negative regulation of telomere maintenance Source: UniProtKB
  • negative regulation of telomere maintenance via recombination Source: BHF-UCL
  • negative regulation of telomere maintenance via semi-conservative replication Source: BHF-UCL
  • negative regulation of telomere single strand break repair Source: BHF-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of nitric-oxide synthase activity Source: BHF-UCL
  • positive regulation of telomere maintenance Source: BHF-UCL
  • protection from non-homologous end joining at telomere Source: BHF-UCL
  • protein localization to chromosome, telomeric region Source: BHF-UCL
  • regulation of telomere maintenance Source: CACAO
  • regulation of telomere maintenance via telomerase Source: BHF-UCL
  • telomere capping Source: BHF-UCL
  • telomere maintenance Source: UniProtKB
  • telomere maintenance via telomerase Source: BHF-UCL
  • telomeric loop formation Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000132604-MONOMER.
ReactomeiR-HSA-1221632. Meiotic synapsis.
R-HSA-171306. Packaging Of Telomere Ends.
R-HSA-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:TRBF2, TRF2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:11729. TERF2.

Subcellular locationi

GO - Cellular componenti

  • chromosome, telomeric region Source: UniProtKB
  • cytoplasm Source: HPA
  • Golgi apparatus Source: HPA
  • nuclear chromosome, telomeric region Source: BHF-UCL
  • nuclear telomere cap complex Source: BHF-UCL
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • telosome Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus, Telomere

Pathology & Biotechi

Organism-specific databases

DisGeNETi7014.
OpenTargetsiENSG00000132604.
PharmGKBiPA36446.

Polymorphism and mutation databases

DMDMi21542277.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001971311 – 542Telomeric repeat-binding factor 2Add BLAST542

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei59Asymmetric dimethylarginine; by PRMT11 Publication1
Modified residuei60Omega-N-methylarginine1 Publication1
Modified residuei230Phosphothreonine; by ATM1 Publication1
Modified residuei365PhosphoserineCombined sources1

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.1 Publication
Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres.1 Publication

Keywords - PTMi

Methylation, Phosphoprotein

Proteomic databases

EPDiQ15554.
PaxDbiQ15554.
PeptideAtlasiQ15554.
PRIDEiQ15554.

PTM databases

iPTMnetiQ15554.
PhosphoSitePlusiQ15554.

Expressioni

Tissue specificityi

Ubiquitous. Highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon and peripheral blood leukocytes.

Gene expression databases

BgeeiENSG00000132604.
CleanExiHS_TERF2.
ExpressionAtlasiQ15554. baseline and differential.
GenevisibleiQ15554. HS.

Organism-specific databases

HPAiCAB010451.
HPA001907.
HPA002735.

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 and TERF2IP/RAP1; the interaction is direct.12 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BLMP541328EBI-706637,EBI-621372
CCDC137Q6PK042EBI-706637,EBI-714654
DCLRE1BQ9H8167EBI-706637,EBI-3508943
DDX21Q9NR302EBI-706637,EBI-357942
EBNA1P032113EBI-706637,EBI-996522From a different organism.
H2AFXP161044EBI-706637,EBI-494830
HDGFRP2Q7Z4V52EBI-706637,EBI-1049136
HEXIM1O949922EBI-706637,EBI-2832510
HMGN2P052042EBI-706637,EBI-1758689
NAIF1Q69YI72EBI-706637,EBI-10249231
ORC1Q134152EBI-706637,EBI-374847
ORC2Q134163EBI-706637,EBI-374957
POT1Q9NUX54EBI-706637,EBI-752420
RPL13P263732EBI-706637,EBI-356849
SLX4Q8IY925EBI-706637,EBI-2370740
TERF2IPQ9NYB012EBI-706637,EBI-750109
TINF2Q9BSI43EBI-706637,EBI-717399
TINF2Q9BSI4-34EBI-706637,EBI-717418
WRNQ141918EBI-706637,EBI-368417
ZC3H18Q86VM92EBI-706637,EBI-1045965

GO - Molecular functioni

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

Protein-protein interaction databases

BioGridi112873. 266 interactors.
DIPiDIP-34052N.
IntActiQ15554. 70 interactors.
MINTiMINT-2831307.
STRINGi9606.ENSP00000254942.

Structurei

Secondary structure

1542
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni87 – 89Combined sources3
Helixi90 – 111Combined sources22
Helixi115 – 128Combined sources14
Helixi137 – 153Combined sources17
Turni154 – 156Combined sources3
Beta strandi163 – 165Combined sources3
Helixi170 – 184Combined sources15
Helixi189 – 209Combined sources21
Helixi213 – 223Combined sources11
Helixi228 – 230Combined sources3
Helixi231 – 243Combined sources13
Turni244 – 246Combined sources3
Helixi249 – 252Combined sources4
Helixi256 – 268Combined sources13
Helixi277 – 285Combined sources9
Turni286 – 288Combined sources3
Helixi327 – 338Combined sources12
Helixi343 – 352Combined sources10
Turni482 – 485Combined sources4
Beta strandi487 – 489Combined sources3
Helixi494 – 507Combined sources14
Helixi512 – 518Combined sources7
Helixi526 – 538Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H6PX-ray2.20A/B85-287[»]
1VF9NMR-A480-542[»]
1VFCNMR-A480-542[»]
1W0UX-ray1.80A/B488-542[»]
1XG1NMR-A480-542[»]
3BU8X-ray2.15A/B84-318[»]
3BUAX-ray2.50A/B/C/D84-287[»]
3K6GX-ray1.95D/E/F317-358[»]
3SJMX-ray1.35A/B483-542[»]
4M7CX-ray2.05A/B87-286[»]
4RQIX-ray2.44A/B/C/D85-287[»]
ProteinModelPortaliQ15554.
SMRiQ15554.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15554.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini484 – 541HTH myb-typePROSITE-ProRule annotationAdd BLAST58

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni84 – 287TRFH dimerizationAdd BLAST204

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi371 – 375Nuclear localization signalSequence analysis5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi55 – 72Arg-rich (basic)Add BLAST18

Domaini

The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2.1 Publication
The HTH domain is an independent structural unit and mediates binding to telomeric DNA.1 Publication

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiENOG410IJXM. Eukaryota.
ENOG4111KJ3. LUCA.
GeneTreeiENSGT00530000063796.
HOGENOMiHOG000154547.
HOVERGENiHBG108560.
InParanoidiQ15554.
KOiK11111.
OMAiITKKQKW.
OrthoDBiEOG091G04CC.
TreeFamiTF333209.

Family and domain databases

CDDicd11654. TRF2_RBM. 1 hit.
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: Q15554-3) [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 AASQPRKRPG REGGEGARRS DTMAGGGGSS
60 70 80 90 100
DGSGRAAGRR ASRSSGRARR GRHEPGLGGP AERGAGEARL EEAVNRWVLK
110 120 130 140 150
FYFHEALRAF RGSRYGDFRQ IRDIMQALLV RPLGKEHTVS RLLRVMQCLS
160 170 180 190 200
RIEEGENLDC SFDMEAELTP LESAINVLEM IKTEFTLTEA VVESSRKLVK
210 220 230 240 250
EAAVIICIKN KEFEKASKIL KKHMSKDPTT QKLRNDLLNI IREKNLAHPV
260 270 280 290 300
IQNFSYETFQ QKMLRFLESH LDDAEPYLLT MAKKALKSES AASSTGKEDK
310 320 330 340 350
QPAPGPVEKP PREPARQLRN PPTTIGMMTL KAAFKTLSGA QDSEAAFAKL
360 370 380 390 400
DQKDLVLPTQ ALPASPALKN KRPRKDENES SAPADGEGGS ELQPKNKRMT
410 420 430 440 450
ISRLVLEEDS QSTEPSAGLN SSQEAASAPP SKPTVLNQPL PGEKNPKVPK
460 470 480 490 500
GKWNSSNGVE EKETWVEEDE LFQVQAAPDE DSTTNITKKQ KWTVEESEWV
510 520 530 540
KAGVQKYGEG NWAAISKNYP FVNRTAVMIK DRWRTMKRLG MN
Length:542
Mass (Da):59,594
Last modified:April 16, 2014 - v3
Checksum:i3A278AC6B594C43A
GO
Isoform 2 (identifier: Q15554-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     281-293: MAKKALKSESAAS → VRLGPSPITMVCP
     294-542: Missing.

Note: No experimental confirmation available.
Show »
Length:293
Mass (Da):32,298
Checksum:iF9B31F886F3D3C23
GO

Sequence cautioni

The sequence AAB81135 differs from that shown. Contaminating sequence. The N-terminus may be contaminated with vector sequence.Curated
The sequence AAB81135 differs from that shown. Reason: Frameshift at position 36.Curated
The sequence AAH24890 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_050196455S → G.Corresponds to variant rs35874485dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_003304281 – 293MAKKA…ESAAS → VRLGPSPITMVCP in isoform 2. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_003305294 – 542Missing in isoform 2. 1 PublicationAdd BLAST249

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC026464 Genomic DNA. No translation available.
BC024890 mRNA. Translation: AAH24890.1. Different initiation.
AF002999 mRNA. Translation: AAB81135.1. Sequence problems.
U95970 mRNA. Translation: AAD00821.1.
X93512 mRNA. Translation: CAA63769.1.
CCDSiCCDS10879.2. [Q15554-3]
PIRiS67923.
RefSeqiNP_005643.2. NM_005652.4. [Q15554-3]
UniGeneiHs.63335.

Genome annotation databases

EnsembliENST00000254942; ENSP00000254942; ENSG00000132604. [Q15554-3]
ENST00000567296; ENSP00000454955; ENSG00000132604. [Q15554-4]
GeneIDi7014.
KEGGihsa:7014.
UCSCiuc002exd.5. human. [Q15554-3]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AC026464 Genomic DNA. No translation available.
BC024890 mRNA. Translation: AAH24890.1. Different initiation.
AF002999 mRNA. Translation: AAB81135.1. Sequence problems.
U95970 mRNA. Translation: AAD00821.1.
X93512 mRNA. Translation: CAA63769.1.
CCDSiCCDS10879.2. [Q15554-3]
PIRiS67923.
RefSeqiNP_005643.2. NM_005652.4. [Q15554-3]
UniGeneiHs.63335.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1H6PX-ray2.20A/B85-287[»]
1VF9NMR-A480-542[»]
1VFCNMR-A480-542[»]
1W0UX-ray1.80A/B488-542[»]
1XG1NMR-A480-542[»]
3BU8X-ray2.15A/B84-318[»]
3BUAX-ray2.50A/B/C/D84-287[»]
3K6GX-ray1.95D/E/F317-358[»]
3SJMX-ray1.35A/B483-542[»]
4M7CX-ray2.05A/B87-286[»]
4RQIX-ray2.44A/B/C/D85-287[»]
ProteinModelPortaliQ15554.
SMRiQ15554.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112873. 266 interactors.
DIPiDIP-34052N.
IntActiQ15554. 70 interactors.
MINTiMINT-2831307.
STRINGi9606.ENSP00000254942.

PTM databases

iPTMnetiQ15554.
PhosphoSitePlusiQ15554.

Polymorphism and mutation databases

DMDMi21542277.

Proteomic databases

EPDiQ15554.
PaxDbiQ15554.
PeptideAtlasiQ15554.
PRIDEiQ15554.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000254942; ENSP00000254942; ENSG00000132604. [Q15554-3]
ENST00000567296; ENSP00000454955; ENSG00000132604. [Q15554-4]
GeneIDi7014.
KEGGihsa:7014.
UCSCiuc002exd.5. human. [Q15554-3]

Organism-specific databases

CTDi7014.
DisGeNETi7014.
GeneCardsiTERF2.
HGNCiHGNC:11729. TERF2.
HPAiCAB010451.
HPA001907.
HPA002735.
MIMi602027. gene.
neXtProtiNX_Q15554.
OpenTargetsiENSG00000132604.
PharmGKBiPA36446.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IJXM. Eukaryota.
ENOG4111KJ3. LUCA.
GeneTreeiENSGT00530000063796.
HOGENOMiHOG000154547.
HOVERGENiHBG108560.
InParanoidiQ15554.
KOiK11111.
OMAiITKKQKW.
OrthoDBiEOG091G04CC.
TreeFamiTF333209.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000132604-MONOMER.
ReactomeiR-HSA-1221632. Meiotic synapsis.
R-HSA-171306. Packaging Of Telomere Ends.
R-HSA-2559586. DNA Damage/Telomere Stress Induced Senescence.

Miscellaneous databases

ChiTaRSiTERF2. human.
EvolutionaryTraceiQ15554.
GeneWikiiTERF2.
GenomeRNAii7014.
PROiQ15554.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132604.
CleanExiHS_TERF2.
ExpressionAtlasiQ15554. baseline and differential.
GenevisibleiQ15554. HS.

Family and domain databases

CDDicd11654. TRF2_RBM. 1 hit.
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...

Entry informationi

Entry nameiTERF2_HUMAN
AccessioniPrimary (citable) accession number: Q15554
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: April 16, 2014
Last modified: November 2, 2016
This is version 179 of the entry and version 3 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.