Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Telomeric repeat-binding factor 2

Gene

TERF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

GO - Biological processi

Keywordsi

Molecular functionDNA-binding
Biological processCell cycle

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000132604.10
HGNCiHGNC:11729 TERF2
MIMi602027 gene
neXtProtiNX_Q15554

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
Cross-linki287Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki335Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki353Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei365PhosphoserineCombined sources1
Cross-linki369Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki375Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Cross-linki452Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined 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.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

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ15554
PaxDbiQ15554
PeptideAtlasiQ15554
PRIDEiQ15554
ProteomicsDBi60629

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 Expressed in 231 organ(s), highest expression level in frontal cortex
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

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112873, 270 interactors
ComplexPortaliCPX-152 Shelterin complex
CPX-484 SLX4-TERF2 complex
CORUMiQ15554
DIPiDIP-34052N
ELMiQ15554
IntActiQ15554, 78 interactors
MINTiQ15554
STRINGi9606.ENSP00000254942

Structurei

Secondary structure

1542
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Phylogenomic databases

eggNOGiENOG410IJXM Eukaryota
ENOG4111KJ3 LUCA
GeneTreeiENSGT00530000063796
HOGENOMiHOG000154547
HOVERGENiHBG108560
InParanoidiQ15554
KOiK11111
OMAiNPKVPKG
OrthoDBiEOG091G04CC
TreeFamiTF333209

Family and domain databases

CDDicd11654 TRF2_RBM, 1 hit
Gene3Di1.25.40.210, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017930 Myb_dom
IPR001005 SANT/Myb
IPR013867 Telomere_rpt-bd_fac_dimer_dom
IPR036507 Telomere_rpt-bd_fac_dimer_sf
IPR017357 TERF1/2
IPR030657 TERF2
IPR031902 TERF2_RBM
PANTHERiPTHR21717:SF13 PTHR21717:SF13, 1 hit
PfamiView protein in Pfam
PF00249 Myb_DNA-binding, 1 hit
PF16772 TERF2_RBM, 1 hit
PF08558 TRF, 1 hit
PIRSFiPIRSF038016 Telomere_bd-1_Pin2, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD014243 Telomere_repeat-bd_fac_dimer, 1 hit
SMARTiView protein in SMART
SM00717 SANT, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
SSF63600 SSF63600, 1 hit
PROSITEiView protein in PROSITE
PS51294 HTH_MYB, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 8 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H3BR06H3BR06_HUMAN
Telomeric repeat-binding factor 2
TERF2
283Annotation score:
U3KQ35U3KQ35_HUMAN
Telomeric repeat-binding factor 2
TERF2
244Annotation score:
J3KSZ6J3KSZ6_HUMAN
Telomeric repeat-binding factor 2
TERF2
144Annotation score:
H3BTA7H3BTA7_HUMAN
Telomeric repeat-binding factor 2
TERF2
206Annotation score:
J3KSJ9J3KSJ9_HUMAN
Telomeric repeat-binding factor 2
TERF2
99Annotation score:
V9GYM1V9GYM1_HUMAN
Telomeric repeat-binding factor 2
TERF2
86Annotation score:
H3BR37H3BR37_HUMAN
Telomeric repeat-binding factor 2
TERF2
60Annotation score:
J3KTN8J3KTN8_HUMAN
Telomeric repeat-binding factor 2
TERF2
49Annotation score:

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 dbSNP:rs35874485Ensembl.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

Similar proteinsi

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[»]
5WQDX-ray3.00A/B/C/D/E/F/G84-287[»]
5XYFX-ray2.20C392-408[»]
ProteinModelPortaliQ15554
SMRiQ15554
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112873, 270 interactors
ComplexPortaliCPX-152 Shelterin complex
CPX-484 SLX4-TERF2 complex
CORUMiQ15554
DIPiDIP-34052N
ELMiQ15554
IntActiQ15554, 78 interactors
MINTiQ15554
STRINGi9606.ENSP00000254942

PTM databases

iPTMnetiQ15554
PhosphoSitePlusiQ15554

Polymorphism and mutation databases

DMDMi21542277

Proteomic databases

EPDiQ15554
PaxDbiQ15554
PeptideAtlasiQ15554
PRIDEiQ15554
ProteomicsDBi60629

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
EuPathDBiHostDB:ENSG00000132604.10
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
OMAiNPKVPKG
OrthoDBiEOG091G04CC
TreeFamiTF333209

Enzyme and pathway databases

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
PROiPR:Q15554
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000132604 Expressed in 231 organ(s), highest expression level in frontal cortex
CleanExiHS_TERF2
ExpressionAtlasiQ15554 baseline and differential
GenevisibleiQ15554 HS

Family and domain databases

CDDicd11654 TRF2_RBM, 1 hit
Gene3Di1.25.40.210, 1 hit
InterProiView protein in InterPro
IPR009057 Homeobox-like_sf
IPR017930 Myb_dom
IPR001005 SANT/Myb
IPR013867 Telomere_rpt-bd_fac_dimer_dom
IPR036507 Telomere_rpt-bd_fac_dimer_sf
IPR017357 TERF1/2
IPR030657 TERF2
IPR031902 TERF2_RBM
PANTHERiPTHR21717:SF13 PTHR21717:SF13, 1 hit
PfamiView protein in Pfam
PF00249 Myb_DNA-binding, 1 hit
PF16772 TERF2_RBM, 1 hit
PF08558 TRF, 1 hit
PIRSFiPIRSF038016 Telomere_bd-1_Pin2, 1 hit
ProDomiView protein in ProDom or Entries sharing at least one domain
PD014243 Telomere_repeat-bd_fac_dimer, 1 hit
SMARTiView protein in SMART
SM00717 SANT, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
SSF63600 SSF63600, 1 hit
PROSITEiView protein in PROSITE
PS51294 HTH_MYB, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiTERF2_HUMAN
AccessioniPrimary (citable) accession number: Q15554
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 20, 2002
Last sequence update: April 16, 2014
Last modified: November 7, 2018
This is version 195 of the entry and version 3 of the sequence. See 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
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again