Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT5XSLT)

• DTT Name: Telomeric repeat-binding factor 2 (TERF2)
• Synonyms: Telomeric DNA-binding protein; TTAGGG repeat-binding factor 2; TRF2; TRBF2
• Gene Name: TERF2
• DTT Type: Literature-reported target; [1]
• UniProt ID: TERF2_HUMAN
• TTD ID: T14181
• Sequence:
  MAAGAGTAGPASGPGVVRDPAASQPRKRPGREGGEGARRSDTMAGGGGSSDGSGRAAGRR
  ASRSSGRARRGRHEPGLGGPAERGAGEARLEEAVNRWVLKFYFHEALRAFRGSRYGDFRQ
  IRDIMQALLVRPLGKEHTVSRLLRVMQCLSRIEEGENLDCSFDMEAELTPLESAINVLEM
  IKTEFTLTEAVVESSRKLVKEAAVIICIKNKEFEKASKILKKHMSKDPTTQKLRNDLLNI
  IREKNLAHPVIQNFSYETFQQKMLRFLESHLDDAEPYLLTMAKKALKSESAASSTGKEDK
  QPAPGPVEKPPREPARQLRNPPTTIGMMTLKAAFKTLSGAQDSEAAFAKLDQKDLVLPTQ
  ALPASPALKNKRPRKDENESSAPADGEGGSELQPKNKRMTISRLVLEEDSQSTEPSAGLN
  SSQEAASAPPSKPTVLNQPLPGEKNPKVPKGKWNSSNGVEEKETWVEEDELFQVQAAPDE
  DSTTNITKKQKWTVEESEWVKAGVQKYGEGNWAAISKNYPFVNRTAVMIKDRWRTMKRLG
  MN
• Function: 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.
• Reactome Pathway:
  Cleavage of the damaged pyrimidine (R-HSA-110329)
  Recognition and association of DNA glycosylase with site containing an affected purine (R-HSA-110330)
  Cleavage of the damaged purine (R-HSA-110331)
  Meiotic synapsis (R-HSA-1221632)
  Packaging Of Telomere Ends (R-HSA-171306)
  Telomere Extension By Telomerase (R-HSA-171319)
  Polymerase switching on the C-strand of the telomere (R-HSA-174411)
  Processive synthesis on the C-strand of the telomere (R-HSA-174414)
  Telomere C-strand (Lagging Strand) Synthesis (R-HSA-174417)
  Telomere C-strand synthesis initiation (R-HSA-174430)
  Removal of the Flap Intermediate from the C-strand (R-HSA-174437)
  DNA Damage/Telomere Stress Induced Senescence (R-HSA-2559586)
  Inhibition of DNA recombination at telomere (R-HSA-9670095)
  Recognition and association of DNA glycosylase with site containing an affected pyrimidine (R-HSA-110328)

References

• [1] Knockdown of telomeric repeat binding factor 2 enhances tumor radiosensitivity regardless of telomerase status. J Cancer Res Clin Oncol. 2015 Sep;141(9):1545-52.