Protein: Telomeric repeat-binding factor 2 (TTAGGG repeat-binding factor 2) (Telomeric DNA-binding protein) (Q15554)
Organism: Homo sapiens (Human)
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.
Subcellular location: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00625, ECO:0000269|PubMed:20655466}. Chromosome, telomere {ECO:0000269|PubMed:20655466}. Note=Colocalizes with telomeric DNA in interphase cells and is located at chromosome ends during metaphase. {ECO:0000269|PubMed:20655466}.
Sequence: MAAGAGTAGPASGPGVVRDPAASQPRKRPGREGGEGARRSDTMAGGGGSSDGSGRAAGRRASRSSGRARRGRHEPGLGGPAERGAGEARLEEAVNRWVLKFYFHEALRAFRGSRYGDFRQIRDIMQALLVRPLGKEHTVSRLLRVMQCLSRIEEGENLDCSFDMEAELTPLESAINVLEMIKTEFTLTEAVVESSRKLVKEAAVIICIKNKEFEKASKILKKHMSKDPTTQKLRNDLLNIIREKNLAHPVIQNFSYETFQQKMLRFLESHLDDAEPYLLTMAKKALKSESAASSTGKEDKQPAPGPVEKPPREPARQLRNPPTTIGMMTLKAAFKTLSGAQDSEAAFAKLDQKDLVLPTQALPASPALKNKRPRKDENESSAPADGEGGSELQPKNKRMTISRLVLEEDSQSTEPSAGLNSSQEAASAPPSKPTVLNQPLPGEKNPKVPKGKWNSSNGVEEKETWVEEDELFQVQAAPDEDSTTNITKKQKWTVEESEWVKAGVQKYGEGNWAAISKNYPFVNRTAVMIKDRWRTMKRLGMN
InterPro domains: - IPR013867: Telomere repeat-binding factor, dimerisation domain (domain) [96-291]
- IPR030657: Telomeric repeat-binding factor 2 (family) [81-542]
- IPR017357: Telomeric repeat-binding factor 1/2 (family) [75-541]
- IPR001005: SANT/Myb domain (domain) [488-539]
- IPR031902: Telomeric repeat-binding factor 2, Rap1-binding domain (domain) [317-358]
- IPR009057: Homedomain-like superfamily (homologous_superfamily) [490-540]
- IPR017930: Myb domain (domain) [484-541]
- IPR036507: Telomere repeat-binding factor, dimerisation domain superfamily (homologous_superfamily) [87-286]
Interaction partners: - Protection of telomeres protein 1
- Telomeric repeat-binding factor 2-interacting protein 1
- Adrenocortical dysplasia protein homolog
- 5' exonuclease Apollo
- TERF1-interacting nuclear factor 2
- Telomeric repeat-binding factor 1
- Structure-specific endonuclease subunit SLX4
- Nibrin
- X-ray repair cross-complementing protein 6
- Double-strand break repair protein MRE11
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:1901363 (heterocyclic compound binding), GO:0044877 (protein-containing complex binding), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0046983 (protein dimerization activity), GO:0042802 (identical protein binding), GO:0042803 (protein homodimerization activity), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0042162 (telomeric DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048519 (negative regulation of biological process), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0019222 (regulation of metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0009892 (negative regulation of metabolic process), GO:0044237 (cellular metabolic process), GO:0048522 (positive regulation of cellular process), GO:0050794 (regulation of cellular process), GO:0009893 (positive regulation of metabolic process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0007017 (microtubule-based process), GO:0048523 (negative regulation of cellular process), GO:0044238 (primary metabolic process), GO:0051172 (negative regulation of nitrogen compound metabolic process), GO:0051129 (negative regulation of cellular component organization), GO:0010604 (positive regulation of macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0051649 (establishment of localization in cell), GO:0060255 (regulation of macromolecule metabolic process), GO:0051130 (positive regulation of cellular component organization), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0031324 (negative regulation of cellular metabolic process), GO:0043170 (macromolecule metabolic process), GO:0007018 (microtubule-based movement), GO:1901360 (organic cyclic compound metabolic process), GO:0046907 (intracellular transport), GO:0006139 (nucleobase-containing compound metabolic process), GO:0031325 (positive regulation of cellular metabolic process), GO:0033554 (cellular response to stress), GO:0010605 (negative regulation of macromolecule metabolic process), GO:0006810 (transport), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0009790 (embryo development), GO:0080090 (regulation of primary metabolic process), GO:0051128 (regulation of cellular component organization), GO:0044260 (cellular macromolecule metabolic process), GO:0051173 (positive regulation of nitrogen compound metabolic process), GO:0010970 (transport along microtubule), GO:0051052 (regulation of DNA metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0051054 (positive regulation of DNA metabolic process), GO:0030705 (cytoskeleton-dependent intracellular transport), GO:0099111 (microtubule-based transport), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0010639 (negative regulation of organelle organization), GO:0051053 (negative regulation of DNA metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0006259 (DNA metabolic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0033043 (regulation of organelle organization), GO:0006996 (organelle organization), GO:0010638 (positive regulation of organelle organization), GO:0045934 (negative regulation of nucleobase-containing compound metabolic process), GO:0009792 (embryo development ending in birth or egg hatching), GO:0043009 (chordate embryonic development), GO:0000018 (regulation of DNA recombination), GO:0032204 (regulation of telomere maintenance), GO:0008088 (axo-dendritic transport), GO:0000723 (telomere maintenance), GO:0051276 (chromosome organization), GO:2001252 (positive regulation of chromosome organization), GO:0045910 (negative regulation of DNA recombination), GO:0032206 (positive regulation of telomere maintenance), GO:0032205 (negative regulation of telomere maintenance), GO:2001251 (negative regulation of chromosome organization), GO:0033044 (regulation of chromosome organization), GO:0098930 (axonal transport), GO:0001701 (in utero embryonic development), GO:0032200 (telomere organization), GO:0000019 (regulation of mitotic recombination), GO:0016233 (telomere capping), GO:0008089 (anterograde axonal transport)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0032993 (protein-DNA complex), GO:0098687 (chromosomal region), GO:0044815 (DNA packaging complex), GO:0140513 (nuclear protein-containing complex), GO:0031974 (membrane-enclosed lumen), GO:0016604 (nuclear body), GO:0005654 (nucleoplasm), GO:0000782 (telomere cap complex), GO:0043229 (intracellular organelle), GO:0043228 (non-membrane-bounded organelle), GO:0043233 (organelle lumen), GO:0000783 (nuclear telomere cap complex), GO:0043227 (membrane-bounded organelle), GO:0000781 (chromosome, telomeric region), GO:0043231 (intracellular membrane-bounded organelle), GO:0043232 (intracellular non-membrane-bounded organelle), GO:0140445 (chromosome, telomeric repeat region), GO:0070013 (intracellular organelle lumen), GO:0005634 (nucleus), GO:0031981 (nuclear lumen), GO:0005694 (chromosome)