{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q15554","uniProtkbId":"TERF2_HUMAN","entryAudit":{"firstPublicDate":"2002-06-20","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2014-04-16","entryVersion":238,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Telomeric repeat-binding factor 2"}},"alternativeNames":[{"fullName":{"value":"TTAGGG repeat-binding factor 2"}},{"fullName":{"value":"Telomeric DNA-binding protein"}}]},"genes":[{"geneName":{"value":"TERF2"},"synonyms":[{"value":"TRBF2"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"28216226"}],"value":"TRF2"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"O35144"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15608617"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16166375"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20655466"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28216226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31595153"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9326950"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9326951"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"9476899"}],"value":"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 (PubMed:15608617, PubMed:16166375, PubMed:20655466, PubMed:28216226, PubMed:31595153, PubMed:9326950, PubMed:9326951, PubMed:9476899). 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 (PubMed:16166375, PubMed:20655466). Component of the shelterin complex (telosome) that is involved in the regulation of telomere length and protection (PubMed:16166375). 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 (PubMed:16166375). 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 (PubMed:20655466). Required both to recruit DCLRE1B/Apollo to telomeres and activate the exonuclease activity of DCLRE1B/Apollo (PubMed:20655466, PubMed:28216226). Preferentially binds to positive supercoiled DNA (PubMed:15608617, PubMed:20655466). 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 (PubMed:20655466). Recruits TERF2IP/RAP1 to telomeres, thereby participating in to repressing homology-directed repair (HDR), which can affect telomere length (By similarity)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"10888888"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15316005"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15383534"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15608617"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16606622"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16730175"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16730176"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18202258"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18468965"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18593705"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19596235"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20655466"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28216226"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31595153"}],"value":"Homodimer (PubMed:15608617). Component of the shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP/RAP1, ACD and POT1 (PubMed:15316005, PubMed:15383534, PubMed:15608617, PubMed:18202258). Interacts with NBN; interaction takes place with unphosphorylated NBN during G1 phase and prevents to prevent ATM activation and non-homologous end joining repair (PubMed:10888888, PubMed:28216226). Interacts with SLX4/BTBD12 (PubMed:19596235). Interacts with DCLRE1B/Apollo and TERF2IP/RAP1; the interaction is direct (PubMed:16606622, PubMed:16730175, PubMed:16730176, PubMed:18468965, PubMed:18593705, PubMed:20655466). Interacts with DSP in the nucleus; the interaction is required for DSP telomere binding (PubMed:31595153)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q13315","geneName":"ATM","intActId":"EBI-495465"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"P54132","geneName":"BLM","intActId":"EBI-621372"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q6PK04","geneName":"CCDC137","intActId":"EBI-714654"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q9H816","geneName":"DCLRE1B","intActId":"EBI-3508943"},"numberOfExperiments":12,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q9NR30","geneName":"DDX21","intActId":"EBI-357942"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"P16104","geneName":"H2AX","intActId":"EBI-494830"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q7Z4V5","geneName":"HDGFL2","intActId":"EBI-1049136"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"O94992","geneName":"HEXIM1","intActId":"EBI-2832510"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"P05204","geneName":"HMGN2","intActId":"EBI-1758689"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q8NEM0","geneName":"MCPH1","intActId":"EBI-1565483"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q69YI7","geneName":"NAIF1","intActId":"EBI-10249231"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q13415","geneName":"ORC1","intActId":"EBI-374847"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q13416","geneName":"ORC2","intActId":"EBI-374957"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q9NUX5","geneName":"POT1","intActId":"EBI-752420"},"numberOfExperiments":10,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"P26373","geneName":"RPL13","intActId":"EBI-356849"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q8IY92","geneName":"SLX4","intActId":"EBI-2370740"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q9NYB0","geneName":"TERF2IP","intActId":"EBI-750109"},"numberOfExperiments":37,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q9BSI4","geneName":"TINF2","intActId":"EBI-717399"},"numberOfExperiments":13,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q9BSI4-3","geneName":"TINF2","intActId":"EBI-717418"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q14191","geneName":"WRN","intActId":"EBI-368417"},"numberOfExperiments":8,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q86VM9","geneName":"ZC3H18","intActId":"EBI-1045965"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"P03211","geneName":"EBNA1","intActId":"EBI-996522"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"Q15554","intActId":"EBI-706637"},"interactantTwo":{"uniProtKBAccession":"Q80W00","geneName":"Ppp1r10","intActId":"EBI-2553719"},"numberOfExperiments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Highly expressed in spleen, thymus, prostate, uterus, testis, small intestine, colon and peripheral blood leukocytes"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18202258"}],"value":"The TRFH dimerization region mediates the interaction with DCLRE1B/Apollo but not TINF2"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18202258"}],"value":"The HTH domain is an independent structural unit and mediates binding to telomeric DNA"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16223874"}],"value":"Phosphorylated upon DNA damage, most probably by ATM. Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly localizes to damage sites"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19596784"}],"value":"Methylated by PRMT1 at multiple arginines within the N-terminal Arg-rich region. Methylation may control association with telomeres"}],"commentType":"PTM"},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Frameshift","sequence":"AAB81135.1","evidences":[{"evidenceCode":"ECO:0000305"}]},{"commentType":"SEQUENCE CAUTION","sequenceCautionType":"Miscellaneous discrepancy","sequence":"AAB81135.1","note":"Contaminating sequence. 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