ID TERF2_HUMAN Reviewed; 542 AA. AC Q15554; DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2014, sequence version 3. DT 27-MAR-2024, entry version 228. DE RecName: Full=Telomeric repeat-binding factor 2; DE AltName: Full=TTAGGG repeat-binding factor 2; DE AltName: Full=Telomeric DNA-binding protein; GN Name=TERF2; Synonyms=TRBF2, TRF2; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15616553; DOI=10.1038/nature03187; RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., RA Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., RA Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J., Buckingham J.M., RA Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., RA Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., RA Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., RA Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., RA Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., RA Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., RA Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., RA Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., RA Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., RA Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., RA Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., RA Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., RA Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., RA Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., RA DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., RA Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., RA Myers R.M., Rubin E.M., Pennacchio L.A.; RT "The sequence and analysis of duplication-rich human chromosome 16."; RL Nature 432:988-994(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Adrenal cortex; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] OF 6-542 (ISOFORM 1). RC TISSUE=Mammary carcinoma; RX PubMed=9326950; DOI=10.1038/ng1097-231; RA Broccoli D., Smogorzewska A., Chong L., de Lange T.; RT "Human telomeres contain two distinct Myb-related proteins, TRF1 and RT TRF2."; RL Nat. Genet. 17:231-235(1997). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] OF 83-542 (ISOFORM 1). RC TISSUE=Cervix carcinoma; RX PubMed=9326951; DOI=10.1038/ng1097-236; RA Bilaud T., Brun C., Ancelin K., Koering C.E., Larouche T., Gilson E.; RT "Telomeric localization of TRF2, a novel human telobox protein."; RL Nat. Genet. 17:236-239(1997). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 480-542 (ISOFORM 1). RC TISSUE=Cervix carcinoma; RX PubMed=8614633; DOI=10.1093/nar/24.7.1294; RA Bilaud T., Koering C.E., Binet-Brasselet E., Ancelin K., Pollice A., RA Gasser S.M., Gilson E.; RT "The telobox, a Myb-related telomeric DNA binding motif found in proteins RT from yeast, plants and human."; RL Nucleic Acids Res. 24:1294-1303(1996). RN [6] RP FUNCTION. RX PubMed=9476899; DOI=10.1016/s0092-8674(00)80932-0; RA van Steensel B., Smogorzewska A., de Lange T.; RT "TRF2 protects human telomeres from end-to-end fusions."; RL Cell 92:401-413(1998). RN [7] RP INTERACTION WITH NBN. RX PubMed=10888888; DOI=10.1038/77139; RA Zhu X.-D., Kuester B., Mann M., Petrini J.H.J., de Lange T.; RT "Cell-cycle-regulated association of RAD50/MRE11/NBS1 with TRF2 and human RT telomeres."; RL Nat. Genet. 25:347-352(2000). RN [8] RP IDENTIFICATION IN THE SHELTERIN COMPLEX. RX PubMed=15316005; DOI=10.1074/jbc.m409047200; RA Ye J.Z.-S., Donigian J.R., van Overbeek M., Loayza D., Luo Y., RA Krutchinsky A.N., Chait B.T., de Lange T.; RT "TIN2 binds TRF1 and TRF2 simultaneously and stabilizes the TRF2 complex on RT telomeres."; RL J. Biol. Chem. 279:47264-47271(2004). RN [9] RP IDENTIFICATION IN THE SHELTERIN COMPLEX. RX PubMed=15383534; DOI=10.1074/jbc.m409293200; RA Liu D., O'Connor M.S., Qin J., Songyang Z.; RT "Telosome, a mammalian telomere-associated complex formed by multiple RT telomeric proteins."; RL J. Biol. Chem. 279:51338-51342(2004). RN [10] RP FUNCTION OF THE SHELTERIN COMPLEX. RX PubMed=16166375; DOI=10.1101/gad.1346005; RA de Lange T.; RT "Shelterin: the protein complex that shapes and safeguards human RT telomeres."; RL Genes Dev. 19:2100-2110(2005). RN [11] RP PHOSPHORYLATION AT THR-230 BY ATM. RX PubMed=16223874; DOI=10.1073/pnas.0507915102; RA Tanaka H., Mendonca M.S., Bradshaw P.S., Hoelz D.J., Malkas L.H., RA Meyn M.S., Gilley D.; RT "DNA damage-induced phosphorylation of the human telomere-associated RT protein TRF2."; RL Proc. Natl. Acad. Sci. U.S.A. 102:15539-15544(2005). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [13] RP INTERACTION WITH DCLRE1B. RX PubMed=16730176; DOI=10.1016/j.cub.2006.05.022; RA van Overbeek M., de Lange T.; RT "Apollo, an Artemis-related nuclease, interacts with TRF2 and protects RT human telomeres in S phase."; RL Curr. Biol. 16:1295-1302(2006). RN [14] RP INTERACTION WITH DCLRE1B. RX PubMed=16730175; DOI=10.1016/j.cub.2006.05.021; RA Lenain C., Bauwens S., Amiard S., Brunori M., Giraud-Panis M.J., Gilson E.; RT "The Apollo 5' exonuclease functions together with TRF2 to protect RT telomeres from DNA repair."; RL Curr. Biol. 16:1303-1310(2006). RN [15] RP INTERACTION WITH DCLRE1B. RX PubMed=16606622; DOI=10.1074/jbc.c600038200; RA Freibaum B.D., Counter C.M.; RT "hSnm1B is a novel telomere-associated protein."; RL J. Biol. Chem. 281:15033-15036(2006). RN [16] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=16964243; DOI=10.1038/nbt1240; RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.; RT "A probability-based approach for high-throughput protein phosphorylation RT analysis and site localization."; RL Nat. Biotechnol. 24:1285-1292(2006). RN [17] RP INTERACTION WITH DCLRE1B. RX PubMed=18468965; DOI=10.1016/j.dnarep.2008.03.020; RA Demuth I., Bradshaw P.S., Lindner A., Anders M., Heinrich S., RA Kallenbach J., Schmelz K., Digweed M., Meyn M.S., Concannon P.; RT "Endogenous hSNM1B/Apollo interacts with TRF2 and stimulates ATM in RT response to ionizing radiation."; RL DNA Repair 7:1192-1201(2008). RN [18] RP INTERACTION WITH DCLRE1B. RX PubMed=18593705; DOI=10.1074/jbc.m800388200; RA Freibaum B.D., Counter C.M.; RT "The protein hSnm1B is stabilized when bound to the telomere-binding RT protein TRF2."; RL J. Biol. Chem. 283:23671-23676(2008). RN [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [21] RP INTERACTION WITH SLX4. RX PubMed=19596235; DOI=10.1016/j.cell.2009.06.030; RA Svendsen J.M., Smogorzewska A., Sowa M.E., O'Connell B.C., Gygi S.P., RA Elledge S.J., Harper J.W.; RT "Mammalian BTBD12/SLX4 assembles a Holliday junction resolvase and is RT required for DNA repair."; RL Cell 138:63-77(2009). RN [22] RP METHYLATION AT ARG-59 AND ARG-60 BY PRMT1. RX PubMed=19596784; DOI=10.1128/mcb.00009-09; RA Mitchell T.R., Glenfield K., Jeyanthan K., Zhu X.D.; RT "Arginine methylation regulates telomere length and stability."; RL Mol. Cell. Biol. 29:4918-4934(2009). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [24] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH DCLRE1B, AND DNA-BINDING. RX PubMed=20655466; DOI=10.1016/j.cell.2010.05.032; RA Ye J., Lenain C., Bauwens S., Rizzo A., Saint-Leger A., Poulet A., RA Benarroch D., Magdinier F., Morere J., Amiard S., Verhoeyen E., Britton S., RA Calsou P., Salles B., Bizard A., Nadal M., Salvati E., Sabatier L., Wu Y., RA Biroccio A., Londono-Vallejo A., Giraud-Panis M.J., Gilson E.; RT "TRF2 and Apollo cooperate with topoisomerase 2alpha to protect human RT telomeres from replicative damage."; RL Cell 142:230-242(2010). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [26] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [29] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-365, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [30] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-287; LYS-335; LYS-353; LYS-369; RP LYS-375 AND LYS-452, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RX PubMed=28112733; DOI=10.1038/nsmb.3366; RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C., RA Nielsen M.L.; RT "Site-specific mapping of the human SUMO proteome reveals co-modification RT with phosphorylation."; RL Nat. Struct. Mol. Biol. 24:325-336(2017). RN [31] RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS). RX PubMed=11545737; DOI=10.1016/s1097-2765(01)00321-5; RA Fairall L., Chapman L., Moss H., de Lange T., Rhodes D.; RT "Structure of the TRFH dimerization domain of the human telomeric proteins RT TRF1 and TRF2."; RL Mol. Cell 8:351-361(2001). RN [32] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 488-542 IN COMPLEX WITH TELOMERIC RP DNA, AND SUBUNIT. RX PubMed=15608617; DOI=10.1038/sj.embor.7400314; RA Court R., Chapman L., Fairall L., Rhodes D.; RT "How the human telomeric proteins TRF1 and TRF2 recognize telomeric DNA: a RT view from high-resolution crystal structures."; RL EMBO Rep. 6:39-45(2005). RN [33] RP X-RAY CRYSTALLOGRAPHY (2.15 ANGSTROMS) OF 84-318 IN COMPLEX WITH TINF2 AND RP DCLRE1B, AND DOMAIN TRFH DIMERIZATION. RX PubMed=18202258; DOI=10.1126/science.1151804; RA Chen Y., Yang Y., van Overbeek M., Donigian J.R., Baciu P., de Lange T., RA Lei M.; RT "A shared docking motif in TRF1 and TRF2 used for differential recruitment RT of telomeric proteins."; RL Science 319:1092-1096(2008). CC -!- FUNCTION: Binds the telomeric double-stranded 5'-TTAGGG-3' repeat and CC plays a central role in telomere maintenance and protection against CC end-to-end fusion of chromosomes. In addition to its telomeric DNA- CC binding role, required to recruit a number of factors and enzymes CC required for telomere protection, including the shelterin complex, CC TERF2IP/RAP1 and DCLRE1B/Apollo. Component of the shelterin complex CC (telosome) that is involved in the regulation of telomere length and CC protection. Shelterin associates with arrays of double-stranded 5'- CC TTAGGG-3' repeats added by telomerase and protects chromosome ends; CC without its protective activity, telomeres are no longer hidden from CC the DNA damage surveillance and chromosome ends are inappropriately CC processed by DNA repair pathways. Together with DCLRE1B/Apollo, plays a CC key role in telomeric loop (T loop) formation by generating 3' single- CC stranded overhang at the leading end telomeres: T loops have been CC proposed to protect chromosome ends from degradation and repair. CC Required both to recruit DCLRE1B/Apollo to telomeres and activate the CC exonuclease activity of DCLRE1B/Apollo. Preferentially binds to CC positive supercoiled DNA. Together with DCLRE1B/Apollo, required to CC control the amount of DNA topoisomerase (TOP1, TOP2A and TOP2B) needed CC for telomere replication during fork passage and prevent aberrant CC telomere topology. Recruits TERF2IP/RAP1 to telomeres, thereby CC participating in to repressing homology-directed repair (HDR), which CC can affect telomere length. {ECO:0000269|PubMed:16166375, CC ECO:0000269|PubMed:20655466, ECO:0000269|PubMed:9476899}. CC -!- SUBUNIT: Homodimer. Component of the shelterin complex (telosome) CC composed of TERF1, TERF2, TINF2, TERF2IP/RAP1, ACD and POT1. Interacts CC with TERF2IP. Interacts with NBN. Interacts with SLX4/BTBD12. Interacts CC with DCLRE1B/Apollo and TERF2IP/RAP1; the interaction is direct. CC {ECO:0000269|PubMed:10888888, ECO:0000269|PubMed:15316005, CC ECO:0000269|PubMed:15383534, ECO:0000269|PubMed:15608617, CC ECO:0000269|PubMed:16606622, ECO:0000269|PubMed:16730175, CC ECO:0000269|PubMed:16730176, ECO:0000269|PubMed:18202258, CC ECO:0000269|PubMed:18468965, ECO:0000269|PubMed:18593705, CC ECO:0000269|PubMed:19596235, ECO:0000269|PubMed:20655466}. CC -!- INTERACTION: CC Q15554; Q13315: ATM; NbExp=2; IntAct=EBI-706637, EBI-495465; CC Q15554; P54132: BLM; NbExp=8; IntAct=EBI-706637, EBI-621372; CC Q15554; Q6PK04: CCDC137; NbExp=2; IntAct=EBI-706637, EBI-714654; CC Q15554; Q9H816: DCLRE1B; NbExp=10; IntAct=EBI-706637, EBI-3508943; CC Q15554; Q9NR30: DDX21; NbExp=2; IntAct=EBI-706637, EBI-357942; CC Q15554; P16104: H2AX; NbExp=4; IntAct=EBI-706637, EBI-494830; CC Q15554; Q7Z4V5: HDGFL2; NbExp=2; IntAct=EBI-706637, EBI-1049136; CC Q15554; O94992: HEXIM1; NbExp=2; IntAct=EBI-706637, EBI-2832510; CC Q15554; P05204: HMGN2; NbExp=2; IntAct=EBI-706637, EBI-1758689; CC Q15554; Q8NEM0: MCPH1; NbExp=5; IntAct=EBI-706637, EBI-1565483; CC Q15554; Q69YI7: NAIF1; NbExp=2; IntAct=EBI-706637, EBI-10249231; CC Q15554; Q13415: ORC1; NbExp=2; IntAct=EBI-706637, EBI-374847; CC Q15554; Q13416: ORC2; NbExp=3; IntAct=EBI-706637, EBI-374957; CC Q15554; Q9NUX5: POT1; NbExp=7; IntAct=EBI-706637, EBI-752420; CC Q15554; P26373: RPL13; NbExp=2; IntAct=EBI-706637, EBI-356849; CC Q15554; Q8IY92: SLX4; NbExp=5; IntAct=EBI-706637, EBI-2370740; CC Q15554; Q9NYB0: TERF2IP; NbExp=36; IntAct=EBI-706637, EBI-750109; CC Q15554; Q9BSI4: TINF2; NbExp=11; IntAct=EBI-706637, EBI-717399; CC Q15554; Q9BSI4-3: TINF2; NbExp=4; IntAct=EBI-706637, EBI-717418; CC Q15554; Q14191: WRN; NbExp=8; IntAct=EBI-706637, EBI-368417; CC Q15554; Q86VM9: ZC3H18; NbExp=2; IntAct=EBI-706637, EBI-1045965; CC Q15554; P03211: EBNA1; Xeno; NbExp=3; IntAct=EBI-706637, EBI-996522; CC Q15554; Q80W00: Ppp1r10; Xeno; NbExp=3; IntAct=EBI-706637, EBI-2553719; CC Q15554-4; P54253: ATXN1; NbExp=6; IntAct=EBI-25840535, EBI-930964; CC Q15554-4; P54252: ATXN3; NbExp=3; IntAct=EBI-25840535, EBI-946046; CC Q15554-4; Q14203-5: DCTN1; NbExp=3; IntAct=EBI-25840535, EBI-25840379; CC Q15554-4; P26378-2: ELAVL4; NbExp=3; IntAct=EBI-25840535, EBI-21603100; CC Q15554-4; P42858: HTT; NbExp=15; IntAct=EBI-25840535, EBI-466029; CC Q15554-4; D3DTS7: PMP22; NbExp=3; IntAct=EBI-25840535, EBI-25882629; CC Q15554-4; O60260-5: PRKN; NbExp=6; IntAct=EBI-25840535, EBI-21251460; CC Q15554-4; P37840: SNCA; NbExp=3; IntAct=EBI-25840535, EBI-985879; CC Q15554-4; P00441: SOD1; NbExp=3; IntAct=EBI-25840535, EBI-990792; CC Q15554-4; Q13148: TARDBP; NbExp=6; IntAct=EBI-25840535, EBI-372899; CC Q15554-4; Q9NUW8: TDP1; NbExp=3; IntAct=EBI-25840535, EBI-2902553; CC Q15554-4; P09936: UCHL1; NbExp=3; IntAct=EBI-25840535, EBI-714860; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00625, CC ECO:0000269|PubMed:20655466}. Chromosome, telomere CC {ECO:0000269|PubMed:20655466}. Note=Colocalizes with telomeric DNA in CC interphase cells and is located at chromosome ends during metaphase. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q15554-3; Sequence=Displayed; CC Name=2; CC IsoId=Q15554-4; Sequence=VSP_003304, VSP_003305; CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed in spleen, thymus, CC prostate, uterus, testis, small intestine, colon and peripheral blood CC leukocytes. CC -!- DOMAIN: The TRFH dimerization region mediates the interaction with CC DCLRE1B/Apollo but not TINF2. {ECO:0000269|PubMed:18202258}. CC -!- DOMAIN: The HTH domain is an independent structural unit and mediates CC binding to telomeric DNA. {ECO:0000269|PubMed:18202258}. CC -!- PTM: Phosphorylated upon DNA damage, most probably by ATM. CC Phosphorylated TERF2 is not bound to telomeric DNA, and rapidly CC localizes to damage sites. {ECO:0000269|PubMed:16223874}. CC -!- PTM: Methylated by PRMT1 at multiple arginines within the N-terminal CC Arg-rich region. Methylation may control association with telomeres. CC {ECO:0000269|PubMed:19596784}. CC -!- SEQUENCE CAUTION: CC Sequence=AAB81135.1; Type=Frameshift; Evidence={ECO:0000305}; CC Sequence=AAB81135.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. The N-terminus may be contaminated with vector sequence.; Evidence={ECO:0000305}; CC Sequence=AAH24890.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC026464; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC024890; AAH24890.1; ALT_INIT; mRNA. DR EMBL; AF002999; AAB81135.1; ALT_SEQ; mRNA. DR EMBL; U95970; AAD00821.1; -; mRNA. DR EMBL; X93512; CAA63769.1; -; mRNA. DR CCDS; CCDS10879.2; -. [Q15554-3] DR PIR; S67923; S67923. DR RefSeq; NP_005643.2; NM_005652.4. [Q15554-3] DR PDB; 1H6P; X-ray; 2.20 A; A/B=85-287. DR PDB; 1VF9; NMR; -; A=480-542. DR PDB; 1VFC; NMR; -; A=480-542. DR PDB; 1W0U; X-ray; 1.80 A; A/B=488-542. DR PDB; 1XG1; NMR; -; A=480-542. DR PDB; 3BU8; X-ray; 2.15 A; A/B=84-318. DR PDB; 3BUA; X-ray; 2.50 A; A/B/C/D=84-287. DR PDB; 3K6G; X-ray; 1.95 A; D/E/F=317-358. DR PDB; 3SJM; X-ray; 1.35 A; A/B=483-542. DR PDB; 4M7C; X-ray; 2.05 A; A/B=87-286. DR PDB; 4RQI; X-ray; 2.44 A; A/B/C/D=85-287. DR PDB; 5WQD; X-ray; 3.00 A; A/B/C/D/E/F/G=84-287. DR PDB; 5XYF; X-ray; 2.20 A; C=392-408. DR PDB; 6J67; X-ray; 2.05 A; A=84-287. DR PDB; 7C5D; X-ray; 2.15 A; A/B=84-287. DR PDBsum; 1H6P; -. DR PDBsum; 1VF9; -. DR PDBsum; 1VFC; -. DR PDBsum; 1W0U; -. DR PDBsum; 1XG1; -. DR PDBsum; 3BU8; -. DR PDBsum; 3BUA; -. DR PDBsum; 3K6G; -. DR PDBsum; 3SJM; -. DR PDBsum; 4M7C; -. DR PDBsum; 4RQI; -. DR PDBsum; 5WQD; -. DR PDBsum; 5XYF; -. DR PDBsum; 6J67; -. DR PDBsum; 7C5D; -. DR AlphaFoldDB; Q15554; -. DR SASBDB; Q15554; -. DR SMR; Q15554; -. DR BioGRID; 112873; 346. DR ComplexPortal; CPX-152; Shelterin complex. DR ComplexPortal; CPX-484; SLX4-TERF2 complex. DR CORUM; Q15554; -. DR DIP; DIP-34052N; -. DR ELM; Q15554; -. DR IntAct; Q15554; 106. DR MINT; Q15554; -. DR STRING; 9606.ENSP00000254942; -. DR BindingDB; Q15554; -. DR ChEMBL; CHEMBL4296012; -. DR GlyGen; Q15554; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q15554; -. DR PhosphoSitePlus; Q15554; -. DR BioMuta; TERF2; -. DR DMDM; 21542277; -. DR CPTAC; CPTAC-3256; -. DR CPTAC; CPTAC-3257; -. DR CPTAC; CPTAC-956; -. DR EPD; Q15554; -. DR jPOST; Q15554; -. DR MassIVE; Q15554; -. DR MaxQB; Q15554; -. DR PaxDb; 9606-ENSP00000254942; -. DR PeptideAtlas; Q15554; -. DR ProteomicsDB; 60629; -. [Q15554-3] DR Pumba; Q15554; -. DR Antibodypedia; 1053; 701 antibodies from 46 providers. DR CPTC; Q15554; 3 antibodies. DR DNASU; 7014; -. DR Ensembl; ENST00000254942.8; ENSP00000254942.3; ENSG00000132604.11. [Q15554-3] DR Ensembl; ENST00000567296.6; ENSP00000454955.2; ENSG00000132604.11. [Q15554-4] DR GeneID; 7014; -. DR KEGG; hsa:7014; -. DR MANE-Select; ENST00000254942.8; ENSP00000254942.3; NM_005652.5; NP_005643.2. DR UCSC; uc002exd.5; human. [Q15554-3] DR AGR; HGNC:11729; -. DR CTD; 7014; -. DR DisGeNET; 7014; -. DR GeneCards; TERF2; -. DR HGNC; HGNC:11729; TERF2. DR HPA; ENSG00000132604; Low tissue specificity. DR MIM; 602027; gene. DR neXtProt; NX_Q15554; -. DR OpenTargets; ENSG00000132604; -. DR PharmGKB; PA36446; -. DR VEuPathDB; HostDB:ENSG00000132604; -. DR eggNOG; ENOG502RYHN; Eukaryota. DR GeneTree; ENSGT00940000158316; -. DR HOGENOM; CLU_034265_1_1_1; -. DR InParanoid; Q15554; -. DR OMA; EKETWME; -. DR OrthoDB; 207546at2759; -. DR PhylomeDB; Q15554; -. DR TreeFam; TF333209; -. DR PathwayCommons; Q15554; -. DR Reactome; R-HSA-110328; Recognition and association of DNA glycosylase with site containing an affected pyrimidine. DR Reactome; R-HSA-110329; Cleavage of the damaged pyrimidine. DR Reactome; R-HSA-110330; Recognition and association of DNA glycosylase with site containing an affected purine. DR Reactome; R-HSA-110331; Cleavage of the damaged purine. DR Reactome; R-HSA-1221632; Meiotic synapsis. DR Reactome; R-HSA-171306; Packaging Of Telomere Ends. DR Reactome; R-HSA-171319; Telomere Extension By Telomerase. DR Reactome; R-HSA-174411; Polymerase switching on the C-strand of the telomere. DR Reactome; R-HSA-174414; Processive synthesis on the C-strand of the telomere. DR Reactome; R-HSA-174417; Telomere C-strand (Lagging Strand) Synthesis. DR Reactome; R-HSA-174430; Telomere C-strand synthesis initiation. DR Reactome; R-HSA-174437; Removal of the Flap Intermediate from the C-strand. DR Reactome; R-HSA-2559586; DNA Damage/Telomere Stress Induced Senescence. DR Reactome; R-HSA-9670095; Inhibition of DNA recombination at telomere. DR SignaLink; Q15554; -. DR SIGNOR; Q15554; -. DR BioGRID-ORCS; 7014; 457 hits in 688 CRISPR screens. DR ChiTaRS; TERF2; human. DR EvolutionaryTrace; Q15554; -. DR GeneWiki; TERF2; -. DR GenomeRNAi; 7014; -. DR Pharos; Q15554; Tchem. DR PRO; PR:Q15554; -. DR Proteomes; UP000005640; Chromosome 16. DR RNAct; Q15554; Protein. DR Bgee; ENSG00000132604; Expressed in cortical plate and 203 other cell types or tissues. DR ExpressionAtlas; Q15554; baseline and differential. DR GO; GO:1904115; C:axon cytoplasm; IEA:GOC. DR GO; GO:0000781; C:chromosome, telomeric region; IDA:UniProtKB. DR GO; GO:0001673; C:male germ cell nucleus; IEA:Ensembl. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0000783; C:nuclear telomere cap complex; IDA:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0070187; C:shelterin complex; IDA:BHF-UCL. DR GO; GO:0003691; F:double-stranded telomeric DNA binding; IDA:BHF-UCL. DR GO; GO:0019899; F:enzyme binding; IPI:BHF-UCL. DR GO; GO:0098505; F:G-rich strand telomeric DNA binding; IDA:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IPI:BHF-UCL. DR GO; GO:0042162; F:telomeric DNA binding; IDA:UniProtKB. DR GO; GO:0008089; P:anterograde axonal transport; IEA:Ensembl. DR GO; GO:0099088; P:axonal transport of messenger ribonucleoprotein complex; IEA:Ensembl. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0090398; P:cellular senescence; NAS:BHF-UCL. DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl. DR GO; GO:1903770; P:negative regulation of beta-galactosidase activity; IDA:BHF-UCL. DR GO; GO:2000773; P:negative regulation of cellular senescence; IMP:BHF-UCL. DR GO; GO:1905778; P:negative regulation of exonuclease activity; IDA:BHF-UCL. DR GO; GO:0010629; P:negative regulation of gene expression; IMP:BHF-UCL. DR GO; GO:1904430; P:negative regulation of t-circle formation; IMP:BHF-UCL. DR GO; GO:1904354; P:negative regulation of telomere capping; IMP:BHF-UCL. DR GO; GO:0032205; P:negative regulation of telomere maintenance; IDA:UniProtKB. DR GO; GO:0032208; P:negative regulation of telomere maintenance via recombination; IMP:BHF-UCL. DR GO; GO:0032214; P:negative regulation of telomere maintenance via semi-conservative replication; NAS:BHF-UCL. DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IDA:BHF-UCL. DR GO; GO:1904357; P:negative regulation of telomere maintenance via telomere lengthening; IMP:BHF-UCL. DR GO; GO:1903824; P:negative regulation of telomere single strand break repair; NAS:BHF-UCL. DR GO; GO:1905839; P:negative regulation of telomeric D-loop disassembly; IDA:BHF-UCL. DR GO; GO:0010628; P:positive regulation of gene expression; IMP:BHF-UCL. DR GO; GO:0051000; P:positive regulation of nitric-oxide synthase activity; IMP:BHF-UCL. DR GO; GO:0032206; P:positive regulation of telomere maintenance; IDA:ComplexPortal. DR GO; GO:0031848; P:protection from non-homologous end joining at telomere; IMP:BHF-UCL. DR GO; GO:0070198; P:protein localization to chromosome, telomeric region; IMP:BHF-UCL. DR GO; GO:0032204; P:regulation of telomere maintenance; IMP:CACAO. DR GO; GO:0032210; P:regulation of telomere maintenance via telomerase; IDA:BHF-UCL. DR GO; GO:0006278; P:RNA-templated DNA biosynthetic process; IEA:GOC. DR GO; GO:0016233; P:telomere capping; IDA:ComplexPortal. DR GO; GO:0000723; P:telomere maintenance; IMP:UniProtKB. DR GO; GO:0061820; P:telomeric D-loop disassembly; IGI:BHF-UCL. DR GO; GO:0031627; P:telomeric loop formation; IDA:BHF-UCL. DR CDD; cd11660; SANT_TRF; 1. DR CDD; cd11654; TRF2_RBM; 1. DR CDD; cd00280; TRFH; 1. DR Gene3D; 1.10.10.60; Homeodomain-like; 1. DR Gene3D; 1.25.40.210; Telomere repeat-binding factor, dimerisation domain; 1. DR InterPro; IPR009057; Homeobox-like_sf. DR InterPro; IPR017930; Myb_dom. DR InterPro; IPR001005; SANT/Myb. DR InterPro; IPR013867; Telomere_rpt-bd_fac_dimer_dom. DR InterPro; IPR036507; Telomere_rpt-bd_fac_dimer_sf. DR InterPro; IPR017357; TERF1/2. DR InterPro; IPR030657; TERF2. DR InterPro; IPR031902; TERF2_RBM. DR PANTHER; PTHR46833:SF1; TELOMERIC REPEAT-BINDING FACTOR 2; 1. DR PANTHER; PTHR46833; TELOMERIC REPEAT-BINDING FACTOR 2 TERF2; 1. DR Pfam; PF00249; Myb_DNA-binding; 1. DR Pfam; PF16772; TERF2_RBM; 1. DR Pfam; PF08558; TRF; 1. DR PIRSF; PIRSF038016; Telomere_bd-1_Pin2; 1. DR SMART; SM00717; SANT; 1. DR SUPFAM; SSF46689; Homeodomain-like; 1. DR SUPFAM; SSF63600; Telomeric repeat binding factor (TRF) dimerisation domain; 1. DR PROSITE; PS51294; HTH_MYB; 1. DR Genevisible; Q15554; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cell cycle; Chromosome; DNA-binding; KW Isopeptide bond; Methylation; Nucleus; Phosphoprotein; Reference proteome; KW Telomere; Ubl conjugation. FT CHAIN 1..542 FT /note="Telomeric repeat-binding factor 2" FT /id="PRO_0000197131" FT DOMAIN 484..541 FT /note="HTH myb-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00625" FT DNA_BIND 512..537 FT /note="H-T-H motif" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00625" FT REGION 1..86 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 84..287 FT /note="TRFH dimerization" FT REGION 288..323 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 358..464 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 371..375 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 24..38 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 405..433 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 59 FT /note="Asymmetric dimethylarginine; by PRMT1" FT /evidence="ECO:0000269|PubMed:19596784" FT MOD_RES 60 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000269|PubMed:19596784" FT MOD_RES 230 FT /note="Phosphothreonine; by ATM" FT /evidence="ECO:0000269|PubMed:16223874" FT MOD_RES 365 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:16964243, FT ECO:0007744|PubMed:17081983, ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT CROSSLNK 287 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 335 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 353 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 369 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 375 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 452 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 281..293 FT /note="MAKKALKSESAAS -> VRLGPSPITMVCP (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_003304" FT VAR_SEQ 294..542 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_003305" FT VARIANT 455 FT /note="S -> G (in dbSNP:rs35874485)" FT /id="VAR_050196" FT TURN 87..89 FT /evidence="ECO:0007829|PDB:3BU8" FT HELIX 90..111 FT /evidence="ECO:0007829|PDB:4M7C" FT HELIX 115..128 FT /evidence="ECO:0007829|PDB:4M7C" FT HELIX 137..153 FT /evidence="ECO:0007829|PDB:4M7C" FT TURN 154..156 FT /evidence="ECO:0007829|PDB:4M7C" FT STRAND 163..165 FT /evidence="ECO:0007829|PDB:3BU8" FT HELIX 170..184 FT /evidence="ECO:0007829|PDB:4M7C" FT HELIX 189..209 FT /evidence="ECO:0007829|PDB:4M7C" FT HELIX 213..223 FT /evidence="ECO:0007829|PDB:4M7C" FT HELIX 228..230 FT /evidence="ECO:0007829|PDB:6J67" FT HELIX 231..243 FT /evidence="ECO:0007829|PDB:4M7C" FT TURN 244..246 FT /evidence="ECO:0007829|PDB:1H6P" FT HELIX 249..252 FT /evidence="ECO:0007829|PDB:4M7C" FT HELIX 256..268 FT /evidence="ECO:0007829|PDB:4M7C" FT HELIX 277..285 FT /evidence="ECO:0007829|PDB:4M7C" FT TURN 286..288 FT /evidence="ECO:0007829|PDB:3BU8" FT HELIX 327..338 FT /evidence="ECO:0007829|PDB:3K6G" FT HELIX 343..352 FT /evidence="ECO:0007829|PDB:3K6G" FT HELIX 401..406 FT /evidence="ECO:0007829|PDB:5XYF" FT TURN 482..485 FT /evidence="ECO:0007829|PDB:1VF9" FT STRAND 487..489 FT /evidence="ECO:0007829|PDB:1XG1" FT HELIX 494..507 FT /evidence="ECO:0007829|PDB:3SJM" FT HELIX 512..518 FT /evidence="ECO:0007829|PDB:3SJM" FT HELIX 526..538 FT /evidence="ECO:0007829|PDB:3SJM" SQ SEQUENCE 542 AA; 59594 MW; 3A278AC6B594C43A CRC64; MAAGAGTAGP ASGPGVVRDP AASQPRKRPG REGGEGARRS DTMAGGGGSS DGSGRAAGRR ASRSSGRARR GRHEPGLGGP AERGAGEARL EEAVNRWVLK FYFHEALRAF RGSRYGDFRQ IRDIMQALLV RPLGKEHTVS RLLRVMQCLS RIEEGENLDC SFDMEAELTP LESAINVLEM IKTEFTLTEA VVESSRKLVK EAAVIICIKN KEFEKASKIL KKHMSKDPTT QKLRNDLLNI IREKNLAHPV IQNFSYETFQ QKMLRFLESH LDDAEPYLLT MAKKALKSES AASSTGKEDK QPAPGPVEKP PREPARQLRN PPTTIGMMTL KAAFKTLSGA QDSEAAFAKL DQKDLVLPTQ ALPASPALKN KRPRKDENES SAPADGEGGS ELQPKNKRMT ISRLVLEEDS QSTEPSAGLN SSQEAASAPP SKPTVLNQPL PGEKNPKVPK GKWNSSNGVE EKETWVEEDE LFQVQAAPDE DSTTNITKKQ KWTVEESEWV KAGVQKYGEG NWAAISKNYP FVNRTAVMIK DRWRTMKRLG MN //