TERF2_HUMAN
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 03-AUG-2022, entry version 219.
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};
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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; 326.
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; Q15554; -.
DR PeptideAtlas; Q15554; -.
DR PRIDE; Q15554; -.
DR ProteomicsDB; 60629; -. [Q15554-3]
DR Antibodypedia; 1053; 632 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 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; 605826at2759; -.
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; 423 hits in 622 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 202 other tissues.
DR ExpressionAtlas; Q15554; baseline and differential.
DR Genevisible; Q15554; HS.
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:0008022; F:protein C-terminus binding; IPI:UniProtKB.
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:0099087; P:anterograde 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; cd11654; TRF2_RBM; 1.
DR Gene3D; 1.25.40.210; -; 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; PTHR46833; 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; SSF46689; 1.
DR SUPFAM; SSF63600; SSF63600; 1.
DR PROSITE; PS51294; HTH_MYB; 1.
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
