POTE1_HUMAN
ID POTE1_HUMAN Reviewed; 634 AA.
AC Q9NUX5; O95018; Q5MJ36; Q9H662; Q9NW19; Q9UG95;
DT 19-JUL-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Protection of telomeres protein 1;
DE Short=hPot1;
DE AltName: Full=POT1-like telomere end-binding protein;
GN Name=POT1;
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 [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP SINGLE-STRANDED TELOMERE DNA-BINDING.
RC TISSUE=Ovary;
RX PubMed=11349150; DOI=10.1126/science.1060036;
RA Baumann P., Cech T.R.;
RT "Pot1, the putative telomere end-binding protein in fission yeast and
RT humans.";
RL Science 292:1171-1175(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS 1
RP AND 2), TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND SINGLE-STRANDED
RP TELOMERE DNA-BINDING.
RX PubMed=12391173; DOI=10.1128/mcb.22.22.8079-8087.2002;
RA Baumann P., Podell E., Cech T.R.;
RT "Human Pot1 (protection of telomeres) protein: cytolocalization, gene
RT structure, and alternative splicing.";
RL Mol. Cell. Biol. 22:8079-8087(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, Small intestine, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Skin;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 499-634 (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [8]
RP FUNCTION IN TELOMERE REGULATION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2),
RP AND SINGLE-STRANDED TELOMERE DNA-BINDING.
RX PubMed=12781132; DOI=10.1016/s0960-9822(03)00339-7;
RA Colgin L.M., Baran K., Baumann P., Cech T.R., Reddel R.R.;
RT "Human POT1 facilitates telomere elongation by telomerase.";
RL Curr. Biol. 13:942-946(2003).
RN [9]
RP FUNCTION IN TELOMERE REGULATION, IDENTIFICATION IN A COMPLEX WITH TERF1;
RP TINF2 AND TNKS1, AND INTERACTION WITH TNKS1.
RX PubMed=12768206; DOI=10.1038/nature01688;
RA Loayza D., De Lange T.;
RT "POT1 as a terminal transducer of TRF1 telomere length control.";
RL Nature 423:1013-1018(2003).
RN [10]
RP SINGLE-STRANDED TELOMERE DNA-BINDING.
RX PubMed=14715659; DOI=10.1074/jbc.m312309200;
RA Loayza D., Parsons H., Donigian J., Hoke K., de Lange T.;
RT "DNA binding features of human POT1: a nonamer 5'-TAGGGTTAG-3' minimal
RT binding site, sequence specificity, and internal binding to multimeric
RT sites.";
RL J. Biol. Chem. 279:13241-13248(2004).
RN [11]
RP INTERACTION WITH ACD.
RX PubMed=15231715; DOI=10.1101/gad.1215404;
RA Ye J.Z.-S., Hockemeyer D., Krutchinsky A.N., Loayza D., Hooper S.M.,
RA Chait B.T., de Lange T.;
RT "POT1-interacting protein PIP1: a telomere length regulator that recruits
RT POT1 to the TIN2/TRF1 complex.";
RL Genes Dev. 18:1649-1654(2004).
RN [12]
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 [13]
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 [14]
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 [15]
RP FUNCTION, SUBUNIT, AND IDENTIFICATION IN A COMPLEX WITH ACD AND
RP SINGLE-STRANDED TELOMERIC DNA.
RX PubMed=17237768; DOI=10.1038/nature05454;
RA Wang F., Podell E.R., Zaug A.J., Yang Y., Baciu P., Cech T.R., Lei M.;
RT "The POT1-TPP1 telomere complex is a telomerase processivity factor.";
RL Nature 445:506-510(2007).
RN [16]
RP IDENTIFICATION IN THE TELOMERASE HOLOENZYME COMPLEX.
RX PubMed=19179534; DOI=10.1126/science.1165357;
RA Venteicher A.S., Abreu E.B., Meng Z., McCann K.E., Terns R.M.,
RA Veenstra T.D., Terns M.P., Artandi S.E.;
RT "A human telomerase holoenzyme protein required for Cajal body localization
RT and telomere synthesis.";
RL Science 323:644-648(2009).
RN [17]
RP FUNCTION.
RX PubMed=20231318; DOI=10.1101/gad.1881810;
RA Zaug A.J., Podell E.R., Nandakumar J., Cech T.R.;
RT "Functional interaction between telomere protein TPP1 and telomerase.";
RL Genes Dev. 24:613-622(2010).
RN [18]
RP INVOLVEMENT IN GLM9, AND VARIANT GLM9 CYS-95.
RX PubMed=25482530; DOI=10.1093/jnci/dju384;
RG Gliogene Consortium;
RA Bainbridge M.N., Armstrong G.N., Gramatges M.M., Bertuch A.A.,
RA Jhangiani S.N., Doddapaneni H., Lewis L., Tombrello J., Tsavachidis S.,
RA Liu Y., Jalali A., Plon S.E., Lau C.C., Parsons D.W., Claus E.B.,
RA Barnholtz-Sloan J., Il'yasova D., Schildkraut J., Ali-Osman F.,
RA Sadetzki S., Johansen C., Houlston R.S., Jenkins R.B., Lachance D.,
RA Olson S.H., Bernstein J.L., Merrell R.T., Wrensch M.R., Walsh K.M.,
RA Davis F.G., Lai R., Shete S., Aldape K., Amos C.I., Thompson P.A.,
RA Muzny D.M., Gibbs R.A., Melin B.S., Bondy M.L.;
RT "Germline mutations in shelterin complex genes are associated with familial
RT glioma.";
RL J. Natl. Cancer Inst. 107:384-384(2015).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 6-299 IN COMPLEX WITH
RP SINGLE-STRANDED TELOMERIC DNA.
RX PubMed=15558049; DOI=10.1038/nsmb867;
RA Lei M., Podell E.R., Cech T.R.;
RT "Structure of human POT1 bound to telomeric single-stranded DNA provides a
RT model for chromosome end-protection.";
RL Nat. Struct. Mol. Biol. 11:1223-1229(2004).
RN [20]
RP INVOLVEMENT IN CMM10, VARIANTS CMM10 CYS-89; GLU-94 AND LEU-273, AND
RP CHARACTERIZATION OF VARIANTS CMM10 CYS-89; GLU-94 AND LEU-273.
RX PubMed=24686849; DOI=10.1038/ng.2947;
RA Robles-Espinoza C.D., Harland M., Ramsay A.J., Aoude L.G., Quesada V.,
RA Ding Z., Pooley K.A., Pritchard A.L., Tiffen J.C., Petljak M., Palmer J.M.,
RA Symmons J., Johansson P., Stark M.S., Gartside M.G., Snowden H.,
RA Montgomery G.W., Martin N.G., Liu J.Z., Choi J., Makowski M., Brown K.M.,
RA Dunning A.M., Keane T.M., Lopez-Otin C., Gruis N.A., Hayward N.K.,
RA Bishop D.T., Newton-Bishop J.A., Adams D.J.;
RT "POT1 loss-of-function variants predispose to familial melanoma.";
RL Nat. Genet. 46:478-481(2014).
RN [21]
RP VARIANTS CMM10 HIS-137; ASN-224; ASN-270; PRO-532 AND HIS-623, AND
RP CHARACTERIZATION OF VARIANTS CMM10 HIS-137; ASN-270 AND HIS-623.
RX PubMed=24686846; DOI=10.1038/ng.2941;
RA Shi J., Yang X.R., Ballew B., Rotunno M., Calista D., Fargnoli M.C.,
RA Ghiorzo P., Bressac-de Paillerets B., Nagore E., Avril M.F., Caporaso N.E.,
RA McMaster M.L., Cullen M., Wang Z., Zhang X., Bruno W., Pastorino L.,
RA Queirolo P., Banuls-Roca J., Garcia-Casado Z., Vaysse A., Mohamdi H.,
RA Riazalhosseini Y., Foglio M., Jouenne F., Hua X., Hyland P.L., Yin J.,
RA Vallabhaneni H., Chai W., Minghetti P., Pellegrini C., Ravichandran S.,
RA Eggermont A., Lathrop M., Peris K., Scarra G.B., Landi G., Savage S.A.,
RA Sampson J.N., He J., Yeager M., Goldin L.R., Demenais F., Chanock S.J.,
RA Tucker M.A., Goldstein A.M., Liu Y., Landi M.T.;
RT "Rare missense variants in POT1 predispose to familial cutaneous malignant
RT melanoma.";
RL Nat. Genet. 46:482-486(2014).
CC -!- FUNCTION: Component of the telomerase ribonucleoprotein (RNP) complex
CC that is essential for the replication of chromosome termini. Is a
CC component of the double-stranded telomeric DNA-binding TRF1 complex
CC which is involved in the regulation of telomere length by cis-
CC inhibition of telomerase. Also acts as a single-stranded telomeric DNA-
CC binding protein and thus may act as a downstream effector of the TRF1
CC complex and may transduce information about telomere maintenance and/or
CC length to the telomere terminus. 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 TTAGGG
CC repeats added by telomerase and protects chromosome ends; without its
CC protective activity, telomeres are no longer hidden from the DNA damage
CC surveillance and chromosome ends are inappropriately processed by DNA
CC repair pathways. Binds to two or more telomeric single-stranded 5'-
CC TTAGGG-3' repeats (G-strand) and with high specificity to a minimal
CC telomeric single-stranded 5'-TAGGGTTAG-3' sequence. Binds telomeric
CC single-stranded sequences internally or at proximity of a 3'-end. Its
CC activity is TERT dependent but it does not increase TERT activity by
CC itself. In contrast, the ACD-POT1 heterodimer enhances telomere
CC elongation by increasing telomerase processivity.
CC {ECO:0000269|PubMed:12768206, ECO:0000269|PubMed:12781132,
CC ECO:0000269|PubMed:16166375, ECO:0000269|PubMed:17237768,
CC ECO:0000269|PubMed:20231318}.
CC -!- SUBUNIT: Homodimer or homooligomer (PubMed:17237768). Component of the
CC shelterin complex (telosome) composed of TERF1, TERF2, TINF2, TERF2IP,
CC ACD and POT1 (PubMed:15316005, PubMed:15383534). Binds single-stranded
CC telomeric DNA as a monomer (PubMed:15558049). Associated component of
CC the telomerase holoenzyme complex (PubMed:19179534). Found in a complex
CC with TERF1, TINF2 and TNKS1 (PubMed:12768206). Interacts with TNKS1.
CC Forms heterodimers with ACD (PubMed:15231715). Identified in a complex
CC with ACD and single-stranded telomeric DNA (PubMed:17237768).
CC {ECO:0000269|PubMed:12768206, ECO:0000269|PubMed:15231715,
CC ECO:0000269|PubMed:15316005, ECO:0000269|PubMed:15383534,
CC ECO:0000269|PubMed:15558049, ECO:0000269|PubMed:17237768,
CC ECO:0000269|PubMed:19179534}.
CC -!- INTERACTION:
CC Q9NUX5; Q96AP0: ACD; NbExp=9; IntAct=EBI-752420, EBI-717666;
CC Q9NUX5; P30838: ALDH3A1; NbExp=2; IntAct=EBI-752420, EBI-3905126;
CC Q9NUX5; P07355: ANXA2; NbExp=2; IntAct=EBI-752420, EBI-352622;
CC Q9NUX5; Q9BV29: CCDC32; NbExp=2; IntAct=EBI-752420, EBI-2874058;
CC Q9NUX5; Q549N0: CFL2; NbExp=3; IntAct=EBI-752420, EBI-10201319;
CC Q9NUX5; Q9Y281: CFL2; NbExp=3; IntAct=EBI-752420, EBI-351218;
CC Q9NUX5; O95833: CLIC3; NbExp=2; IntAct=EBI-752420, EBI-10192241;
CC Q9NUX5; Q6PJW8: CNST; NbExp=2; IntAct=EBI-752420, EBI-750390;
CC Q9NUX5; O60496: DOK2; NbExp=2; IntAct=EBI-752420, EBI-1046024;
CC Q9NUX5; O94808: GFPT2; NbExp=2; IntAct=EBI-752420, EBI-6916534;
CC Q9NUX5; Q99795: GPA33; NbExp=2; IntAct=EBI-752420, EBI-4289554;
CC Q9NUX5; P46952: HAAO; NbExp=2; IntAct=EBI-752420, EBI-743215;
CC Q9NUX5; P50747: HLCS; NbExp=2; IntAct=EBI-752420, EBI-3915568;
CC Q9NUX5; P09601: HMOX1; NbExp=2; IntAct=EBI-752420, EBI-2806151;
CC Q9NUX5; P0DMV8: HSPA1A; NbExp=2; IntAct=EBI-752420, EBI-11052499;
CC Q9NUX5; Q9NPH2: ISYNA1; NbExp=2; IntAct=EBI-752420, EBI-720563;
CC Q9NUX5; Q96A73: KIAA1191; NbExp=2; IntAct=EBI-752420, EBI-725897;
CC Q9NUX5; Q8WXG6: MADD; NbExp=2; IntAct=EBI-752420, EBI-310528;
CC Q9NUX5; P43358: MAGEA4; NbExp=2; IntAct=EBI-752420, EBI-743122;
CC Q9NUX5; Q12851: MAP4K2; NbExp=2; IntAct=EBI-752420, EBI-49783;
CC Q9NUX5; Q03426: MVK; NbExp=2; IntAct=EBI-752420, EBI-740630;
CC Q9NUX5; Q9BY11: PACSIN1; NbExp=2; IntAct=EBI-752420, EBI-721769;
CC Q9NUX5; Q96GU1: PAGE5; NbExp=2; IntAct=EBI-752420, EBI-11305258;
CC Q9NUX5; Q01064: PDE1B; NbExp=2; IntAct=EBI-752420, EBI-7413304;
CC Q9NUX5; Q5SRE7: PHYHD1; NbExp=2; IntAct=EBI-752420, EBI-2623130;
CC Q9NUX5; Q8IUZ5: PHYKPL; NbExp=2; IntAct=EBI-752420, EBI-751947;
CC Q9NUX5; Q9P0Z9: PIPOX; NbExp=2; IntAct=EBI-752420, EBI-725582;
CC Q9NUX5; Q86WR7: PROSER2; NbExp=2; IntAct=EBI-752420, EBI-2880603;
CC Q9NUX5; Q9BRP8: PYM1; NbExp=2; IntAct=EBI-752420, EBI-2352802;
CC Q9NUX5; Q9BWH6: RPAP1; NbExp=2; IntAct=EBI-752420, EBI-1048085;
CC Q9NUX5; O43704: SULT1B1; NbExp=2; IntAct=EBI-752420, EBI-10179062;
CC Q9NUX5; Q9BR01: SULT4A1; NbExp=2; IntAct=EBI-752420, EBI-6690555;
CC Q9NUX5; Q96A49: SYAP1; NbExp=2; IntAct=EBI-752420, EBI-10770179;
CC Q9NUX5; Q15554: TERF2; NbExp=7; IntAct=EBI-752420, EBI-706637;
CC Q9NUX5; Q9BSI4: TINF2; NbExp=3; IntAct=EBI-752420, EBI-717399;
CC Q9NUX5; P63313: TMSB10; NbExp=2; IntAct=EBI-752420, EBI-2688673;
CC Q9NUX5; Q9Y4P8: WIPI2; NbExp=2; IntAct=EBI-752420, EBI-719396;
CC Q9NUX5-1; Q96AP0: ACD; NbExp=4; IntAct=EBI-15593881, EBI-717666;
CC Q9NUX5-2; Q96AP0: ACD; NbExp=3; IntAct=EBI-752435, EBI-717666;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:12391173}.
CC Chromosome, telomere {ECO:0000269|PubMed:12391173}. Note=Colocalizes
CC with telomeric DNA.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=A number of isoforms are produced.;
CC Name=1; Synonyms=Variant 1;
CC IsoId=Q9NUX5-1; Sequence=Displayed;
CC Name=2; Synonyms=Variant 3;
CC IsoId=Q9NUX5-2; Sequence=VSP_010846, VSP_010847;
CC -!- TISSUE SPECIFICITY: Ubiquitous. {ECO:0000269|PubMed:11349150,
CC ECO:0000269|PubMed:12391173}.
CC -!- DISEASE: Melanoma, cutaneous malignant 10 (CMM10) [MIM:615848]: A
CC malignant neoplasm of melanocytes, arising de novo or from a pre-
CC existing benign nevus, which occurs most often in the skin but also may
CC involve other sites. {ECO:0000269|PubMed:24686846,
CC ECO:0000269|PubMed:24686849}. Note=Disease susceptibility is associated
CC with variants affecting the gene represented in this entry.
CC -!- DISEASE: Glioma 9 (GLM9) [MIM:616568]: Gliomas are benign or malignant
CC central nervous system neoplasms derived from glial cells. They
CC comprise astrocytomas and glioblastoma multiforme that are derived from
CC astrocytes, oligodendrogliomas derived from oligodendrocytes and
CC ependymomas derived from ependymocytes. {ECO:0000269|PubMed:25482530}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- SIMILARITY: Belongs to the telombin family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15404.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AY823520; AAW22613.1; -; mRNA.
DR EMBL; AK001230; BAA91568.1; -; mRNA.
DR EMBL; AK001935; BAA91988.1; -; mRNA.
DR EMBL; AK022580; BAB14110.1; -; mRNA.
DR EMBL; AK026234; BAB15404.1; ALT_INIT; mRNA.
DR EMBL; AC004925; AAD08852.1; -; Genomic_DNA.
DR EMBL; AC096665; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC110791; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471070; EAW83616.1; -; Genomic_DNA.
DR EMBL; BC002923; AAH02923.1; -; mRNA.
DR EMBL; AL050120; CAB43281.1; -; mRNA.
DR CCDS; CCDS5793.1; -. [Q9NUX5-1]
DR PIR; T08766; T08766.
DR RefSeq; NP_001036059.1; NM_001042594.1.
DR RefSeq; NP_056265.2; NM_015450.2. [Q9NUX5-1]
DR RefSeq; XP_006715980.1; XM_006715917.3.
DR PDB; 1XJV; X-ray; 1.73 A; A=6-299.
DR PDB; 3KJO; X-ray; 1.80 A; A=1-299.
DR PDB; 3KJP; X-ray; 1.80 A; A=1-299.
DR PDB; 5H65; X-ray; 2.10 A; A=341-634.
DR PDB; 5UN7; X-ray; 2.10 A; A=330-634.
DR PDB; 7QXB; EM; 3.91 A; P=1-634.
DR PDB; 7QXS; EM; 3.91 A; P=1-634.
DR PDB; 7S1O; X-ray; 2.55 A; A/B=325-634.
DR PDB; 7S1T; X-ray; 2.90 A; A/D/G/J=325-634.
DR PDB; 7S1U; X-ray; 2.55 A; A/B=331-634.
DR PDBsum; 1XJV; -.
DR PDBsum; 3KJO; -.
DR PDBsum; 3KJP; -.
DR PDBsum; 5H65; -.
DR PDBsum; 5UN7; -.
DR PDBsum; 7QXB; -.
DR PDBsum; 7QXS; -.
DR PDBsum; 7S1O; -.
DR PDBsum; 7S1T; -.
DR PDBsum; 7S1U; -.
DR AlphaFoldDB; Q9NUX5; -.
DR SMR; Q9NUX5; -.
DR BioGRID; 117417; 229.
DR ComplexPortal; CPX-152; Shelterin complex.
DR CORUM; Q9NUX5; -.
DR DIP; DIP-29610N; -.
DR IntAct; Q9NUX5; 183.
DR STRING; 9606.ENSP00000350249; -.
DR BindingDB; Q9NUX5; -.
DR ChEMBL; CHEMBL5908; -.
DR MoonDB; Q9NUX5; Predicted.
DR iPTMnet; Q9NUX5; -.
DR PhosphoSitePlus; Q9NUX5; -.
DR BioMuta; POT1; -.
DR DMDM; 50401179; -.
DR EPD; Q9NUX5; -.
DR jPOST; Q9NUX5; -.
DR MassIVE; Q9NUX5; -.
DR MaxQB; Q9NUX5; -.
DR PaxDb; Q9NUX5; -.
DR PeptideAtlas; Q9NUX5; -.
DR PRIDE; Q9NUX5; -.
DR ProteomicsDB; 82726; -. [Q9NUX5-1]
DR ProteomicsDB; 82727; -. [Q9NUX5-2]
DR Antibodypedia; 31798; 317 antibodies from 32 providers.
DR DNASU; 25913; -.
DR Ensembl; ENST00000357628.8; ENSP00000350249.3; ENSG00000128513.16. [Q9NUX5-1]
DR Ensembl; ENST00000653241.1; ENSP00000499476.1; ENSG00000128513.16. [Q9NUX5-1]
DR Ensembl; ENST00000655761.1; ENSP00000499635.1; ENSG00000128513.16. [Q9NUX5-1]
DR Ensembl; ENST00000664366.1; ENSP00000499290.1; ENSG00000128513.16. [Q9NUX5-1]
DR Ensembl; ENST00000668382.1; ENSP00000499546.1; ENSG00000128513.16. [Q9NUX5-1]
DR GeneID; 25913; -.
DR KEGG; hsa:25913; -.
DR MANE-Select; ENST00000357628.8; ENSP00000350249.3; NM_015450.3; NP_056265.2.
DR UCSC; uc003vlm.4; human. [Q9NUX5-1]
DR CTD; 25913; -.
DR DisGeNET; 25913; -.
DR GeneCards; POT1; -.
DR GeneReviews; POT1; -.
DR HGNC; HGNC:17284; POT1.
DR HPA; ENSG00000128513; Low tissue specificity.
DR MalaCards; POT1; -.
DR MIM; 606478; gene.
DR MIM; 615848; phenotype.
DR MIM; 616568; phenotype.
DR neXtProt; NX_Q9NUX5; -.
DR OpenTargets; ENSG00000128513; -.
DR Orphanet; 251630; Anaplastic oligodendroglioma.
DR Orphanet; 67038; B-cell chronic lymphocytic leukemia.
DR Orphanet; 618; Familial melanoma.
DR Orphanet; 251627; Oligodendroglioma.
DR PharmGKB; PA134934904; -.
DR VEuPathDB; HostDB:ENSG00000128513; -.
DR eggNOG; KOG4757; Eukaryota.
DR GeneTree; ENSGT00390000018285; -.
DR HOGENOM; CLU_019567_0_0_1; -.
DR InParanoid; Q9NUX5; -.
DR OMA; RKITIHF; -.
DR PhylomeDB; Q9NUX5; -.
DR TreeFam; TF328398; -.
DR PathwayCommons; Q9NUX5; -.
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; Q9NUX5; -.
DR SIGNOR; Q9NUX5; -.
DR BioGRID-ORCS; 25913; 369 hits in 1090 CRISPR screens.
DR ChiTaRS; POT1; human.
DR EvolutionaryTrace; Q9NUX5; -.
DR GeneWiki; POT1; -.
DR GenomeRNAi; 25913; -.
DR Pharos; Q9NUX5; Tbio.
DR PRO; PR:Q9NUX5; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q9NUX5; protein.
DR Bgee; ENSG00000128513; Expressed in secondary oocyte and 192 other tissues.
DR ExpressionAtlas; Q9NUX5; baseline and differential.
DR Genevisible; Q9NUX5; HS.
DR GO; GO:0000781; C:chromosome, telomeric region; IDA:UniProtKB.
DR GO; GO:0000783; C:nuclear telomere cap complex; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0070187; C:shelterin complex; IDA:BHF-UCL.
DR GO; GO:1905773; F:8-hydroxy-2'-deoxyguanosine DNA binding; IDA:BHF-UCL.
DR GO; GO:0017151; F:DEAD/H-box RNA helicase binding; IPI:BHF-UCL.
DR GO; GO:1990955; F:G-rich single-stranded DNA binding; IDA:BHF-UCL.
DR GO; GO:0098505; F:G-rich strand telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0043047; F:single-stranded telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0010521; F:telomerase inhibitor activity; IDA:BHF-UCL.
DR GO; GO:0061821; F:telomeric D-loop binding; IDA:BHF-UCL.
DR GO; GO:0042162; F:telomeric DNA binding; IDA:BHF-UCL.
DR GO; GO:0032508; P:DNA duplex unwinding; IDA:BHF-UCL.
DR GO; GO:0070200; P:establishment of protein localization to telomere; IMP:BHF-UCL.
DR GO; GO:0051974; P:negative regulation of telomerase activity; IDA:BHF-UCL.
DR GO; GO:0032211; P:negative regulation of telomere maintenance via telomerase; IGI:BHF-UCL.
DR GO; GO:1905776; P:positive regulation of DNA helicase activity; IDA:BHF-UCL.
DR GO; GO:0060383; P:positive regulation of DNA strand elongation; IDA:BHF-UCL.
DR GO; GO:0051096; P:positive regulation of helicase activity; IDA:BHF-UCL.
DR GO; GO:0051973; P:positive regulation of telomerase activity; IDA:BHF-UCL.
DR GO; GO:0032206; P:positive regulation of telomere maintenance; IC:ComplexPortal.
DR GO; GO:0032212; P:positive regulation of telomere maintenance via telomerase; IDA:BHF-UCL.
DR GO; GO:1905774; P:regulation of DNA helicase activity; IDA:BHF-UCL.
DR GO; GO:2001032; P:regulation of double-strand break repair via nonhomologous end joining; IDA:CACAO.
DR GO; GO:0032210; P:regulation of telomere maintenance via telomerase; IGI:BHF-UCL.
DR GO; GO:0032202; P:telomere assembly; IDA:BHF-UCL.
DR GO; GO:0016233; P:telomere capping; IDA:ComplexPortal.
DR GO; GO:0007004; P:telomere maintenance via telomerase; IDA:UniProtKB.
DR GO; GO:0061820; P:telomeric D-loop disassembly; IGI:BHF-UCL.
DR Gene3D; 2.40.50.140; -; 2.
DR InterPro; IPR012340; NA-bd_OB-fold.
DR InterPro; IPR028389; POT1.
DR InterPro; IPR032042; POT1PC.
DR InterPro; IPR011564; Telomer_end-bd_POT1/Cdc13.
DR PANTHER; PTHR14513; PTHR14513; 1.
DR Pfam; PF02765; POT1; 1.
DR Pfam; PF16686; POT1PC; 1.
DR SMART; SM00976; Telo_bind; 1.
DR SUPFAM; SSF50249; SSF50249; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chromosome; Disease variant;
KW DNA-binding; Nucleus; Reference proteome; Telomere.
FT CHAIN 1..634
FT /note="Protection of telomeres protein 1"
FT /id="PRO_0000121728"
FT REGION 33..48
FT /note="DNA-binding"
FT REGION 270..273
FT /note="DNA-binding"
FT SITE 243
FT /note="DNA-binding"
FT VAR_SEQ 532..538
FT /note="ALGIVPL -> DVNSVLV (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_010846"
FT VAR_SEQ 539..634
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_010847"
FT VARIANT 89
FT /note="Y -> C (in CMM10; complete abolition of POT1-DNA
FT complex formation, thus disrupting the interaction with
FT telomeres and leading to elongated telomeres;
FT dbSNP:rs587777472)"
FT /evidence="ECO:0000269|PubMed:24686849"
FT /id="VAR_071390"
FT VARIANT 94
FT /note="Q -> E (in CMM10; complete abolition of POT1-DNA
FT complex formation, thus disrupting the interaction with
FT telomeres and leading to elongated telomeres;
FT dbSNP:rs587777474)"
FT /evidence="ECO:0000269|PubMed:24686849"
FT /id="VAR_071391"
FT VARIANT 95
FT /note="G -> C (in GLM9; dbSNP:rs797045168)"
FT /evidence="ECO:0000269|PubMed:25482530"
FT /id="VAR_075717"
FT VARIANT 137
FT /note="R -> H (in CMM10; increased telomere intensity
FT signals and telomere fragility; dbSNP:rs587777475)"
FT /evidence="ECO:0000269|PubMed:24686846"
FT /id="VAR_071392"
FT VARIANT 224
FT /note="D -> N (in CMM10; dbSNP:rs202187871)"
FT /evidence="ECO:0000269|PubMed:24686846"
FT /id="VAR_071393"
FT VARIANT 270
FT /note="S -> N (in CMM10; significantly increased telomere
FT length and numbers of fragile telomeres;
FT dbSNP:rs587777477)"
FT /evidence="ECO:0000269|PubMed:24686846"
FT /id="VAR_071394"
FT VARIANT 273
FT /note="R -> L (in CMM10; complete abolition of POT1-DNA
FT complex formation, thus disrupting the interaction with
FT telomeres and leading to elongated telomeres;
FT dbSNP:rs587777476)"
FT /evidence="ECO:0000269|PubMed:24686849"
FT /id="VAR_071395"
FT VARIANT 529
FT /note="V -> M (in dbSNP:rs34973253)"
FT /id="VAR_034393"
FT VARIANT 532
FT /note="A -> P (in CMM10; dbSNP:rs537377921)"
FT /evidence="ECO:0000269|PubMed:24686846"
FT /id="VAR_071396"
FT VARIANT 623
FT /note="Q -> H (in CMM10; increased telomere intensity
FT signals and telomere fragility; dbSNP:rs587777478)"
FT /evidence="ECO:0000269|PubMed:24686846"
FT /id="VAR_071397"
FT CONFLICT 410
FT /note="D -> V (in Ref. 3; BAA91568)"
FT /evidence="ECO:0000305"
FT CONFLICT 412
FT /note="K -> Q (in Ref. 3; BAB15404)"
FT /evidence="ECO:0000305"
FT CONFLICT 499
FT /note="H -> D (in Ref. 7; CAB43281)"
FT /evidence="ECO:0000305"
FT HELIX 14..16
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 19..37
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 39..50
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 56..65
FT /evidence="ECO:0007829|PDB:1XJV"
FT HELIX 66..68
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 78..89
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 92..106
FT /evidence="ECO:0007829|PDB:1XJV"
FT HELIX 127..143
FT /evidence="ECO:0007829|PDB:1XJV"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 161..173
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 175..184
FT /evidence="ECO:0007829|PDB:1XJV"
FT TURN 200..202
FT /evidence="ECO:0007829|PDB:3KJP"
FT HELIX 207..213
FT /evidence="ECO:0007829|PDB:1XJV"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 217..223
FT /evidence="ECO:0007829|PDB:1XJV"
FT HELIX 226..232
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 238..251
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 257..265
FT /evidence="ECO:0007829|PDB:1XJV"
FT HELIX 270..272
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 274..278
FT /evidence="ECO:0007829|PDB:1XJV"
FT HELIX 283..297
FT /evidence="ECO:0007829|PDB:1XJV"
FT STRAND 334..339
FT /evidence="ECO:0007829|PDB:5UN7"
FT HELIX 348..352
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 359..370
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 374..377
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 378..381
FT /evidence="ECO:0007829|PDB:5H65"
FT TURN 383..385
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 388..390
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 394..404
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 411..413
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 417..425
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 427..429
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 433..439
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 448..450
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 452..457
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 460..469
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 470..478
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 480..486
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 492..495
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 498..500
FT /evidence="ECO:0007829|PDB:5H65"
FT TURN 504..506
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 512..517
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 521..523
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 526..532
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 539..549
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 554..563
FT /evidence="ECO:0007829|PDB:5H65"
FT TURN 564..566
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 570..573
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 577..590
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 593..595
FT /evidence="ECO:0007829|PDB:5H65"
FT HELIX 597..599
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 603..611
FT /evidence="ECO:0007829|PDB:5H65"
FT STRAND 614..616
FT /evidence="ECO:0007829|PDB:7S1T"
FT STRAND 620..626
FT /evidence="ECO:0007829|PDB:5H65"
FT TURN 630..632
FT /evidence="ECO:0007829|PDB:5H65"
SQ SEQUENCE 634 AA; 71442 MW; 123A12CABE708C91 CRC64;
MSLVPATNYI YTPLNQLKGG TIVNVYGVVK FFKPPYLSKG TDYCSVVTIV DQTNVKLTCL
LFSGNYEALP IIYKNGDIVR FHRLKIQVYK KETQGITSSG FASLTFEGTL GAPIIPRTSS
KYFNFTTEDH KMVEALRVWA STHMSPSWTL LKLCDVQPMQ YFDLTCQLLG KAEVDGASFL
LKVWDGTRTP FPSWRVLIQD LVLEGDLSHI HRLQNLTIDI LVYDNHVHVA RSLKVGSFLR
IYSLHTKLQS MNSENQTMLS LEFHLHGGTS YGRGIRVLPE SNSDVDQLKK DLESANLTAN
QHSDVICQSE PDDSFPSSGS VSLYEVERCQ QLSATILTDH QYLERTPLCA ILKQKAPQQY
RIRAKLRSYK PRRLFQSVKL HCPKCHLLQE VPHEGDLDII FQDGATKTPD VKLQNTSLYD
SKIWTTKNQK GRKVAVHFVK NNGILPLSNE CLLLIEGGTL SEICKLSNKF NSVIPVRSGH
EDLELLDLSA PFLIQGTIHH YGCKQCSSLR SIQNLNSLVD KTSWIPSSVA EALGIVPLQY
VFVMTFTLDD GTGVLEAYLM DSDKFFQIPA SEVLMDDDLQ KSVDMIMDMF CPPGIKIDAY
PWLECFIKSY NVTNGTDNQI CYQIFDTTVA EDVI
