Full text data of TERF2IP
TERF2IP
(DRIP5, RAP1)
[Confidence: low (only semi-automatic identification from reviews)]
Telomeric repeat-binding factor 2-interacting protein 1; TERF2-interacting telomeric protein 1; TRF2-interacting telomeric protein 1 (Dopamine receptor-interacting protein 5; Repressor/activator protein 1 homolog; RAP1 homolog; hRap1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Telomeric repeat-binding factor 2-interacting protein 1; TERF2-interacting telomeric protein 1; TRF2-interacting telomeric protein 1 (Dopamine receptor-interacting protein 5; Repressor/activator protein 1 homolog; RAP1 homolog; hRap1)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q9NYB0
ID TE2IP_HUMAN Reviewed; 399 AA.
AC Q9NYB0; B4DQN4; Q4W4Y2; Q8WYZ3; Q9NWR2;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Telomeric repeat-binding factor 2-interacting protein 1;
DE Short=TERF2-interacting telomeric protein 1;
DE Short=TRF2-interacting telomeric protein 1;
DE AltName: Full=Dopamine receptor-interacting protein 5;
DE AltName: Full=Repressor/activator protein 1 homolog;
DE Short=RAP1 homolog;
DE Short=hRap1;
GN Name=TERF2IP; Synonyms=DRIP5, RAP1; ORFNames=PP8000;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cervix carcinoma;
RX PubMed=10850490; DOI=10.1016/S0092-8674(00)80858-2;
RA Li B., Oestreich S., de Lange T.;
RT "Identification of human RAP1: implications for telomere evolution.";
RL Cell 101:471-483(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lafuente M.J., Nasir J.;
RT "Cloning and characterization of DRIP5, a new protein that
RT specifically interacts with the D1 dopamine receptor.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ileal mucosa, 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
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.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA 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.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Lung, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP BIDIRECTIONAL PROMOTER WITH KARS.
RX PubMed=14659874; DOI=10.1016/j.gene.2003.08.026;
RA Tan M., Wei C., Price C.M.;
RT "The telomeric protein Rap1 is conserved in vertebrates and is
RT expressed from a bidirectional promoter positioned between the Rap1
RT and KARS genes.";
RL Gene 323:1-10(2003).
RN [9]
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
RT complex on telomeres.";
RL J. Biol. Chem. 279:47264-47271(2004).
RN [10]
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156 AND SER-203, AND
RP MASS SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-154 AND SER-203,
RP AND MASS SPECTROMETRY.
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
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 [17]
RP FUNCTION.
RX PubMed=19763083; DOI=10.1038/emboj.2009.275;
RA Sarthy J., Bae N.S., Scrafford J., Baumann P.;
RT "Human RAP1 inhibits non-homologous end joining at telomeres.";
RL EMBO J. 28:3390-3399(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154 AND SER-203, AND
RP MASS SPECTROMETRY.
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-154 AND SER-203,
RP AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
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.,
RA Buerckstuemmer T., 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP STRUCTURE BY NMR OF 132-190.
RX PubMed=11545594; DOI=10.1006/jmbi.2001.4924;
RA Hanaoka S., Nagadoi A., Yoshimura S., Aimoto S., Li B., de Lange T.,
RA Nishimura Y.;
RT "NMR structure of the hRap1 Myb motif reveals a canonical three-helix
RT bundle lacking the positive surface charge typical of Myb DNA-binding
RT domains.";
RL J. Mol. Biol. 312:167-175(2001).
CC -!- FUNCTION: Acts both as a regulator of telomere function and as a
CC transcription regulator. Involved in the regulation of telomere
CC length and protection as a component of the shelterin complex
CC (telosome). In contrast to other components of the shelterin
CC complex, it is dispensible for telomere capping and does not
CC participate in the protection of telomeres against non-homologous
CC end-joining (NHEJ)-mediated repair. Instead, it is required to
CC negatively regulate telomere recombination and is essential for
CC repressing homology-directed repair (HDR), which can affect
CC telomere length. Does not bind DNA directly: recruited to
CC telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction
CC with TERF2. Independently of its function in telomeres, also acts
CC as a transcription regulator: recruited to extratelomeric 5'-
CC TTAGGG-3' sites via its association with TERF2 or other factors,
CC and regulates gene expression. When cytoplasmic, associates with
CC the I-kappa-B-kinase (IKK) complex and acts as a regulator of the
CC NF-kappa-B signaling by promoting IKK-mediated phosphorylation of
CC RELA/p65, leading to activate expression of NF-kappa-B target
CC genes.
CC -!- SUBUNIT: Associates with the I-kappa-B-kinase (IKK) core complex,
CC composed of CHUK, IKBKB and IKBKG (By similarity). Homodimer.
CC Component of the shelterin complex (telosome) composed of TERF1,
CC TERF2, TINF2, TERF2IP ACD and POT1. Interacts with TERF2; the
CC interaction is direct. Does not interact with TERF1. Interacts
CC with SLX4/BTBD12.
CC -!- INTERACTION:
CC Q8IY92:SLX4; NbExp=4; IntAct=EBI-750109, EBI-2370740;
CC Q15554:TERF2; NbExp=7; IntAct=EBI-750109, EBI-706637;
CC Q9BSI4-3:TINF2; NbExp=3; IntAct=EBI-750109, EBI-717418;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm (By similarity).
CC Chromosome. Chromosome, telomere. Note=Associates with
CC chromosomes, both at telomeres and in extratelomeric sites. Also
CC exists as a cytoplasmic form, where it associates with the IKK
CC complex (By similarity).
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed.
CC -!- MISCELLANEOUS: Shares a bidirectional promoter with KARS
CC (PubMed:14659874).
CC -!- SIMILARITY: Belongs to the RAP1 family.
CC -!- SIMILARITY: Contains 1 BRCT domain.
CC -!- SIMILARITY: Contains 1 Myb-like domain.
CC -!- CAUTION: Was reported to participate in the protection of
CC telomeres against non-homologous end-joining (NHEJ)-mediated
CC repair in the absence of TERF2 (PubMed:19763083). However, this
CC probably does not corresponds to its primary function and
CC experiments in mouse showed that it is dispensible for such
CC process and is required for repressiion of homology-directed
CC repair (HDR).
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL55783.1; Type=Frameshift; Positions=151;
CC Sequence=BAA91317.1; Type=Erroneous termination; Positions=299; Note=Translated as Glu;
CC Sequence=BAG60996.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF262988; AAF72711.1; -; mRNA.
DR EMBL; AF250393; AAQ14259.1; -; mRNA.
DR EMBL; AF289599; AAL55783.1; ALT_FRAME; mRNA.
DR EMBL; AK000669; BAA91317.1; ALT_SEQ; mRNA.
DR EMBL; AK298880; BAG60996.1; ALT_INIT; mRNA.
DR EMBL; AC025287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471114; EAW95616.1; -; Genomic_DNA.
DR EMBL; CH471114; EAW95618.1; -; Genomic_DNA.
DR EMBL; BC004465; AAH04465.1; -; mRNA.
DR EMBL; BC005841; AAH05841.1; -; mRNA.
DR EMBL; BC022428; AAH22428.1; -; mRNA.
DR EMBL; BC078171; AAH78171.1; -; mRNA.
DR RefSeq; NP_061848.2; NM_018975.3.
DR UniGene; Hs.301419; -.
DR PDB; 1FEX; NMR; -; A=132-190.
DR PDB; 3K6G; X-ray; 1.95 A; A/B/C=303-399.
DR PDBsum; 1FEX; -.
DR PDBsum; 3K6G; -.
DR ProteinModelPortal; Q9NYB0; -.
DR SMR; Q9NYB0; 132-190, 306-398.
DR DIP; DIP-34868N; -.
DR IntAct; Q9NYB0; 16.
DR MINT; MINT-1454139; -.
DR STRING; 9606.ENSP00000300086; -.
DR PhosphoSite; Q9NYB0; -.
DR DMDM; 21542267; -.
DR PaxDb; Q9NYB0; -.
DR PeptideAtlas; Q9NYB0; -.
DR PRIDE; Q9NYB0; -.
DR DNASU; 54386; -.
DR Ensembl; ENST00000300086; ENSP00000300086; ENSG00000166848.
DR GeneID; 54386; -.
DR KEGG; hsa:54386; -.
DR UCSC; uc002fet.2; human.
DR CTD; 54386; -.
DR GeneCards; GC16P075681; -.
DR HGNC; HGNC:19246; TERF2IP.
DR HPA; CAB018660; -.
DR HPA; CAB018749; -.
DR HPA; HPA006719; -.
DR MIM; 605061; gene.
DR neXtProt; NX_Q9NYB0; -.
DR PharmGKB; PA134976325; -.
DR eggNOG; NOG39788; -.
DR HOGENOM; HOG000120115; -.
DR HOVERGEN; HBG054209; -.
DR InParanoid; Q9NYB0; -.
DR KO; K11113; -.
DR OMA; SISFYVR; -.
DR OrthoDB; EOG7KDFBG; -.
DR PhylomeDB; Q9NYB0; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_120956; Cellular responses to stress.
DR ChiTaRS; TERF2IP; human.
DR EvolutionaryTrace; Q9NYB0; -.
DR GeneWiki; TERF2IP; -.
DR GenomeRNAi; 54386; -.
DR NextBio; 56609; -.
DR PRO; PR:Q9NYB0; -.
DR ArrayExpress; Q9NYB0; -.
DR Bgee; Q9NYB0; -.
DR CleanEx; HS_TERF2IP; -.
DR Genevestigator; Q9NYB0; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000783; C:nuclear telomere cap complex; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0048239; P:negative regulation of DNA recombination at telomere; ISS:UniProtKB.
DR GO; GO:0032205; P:negative regulation of telomere maintenance; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
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:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0007004; P:telomere maintenance via telomerase; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.60; -; 1.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR021661; Rap1_C.
DR InterPro; IPR015010; Rap1_Myb_dom.
DR Pfam; PF08914; Myb_DNA-bind_2; 1.
DR Pfam; PF11626; Rap1_C; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50172; BRCT; FALSE_NEG.
DR PROSITE; PS50090; MYB_LIKE; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Chromosome; Complete proteome;
KW Cytoplasm; Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW Telomere; Transcription; Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 399 Telomeric repeat-binding factor 2-
FT interacting protein 1.
FT /FTId=PRO_0000197126.
FT DOMAIN 78 101 BRCT.
FT DOMAIN 128 188 Myb-like.
FT MOTIF 383 399 Nuclear localization signal (Potential).
FT COMPBIAS 214 304 Asp/Glu-rich (acidic).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 36 36 Phosphoserine.
FT MOD_RES 154 154 Phosphoserine.
FT MOD_RES 156 156 Phosphoserine.
FT MOD_RES 203 203 Phosphoserine.
FT VARIANT 324 324 K -> E (in dbSNP:rs4888444).
FT /FTId=VAR_050195.
FT CONFLICT 83 83 Y -> H (in Ref. 4; BAA91317).
FT HELIX 138 150
FT TURN 155 159
FT HELIX 162 169
FT STRAND 172 174
FT HELIX 178 187
FT HELIX 308 324
FT HELIX 329 338
FT TURN 339 341
FT HELIX 343 352
FT HELIX 364 370
FT HELIX 375 385
FT HELIX 387 397
SQ SEQUENCE 399 AA; 44260 MW; EAA615777F9D3D3D CRC64;
MAEAMDLGKD PNGPTHSSTL FVRDDGSSMS FYVRPSPAKR RLSTLILHGG GTVCRVQEPG
AVLLAQPGEA LAEASGDFIS TQYILDCVER NERLELEAYR LGPASAADTG SEAKPGALAE
GAAEPEPQRH AGRIAFTDAD DVAILTYVKE NARSPSSVTG NALWKAMEKS SLTQHSWQSL
KDRYLKHLRG QEHKYLLGDA PVSPSSQKLK RKAEEDPEAA DSGEPQNKRT PDLPEEEYVK
EEIQENEEAV KKMLVEATRE FEEVVVDESP PDFEIHITMC DDDPPTPEED SETQPDEEEE
EEEEKVSQPE VGAAIKIIRQ LMEKFNLDLS TVTQAFLKNS GELEATSAFL ASGQRADGYP
IWSRQDDIDL QKDDEDTREA LVKKFGAQNV ARRIEFRKK
//
ID TE2IP_HUMAN Reviewed; 399 AA.
AC Q9NYB0; B4DQN4; Q4W4Y2; Q8WYZ3; Q9NWR2;
DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-2000, sequence version 1.
DT 22-JAN-2014, entry version 135.
DE RecName: Full=Telomeric repeat-binding factor 2-interacting protein 1;
DE Short=TERF2-interacting telomeric protein 1;
DE Short=TRF2-interacting telomeric protein 1;
DE AltName: Full=Dopamine receptor-interacting protein 5;
DE AltName: Full=Repressor/activator protein 1 homolog;
DE Short=RAP1 homolog;
DE Short=hRap1;
GN Name=TERF2IP; Synonyms=DRIP5, RAP1; ORFNames=PP8000;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Cervix carcinoma;
RX PubMed=10850490; DOI=10.1016/S0092-8674(00)80858-2;
RA Li B., Oestreich S., de Lange T.;
RT "Identification of human RAP1: implications for telomere evolution.";
RL Cell 101:471-483(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Lafuente M.J., Nasir J.;
RT "Cloning and characterization of DRIP5, a new protein that
RT specifically interacts with the D1 dopamine receptor.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H.,
RA Qiu X., Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y.,
RA Shu H., Chen X., Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S.,
RA Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ileal mucosa, 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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [5]
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.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA 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.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, Lung, and 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP BIDIRECTIONAL PROMOTER WITH KARS.
RX PubMed=14659874; DOI=10.1016/j.gene.2003.08.026;
RA Tan M., Wei C., Price C.M.;
RT "The telomeric protein Rap1 is conserved in vertebrates and is
RT expressed from a bidirectional promoter positioned between the Rap1
RT and KARS genes.";
RL Gene 323:1-10(2003).
RN [9]
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
RT complex on telomeres.";
RL J. Biol. Chem. 279:47264-47271(2004).
RN [10]
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 [11]
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 [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156 AND SER-203, AND
RP MASS SPECTROMETRY.
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
RT phosphorylation analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-154 AND SER-203,
RP AND MASS SPECTROMETRY.
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [16]
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 [17]
RP FUNCTION.
RX PubMed=19763083; DOI=10.1038/emboj.2009.275;
RA Sarthy J., Bae N.S., Scrafford J., Baumann P.;
RT "Human RAP1 inhibits non-homologous end joining at telomeres.";
RL EMBO J. 28:3390-3399(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154 AND SER-203, AND
RP MASS SPECTROMETRY.
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 [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-154 AND SER-203,
RP AND MASS SPECTROMETRY.
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.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
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.,
RA Buerckstuemmer T., 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 [21]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [22]
RP STRUCTURE BY NMR OF 132-190.
RX PubMed=11545594; DOI=10.1006/jmbi.2001.4924;
RA Hanaoka S., Nagadoi A., Yoshimura S., Aimoto S., Li B., de Lange T.,
RA Nishimura Y.;
RT "NMR structure of the hRap1 Myb motif reveals a canonical three-helix
RT bundle lacking the positive surface charge typical of Myb DNA-binding
RT domains.";
RL J. Mol. Biol. 312:167-175(2001).
CC -!- FUNCTION: Acts both as a regulator of telomere function and as a
CC transcription regulator. Involved in the regulation of telomere
CC length and protection as a component of the shelterin complex
CC (telosome). In contrast to other components of the shelterin
CC complex, it is dispensible for telomere capping and does not
CC participate in the protection of telomeres against non-homologous
CC end-joining (NHEJ)-mediated repair. Instead, it is required to
CC negatively regulate telomere recombination and is essential for
CC repressing homology-directed repair (HDR), which can affect
CC telomere length. Does not bind DNA directly: recruited to
CC telomeric double-stranded 5'-TTAGGG-3' repeats via its interaction
CC with TERF2. Independently of its function in telomeres, also acts
CC as a transcription regulator: recruited to extratelomeric 5'-
CC TTAGGG-3' sites via its association with TERF2 or other factors,
CC and regulates gene expression. When cytoplasmic, associates with
CC the I-kappa-B-kinase (IKK) complex and acts as a regulator of the
CC NF-kappa-B signaling by promoting IKK-mediated phosphorylation of
CC RELA/p65, leading to activate expression of NF-kappa-B target
CC genes.
CC -!- SUBUNIT: Associates with the I-kappa-B-kinase (IKK) core complex,
CC composed of CHUK, IKBKB and IKBKG (By similarity). Homodimer.
CC Component of the shelterin complex (telosome) composed of TERF1,
CC TERF2, TINF2, TERF2IP ACD and POT1. Interacts with TERF2; the
CC interaction is direct. Does not interact with TERF1. Interacts
CC with SLX4/BTBD12.
CC -!- INTERACTION:
CC Q8IY92:SLX4; NbExp=4; IntAct=EBI-750109, EBI-2370740;
CC Q15554:TERF2; NbExp=7; IntAct=EBI-750109, EBI-706637;
CC Q9BSI4-3:TINF2; NbExp=3; IntAct=EBI-750109, EBI-717418;
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm (By similarity).
CC Chromosome. Chromosome, telomere. Note=Associates with
CC chromosomes, both at telomeres and in extratelomeric sites. Also
CC exists as a cytoplasmic form, where it associates with the IKK
CC complex (By similarity).
CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed.
CC -!- MISCELLANEOUS: Shares a bidirectional promoter with KARS
CC (PubMed:14659874).
CC -!- SIMILARITY: Belongs to the RAP1 family.
CC -!- SIMILARITY: Contains 1 BRCT domain.
CC -!- SIMILARITY: Contains 1 Myb-like domain.
CC -!- CAUTION: Was reported to participate in the protection of
CC telomeres against non-homologous end-joining (NHEJ)-mediated
CC repair in the absence of TERF2 (PubMed:19763083). However, this
CC probably does not corresponds to its primary function and
CC experiments in mouse showed that it is dispensible for such
CC process and is required for repressiion of homology-directed
CC repair (HDR).
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL55783.1; Type=Frameshift; Positions=151;
CC Sequence=BAA91317.1; Type=Erroneous termination; Positions=299; Note=Translated as Glu;
CC Sequence=BAG60996.1; Type=Erroneous initiation; Note=Translation N-terminally extended;
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DR EMBL; AF262988; AAF72711.1; -; mRNA.
DR EMBL; AF250393; AAQ14259.1; -; mRNA.
DR EMBL; AF289599; AAL55783.1; ALT_FRAME; mRNA.
DR EMBL; AK000669; BAA91317.1; ALT_SEQ; mRNA.
DR EMBL; AK298880; BAG60996.1; ALT_INIT; mRNA.
DR EMBL; AC025287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471114; EAW95616.1; -; Genomic_DNA.
DR EMBL; CH471114; EAW95618.1; -; Genomic_DNA.
DR EMBL; BC004465; AAH04465.1; -; mRNA.
DR EMBL; BC005841; AAH05841.1; -; mRNA.
DR EMBL; BC022428; AAH22428.1; -; mRNA.
DR EMBL; BC078171; AAH78171.1; -; mRNA.
DR RefSeq; NP_061848.2; NM_018975.3.
DR UniGene; Hs.301419; -.
DR PDB; 1FEX; NMR; -; A=132-190.
DR PDB; 3K6G; X-ray; 1.95 A; A/B/C=303-399.
DR PDBsum; 1FEX; -.
DR PDBsum; 3K6G; -.
DR ProteinModelPortal; Q9NYB0; -.
DR SMR; Q9NYB0; 132-190, 306-398.
DR DIP; DIP-34868N; -.
DR IntAct; Q9NYB0; 16.
DR MINT; MINT-1454139; -.
DR STRING; 9606.ENSP00000300086; -.
DR PhosphoSite; Q9NYB0; -.
DR DMDM; 21542267; -.
DR PaxDb; Q9NYB0; -.
DR PeptideAtlas; Q9NYB0; -.
DR PRIDE; Q9NYB0; -.
DR DNASU; 54386; -.
DR Ensembl; ENST00000300086; ENSP00000300086; ENSG00000166848.
DR GeneID; 54386; -.
DR KEGG; hsa:54386; -.
DR UCSC; uc002fet.2; human.
DR CTD; 54386; -.
DR GeneCards; GC16P075681; -.
DR HGNC; HGNC:19246; TERF2IP.
DR HPA; CAB018660; -.
DR HPA; CAB018749; -.
DR HPA; HPA006719; -.
DR MIM; 605061; gene.
DR neXtProt; NX_Q9NYB0; -.
DR PharmGKB; PA134976325; -.
DR eggNOG; NOG39788; -.
DR HOGENOM; HOG000120115; -.
DR HOVERGEN; HBG054209; -.
DR InParanoid; Q9NYB0; -.
DR KO; K11113; -.
DR OMA; SISFYVR; -.
DR OrthoDB; EOG7KDFBG; -.
DR PhylomeDB; Q9NYB0; -.
DR Reactome; REACT_111183; Meiosis.
DR Reactome; REACT_115566; Cell Cycle.
DR Reactome; REACT_120956; Cellular responses to stress.
DR ChiTaRS; TERF2IP; human.
DR EvolutionaryTrace; Q9NYB0; -.
DR GeneWiki; TERF2IP; -.
DR GenomeRNAi; 54386; -.
DR NextBio; 56609; -.
DR PRO; PR:Q9NYB0; -.
DR ArrayExpress; Q9NYB0; -.
DR Bgee; Q9NYB0; -.
DR CleanEx; HS_TERF2IP; -.
DR Genevestigator; Q9NYB0; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0000783; C:nuclear telomere cap complex; IDA:BHF-UCL.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IEA:InterPro.
DR GO; GO:0048239; P:negative regulation of DNA recombination at telomere; ISS:UniProtKB.
DR GO; GO:0032205; P:negative regulation of telomere maintenance; IDA:UniProtKB.
DR GO; GO:0043123; P:positive regulation of I-kappaB kinase/NF-kappaB cascade; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
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:0010569; P:regulation of double-strand break repair via homologous recombination; ISS:UniProtKB.
DR GO; GO:0007004; P:telomere maintenance via telomerase; TAS:ProtInc.
DR GO; GO:0006351; P:transcription, DNA-dependent; IEA:UniProtKB-KW.
DR Gene3D; 1.10.10.60; -; 1.
DR InterPro; IPR009057; Homeodomain-like.
DR InterPro; IPR021661; Rap1_C.
DR InterPro; IPR015010; Rap1_Myb_dom.
DR Pfam; PF08914; Myb_DNA-bind_2; 1.
DR Pfam; PF11626; Rap1_C; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS50172; BRCT; FALSE_NEG.
DR PROSITE; PS50090; MYB_LIKE; FALSE_NEG.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Activator; Chromosome; Complete proteome;
KW Cytoplasm; Nucleus; Phosphoprotein; Polymorphism; Reference proteome;
KW Telomere; Transcription; Transcription regulation.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 399 Telomeric repeat-binding factor 2-
FT interacting protein 1.
FT /FTId=PRO_0000197126.
FT DOMAIN 78 101 BRCT.
FT DOMAIN 128 188 Myb-like.
FT MOTIF 383 399 Nuclear localization signal (Potential).
FT COMPBIAS 214 304 Asp/Glu-rich (acidic).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 36 36 Phosphoserine.
FT MOD_RES 154 154 Phosphoserine.
FT MOD_RES 156 156 Phosphoserine.
FT MOD_RES 203 203 Phosphoserine.
FT VARIANT 324 324 K -> E (in dbSNP:rs4888444).
FT /FTId=VAR_050195.
FT CONFLICT 83 83 Y -> H (in Ref. 4; BAA91317).
FT HELIX 138 150
FT TURN 155 159
FT HELIX 162 169
FT STRAND 172 174
FT HELIX 178 187
FT HELIX 308 324
FT HELIX 329 338
FT TURN 339 341
FT HELIX 343 352
FT HELIX 364 370
FT HELIX 375 385
FT HELIX 387 397
SQ SEQUENCE 399 AA; 44260 MW; EAA615777F9D3D3D CRC64;
MAEAMDLGKD PNGPTHSSTL FVRDDGSSMS FYVRPSPAKR RLSTLILHGG GTVCRVQEPG
AVLLAQPGEA LAEASGDFIS TQYILDCVER NERLELEAYR LGPASAADTG SEAKPGALAE
GAAEPEPQRH AGRIAFTDAD DVAILTYVKE NARSPSSVTG NALWKAMEKS SLTQHSWQSL
KDRYLKHLRG QEHKYLLGDA PVSPSSQKLK RKAEEDPEAA DSGEPQNKRT PDLPEEEYVK
EEIQENEEAV KKMLVEATRE FEEVVVDESP PDFEIHITMC DDDPPTPEED SETQPDEEEE
EEEEKVSQPE VGAAIKIIRQ LMEKFNLDLS TVTQAFLKNS GELEATSAFL ASGQRADGYP
IWSRQDDIDL QKDDEDTREA LVKKFGAQNV ARRIEFRKK
//
MIM
605061
*RECORD*
*FIELD* NO
605061
*FIELD* TI
*605061 TERF2-INTERACTING PROTEIN; TERF2IP
;;TRF2-INTERACTING TELOMERIC PROTEIN;;
RAP1, YEAST, HOMOLOG OF; RAP1
read more*FIELD* TX
CLONING
By performing a yeast 2-hybrid screen on a HeLa cell cDNA library using
telomeric repeat-binding factor-2, or TRF2 (TERF2; 602027), as bait,
followed by screening a breast cancer cDNA library, Li et al. (2000)
isolated a full-length cDNA encoding RAP1, an ortholog of the yeast
telomeric protein Rap1. The RAP1 cDNA is identical to the KAIA804 cDNA
(GenBank GENBANK AK000669) reported by the NEDO Japanese sequencing
project. The predicted 47-kD RAP1 protein contains 399 amino acids. A
motif search revealed that RAP1 has an N-terminal BRCT domain and a
central Myb-type helix-turn-helix motif. RAP1 also has an acidic C
terminus (amino acids 214 to 382; pI around 3.8) featuring a predicted
33-amino acid coiled-coil region and a bipartite nuclear localization
signal. Sequence alignments showed an additional region of sequence
similarity in the C termini of yeast and human RAP1 that coincides with
the main protein-protein interaction domain of S. cerevisiae Rap1. Thus,
human RAP1 has 3 conserved sequence motifs in common with yeast Rap1.
Northern blot analysis detected ubiquitous expression of a 2.5-kb RAP1
transcript. The authors found that RAP1 is localized to telomeres and
affects telomere length. However, while yeast Rap1 binds telomeric DNA
directly, human RAP1 is recruited to telomeres by TRF2. Extending the
comparison of telomeric proteins to fission yeast, Li et al. (2000)
identified the S. pombe Taz1 protein as a TRF ortholog, indicating that
TRFs are conserved at eukaryotic telomeres. The data suggested that
ancestral telomeres, like those of vertebrates, contained a TRF-like
protein as well as RAP1. The authors proposed that budding yeast
preserved Rap1 at telomeres but lost the TRF component, possibly
concomitant with a change in the telomeric repeat sequence.
GENE FUNCTION
Lieb et al. (2001) determined the distribution of RAP1 in vivo on the
entire yeast genome, at a resolution of 2 kb. RAP1 is central to the
cellular economy during rapid growth, targeting 294 loci, about 5% of
yeast genes, and participating in the activation of 37% of all RNA
polymerase II (see 180660) initiation events in exponentially growing
cells. Although the DNA sequence recognized by RAP1 is found in both
coding and intergenic sequences, the binding of RAP1 to the genome was
highly specific to intergenic regions with the potential to act as
promoters. Lieb et al. (2001) concluded that this global phenomenon,
which may be a general characteristic of sequence-specific
transcriptional factors, indicates the existence of a genomewide
molecular mechanism for marking promoter regions.
Sfeir et al. (2010) removed Rap1 from mouse telomeres either through
gene deletion or by replacing Trf2 (602027) with a mutant that does not
bind Rap1. Rap1 was dispensable for the essential functions of
Trf2--repression of ATM kinase signaling and nonhomologous
end-joining--and mice lacking telomeric Rap1 were viable and fertile.
However, Rap1 was critical for the repression of homology-directed
repair, which can alter telomere length. The data of Sfeir et al. (2010)
revealed that homology-directed repair at telomeres can take place in
the absence of DNA damage foci and underscore the functional
compartmentalization within the shelterin complex.
BIOCHEMICAL FEATURES
- Cryoelectron Microscopy
Papai et al. (2010) used cryoelectron microscopy to determine the
architecture of nucleoprotein complexes composed of TFIID (313650),
TFIIA (see 600519), the transcriptional activator RAP1, and yeast
enhancer-promoter DNA. These structures revealed the mode of binding of
RAP1 and TFIIA to TFIID, as well as a reorganization of TFIIA induced by
its interaction with RAP1. Papai et al. (2010) proposed that this change
in position increases the exposure of TATA box-binding protein within
TFIID, consequently enhancing its ability to interact with the promoter.
A large RAP1-dependent DNA loop forms between the activator-binding site
and the proximal promoter region. This loop is topologically locked by a
TFIIA-RAP1 protein bridge that folds over the DNA. These results
highlighted the role of TFIIA in transcriptional activation, defined the
molecular mechanism for enhancer-promoter communication, and provided
structural insights into the pathways of intramolecular communication
that convey transcription activation signals through the TFIID complex.
*FIELD* RF
1. Li, B.; Oestreich, S.; de Lange, T.: Identification of human Rap1:
implications for telomere evolution. Cell 101: 471-483, 2000.
2. Lieb, J. D.; Liu, X.; Botstein, D.; Brown, P. O.: Promoter-specific
binding of Rap1 revealed by genome-wide maps of protein-DNA association. Nature
Genet. 28: 327-334, 2001. Note: Erratum: Nature Genet. 29: 100 only,
2001.
3. Papai, G.; Tripathi, M. K.; Ruhlmann, C.; Layer, J. H.; Weil, P.
A.; Schultz, P.: TFIIA and the transactivator Rap1 cooperate to commit
TFIID for transcription initiation. Nature 465: 956-960, 2010.
4. Sfeir, A.; Kabir, S.; van Overbeek, M.; Celli, G. B.; de Lange,
T.: Loss of Rap1 induces telomere recombination in the absence of
NHEJ or a DNA damage signal. Science 327: 1657-1661, 2010.
*FIELD* CN
Ada Hamosh - updated: 7/1/2010
Ada Hamosh - updated: 4/14/2010
Ada Hamosh - updated: 7/13/2001
Ada Hamosh - updated: 6/27/2001
*FIELD* CD
Stylianos E. Antonarakis: 6/19/2000
*FIELD* ED
alopez: 07/02/2010
alopez: 7/2/2010
terry: 7/1/2010
alopez: 4/22/2010
terry: 4/14/2010
alopez: 11/24/2009
carol: 8/23/2005
mgross: 9/18/2002
mgross: 9/9/2002
alopez: 8/2/2001
alopez: 7/16/2001
terry: 7/13/2001
mgross: 6/27/2001
terry: 6/27/2001
mgross: 6/19/2000
*RECORD*
*FIELD* NO
605061
*FIELD* TI
*605061 TERF2-INTERACTING PROTEIN; TERF2IP
;;TRF2-INTERACTING TELOMERIC PROTEIN;;
RAP1, YEAST, HOMOLOG OF; RAP1
read more*FIELD* TX
CLONING
By performing a yeast 2-hybrid screen on a HeLa cell cDNA library using
telomeric repeat-binding factor-2, or TRF2 (TERF2; 602027), as bait,
followed by screening a breast cancer cDNA library, Li et al. (2000)
isolated a full-length cDNA encoding RAP1, an ortholog of the yeast
telomeric protein Rap1. The RAP1 cDNA is identical to the KAIA804 cDNA
(GenBank GENBANK AK000669) reported by the NEDO Japanese sequencing
project. The predicted 47-kD RAP1 protein contains 399 amino acids. A
motif search revealed that RAP1 has an N-terminal BRCT domain and a
central Myb-type helix-turn-helix motif. RAP1 also has an acidic C
terminus (amino acids 214 to 382; pI around 3.8) featuring a predicted
33-amino acid coiled-coil region and a bipartite nuclear localization
signal. Sequence alignments showed an additional region of sequence
similarity in the C termini of yeast and human RAP1 that coincides with
the main protein-protein interaction domain of S. cerevisiae Rap1. Thus,
human RAP1 has 3 conserved sequence motifs in common with yeast Rap1.
Northern blot analysis detected ubiquitous expression of a 2.5-kb RAP1
transcript. The authors found that RAP1 is localized to telomeres and
affects telomere length. However, while yeast Rap1 binds telomeric DNA
directly, human RAP1 is recruited to telomeres by TRF2. Extending the
comparison of telomeric proteins to fission yeast, Li et al. (2000)
identified the S. pombe Taz1 protein as a TRF ortholog, indicating that
TRFs are conserved at eukaryotic telomeres. The data suggested that
ancestral telomeres, like those of vertebrates, contained a TRF-like
protein as well as RAP1. The authors proposed that budding yeast
preserved Rap1 at telomeres but lost the TRF component, possibly
concomitant with a change in the telomeric repeat sequence.
GENE FUNCTION
Lieb et al. (2001) determined the distribution of RAP1 in vivo on the
entire yeast genome, at a resolution of 2 kb. RAP1 is central to the
cellular economy during rapid growth, targeting 294 loci, about 5% of
yeast genes, and participating in the activation of 37% of all RNA
polymerase II (see 180660) initiation events in exponentially growing
cells. Although the DNA sequence recognized by RAP1 is found in both
coding and intergenic sequences, the binding of RAP1 to the genome was
highly specific to intergenic regions with the potential to act as
promoters. Lieb et al. (2001) concluded that this global phenomenon,
which may be a general characteristic of sequence-specific
transcriptional factors, indicates the existence of a genomewide
molecular mechanism for marking promoter regions.
Sfeir et al. (2010) removed Rap1 from mouse telomeres either through
gene deletion or by replacing Trf2 (602027) with a mutant that does not
bind Rap1. Rap1 was dispensable for the essential functions of
Trf2--repression of ATM kinase signaling and nonhomologous
end-joining--and mice lacking telomeric Rap1 were viable and fertile.
However, Rap1 was critical for the repression of homology-directed
repair, which can alter telomere length. The data of Sfeir et al. (2010)
revealed that homology-directed repair at telomeres can take place in
the absence of DNA damage foci and underscore the functional
compartmentalization within the shelterin complex.
BIOCHEMICAL FEATURES
- Cryoelectron Microscopy
Papai et al. (2010) used cryoelectron microscopy to determine the
architecture of nucleoprotein complexes composed of TFIID (313650),
TFIIA (see 600519), the transcriptional activator RAP1, and yeast
enhancer-promoter DNA. These structures revealed the mode of binding of
RAP1 and TFIIA to TFIID, as well as a reorganization of TFIIA induced by
its interaction with RAP1. Papai et al. (2010) proposed that this change
in position increases the exposure of TATA box-binding protein within
TFIID, consequently enhancing its ability to interact with the promoter.
A large RAP1-dependent DNA loop forms between the activator-binding site
and the proximal promoter region. This loop is topologically locked by a
TFIIA-RAP1 protein bridge that folds over the DNA. These results
highlighted the role of TFIIA in transcriptional activation, defined the
molecular mechanism for enhancer-promoter communication, and provided
structural insights into the pathways of intramolecular communication
that convey transcription activation signals through the TFIID complex.
*FIELD* RF
1. Li, B.; Oestreich, S.; de Lange, T.: Identification of human Rap1:
implications for telomere evolution. Cell 101: 471-483, 2000.
2. Lieb, J. D.; Liu, X.; Botstein, D.; Brown, P. O.: Promoter-specific
binding of Rap1 revealed by genome-wide maps of protein-DNA association. Nature
Genet. 28: 327-334, 2001. Note: Erratum: Nature Genet. 29: 100 only,
2001.
3. Papai, G.; Tripathi, M. K.; Ruhlmann, C.; Layer, J. H.; Weil, P.
A.; Schultz, P.: TFIIA and the transactivator Rap1 cooperate to commit
TFIID for transcription initiation. Nature 465: 956-960, 2010.
4. Sfeir, A.; Kabir, S.; van Overbeek, M.; Celli, G. B.; de Lange,
T.: Loss of Rap1 induces telomere recombination in the absence of
NHEJ or a DNA damage signal. Science 327: 1657-1661, 2010.
*FIELD* CN
Ada Hamosh - updated: 7/1/2010
Ada Hamosh - updated: 4/14/2010
Ada Hamosh - updated: 7/13/2001
Ada Hamosh - updated: 6/27/2001
*FIELD* CD
Stylianos E. Antonarakis: 6/19/2000
*FIELD* ED
alopez: 07/02/2010
alopez: 7/2/2010
terry: 7/1/2010
alopez: 4/22/2010
terry: 4/14/2010
alopez: 11/24/2009
carol: 8/23/2005
mgross: 9/18/2002
mgross: 9/9/2002
alopez: 8/2/2001
alopez: 7/16/2001
terry: 7/13/2001
mgross: 6/27/2001
terry: 6/27/2001
mgross: 6/19/2000