ID TE2IP_HUMAN Reviewed; 399 AA. AC Q9NYB0; Q8WYZ3; Q9NWR2; DT 20-JUN-2002, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 13-OCT-2009, entry version 93. DE RecName: Full=Telomeric repeat-binding factor 2-interacting protein 1; DE AltName: Full=TRF2-interacting telomeric protein Rap1; DE Short=hRap1; GN Name=TERF2IP; Synonyms=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 MEDLINE=20306663; 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 [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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Ileal mucosa; 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 [4] 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 [5] 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 [6] 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154, AND MASS RP SPECTROMETRY. RC TISSUE=Epithelium; RX PubMed=15302935; DOI=10.1073/pnas.0404720101; RA Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., RA Li J., Cohn M.A., Cantley L.C., Gygi S.P.; RT "Large-scale characterization of HeLa cell nuclear phosphoproteins."; RL Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004). RN [8] 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 [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-154; SER-156 AND RP SER-203, AND MASS SPECTROMETRY. RC TISSUE=Epithelium; 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 [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND MASS RP SPECTROMETRY. RX PubMed=17287340; DOI=10.1073/pnas.0611217104; RA Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A.; RT "Global proteomic profiling of phosphopeptides using electron transfer RT dissociation tandem mass spectrometry."; RL Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203 AND SER-206, AND RP MASS SPECTROMETRY. 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-203, AND MASS RP SPECTROMETRY. RX PubMed=18187866; DOI=10.2116/analsci.24.161; RA Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y.; RT "Automated phosphoproteome analysis for cultured cancer cells by two- RT dimensional nanoLC-MS using a calcined titania/C18 biphasic column."; RL Anal. Sci. 24:161-166(2008). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36; SER-154 AND SER-203, RP AND MASS SPECTROMETRY. 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 [14] RP IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [15] RP INTERACTION WITH BTBD12. 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 [16] RP STRUCTURE BY NMR OF 132-190. RX MEDLINE=21431821; 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: May play a role in telomere length regulation. Component CC of the shelterin complex (telosome) that is involved in the CC regulation of telomere length and protection. Shelterin associates CC with arrays of double-stranded TTAGGG repeats added by telomerase CC and protects chromosome ends; without its protective activity, CC telomeres are no longer hidden from the DNA damage surveillance CC and chromosome ends are inappropriately processed by DNA repair CC pathways. CC -!- SUBUNIT: Homodimer. Component of the shelterin complex (telosome) CC composed of TERF1, TERF2, TINF2, TERF2IP ACD and POT1. Binds to CC TRF2 (but not TRF1) with its C-terminus. Interacts with CC BTBD12/SLX4. CC -!- INTERACTION: CC Q9BSI4-3:TINF2; NbExp=1; IntAct=EBI-750109, EBI-717418; CC -!- SUBCELLULAR LOCATION: Nucleus. Telomere. Note=Colocalizes with CC telomeric DNA in interphase and metaphase cells. CC -!- TISSUE SPECIFICITY: Ubiquitous. Highly expressed. CC -!- PTM: Phosphorylated upon DNA damage, probably by ATM or ATR. CC -!- MISCELLANEOUS: Recruited to telomeres by TRF2; seemingly it does CC not directly bind to DNA itself. CC -!- SIMILARITY: Contains 1 BRCT domain. CC -!- SIMILARITY: Contains 1 Myb-like domain. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF262988; AAF72711.1; -; mRNA. DR EMBL; AF289599; AAL55783.1; ALT_FRAME; mRNA. DR EMBL; AK000669; BAA91317.1; ALT_SEQ; mRNA. 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 IPI; IPI00008961; -. DR RefSeq; NP_061848.2; -. DR UniGene; Hs.301419; -. DR PDB; 1FEX; NMR; -; A=132-190. DR PDBsum; 1FEX; -. DR IntAct; Q9NYB0; 10. DR STRING; Q9NYB0; -. DR PhosphoSite; Q9NYB0; -. DR PeptideAtlas; Q9NYB0; -. DR PRIDE; Q9NYB0; -. DR Ensembl; ENST00000300086; ENSP00000300086; ENSG00000166848; Homo sapiens. DR GeneID; 54386; -. DR KEGG; hsa:54386; -. DR UCSC; uc002fet.1; human. DR CTD; 54386; -. DR GeneCards; GC16P074239; -. DR H-InvDB; HIX0013251; -. DR HGNC; HGNC:19246; TERF2IP. DR HPA; CAB018660; -. DR HPA; CAB018749; -. DR HPA; HPA006719; -. DR MIM; 605061; gene. DR PharmGKB; PA134976325; -. DR HOGENOM; Q9NYB0; -. DR HOVERGEN; Q9NYB0; -. DR OMA; Q9NYB0; HGGGTVC. DR Pathway_Interaction_DB; telomerasepathway; Regulation of Telomerase. DR Reactome; REACT_7970; Telomere Maintenance. DR NextBio; 56609; -. DR ArrayExpress; Q9NYB0; -. DR Bgee; Q9NYB0; -. DR CleanEx; HS_TERF2IP; -. DR Genevestigator; Q9NYB0; -. DR GermOnline; ENSG00000166848; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IDA:HPA. DR GO; GO:0030870; C:Mre11 complex; IDA:UniProtKB. DR GO; GO:0000783; C:nuclear telomere cap complex; IDA:UniProtKB. DR GO; GO:0005654; C:nucleoplasm; EXP:Reactome. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0005515; F:protein binding; IPI:UniProtKB. DR GO; GO:0032205; P:negative regulation of telomere maintenance; IDA:UniProtKB. DR GO; GO:0031848; P:protection from non-homologous end joining ...; IMP:UniProtKB. DR GO; GO:0070198; P:protein localization to telomere; IMP:UniProtKB. DR GO; GO:0045449; P:regulation of transcription; IEA:InterPro. DR GO; GO:0007004; P:telomere maintenance via telomerase; TAS:ProtInc. DR InterPro; IPR012287; Homeodomain-rel. DR InterPro; IPR015010; Myb_DNA-bd_2. DR Gene3D; G3DSA:1.10.10.60; Homeodomain-rel; 1. DR Pfam; PF08914; Myb_DNA-bind_2; 1. DR PROSITE; PS50172; BRCT; FALSE_NEG. DR PROSITE; PS50090; MYB_LIKE; FALSE_NEG. PE 1: Evidence at protein level; KW 3D-structure; Chromosomal protein; Complete proteome; Nucleus; KW Phosphoprotein; Polymorphism; Telomere. FT CHAIN 1 399 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 36 36 Phosphoserine. FT MOD_RES 154 154 Phosphoserine. FT MOD_RES 156 156 Phosphoserine. FT MOD_RES 203 203 Phosphoserine. FT MOD_RES 206 206 Phosphoserine. FT VARIANT 324 324 K -> E (in dbSNP:rs4888444). FT /FTId=VAR_050195. FT CONFLICT 83 83 Y -> H (in Ref. 3; BAA91317). FT HELIX 138 150 FT TURN 155 159 FT HELIX 162 169 FT STRAND 172 174 FT HELIX 178 187 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 //