ID 4ET_HUMAN Reviewed; 985 AA. AC Q9NRA8; B1AKL2; B2RBF1; Q8NCF2; Q9H708; DT 02-AUG-2002, integrated into UniProtKB/Swiss-Prot. DT 02-AUG-2002, sequence version 2. DT 19-JAN-2010, entry version 78. DE RecName: Full=Eukaryotic translation initiation factor 4E transporter; DE Short=eIF4E transporter; DE Short=4E-T; DE AltName: Full=Eukaryotic translation initiation factor 4E nuclear import factor 1; GN Name=EIF4ENIF1; 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] (ISOFORM 1), CHARACTERIZATION, RP PHOSPHORYLATION, AND MUTAGENESIS OF TYR-30 AND 195-ARG-ARG-196. RC TISSUE=Fetal brain; RX MEDLINE=20315895; PubMed=10856257; DOI=10.1093/emboj/19.12.3142; RA Dostie J., Ferraiuolo M., Pause A., Adam S.A., Sonenberg N.; RT "A novel shuttling protein, 4E-T, mediates the nuclear import of the RT mRNA 5' cap-binding protein, eIF4E."; RL EMBO J. 19:3142-3156(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84; RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., RA Beare D.M., Dunham I.; RT "A genome annotation-driven approach to cloning the human ORFeome."; RL Genome Biol. 5:R84.1-R84.11(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Colon, Placenta, 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX MEDLINE=20057165; PubMed=10591208; DOI=10.1038/990031; RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., RA Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., RA Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Buck D., Burgess J., RA Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., RA Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., RA Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., RA Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., RA Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., RA Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., RA Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., RA Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., RA Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., RA Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., RA Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., RA Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., RA Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., RA Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., RA Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., RA Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., RA Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., RA Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., RA Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., RA Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., RA Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., RA Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., RA Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., RA Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., RA Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., RA Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., RA Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., RA Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., RA Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., RA O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., RA Khan A.S., Lane L., Tilahun Y., Wright H.; RT "The DNA sequence of human chromosome 22."; RL Nature 402:489-495(1999). RN [5] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Testis; 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 [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-914 AND SER-920, AND RP MASS SPECTROMETRY. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-74, AND MASS RP SPECTROMETRY. RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-120; SER-136; SER-138; RP SER-345; SER-564 AND SER-951, 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 [10] RP IDENTIFICATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-564, AND MASS RP SPECTROMETRY. 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-5; SER-564; SER-587; RP SER-693 AND SER-951, AND MASS SPECTROMETRY. RC TISSUE=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 [13] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-486, AND MASS SPECTROMETRY. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). CC -!- FUNCTION: Nucleoplasmic shuttling protein. Mediates the nuclear CC import of EIF4E by a piggy-back mechanism. CC -!- SUBUNIT: Interacts with EIF4E. Interacts with importin beta only CC in the presence of importin alpha, suggesting a direct interaction CC with importin alpha. CC -!- INTERACTION: CC P06730:EIF4E; NbExp=1; IntAct=EBI-301024, EBI-73440; CC O60573:EIF4E2; NbExp=2; IntAct=EBI-301024, EBI-398610; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly CC cytoplasmic. Shuttles between the nucleus and the cytoplasm in a CC CRM1-dependent manner. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9NRA8-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9NRA8-2; Sequence=VSP_003783, VSP_003784; CC Note=No experimental confirmation available; CC -!- TISSUE SPECIFICITY: Widely expressed. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- DR EMBL; AF240775; AAF81693.1; -; mRNA. DR EMBL; CR456386; CAG30272.1; -; mRNA. DR EMBL; AK025254; BAB15092.1; ALT_INIT; mRNA. DR EMBL; AK074768; BAC11194.1; ALT_INIT; mRNA. DR EMBL; AK314636; BAG37198.1; -; mRNA. DR EMBL; AL096701; CAI12878.1; -; Genomic_DNA. DR EMBL; CH471095; EAW59977.1; -; Genomic_DNA. DR EMBL; BC032941; AAH32941.1; -; mRNA. DR EMBL; BC033028; AAH33028.1; -; mRNA. DR IPI; IPI00291800; -. DR IPI; IPI00550518; -. DR RefSeq; NP_001157973.1; -. DR RefSeq; NP_001157974.1; -. DR RefSeq; NP_062817.2; -. DR UniGene; Hs.517559; -. DR IntAct; Q9NRA8; 9. DR STRING; Q9NRA8; -. DR PhosphoSite; Q9NRA8; -. DR PRIDE; Q9NRA8; -. DR Ensembl; ENST00000330125; ENSP00000328103; ENSG00000184708; Homo sapiens. DR Ensembl; ENST00000397525; ENSP00000380659; ENSG00000184708; Homo sapiens. DR Ensembl; ENST00000420671; ENSP00000409372; ENSG00000184708; Homo sapiens. DR GeneID; 56478; -. DR KEGG; hsa:56478; -. DR UCSC; uc003akx.1; human. DR UCSC; uc003akz.1; human. DR CTD; 56478; -. DR GeneCards; GC22M030159; -. DR HGNC; HGNC:16687; EIF4ENIF1. DR HPA; HPA001619; -. DR HPA; HPA002078; -. DR MIM; 607445; gene. DR PharmGKB; PA38410; -. DR eggNOG; prNOG15714; -. DR HOGENOM; HBG267574; -. DR HOVERGEN; Q9NRA8; -. DR InParanoid; Q9NRA8; -. DR OMA; GRKTPTL; -. DR OrthoDB; EOG9VQD7M; -. DR PhylomeDB; Q9NRA8; -. DR NextBio; 62017; -. DR ArrayExpress; Q9NRA8; -. DR Bgee; Q9NRA8; -. DR CleanEx; HS_EIF4ENIF1; -. DR Genevestigator; Q9NRA8; -. DR GermOnline; ENSG00000184708; Homo sapiens. DR GO; GO:0005634; C:nucleus; IDA:HPA. DR GO; GO:0005515; F:protein binding; IPI:IntAct. DR GO; GO:0008565; F:protein transporter activity; TAS:ProtInc. DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW. DR InterPro; IPR018862; eIF4E_transporter. DR Pfam; PF10477; EIF4E-T; 1. PE 1: Evidence at protein level; KW Acetylation; Alternative splicing; Complete proteome; Cytoplasm; KW Nucleus; Phosphoprotein; Protein transport; Transport. FT CHAIN 1 985 Eukaryotic translation initiation factor FT 4E transporter. FT /FTId=PRO_0000064381. FT REGION 30 36 EIF4E-binding. FT MOTIF 195 211 Nuclear localization signal. FT MOTIF 438 447 Nuclear export signal. FT MOTIF 613 638 Nuclear export signal. FT COMPBIAS 148 210 Arg-rich. FT MOD_RES 5 5 Phosphoserine. FT MOD_RES 74 74 Phosphoserine. FT MOD_RES 78 78 Phosphoserine (By similarity). FT MOD_RES 120 120 Phosphoserine. FT MOD_RES 136 136 Phosphoserine. FT MOD_RES 138 138 Phosphoserine. FT MOD_RES 345 345 Phosphoserine. FT MOD_RES 486 486 N6-acetyllysine. FT MOD_RES 564 564 Phosphoserine. FT MOD_RES 587 587 Phosphoserine. FT MOD_RES 693 693 Phosphoserine. FT MOD_RES 914 914 Phosphoserine. FT MOD_RES 920 920 Phosphoserine. FT MOD_RES 951 951 Phosphoserine. FT VAR_SEQ 100 262 Missing (in isoform 2). FT /FTId=VSP_003783. FT VAR_SEQ 493 504 Missing (in isoform 2). FT /FTId=VSP_003784. FT MUTAGEN 30 30 Y->A: Abolishes interaction with EIF4E. FT MUTAGEN 195 196 RR->NS: Abolishes the nuclear FT localization. FT CONFLICT 114 114 L -> F (in Ref. 1; AAF81693). FT CONFLICT 616 616 Q -> QQ (in Ref. 3; BAB15092 and 6; FT AAH32941). FT CONFLICT 825 825 Q -> R (in Ref. 6; AAH33028). SQ SEQUENCE 985 AA; 108201 MW; 4C898E0488903C04 CRC64; MDRRSMGETE SGDAFLDLKK PPASKCPHRY TKEELLDIKE LPHSKQRPSC LSEKYDSDGV WDPEKWHASL YPASGRSSPV ESLKKELDTD RPSLVRRIVD PRERVKEDDL DVVLSPQRRS FGGGCHVTAA VSSRRSGSPL EKDSDGLRLL GGRRIGSGRI ISARTFEKDH RLSDKDLRDL RDRDRERDFK DKRFRREFGD SKRVFGERRR NDSYTEEEPE WFSAGPTSQS ETIELTGFDD KILEEDHKGR KRTRRRTASV KEGIVECNGG VAEEDEVEVI LAQEPAADQE VPRDAVLPEQ SPGDFDFNEF FNLDKVPCLA SMIEDVLGEG SVSASRFSRW FSNPSRSGSR SSSLGSTPHE ELERLAGLEQ AILSPGQNSG NYFAPIPLED HAENKVDILE MLQKAKVDLK PLLSSLSANK EKLKESSHSG VVLSVEEVEA GLKGLKVDQQ VKNSTPFMAE HLEETLSAVT NNRQLKKDGD MTAFNKLVST MKASGTLPSQ PKVSRNLESH LMSPAEIPGQ PVPKNILQEL LGQPVQRPAS SNLLSGLMGS LEPTTSLLGQ RAPSPPLSQV FQTRAASADY LRPRIPSPIG FTPGPQQLLG DPFQGMRKPM SPITAQMSQL ELQQAALEGL ALPHDLAVQA ANFYQPGFGK PQVDRTRDGF RNRQQRVTKS PAPVHRGNSS SPAPAASITS MLSPSFTPTS VIRKMYESKE KSKEEPASGK AALGDSKEDT QKASEENLLS SSSVPSADRD SSPTTNSKLS ALQRSSCSTP LSQANRYTKE QDYRPKATGR KTPTLASPVP TTPFLRPVHQ VPLVPHVPMV RPAHQLHPGL VQRMLAQGVH PQHLPSLLQT GVLPPGMDLS HLQGISGPIL GQPFYPLPAA SHPLLNPRPG TPLHLAMVQQ QLQRSVLHPP GSGSHAAAVS VQTTPQNVPS RSGLPHMHSQ LEHRPSQRSS SPVGLAKWFG SDVLQQPLPS MPAKVISVDE LEYRQ //