ID IF4E2_HUMAN Reviewed; 245 AA. AC O60573; B8ZZJ9; O75349; DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 28-JAN-2026, entry version 202. DE RecName: Full=Eukaryotic translation initiation factor 4E type 2 {ECO:0000303|PubMed:15153109}; DE Short=eIF-4E type 2 {ECO:0000303|PubMed:15153109}; DE Short=eIF4E type 2 {ECO:0000303|PubMed:15153109}; DE AltName: Full=Eukaryotic translation initiation factor 4E homologous protein; DE AltName: Full=Eukaryotic translation initiation factor 4E-like 3; DE AltName: Full=eIF4E-like protein 4E-LP {ECO:0000303|PubMed:15153109}; DE AltName: Full=mRNA cap-binding protein 4EHP {ECO:0000303|PubMed:23991149}; DE Short=h4EHP {ECO:0000303|PubMed:17368478}; DE AltName: Full=mRNA cap-binding protein type 3; GN Name=EIF4E2 {ECO:0000303|PubMed:15153109, ECO:0000312|HGNC:HGNC:3293}; GN Synonyms=EIF4EL3; 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), FUNCTION, 3D-STRUCTURE MODELING, RP AND MUTAGENESIS OF TRP-63; TRP-95; 124-TRP--ASP-126; TRP-124; GLU-125; RP ASP-126; TRP-135; TRP-148 AND TRP-183. RC TISSUE=Follicular cell; RX PubMed=9582349; DOI=10.1074/jbc.273.21.13104; RA Rom E., Kim H.C., Gingras A.-C., Marcotrigiano J., Favre D., Olsen H., RA Burley S.K., Sonenberg N.; RT "Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap- RT binding protein."; RL J. Biol. Chem. 273:13104-13109(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND INTERACTION WITH EIF4EBP1; RP EIF4EBP2 AND EIF4EBP3. RC TISSUE=Mammary gland; RX PubMed=15153109; DOI=10.1111/j.1432-1033.2004.04149.x; RA Joshi B., Cameron A., Jagus R.; RT "Characterization of mammalian eIF4E-family members."; RL Eur. J. Biochem. 271:2189-2203(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Umbilical cord blood; RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175; RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., RA Wang Y.-X., Chen S.-J., Chen Z.; RT "Identification of genes expressed in human CD34(+) hematopoietic RT stem/progenitor cells by expressed sequence tags and efficient full-length RT cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). 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=Muscle, Urinary bladder, and Uterus; 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 UBIQUITINATION BY ARIH1. RX PubMed=14623119; DOI=10.1016/s0014-5793(03)01235-3; RA Tan N.G., Ardley H.C., Scott G.B., Rose S.A., Markham A.F., Robinson P.A.; RT "Human homologue of ariadne promotes the ubiquitylation of translation RT initiation factor 4E homologous protein, 4EHP."; RL FEBS Lett. 554:501-504(2003). RN [8] RP ISGYLATION AT LYS-134 AND LYS-222. RX PubMed=17289916; DOI=10.1101/gad.1521607; RA Okumura F., Zou W., Zhang D.E.; RT "ISG15 modification of the eIF4E cognate 4EHP enhances cap structure- RT binding activity of 4EHP."; RL Genes Dev. 21:255-260(2007). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-134, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19608861; DOI=10.1126/science.1175371; RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., 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). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP FUNCTION, AND IDENTIFICATION IN THE 4EHP-GYF2 COMPLEX. RX PubMed=22751931; DOI=10.1128/mcb.00455-12; RA Morita M., Ler L.W., Fabian M.R., Siddiqui N., Mullin M., Henderson V.C., RA Alain T., Fonseca B.D., Karashchuk G., Bennett C.F., Kabuta T., Higashi S., RA Larsson O., Topisirovic I., Smith R.J., Gingras A.C., Sonenberg N.; RT "A novel 4EHP-GIGYF2 translational repressor complex is essential for RT mammalian development."; RL Mol. Cell. Biol. 32:3585-3593(2012). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [14] RP SUBCELLULAR LOCATION, AND INTERACTION WITH EIF4ENIF1. RX PubMed=23991149; DOI=10.1371/journal.pone.0072761; RA Kubacka D., Kamenska A., Broomhead H., Minshall N., Darzynkiewicz E., RA Standart N.; RT "Investigating the consequences of eIF4E2 (4EHP) interaction with 4E- RT transporter on its cellular distribution in HeLa cells."; RL PLoS ONE 8:e72761-e72761(2013). RN [15] RP FUNCTION, UBIQUITINATION, AND MUTAGENESIS OF LYS-121; LYS-130; LYS-134 AND RP LYS-222. RX PubMed=25624349; DOI=10.1128/mcb.01152-14; RA von Stechow L., Typas D., Carreras Puigvert J., Oort L., Siddappa R., RA Pines A., Vrieling H., van de Water B., Mullenders L.H., Danen E.H.; RT "The E3 ubiquitin ligase ARIH1 protects against genotoxic stress by RT initiating a 4EHP-mediated mRNA translation arrest."; RL Mol. Cell. Biol. 35:1254-1268(2015). RN [16] RP FUNCTION, AND INTERACTION WITH EIF4ENIF1. RX PubMed=28487484; DOI=10.1073/pnas.1701488114; RA Chapat C., Jafarnejad S.M., Matta-Camacho E., Hesketh G.G., Gelbart I.A., RA Attig J., Gkogkas C.G., Alain T., Stern-Ginossar N., Fabian M.R., RA Gingras A.C., Duchaine T.F., Sonenberg N.; RT "Cap-binding protein 4EHP effects translation silencing by microRNAs."; RL Proc. Natl. Acad. Sci. U.S.A. 114:5425-5430(2017). RN [17] RP FUNCTION, AND IDENTIFICATION IN THE 4EHP-GYF2 COMPLEX. RX PubMed=32726578; DOI=10.1016/j.molcel.2020.07.007; RA Hickey K.L., Dickson K., Cogan J.Z., Replogle J.M., Schoof M., RA D'Orazio K.N., Sinha N.K., Hussmann J.A., Jost M., Frost A., Green R., RA Weissman J.S., Kostova K.K.; RT "GIGYF2 and 4EHP Inhibit Translation Initiation of Defective Messenger RNAs RT to Assist Ribosome-Associated Quality Control."; RL Mol. Cell 79:950.e6-962.e6(2020). RN [18] RP FUNCTION. RX PubMed=33581076; DOI=10.1016/j.molcel.2021.01.030; RA Zhang X., Chapat C., Wang P., Choi J.H., Li Q., Luo J., Wiebe S., Kim S.H., RA Robichaud N., Karam I.F., Dai D., Hackett A.P., Lin R., Alain T., Yang L., RA Jafarnejad S.M., Sonenberg N.; RT "microRNA-induced translational control of antiviral immunity by the cap- RT binding protein 4EHP."; RL Mol. Cell 81:1187.e5-1199.e5(2021). RN [19] RP FUNCTION, FUNCTION (MICROBIAL INFECTION), AND INTERACTION WITH GIGYF2. RX PubMed=35878012; DOI=10.1073/pnas.2204539119; RA Xu Z., Choi J.H., Dai D.L., Luo J., Ladak R.J., Li Q., Wang Y., Zhang C., RA Wiebe S., Liu A.C.H., Ran X., Yang J., Naeli P., Garzia A., Zhou L., RA Mahmood N., Deng Q., Elaish M., Lin R., Mahal L.K., Hobman T.C., RA Pelletier J., Alain T., Vidal S.M., Duchaine T., Mazhab-Jafari M.T., RA Mao X., Jafarnejad S.M., Sonenberg N.; RT "SARS-CoV-2 impairs interferon production via NSP2-induced repression of RT mRNA translation."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2204539119-e2204539119(2022). RN [20] {ECO:0007744|PDB:2JGB, ECO:0007744|PDB:2JGC} RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 45-234 IN COMPLEXES WITH THE MRNA RP CAP ANALOG N7-METHYLGUANOSINE 5'-TRIPHOSPHATE AND EIF4EBP1, INTERACTION RP WITH EIF4EBP1, AND FUNCTION. RX PubMed=17368478; DOI=10.1016/j.jmb.2007.02.019; RA Rosettani P., Knapp S., Vismara M.-G., Rusconi L., Cameron A.D.; RT "Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP- RT bound and unliganded forms."; RL J. Mol. Biol. 368:691-705(2007). CC -!- FUNCTION: Recognizes and binds the 7-methylguanosine-containing mRNA CC cap during an early step in the initiation. Acts as a repressor of CC translation initiation (PubMed:17368478, PubMed:22751931, CC PubMed:25624349, PubMed:33581076, PubMed:9582349). In contrast to CC EIF4E, it is unable to bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), CC suggesting that it acts by competing with EIF4E and block assembly of CC eIF4F at the cap (By similarity). In P-bodies, component of a complex CC that promotes miRNA-mediated translational repression CC (PubMed:28487484). Involved in virus-induced host response by mediating CC miRNA MIR34A-induced translational silencing which controls IFNB1 CC production by a negative feedback mechanism (PubMed:28487484, CC PubMed:33581076). {ECO:0000250|UniProtKB:Q8BMB3, CC ECO:0000269|PubMed:17368478, ECO:0000269|PubMed:22751931, CC ECO:0000269|PubMed:25624349, ECO:0000269|PubMed:28487484, CC ECO:0000269|PubMed:33581076, ECO:0000269|PubMed:9582349}. CC -!- FUNCTION: Component of the 4EHP-GYF2 complex, a multiprotein complex CC that acts as a repressor of translation initiation (PubMed:22751931, CC PubMed:35878012). In association with GIGYF2, assists ribosome- CC associated quality control (RQC) by sequestering the mRNA cap, blocking CC ribosome initiation and decreasing the translational load on CC problematic messages. Part of a pathway that works in parallel to RQC- CC mediated degradation of the stalled nascent polypeptide. GIGYF2 and CC EIF4E2 work downstream and independently of ZNF598, which seems to work CC as a scaffold that can recruit them to faulty mRNA even if alternative CC recruitment mechanisms may exist (PubMed:32726578). CC {ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:32726578, CC ECO:0000269|PubMed:35878012}. CC -!- FUNCTION: (Microbial infection) Upon SARS coronavirus-2/SARS-CoV-2 CC infection, the interaction with non-structural protein 2 (nsp2) with CC GIGYF2 enhances GIGYF2 binding to EIF4E2 and increases repression of CC translation initiation of genes involved in antiviral innate immune CC response such as IFNB1. {ECO:0000269|PubMed:35878012}. CC -!- SUBUNIT: Interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 CC (PubMed:15153109, PubMed:17368478). Does not interact with eIF4G CC (EIF4G1, EIF4G2 or EIF4G3) (By similarity). Component of the 4EHP-GYF2 CC complex, at least composed of EIF4E2, GIGYF2 and ZNF598 CC (PubMed:22751931, PubMed:32726578). Interacts with GIGYF2 (via the CC 4EHP-binding motif); the interaction is direct (PubMed:22751931, CC PubMed:32726578, PubMed:33581076). Interacts with EIF4ENIF1/4E-T (via CC YXXXXLphi motif); increasing affinity for the 7-methylguanosine- CC containing mRNA cap (PubMed:23991149, PubMed:28487484). CC {ECO:0000250|UniProtKB:Q8BMB3, ECO:0000269|PubMed:15153109, CC ECO:0000269|PubMed:17368478, ECO:0000269|PubMed:22751931, CC ECO:0000269|PubMed:23991149, ECO:0000269|PubMed:28487484, CC ECO:0000269|PubMed:32726578, ECO:0000269|PubMed:33581076}. CC -!- INTERACTION: CC O60573; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-398610, EBI-10173507; CC O60573; Q9Y2J4-4: AMOTL2; NbExp=3; IntAct=EBI-398610, EBI-10187270; CC O60573; Q9H257: CARD9; NbExp=3; IntAct=EBI-398610, EBI-751319; CC O60573; Q8NA61: CBY2; NbExp=3; IntAct=EBI-398610, EBI-741724; CC O60573; Q01850: CDR2; NbExp=3; IntAct=EBI-398610, EBI-1181367; CC O60573; Q13541: EIF4EBP1; NbExp=3; IntAct=EBI-398610, EBI-74090; CC O60573; Q9NRA8: EIF4ENIF1; NbExp=7; IntAct=EBI-398610, EBI-301024; CC O60573; Q99814: EPAS1; NbExp=2; IntAct=EBI-398610, EBI-447470; CC O60573; O75420: GIGYF1; NbExp=5; IntAct=EBI-398610, EBI-947774; CC O60573; Q6Y7W6: GIGYF2; NbExp=4; IntAct=EBI-398610, EBI-765394; CC O60573; Q8IX15-3: HOMEZ; NbExp=3; IntAct=EBI-398610, EBI-10172004; CC O60573; P42858: HTT; NbExp=4; IntAct=EBI-398610, EBI-466029; CC O60573; A1A4E9: KRT13; NbExp=3; IntAct=EBI-398610, EBI-10171552; CC O60573; P08727: KRT19; NbExp=3; IntAct=EBI-398610, EBI-742756; CC O60573; Q15323: KRT31; NbExp=3; IntAct=EBI-398610, EBI-948001; CC O60573; Q6A162: KRT40; NbExp=3; IntAct=EBI-398610, EBI-10171697; CC O60573; P60370: KRTAP10-5; NbExp=3; IntAct=EBI-398610, EBI-10172150; CC O60573; P60410: KRTAP10-8; NbExp=3; IntAct=EBI-398610, EBI-10171774; CC O60573; P60411: KRTAP10-9; NbExp=3; IntAct=EBI-398610, EBI-10172052; CC O60573; Q9BRK4: LZTS2; NbExp=3; IntAct=EBI-398610, EBI-741037; CC O60573; Q9Y5V3: MAGED1; NbExp=3; IntAct=EBI-398610, EBI-716006; CC O60573; Q9UPY8: MAPRE3; NbExp=3; IntAct=EBI-398610, EBI-726739; CC O60573; Q8TD10: MIPOL1; NbExp=3; IntAct=EBI-398610, EBI-2548751; CC O60573; P15173: MYOG; NbExp=4; IntAct=EBI-398610, EBI-3906629; CC O60573; Q7Z6G3-2: NECAB2; NbExp=3; IntAct=EBI-398610, EBI-10172876; CC O60573; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-398610, EBI-945833; CC O60573; Q9GZV8: PRDM14; NbExp=3; IntAct=EBI-398610, EBI-3957793; CC O60573; Q04864: REL; NbExp=3; IntAct=EBI-398610, EBI-307352; CC O60573; Q96R06: SPAG5; NbExp=3; IntAct=EBI-398610, EBI-413317; CC O60573; O43597: SPRY2; NbExp=3; IntAct=EBI-398610, EBI-742487; CC O60573; O75478: TADA2A; NbExp=3; IntAct=EBI-398610, EBI-742268; CC O60573; P15884: TCF4; NbExp=3; IntAct=EBI-398610, EBI-533224; CC O60573; Q08117: TLE5; NbExp=3; IntAct=EBI-398610, EBI-717810; CC O60573; P14373: TRIM27; NbExp=3; IntAct=EBI-398610, EBI-719493; CC O60573; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-398610, EBI-2130429; CC O60573; Q5T124: UBXN11; NbExp=3; IntAct=EBI-398610, EBI-746004; CC O60573; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-398610, EBI-739895; CC O60573; Q70EL1: USP54; NbExp=3; IntAct=EBI-398610, EBI-946185; CC O60573; P63104: YWHAZ; NbExp=2; IntAct=EBI-398610, EBI-347088; CC O60573; Q96C00: ZBTB9; NbExp=4; IntAct=EBI-398610, EBI-395708; CC O60573-1; Q13541: EIF4EBP1; NbExp=6; IntAct=EBI-32715389, EBI-74090; CC O60573-1; Q9NRA8: EIF4ENIF1; NbExp=3; IntAct=EBI-32715389, EBI-301024; CC O60573-1; O75420: GIGYF1; NbExp=12; IntAct=EBI-32715389, EBI-947774; CC O60573-1; Q6Y7W6: GIGYF2; NbExp=6; IntAct=EBI-32715389, EBI-765394; CC O60573-1; Q6Y7W6-1: GIGYF2; NbExp=11; IntAct=EBI-32715389, EBI-25762361; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:23991149}. CC Cytoplasm, P-body {ECO:0000269|PubMed:23991149}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O60573-1; Sequence=Displayed; CC Name=2; CC IsoId=O60573-2; Sequence=VSP_054783, VSP_054784; CC -!- PTM: Ubiquitinated by ARIH1 (PubMed:14623119, PubMed:25624349). The CC consequences of ubiquitination are however unclear: according to a CC report, EIF4E2 ubiquitination leads to promote EIF4E2 cap-binding and CC protein translation arrest (PubMed:25624349). According to another CC report ubiquitination leads to its subsequent degradation CC (PubMed:14623119). {ECO:0000269|PubMed:14623119, CC ECO:0000269|PubMed:25624349}. CC -!- PTM: ISGylation enhances its cap structure-binding activity and CC translation-inhibition activity. {ECO:0000269|PubMed:17289916}. CC -!- SIMILARITY: Belongs to the eukaryotic initiation factor 4E family. CC {ECO:0000305}. 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; AF047695; AAC18565.1; -; mRNA. DR EMBL; AF068117; AAC19374.1; -; mRNA. DR EMBL; AF038957; AAC39871.1; -; mRNA. DR EMBL; AC073254; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC092165; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC093383; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471063; EAW71008.1; -; Genomic_DNA. DR EMBL; BC005392; AAH05392.1; -; mRNA. DR EMBL; BC005874; AAH05874.1; -; mRNA. DR EMBL; BC021226; AAH21226.1; -; mRNA. DR EMBL; BC021690; AAH21690.1; -; mRNA. DR CCDS; CCDS2496.1; -. [O60573-1] DR CCDS; CCDS63159.1; -. [O60573-2] DR RefSeq; NP_001263265.1; NM_001276336.2. [O60573-2] DR RefSeq; NP_004837.1; NM_004846.4. [O60573-1] DR PDB; 2JGB; X-ray; 1.70 A; A=45-234. DR PDB; 2JGC; X-ray; 2.40 A; A=45-234. DR PDB; 5NVK; X-ray; 2.90 A; A/C/E/G=52-234. DR PDB; 5NVL; X-ray; 2.30 A; A/C=52-234. DR PDB; 5NVM; X-ray; 2.00 A; A/C=52-234. DR PDB; 5NVN; X-ray; 1.90 A; A/C=52-234. DR PDB; 5XLN; X-ray; 1.90 A; A=45-234. DR PDBsum; 2JGB; -. DR PDBsum; 2JGC; -. DR PDBsum; 5NVK; -. DR PDBsum; 5NVL; -. DR PDBsum; 5NVM; -. DR PDBsum; 5NVN; -. DR PDBsum; 5XLN; -. DR AlphaFoldDB; O60573; -. DR SMR; O60573; -. DR BioGRID; 114856; 269. DR ComplexPortal; CPX-2332; 4EHP-GIGYF2 co-translational mRNA decay complex, ZNF598 variant. DR ComplexPortal; CPX-2336; 4EHP-GIGYF1 co-translational mRNA decay complex, ZNF598 variant. DR ComplexPortal; CPX-2338; 4EHP-GIGYF2 co-translational mRNA decay complex, DDX6 variant. DR ComplexPortal; CPX-2342; 4EHP-GIGYF1 co-translational mRNA decay complex, DDX6 variant. DR CORUM; O60573; -. DR DIP; DIP-32578N; -. DR FunCoup; O60573; 2624. DR IntAct; O60573; 170. DR MINT; O60573; -. DR STRING; 9606.ENSP00000258416; -. DR GlyGen; O60573; 1 site, 1 N-linked glycan (1 site). DR iPTMnet; O60573; -. DR PhosphoSitePlus; O60573; -. DR BioMuta; EIF4E2; -. DR jPOST; O60573; -. DR MassIVE; O60573; -. DR PaxDb; 9606-ENSP00000258416; -. DR PeptideAtlas; O60573; -. DR ProteomicsDB; 49475; -. [O60573-1] DR ProteomicsDB; 7393; -. DR Pumba; O60573; -. DR Antibodypedia; 20222; 435 antibodies from 31 providers. DR DNASU; 9470; -. DR Ensembl; ENST00000258416.8; ENSP00000258416.3; ENSG00000135930.16. [O60573-1] DR Ensembl; ENST00000409098.5; ENSP00000386996.1; ENSG00000135930.16. [O60573-2] DR GeneID; 9470; -. DR KEGG; hsa:9470; -. DR MANE-Select; ENST00000258416.8; ENSP00000258416.3; NM_004846.4; NP_004837.1. DR UCSC; uc002vtb.3; human. [O60573-1] DR AGR; HGNC:3293; -. DR ClinPGx; PA27720; -. DR CTD; 9470; -. DR DisGeNET; 9470; -. DR GeneCards; EIF4E2; -. DR HGNC; HGNC:3293; EIF4E2. DR HPA; ENSG00000135930; Low tissue specificity. DR MIM; 605895; gene. DR OpenTargets; ENSG00000135930; -. DR VEuPathDB; HostDB:ENSG00000135930; -. DR eggNOG; KOG1669; Eukaryota. DR GeneTree; ENSGT00940000154694; -. DR InParanoid; O60573; -. DR OMA; VWNKTAN; -. DR OrthoDB; 590761at2759; -. DR PAN-GO; O60573; 3 GO annotations based on evolutionary models. DR PhylomeDB; O60573; -. DR PathwayCommons; O60573; -. DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism. DR SignaLink; O60573; -. DR SIGNOR; O60573; -. DR Agora; ENSG00000135930; -. DR BioGRID-ORCS; 9470; 121 hits in 1177 CRISPR screens. DR CD-CODE; 232F8A39; P-body. DR CD-CODE; DEE660B4; Stress granule. DR ChiTaRS; EIF4E2; human. DR EvolutionaryTrace; O60573; -. DR GeneWiki; EIF4E2; -. DR GenomeRNAi; 9470; -. DR Pharos; O60573; Tbio. DR PRO; PR:O60573; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; O60573; protein. DR Bgee; ENSG00000135930; Expressed in monocyte and 195 other cell types or tissues. DR ExpressionAtlas; O60573; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0016281; C:eukaryotic translation initiation factor 4F complex; IBA:GO_Central. DR GO; GO:0000932; C:P-body; IDA:UniProtKB. DR GO; GO:0098808; F:mRNA cap binding; IDA:UniProtKB. DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:UniProt. DR GO; GO:0003723; F:RNA binding; HDA:UniProtKB. DR GO; GO:0000339; F:RNA cap binding; TAS:ProtInc. DR GO; GO:0008135; F:translation factor activity, RNA binding; TAS:ProtInc. DR GO; GO:0003743; F:translation initiation factor activity; IBA:GO_Central. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IDA:UniProtKB. DR GO; GO:0017148; P:negative regulation of translation; IMP:MGI. DR GO; GO:0045947; P:negative regulation of translational initiation; IDA:UniProt. DR GO; GO:0060339; P:negative regulation of type I interferon-mediated signaling pathway; IDA:UniProt. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProt. DR GO; GO:0006413; P:translational initiation; IBA:GO_Central. DR FunFam; 3.30.760.10:FF:000001; Eukaryotic translation initiation factor 4E type 2 isoformX2; 1. DR Gene3D; 3.30.760.10; RNA Cap, Translation Initiation Factor Eif4e; 1. DR IDEAL; IID00342; -. DR InterPro; IPR023398; TIF_eIF4e-like. DR InterPro; IPR001040; TIF_eIF_4E. DR InterPro; IPR019770; TIF_eIF_4E_CS. DR PANTHER; PTHR11960; EUKARYOTIC TRANSLATION INITIATION FACTOR 4E RELATED; 1. DR PANTHER; PTHR11960:SF17; EUKARYOTIC TRANSLATION INITIATION FACTOR 4E TYPE 2; 1. DR Pfam; PF01652; IF4E; 1. DR SUPFAM; SSF55418; eIF4e-like; 1. DR PROSITE; PS00813; IF4E; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; KW Initiation factor; Isopeptide bond; Phosphoprotein; Protein biosynthesis; KW Proteomics identification; Reference proteome; RNA-binding; KW RNA-mediated gene silencing; Translation regulation; Ubl conjugation. FT CHAIN 1..245 FT /note="Eukaryotic translation initiation factor 4E type 2" FT /id="PRO_0000193664" FT REGION 1..52 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 54..57 FT /note="EIF4EBP1/2/3 binding" FT /evidence="ECO:0000269|PubMed:17368478" FT REGION 95..99 FT /note="EIF4EBP1/2/3 binding" FT /evidence="ECO:0000269|PubMed:17368478" FT REGION 150..157 FT /note="EIF4EBP1/2/3 binding" FT /evidence="ECO:0000269|PubMed:17368478" FT COMPBIAS 1..38 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 78..79 FT /ligand="mRNA" FT /ligand_id="ChEBI:CHEBI:33699" FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group" FT /ligand_part_id="ChEBI:CHEBI:74429" FT /ligand_part_note="m7GTP residue in mRNA cap" FT /evidence="ECO:0000250|UniProtKB:P06730" FT BINDING 110 FT /ligand="mRNA" FT /ligand_id="ChEBI:CHEBI:33699" FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group" FT /ligand_part_id="ChEBI:CHEBI:74429" FT /ligand_part_note="m7GTP residue in mRNA cap" FT /evidence="ECO:0000269|PubMed:17368478" FT BINDING 124..125 FT /ligand="mRNA" FT /ligand_id="ChEBI:CHEBI:33699" FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group" FT /ligand_part_id="ChEBI:CHEBI:74429" FT /ligand_part_note="m7GTP residue in mRNA cap" FT /evidence="ECO:0000269|PubMed:17368478" FT BINDING 174..179 FT /ligand="mRNA" FT /ligand_id="ChEBI:CHEBI:33699" FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group" FT /ligand_part_id="ChEBI:CHEBI:74429" FT /ligand_part_note="m7GTP residue in mRNA cap" FT /evidence="ECO:0000269|PubMed:17368478" FT BINDING 222..224 FT /ligand="mRNA" FT /ligand_id="ChEBI:CHEBI:33699" FT /ligand_part="N(7)-methylguanosine 5'-triphosphate group" FT /ligand_part_id="ChEBI:CHEBI:74429" FT /ligand_part_note="m7GTP residue in mRNA cap" FT /evidence="ECO:0000250|UniProtKB:P06730" FT MOD_RES 13 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 134 FT /note="N6-acetyllysine; alternate" FT /evidence="ECO:0007744|PubMed:19608861" FT CROSSLNK 134 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15); alternate" FT /evidence="ECO:0000269|PubMed:17289916" FT CROSSLNK 222 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ISG15)" FT /evidence="ECO:0000269|PubMed:17289916" FT VAR_SEQ 223..234 FT /note="MPGRLGPQRLLF -> DNSSFRNTKITL (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_054783" FT VAR_SEQ 235..245 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_054784" FT MUTAGEN 63 FT /note="W->A: Unable to bind capped mRNA." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 95 FT /note="W->A: Ability to bind capped mRNA reduced to 40% of FT wild-type." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 121 FT /note="K->R: Does not affect ubiquitination by ARIH1; when FT associated with R-130; R-134 and R-222." FT /evidence="ECO:0000269|PubMed:25624349" FT MUTAGEN 124..126 FT /note="WED->FAA: Unable to bind capped mRNA." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 124 FT /note="W->A: Ability to bind capped mRNA reduced to less FT than 10% of wild-type." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 124 FT /note="W->F: Ability to bind capped mRNA reduced to 13% of FT wild-type." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 125 FT /note="E->A: Ability to bind capped mRNA reduced to less FT than 10% of wild-type." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 126 FT /note="D->A: Slight reduction in ability to bind capped FT mRNA." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 130 FT /note="K->R: Does not affect ubiquitination by ARIH1; when FT associated with R-121; R-134 and R-222." FT /evidence="ECO:0000269|PubMed:25624349" FT MUTAGEN 134 FT /note="K->R: Does not affect ubiquitination by ARIH1; when FT associated with R-121; R-130 and R-222." FT /evidence="ECO:0000269|PubMed:25624349" FT MUTAGEN 135 FT /note="W->A: Unable to bind capped mRNA." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 148 FT /note="W->A: Unable to bind capped mRNA." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 183 FT /note="W->A: Ability to bind capped mRNA reduced to less FT than 10% of wild-type." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 183 FT /note="W->F: Unable to bind capped mRNA." FT /evidence="ECO:0000269|PubMed:9582349" FT MUTAGEN 222 FT /note="K->R: Does not affect ubiquitination by ARIH1; when FT associated with R-121; R-130 and R-134." FT /evidence="ECO:0000269|PubMed:25624349" FT CONFLICT 1..27 FT /note="MNNKFDALKDDDSGDHDQNEENSTQKD -> MMTVGTMIRMKKTAHRKI FT (in Ref. 3; AAC39871)" FT /evidence="ECO:0000305" FT STRAND 55..67 FT /evidence="ECO:0007829|PDB:2JGB" FT HELIX 75..81 FT /evidence="ECO:0007829|PDB:2JGB" FT STRAND 82..90 FT /evidence="ECO:0007829|PDB:2JGB" FT HELIX 91..98 FT /evidence="ECO:0007829|PDB:2JGB" FT HELIX 104..106 FT /evidence="ECO:0007829|PDB:2JGB" FT STRAND 109..117 FT /evidence="ECO:0007829|PDB:2JGB" FT TURN 127..131 FT /evidence="ECO:0007829|PDB:2JGB" FT STRAND 133..139 FT /evidence="ECO:0007829|PDB:2JGB" FT HELIX 144..156 FT /evidence="ECO:0007829|PDB:2JGB" FT TURN 157..160 FT /evidence="ECO:0007829|PDB:5XLN" FT STRAND 166..173 FT /evidence="ECO:0007829|PDB:2JGB" FT STRAND 178..185 FT /evidence="ECO:0007829|PDB:2JGB" FT HELIX 190..203 FT /evidence="ECO:0007829|PDB:2JGB" FT STRAND 212..216 FT /evidence="ECO:0007829|PDB:2JGB" FT HELIX 217..222 FT /evidence="ECO:0007829|PDB:2JGB" SQ SEQUENCE 245 AA; 28362 MW; 3D3075BFA48B3C12 CRC64; MNNKFDALKD DDSGDHDQNE ENSTQKDGEK EKTERDKNQS SSKRKAVVPG PAEHPLQYNY TFWYSRRTPG RPTSSQSYEQ NIKQIGTFAS VEQFWRFYSH MVRPGDLTGH SDFHLFKEGI KPMWEDDANK NGGKWIIRLR KGLASRCWEN LILAMLGEQF MVGEEICGAV VSVRFQEDII SIWNKTASDQ ATTARIRDTL RRVLNLPPNT IMEYKTHTDS IKMPGRLGPQ RLLFQNLWKP RLNVP //