IF4E2_HUMAN
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 03-AUG-2022, entry version 185.
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] {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 (PubMed:17368478,
CC PubMed:25624349, PubMed:9582349). Acts as a repressor of translation
CC initiation (PubMed:22751931). In contrast to EIF4E, it is unable to
CC bind eIF4G (EIF4G1, EIF4G2 or EIF4G3), suggesting that it acts by
CC competing with EIF4E and block assembly of eIF4F at the cap (By
CC similarity). In P-bodies, component of a complex that promotes miRNA-
CC mediated translational repression (PubMed:28487484).
CC {ECO:0000250|UniProtKB:Q8BMB3, ECO:0000269|PubMed:17368478,
CC ECO:0000269|PubMed:22751931, ECO:0000269|PubMed:25624349,
CC ECO:0000269|PubMed:28487484, ECO:0000269|PubMed:9582349}.
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). Interacts with GIGYF2 (via the 4EHP-binding motif);
CC the interaction is direct (PubMed:22751931). Interacts with
CC EIF4ENIF1/4E-T (via YXXXXLphi motif); increasing affinity for the 7-
CC methylguanosine-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 -!- 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; Q9NRA8: EIF4ENIF1; NbExp=4; IntAct=EBI-398610, EBI-301024;
CC O60573; Q99814: EPAS1; NbExp=2; IntAct=EBI-398610, EBI-447470;
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; Q96C00: ZBTB9; NbExp=4; IntAct=EBI-398610, EBI-395708;
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}.
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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_001276336.1. [O60573-2]
DR RefSeq; NP_004837.1; NM_004846.3. [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; 235.
DR DIP; DIP-32578N; -.
DR IntAct; O60573; 80.
DR MINT; O60573; -.
DR STRING; 9606.ENSP00000258416; -.
DR iPTMnet; O60573; -.
DR PhosphoSitePlus; O60573; -.
DR BioMuta; EIF4E2; -.
DR EPD; O60573; -.
DR jPOST; O60573; -.
DR MassIVE; O60573; -.
DR MaxQB; O60573; -.
DR PaxDb; O60573; -.
DR PeptideAtlas; O60573; -.
DR PRIDE; O60573; -.
DR ProteomicsDB; 49475; -. [O60573-1]
DR ProteomicsDB; 7393; -.
DR Antibodypedia; 20222; 431 antibodies from 30 providers.
DR DNASU; 9470; -.
DR Ensembl; ENST00000258416.8; ENSP00000258416.3; ENSG00000135930.15. [O60573-1]
DR Ensembl; ENST00000409098.5; ENSP00000386996.1; ENSG00000135930.15. [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 CTD; 9470; -.
DR DisGeNET; 9470; -.
DR GeneCards; EIF4E2; -.
DR HGNC; HGNC:3293; EIF4E2.
DR HPA; ENSG00000135930; Low tissue specificity.
DR MIM; 605895; gene.
DR neXtProt; NX_O60573; -.
DR OpenTargets; ENSG00000135930; -.
DR PharmGKB; PA27720; -.
DR VEuPathDB; HostDB:ENSG00000135930; -.
DR eggNOG; KOG1669; Eukaryota.
DR GeneTree; ENSGT00940000154694; -.
DR InParanoid; O60573; -.
DR OMA; ANCHGGK; -.
DR PhylomeDB; O60573; -.
DR TreeFam; TF101529; -.
DR PathwayCommons; O60573; -.
DR Reactome; R-HSA-1169408; ISG15 antiviral mechanism.
DR SignaLink; O60573; -.
DR SIGNOR; O60573; -.
DR BioGRID-ORCS; 9470; 116 hits in 1095 CRISPR screens.
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 193 other tissues.
DR ExpressionAtlas; O60573; baseline and differential.
DR Genevisible; O60573; HS.
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:0005845; C:mRNA cap binding complex; IDA:UniProtKB.
DR GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IBA:GO_Central.
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 Gene3D; 3.30.760.10; -; 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; PTHR11960; 1.
DR Pfam; PF01652; IF4E; 1.
DR SUPFAM; SSF55418; SSF55418; 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 Reference proteome; RNA-binding; RNA-mediated gene silencing;
KW 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..42
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
