ID IF4E2_HUMAN Reviewed; 245 AA. AC O60573; O75349; DT 11-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 25-JAN-2012, entry version 102. DE RecName: Full=Eukaryotic translation initiation factor 4E type 2; DE Short=eIF-4E type 2; DE Short=eIF4E type 2; 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; DE AltName: Full=mRNA cap-binding protein 4EHP; DE AltName: Full=mRNA cap-binding protein type 3; GN Name=EIF4E2; Synonyms=EIF4EL3; 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], CHARACTERIZATION, 3D-STRUCTURE MODELING, RP AND MUTAGENESIS. RC TISSUE=Follicular cell; RX MEDLINE=98250763; 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 RT cap-binding protein."; RL J. Biol. Chem. 273:13104-13109(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], AND INTERACTION WITH EIF4EBP1; EIF4EBP2 RP 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]. RC TISSUE=Umbilical cord blood; RX MEDLINE=98318631; 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- RT length cDNA cloning."; RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] 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., RA 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 [6] RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-134, 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). RN [7] 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 [8] RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 45-234 IN COMPLEX WITH MRNA RP CAP ANALOGS AND EIF4EBP1. 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 RT m7GTP-bound and unliganded forms."; RL J. Mol. Biol. 368:691-705(2007). CC -!- FUNCTION: Recognizes and binds the 7-methylguanosine-containing CC mRNA cap during an early step in the initiation of protein CC synthesis and facilitates ribosome binding by inducing the CC unwinding of the mRNAs secondary structures. CC -!- SUBUNIT: eIF4F is a multi-subunit complex, the composition of CC which varies with external and internal environmental conditions. CC It is composed of at least eIF4A, eIF4E and eIF4G. eIF4E is also CC known to interact with other partners (By similarity). EIF4E2 CC interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 but not with eIF4G. CC -!- INTERACTION: CC Q9NRA8:EIF4ENIF1; NbExp=3; IntAct=EBI-398610, EBI-301024; CC -!- PTM: Ubiquitinated by ARIH1, leading to its degradation by the CC proteasome. CC -!- SIMILARITY: Belongs to the eukaryotic initiation factor 4E family. 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; AF047695; AAC18565.1; -; mRNA. DR EMBL; AF068117; AAC19374.1; -; mRNA. DR EMBL; AF038957; AAC39871.1; -; mRNA. 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 IPI; IPI00744211; -. DR RefSeq; NP_004837.1; NM_004846.2. DR UniGene; Hs.292026; -. DR UniGene; Hs.700929; -. DR PDB; 2JGB; X-ray; 1.70 A; A=45-234. DR PDB; 2JGC; X-ray; 2.40 A; A=45-234. DR PDBsum; 2JGB; -. DR PDBsum; 2JGC; -. DR ProteinModelPortal; O60573; -. DR SMR; O60573; 45-234. DR IntAct; O60573; 11. DR MINT; MINT-1440115; -. DR STRING; O60573; -. DR PhosphoSite; O60573; -. DR PRIDE; O60573; -. DR Ensembl; ENST00000258416; ENSP00000258416; ENSG00000135930. DR GeneID; 9470; -. DR KEGG; hsa:9470; -. DR UCSC; uc002vta.1; human. DR CTD; 9470; -. DR GeneCards; GC02P233414; -. DR H-InvDB; HIX0002926; -. DR HGNC; HGNC:3293; EIF4E2. DR HPA; HPA019253; -. DR MIM; 605895; gene. DR neXtProt; NX_O60573; -. DR PharmGKB; PA27720; -. DR eggNOG; prNOG08839; -. DR HOGENOM; HBG559144; -. DR HOVERGEN; HBG107087; -. DR InParanoid; O60573; -. DR OMA; LWKPRLN; -. DR OrthoDB; EOG4K0QPD; -. DR PhylomeDB; O60573; -. DR NextBio; 35490; -. DR ArrayExpress; O60573; -. DR Bgee; O60573; -. DR CleanEx; HS_EIF4E2; -. DR Genevestigator; O60573; -. DR GermOnline; ENSG00000135930; Homo sapiens. DR GO; GO:0005737; C:cytoplasm; IEA:InterPro. DR GO; GO:0005845; C:mRNA cap binding complex; IDA:UniProtKB. DR GO; GO:0000339; F:RNA cap binding; TAS:ProtInc. DR GO; GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-KW. DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB. DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW. DR InterPro; IPR023398; TIF_eIF4e-like_dom. DR InterPro; IPR001040; TIF_eIF_4E. DR InterPro; IPR019770; TIF_eIF_4E_CS. DR Gene3D; G3DSA:3.30.760.10; TIF_eIF_4E; 1. DR KO; K03259; -. DR PANTHER; PTHR11960; TIF_eIF_4E; 1. DR Pfam; PF01652; IF4E; 1. DR SUPFAM; SSF55418; TIF_eIF_4E; 1. DR PROSITE; PS00813; IF4E; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Complete proteome; Initiation factor; KW Protein biosynthesis; Reference proteome; RNA-binding; KW Translation regulation; Ubl conjugation. FT CHAIN 1 245 Eukaryotic translation initiation factor FT 4E type 2. FT /FTId=PRO_0000193664. FT REGION 54 57 EIF4EBP1/2/3 binding. FT REGION 78 79 7-methylguanosine-containing mRNA cap FT binding (By similarity). FT REGION 95 99 EIF4EBP1/2/3 binding. FT REGION 124 125 7-methylguanosine-containing mRNA cap FT binding. FT REGION 150 157 EIF4EBP1/2/3 binding. FT REGION 174 179 7-methylguanosine-containing mRNA cap FT binding. FT REGION 222 224 7-methylguanosine-containing mRNA cap FT binding (By similarity). FT BINDING 110 110 7-methylguanosine-containing mRNA cap. FT MOD_RES 134 134 N6-acetyllysine. FT MUTAGEN 63 63 W->A: Unable to bind capped mRNA. FT MUTAGEN 95 95 W->A: Ability to bind capped mRNA reduced FT to 40% of wild-type. FT MUTAGEN 124 126 WED->FAA: Unable to bind capped mRNA. FT MUTAGEN 124 124 W->A: Ability to bind capped mRNA reduced FT to less than 10% of wild-type. FT MUTAGEN 124 124 W->F: Ability to bind capped mRNA reduced FT to 13% of wild-type. FT MUTAGEN 125 125 E->A: Ability to bind capped mRNA reduced FT to less than 10% of wild-type. FT MUTAGEN 126 126 D->A: Slight reduction in ability to bind FT capped mRNA. FT MUTAGEN 135 135 W->A: Unable to bind capped mRNA. FT MUTAGEN 148 148 W->A: Unable to bind capped mRNA. FT MUTAGEN 183 183 W->A: Ability to bind capped mRNA reduced FT to less than 10% of wild-type. FT MUTAGEN 183 183 W->F: Unable to bind capped mRNA. FT CONFLICT 1 27 MNNKFDALKDDDSGDHDQNEENSTQKD -> MMTVGTMIRM FT KKTAHRKI (in Ref. 3; AAC39871). FT STRAND 55 67 FT HELIX 75 81 FT STRAND 82 90 FT HELIX 91 98 FT HELIX 104 106 FT STRAND 109 117 FT TURN 127 131 FT STRAND 133 139 FT HELIX 144 156 FT STRAND 166 173 FT STRAND 178 185 FT HELIX 190 203 FT STRAND 212 216 FT HELIX 217 222 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 //