IF4E3_CAEEL
ID IF4E3_CAEEL Reviewed; 251 AA.
AC O61955; Q8MNX5; Q95X31;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 2.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Eukaryotic translation initiation factor 4E-3;
DE Short=eIF-4E-3;
DE Short=eIF4E-3;
DE AltName: Full=eIF-4F 25 kDa subunit;
DE AltName: Full=mRNA cap-binding protein;
GN Name=ife-3 {ECO:0000312|WormBase:B0348.6b};
GN ORFNames=B0348.6 {ECO:0000312|WormBase:B0348.6b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=9553113; DOI=10.1074/jbc.273.17.10538;
RA Jankowska-Anyszka M., Lamphear B.J., Aamodt E.J., Harrington T.,
RA Darzynkiewicz E., Stolarski R., Rhoads R.E.;
RT "Multiple isoforms of eukaryotic protein synthesis initiation factor 4E in
RT Caenorhabditis elegans can distinguish between mono- and trimethylated mRNA
RT cap structures.";
RL J. Biol. Chem. 273:10538-10542(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=10744754; DOI=10.1074/jbc.275.14.10590;
RA Keiper B.D., Lamphear B.J., Deshpande A.M., Jankowska-Anyszka M.,
RA Aamodt E.J., Blumenthal T., Rhoads R.E.;
RT "Functional characterization of five eIF4E isoforms in Caenorhabditis
RT elegans.";
RL J. Biol. Chem. 275:10590-10596(2000).
RN [4]
RP TISSUE SPECIFICITY.
RC STRAIN=Bristol N2;
RX PubMed=11641215; DOI=10.1242/dev.128.20.3899;
RA Amiri A., Keiper B.D., Kawasaki I., Fan Y., Kohara Y., Rhoads R.E.,
RA Strome S.;
RT "An isoform of eIF4E is a component of germ granules and is required for
RT spermatogenesis in C. elegans.";
RL Development 128:3899-3912(2001).
RN [5]
RP FUNCTION.
RX PubMed=12422237;
RA Stachelska A., Wieczorek Z., Ruszczynska K., Stolarski R., Pietrzak M.,
RA Lamphear B.J., Rhoads R.E., Darzynkiewicz E., Jankowska-Anyszka M.;
RT "Interaction of three Caenorhabditis elegans isoforms of translation
RT initiation factor eIF4E with mono- and trimethylated mRNA 5' cap
RT analogues.";
RL Acta Biochim. Pol. 49:671-682(2002).
RN [6]
RP FUNCTION, IDENTIFICATION IN THE PETISCO COMPLEXES, INTERACTION WITH TOFU-6,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=31216475; DOI=10.1016/j.celrep.2019.05.076;
RA Zeng C., Weng C., Wang X., Yan Y.H., Li W.J., Xu D., Hong M., Liao S.,
RA Dong M.Q., Feng X., Xu C., Guang S.;
RT "Functional Proteomics Identifies a PICS Complex Required for piRNA
RT Maturation and Chromosome Segregation.";
RL Cell Rep. 27:3561-3572(2019).
RN [7]
RP FUNCTION, IDENTIFICATION IN THE PETISCO COMPLEXES, INTERACTION WITH TOFU-6,
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND
RP DISRUPTION PHENOTYPE.
RX PubMed=31147388; DOI=10.1101/gad.322446.118;
RA Cordeiro Rodrigues R.J., de Jesus Domingues A.M., Hellmann S., Dietz S.,
RA de Albuquerque B.F.M., Renz C., Ulrich H.D., Sarkies P., Butter F.,
RA Ketting R.F.;
RT "PETISCO is a novel protein complex required for 21U RNA biogenesis and
RT embryonic viability.";
RL Genes Dev. 33:857-870(2019).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 30-215 IN COMPLEX WITH MXT,
RP INTERACTION WITH MXT, AND MUTAGENESIS OF VAL-58 AND ILE-74.
RX PubMed=26294658; DOI=10.1101/gad.269068.115;
RA Peter D., Weber R., Kone C., Chung M.Y., Ebertsch L., Truffault V.,
RA Weichenrieder O., Igreja C., Izaurralde E.;
RT "Mextli proteins use both canonical bipartite and novel tripartite binding
RT modes to form eIF4E complexes that display differential sensitivity to 4E-
RT BP regulation.";
RL Genes Dev. 29:1835-1849(2015).
CC -!- FUNCTION: Recognizes and binds the 7-methylguanosine-containing mRNA
CC cap during an early step in the initiation of protein synthesis and
CC facilitates ribosome binding by inducing the unwinding of the mRNAs
CC secondary structures. All 5 eIF4E proteins bind monomethyl cap
CC structures. Only ife-1, ife-2 and ife-5 bind trimethyl cap structures
CC which result from trans-splicing. Translation of trimethyl cap
CC structure mRNAs may be regulated by intracellular redox state;
CC disulfide bonds change the width and depth of the cap-binding cavity
CC determining selectivity to mRNA caps. Ife-3 is essential for viability.
CC Component of the pid-1 and tost-1 variants of the PETISCO complexes,
CC which have roles in the biogenesis of a class of 21 nucleotide PIWI-
CC interacting RNAs (piRNAs) that possess a uracil residue at the 5'-end
CC (also called 21U-RNAs) and embryogenesis, respectively
CC (PubMed:31147388, PubMed:31216475). Within the pid-1 variant of the
CC PETISCO complex binds to capped 21U-RNA precursor molecules, possibly
CC playing a role in the processing of the 5' end of the molecules to
CC promote binding of other complex components such as pid-3
CC (PubMed:31147388). However, it is not essential for the biogenesis of
CC 21U-RNAs by itself (PubMed:31147388). Within the tost-1 variant of the
CC PETISCO complex binds to splice leader SL1 RNA fragments to possibly
CC play a role in their processing (PubMed:31147388).
CC {ECO:0000269|PubMed:10744754, ECO:0000269|PubMed:12422237,
CC ECO:0000269|PubMed:31147388, ECO:0000269|PubMed:9553113,
CC ECO:0000305|PubMed:31216475}.
CC -!- SUBUNIT: eIF4F is a multi-subunit complex, the composition of which
CC varies with external and internal environmental conditions. It is
CC composed of at least eIF4A, eIF4E and eIF4G. eIF4E is also known to
CC interact with other partners. Interacts with mxt (PubMed:26294658).
CC Component of the pid-1 variant of the PETISCO complex (also called the
CC pid-3, erh-2, tofu-6, and ife-3 small RNA complex) containing at least
CC pid-1, tofu-6, ife-3, pid-3, and erh-2, which is required for the
CC biogenesis of a class of 21 nucleotide PIWI-interacting RNAs (piRNAs)
CC that possess a uracil residue at the 5'-end (also called 21U-RNAs)
CC (PubMed:31147388, PubMed:31216475). Component of the tost-1 variant of
CC the PETISCO complex (also called the pid-3, erh-2, tofu-6, and ife-3
CC small RNA complex) containing at least tost-1, tofu-6, ife-3, pid-3,
CC and erh-2, which plays an essential role in embryogenesis
CC (PubMed:31147388, PubMed:31216475). Within the pid-1 and tost-1
CC variants of the PETISCO complexes interacts with tofu-6 (via C-
CC terminus) (PubMed:31216475, PubMed:31147388). In contrast to the pid-1
CC variant of the PETISCO complex, the tost-1 variant of the PETISCO
CC complex plays a minor role in the biogenesis of 21U-RNAs
CC (PubMed:31147388). {ECO:0000269|PubMed:26294658,
CC ECO:0000269|PubMed:31147388, ECO:0000269|PubMed:31216475,
CC ECO:0000305|PubMed:31216475}.
CC -!- INTERACTION:
CC O61955; Q22497: CELE_T14G10.8; NbExp=5; IntAct=EBI-330119, EBI-2411746;
CC O61955; Q20898: ifet-1; NbExp=3; IntAct=EBI-330119, EBI-2001916;
CC O61955; Q9XW13: mxt-1; NbExp=5; IntAct=EBI-330119, EBI-330111;
CC O61955; Q09293: tofu-6; NbExp=5; IntAct=EBI-330119, EBI-2001908;
CC -!- SUBCELLULAR LOCATION: Cytoplasmic granule
CC {ECO:0000269|PubMed:31147388}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:31147388, ECO:0000269|PubMed:31216475}.
CC Note=Localizes to cytoplasmic granules in early embryos
CC (PubMed:31147388). Localizes to puncta in the perinuclear region in the
CC germline syncytium (PubMed:31216475, PubMed:31147388).
CC {ECO:0000269|PubMed:31147388, ECO:0000269|PubMed:31216475}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=b {ECO:0000312|WormBase:B0348.6b};
CC IsoId=O61955-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:B0348.6a};
CC IsoId=O61955-2; Sequence=VSP_008297;
CC Name=c {ECO:0000312|WormBase:B0348.6c};
CC IsoId=O61955-3; Sequence=VSP_008298;
CC -!- TISSUE SPECIFICITY: Highly expressed in the germline (at protein
CC level). {ECO:0000269|PubMed:11641215, ECO:0000269|PubMed:31147388,
CC ECO:0000269|PubMed:31216475}.
CC -!- DEVELOPMENTAL STAGE: Expressed from early embryogenesis (at protein
CC level). {ECO:0000269|PubMed:31147388}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in maternal
CC effect lethal (Mel phenotype) and masculinization of the germline (Mog
CC phenotype) phenotypes (PubMed:31147388). RNAi-mediated knockdown
CC results in defective activity of the PIWI-interacting RNA (piRNA)
CC silencing pathway (PubMed:31147388). {ECO:0000269|PubMed:31147388}.
CC -!- MISCELLANEOUS: Inactivation of ife-3 results in 100% embryonic
CC lethality.
CC -!- SIMILARITY: Belongs to the eukaryotic initiation factor 4E family.
CC {ECO:0000305}.
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DR EMBL; BX284605; CCD61786.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD61787.1; -; Genomic_DNA.
DR EMBL; BX284605; CCD61788.1; -; Genomic_DNA.
DR PIR; T33281; T33281.
DR RefSeq; NP_503123.1; NM_070722.3. [O61955-1]
DR RefSeq; NP_503124.1; NM_070723.6. [O61955-2]
DR RefSeq; NP_741502.1; NM_171920.3. [O61955-3]
DR PDB; 5ABX; X-ray; 1.66 A; A=30-215.
DR PDB; 5ABY; X-ray; 1.95 A; A/C/E=30-215.
DR PDBsum; 5ABX; -.
DR PDBsum; 5ABY; -.
DR AlphaFoldDB; O61955; -.
DR SMR; O61955; -.
DR BioGRID; 43611; 26.
DR ComplexPortal; CPX-3482; Eukaryotic translation initiation factor 4E-Mxt complex.
DR ComplexPortal; CPX-4306; PETISCO, pid-1 variant.
DR ComplexPortal; CPX-4307; PETISCO, tost-1 variant.
DR DIP; DIP-24919N; -.
DR IntAct; O61955; 21.
DR STRING; 6239.B0348.6b.1; -.
DR iPTMnet; O61955; -.
DR EPD; O61955; -.
DR PaxDb; O61955; -.
DR PeptideAtlas; O61955; -.
DR EnsemblMetazoa; B0348.6a.1; B0348.6a.1; WBGene00002061. [O61955-2]
DR EnsemblMetazoa; B0348.6b.1; B0348.6b.1; WBGene00002061. [O61955-1]
DR EnsemblMetazoa; B0348.6c.1; B0348.6c.1; WBGene00002061. [O61955-3]
DR GeneID; 178536; -.
DR KEGG; cel:CELE_B0348.6; -.
DR UCSC; B0348.6a.2; c. elegans. [O61955-1]
DR CTD; 178536; -.
DR WormBase; B0348.6a; CE17331; WBGene00002061; ife-3. [O61955-2]
DR WormBase; B0348.6b; CE27570; WBGene00002061; ife-3. [O61955-1]
DR WormBase; B0348.6c; CE30590; WBGene00002061; ife-3. [O61955-3]
DR eggNOG; KOG1670; Eukaryota.
DR GeneTree; ENSGT00940000166192; -.
DR InParanoid; O61955; -.
DR OMA; VKPRICL; -.
DR OrthoDB; 1394271at2759; -.
DR PhylomeDB; O61955; -.
DR Reactome; R-CEL-1169408; ISG15 antiviral mechanism.
DR Reactome; R-CEL-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-CEL-159227; Transport of the SLBP independent Mature mRNA.
DR Reactome; R-CEL-159230; Transport of the SLBP Dependant Mature mRNA.
DR Reactome; R-CEL-159231; Transport of Mature mRNA Derived from an Intronless Transcript.
DR Reactome; R-CEL-72662; Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
DR Reactome; R-CEL-72702; Ribosomal scanning and start codon recognition.
DR PRO; PR:O61955; -.
DR Proteomes; UP000001940; Chromosome V.
DR Bgee; WBGene00002061; Expressed in adult organism and 4 other tissues.
DR GO; GO:0016281; C:eukaryotic translation initiation factor 4F complex; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0034518; C:RNA cap binding complex; IPI:ComplexPortal.
DR GO; GO:0070992; C:translation initiation complex; IC:ComplexPortal.
DR GO; GO:0000340; F:RNA 7-methylguanosine cap binding; IDA:WormBase.
DR GO; GO:0003743; F:translation initiation factor activity; IBA:GO_Central.
DR GO; GO:0034585; P:21U-RNA metabolic process; IC:ComplexPortal.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0031047; P:gene silencing by RNA; IEA:UniProtKB-KW.
DR GO; GO:0006413; P:translational initiation; IC:ComplexPortal.
DR Gene3D; 3.30.760.10; -; 1.
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; Alternative splicing; Cytoplasm; Initiation factor;
KW Protein biosynthesis; Reference proteome; RNA-binding;
KW RNA-mediated gene silencing; Translation regulation.
FT CHAIN 1..251
FT /note="Eukaryotic translation initiation factor 4E-3"
FT /id="PRO_0000193645"
FT REGION 200..251
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 229..251
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 115..117
FT /note="Missing (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_008297"
FT VAR_SEQ 116
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_008298"
FT MUTAGEN 58
FT /note="V->A: Abolishes interaction with mxt; when
FT associated with A-74."
FT /evidence="ECO:0000269|PubMed:26294658"
FT MUTAGEN 74
FT /note="I->A: Abolishes interaction with mxt; when
FT associated with A-74."
FT /evidence="ECO:0000269|PubMed:26294658"
FT STRAND 33..43
FT /evidence="ECO:0007829|PDB:5ABX"
FT HELIX 51..54
FT /evidence="ECO:0007829|PDB:5ABX"
FT STRAND 55..63
FT /evidence="ECO:0007829|PDB:5ABX"
FT HELIX 64..72
FT /evidence="ECO:0007829|PDB:5ABX"
FT HELIX 77..79
FT /evidence="ECO:0007829|PDB:5ABX"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:5ABX"
FT TURN 100..104
FT /evidence="ECO:0007829|PDB:5ABX"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:5ABX"
FT HELIX 122..136
FT /evidence="ECO:0007829|PDB:5ABX"
FT HELIX 141..146
FT /evidence="ECO:0007829|PDB:5ABX"
FT STRAND 147..153
FT /evidence="ECO:0007829|PDB:5ABX"
FT STRAND 159..166
FT /evidence="ECO:0007829|PDB:5ABX"
FT HELIX 171..185
FT /evidence="ECO:0007829|PDB:5ABX"
FT STRAND 193..197
FT /evidence="ECO:0007829|PDB:5ABX"
FT HELIX 198..202
FT /evidence="ECO:0007829|PDB:5ABX"
FT STRAND 212..215
FT /evidence="ECO:0007829|PDB:5ABX"
SQ SEQUENCE 251 AA; 28179 MW; EF78008417099EE7 CRC64;
MSTSVAENKA LSASGDVNAS DASVPPELLT RHPLQNRWAL WYLKADRNKE WEDCLKMVSL
FDTVEDFWSL YNHIQSAGGL NWGSDYYLFK EGIKPMWEDV NNVQGGRWLV VVDKQKLQRR
TQLLDHYWLE LLMAIVGEQF DEYGDYICGA VVNVRQKGDK VSLWTRDATR DDVNLRIGQV
LKQKLSIPDT EILRYEVHKD SSARTSSTVK PRICLPAKDP APVKEKGPAA TTSPSNPGTE
ATGTSPATPT P
