4EBP1_RAT
ID 4EBP1_RAT Reviewed; 117 AA.
AC Q62622;
DT 19-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=Eukaryotic translation initiation factor 4E-binding protein 1;
DE Short=4E-BP1;
DE Short=eIF4E-binding protein 1;
DE AltName: Full=Phosphorylated heat- and acid-stable protein regulated by insulin 1;
DE Short=PHAS-I;
GN Name=Eif4ebp1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116 {ECO:0000312|EMBL:AAA86938.1};
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-33; 43-53; 62-80 AND
RP 98-117, PHOSPHORYLATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley {ECO:0000269|PubMed:8170978};
RC TISSUE=Adipocyte {ECO:0000269|PubMed:8170978}, and
RC Skeletal muscle {ECO:0000312|EMBL:AAA86938.1};
RX PubMed=8170978; DOI=10.1073/pnas.91.9.3730;
RA Hu C., Pang S., Kong X., Velleca M., Lawrence J.C. Jr.;
RT "Molecular cloning and tissue distribution of PHAS-I, an intracellular
RT target for insulin and growth factors.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:3730-3734(1994).
RN [2]
RP FUNCTION, INTERACTION WITH EIF4E, PHOSPHORYLATION AT SER-64 BY MAPK1 AND
RP MAPK3, AND MUTAGENESIS OF SER-64.
RX PubMed=7939721; DOI=10.1126/science.7939721;
RA Lin T.-A., Kong X., Haystead T.A.J., Pause A., Belsham G.J., Sonenberg N.,
RA Lawrence J.C. Jr.;
RT "PHAS-I as a link between mitogen-activated protein kinase and translation
RT initiation.";
RL Science 266:653-656(1994).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-36, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Repressor of translation initiation that regulates EIF4E
CC activity by preventing its assembly into the eIF4F complex:
CC hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds
CC to EIF4E, leading to repress translation. In contrast,
CC hyperphosphorylated form dissociates from EIF4E, allowing interaction
CC between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation
CC (By similarity). Mediates the regulation of protein translation by
CC hormones, growth factors and other stimuli that signal through the MAP
CC kinase and mTORC1 pathways (PubMed:7939721).
CC {ECO:0000250|UniProtKB:Q13541, ECO:0000269|PubMed:7939721}.
CC -!- SUBUNIT: Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to
CC interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or
CC mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex
CC allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation
CC (PubMed:7939721). Interacts (via TOS motif) with RPTOR; promoting
CC phosphorylation by mTORC1 (By similarity).
CC {ECO:0000250|UniProtKB:Q13541, ECO:0000269|PubMed:7939721}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined; highest levels
CC in fat and skeletal tissue, lowest levels in kidney.
CC {ECO:0000269|PubMed:7939721, ECO:0000269|PubMed:8170978}.
CC -!- DOMAIN: The TOS motif mediates interaction with RPTOR, leading to
CC promote phosphorylation by mTORC1 complex.
CC {ECO:0000250|UniProtKB:Q13541}.
CC -!- PTM: Phosphorylated on serine and threonine residues in response to
CC insulin, EGF and PDGF. Phosphorylation at Thr-36, Thr-45, Ser-64 and
CC Thr-69, corresponding to the hyperphosphorylated form, is regulated by
CC mTORC1 and abolishes binding to EIF4E. {ECO:0000269|PubMed:7939721,
CC ECO:0000269|PubMed:8170978}.
CC -!- PTM: Ubiquitinated: when eIF4E levels are low, hypophosphorylated form
CC is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation
CC and serving as a homeostatic mechanism to maintain translation and
CC prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated
CC when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or
CC associated with eIF4E. {ECO:0000250|UniProtKB:Q13541}.
CC -!- SIMILARITY: Belongs to the eIF4E-binding protein family. {ECO:0000305}.
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DR EMBL; U05014; AAA86938.1; -; mRNA.
DR PIR; A55258; A55258.
DR RefSeq; NP_446309.1; NM_053857.2.
DR AlphaFoldDB; Q62622; -.
DR SMR; Q62622; -.
DR BioGRID; 250521; 6.
DR DIP; DIP-267N; -.
DR ELM; Q62622; -.
DR MINT; Q62622; -.
DR STRING; 10116.ENSRNOP00000016885; -.
DR iPTMnet; Q62622; -.
DR PhosphoSitePlus; Q62622; -.
DR PaxDb; Q62622; -.
DR PRIDE; Q62622; -.
DR Ensembl; ENSRNOT00000096679; ENSRNOP00000087155; ENSRNOG00000012582.
DR GeneID; 116636; -.
DR KEGG; rno:116636; -.
DR UCSC; RGD:620259; rat.
DR CTD; 1978; -.
DR RGD; 620259; Eif4ebp1.
DR eggNOG; ENOG502S4SY; Eukaryota.
DR GeneTree; ENSGT00940000159932; -.
DR HOGENOM; CLU_111706_0_0_1; -.
DR InParanoid; Q62622; -.
DR OMA; QMPDVYS; -.
DR OrthoDB; 1597535at2759; -.
DR PhylomeDB; Q62622; -.
DR TreeFam; TF101530; -.
DR Reactome; R-RNO-166208; mTORC1-mediated signalling.
DR Reactome; R-RNO-72662; Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S.
DR PRO; PR:Q62622; -.
DR Proteomes; UP000002494; Chromosome 16.
DR Bgee; ENSRNOG00000012582; Expressed in pancreas and 19 other tissues.
DR Genevisible; Q62622; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005829; C:cytosol; ISS:AgBase.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0099524; C:postsynaptic cytosol; IDA:SynGO.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0008190; F:eukaryotic initiation factor 4E binding; IPI:RGD.
DR GO; GO:0051721; F:protein phosphatase 2A binding; IPI:RGD.
DR GO; GO:0031369; F:translation initiation factor binding; IPI:RGD.
DR GO; GO:0030371; F:translation repressor activity; ISS:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; ISO:RGD.
DR GO; GO:0071456; P:cellular response to hypoxia; IDA:RGD.
DR GO; GO:0000082; P:G1/S transition of mitotic cell cycle; ISO:RGD.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:RGD.
DR GO; GO:0002192; P:IRES-dependent translational initiation of linear mRNA; ISO:RGD.
DR GO; GO:0030324; P:lung development; IEP:RGD.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IMP:RGD.
DR GO; GO:0045947; P:negative regulation of translational initiation; IMP:RGD.
DR GO; GO:0045931; P:positive regulation of mitotic cell cycle; ISO:RGD.
DR GO; GO:1990928; P:response to amino acid starvation; IDA:RGD.
DR GO; GO:0045471; P:response to ethanol; IEP:RGD.
DR GO; GO:0002931; P:response to ischemia; IEP:RGD.
DR GO; GO:0031929; P:TOR signaling; ISS:UniProtKB.
DR InterPro; IPR008606; EIF4EBP.
DR InterPro; IPR037582; EIF4EBP1.
DR PANTHER; PTHR12669:SF14; PTHR12669:SF14; 1.
DR Pfam; PF05456; eIF_4EBP; 1.
PE 1: Evidence at protein level;
KW Acetylation; Direct protein sequencing; Isopeptide bond; Phosphoprotein;
KW Protein synthesis inhibitor; Reference proteome; Translation regulation;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT CHAIN 2..117
FT /note="Eukaryotic translation initiation factor 4E-binding
FT protein 1"
FT /id="PRO_0000190515"
FT REGION 1..47
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 64..117
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 53..59
FT /note="YXXXXLphi motif"
FT /evidence="ECO:0000250|UniProtKB:P70445"
FT MOTIF 113..117
FT /note="TOS motif"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT COMPBIAS 1..15
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 33..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..97
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 98..117
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 36
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 40
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60876"
FT MOD_RES 45
FT /note="Phosphothreonine; by MTOR"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 49
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 53
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 64
FT /note="Phosphoserine; by DYRK2, MAPK1, MAPK3 and MTOR"
FT /evidence="ECO:0000269|PubMed:7939721"
FT MOD_RES 69
FT /note="Phosphothreonine; by MTOR"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 76
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 95
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60876"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q60876"
FT MOD_RES 100
FT /note="Phosphoserine; by DYRK2"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MOD_RES 111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT CROSSLNK 56
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q13541"
FT MUTAGEN 64
FT /note="S->A: Decreases phosphorylation by MAPK1 and MAPK3."
FT /evidence="ECO:0000269|PubMed:7939721"
FT CONFLICT 19
FT /note="R -> N (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 69
FT /note="T -> P (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 75
FT /note="P -> L (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 117 AA; 12404 MW; 3449D57B09FA101A CRC64;
MSAGSSCSQT PSRAIPTRRV ALGDGVQLPP GDYSTTPGGT LFSTTPGGTR IIYDRKFLME
CRNSPVAKTP PKDLPTIPGV TSPTSDEPPM QASQSHLHSS PEDKRAGGEE SQFEMDI
