UniProt functional annotation for Q13541



	UniProt functional annotation for Q13541

UniProt code: Q13541.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. {ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836}.

Subunit: Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:12150926, PubMed:16271312, PubMed:17368478, PubMed:17631896, PubMed:22578813, PubMed:7935836, PubMed:8521827, PubMed:25702871). Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:12747827). {ECO:0000269|PubMed:12150926, ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:17368478, ECO:0000269|PubMed:17631896, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:25702871, ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:8521827}.

Domain: The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex. {ECO:0000269|PubMed:12747827}.

Ptm: Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E. {ECO:0000269|PubMed:12588975, ECO:0000269|PubMed:12747827, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:7935836, ECO:0000269|PubMed:9465032}.

Ptm: Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E. {ECO:0000269|PubMed:22578813}.

Similarity: Belongs to the eIF4E-binding protein family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. {ECO:0000269\|PubMed:22578813, ECO:0000269\|PubMed:7935836}.


Subunit:		Hypophosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) or mTORC1 phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:12150926, PubMed:16271312, PubMed:17368478, PubMed:17631896, PubMed:22578813, PubMed:7935836, PubMed:8521827, PubMed:25702871). Interacts (via TOS motif) with RPTOR; promoting phosphorylation by mTORC1 (PubMed:12747827). {ECO:0000269\|PubMed:12150926, ECO:0000269\|PubMed:12747827, ECO:0000269\|PubMed:16271312, ECO:0000269\|PubMed:17368478, ECO:0000269\|PubMed:17631896, ECO:0000269\|PubMed:22578813, ECO:0000269\|PubMed:25702871, ECO:0000269\|PubMed:7935836, ECO:0000269\|PubMed:8521827}.
Domain:		The TOS motif mediates interaction with RPTOR, leading to promote phosphorylation by mTORC1 complex. {ECO:0000269\|PubMed:12747827}.
Ptm:		Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E. {ECO:0000269\|PubMed:12588975, ECO:0000269\|PubMed:12747827, ECO:0000269\|PubMed:22578813, ECO:0000269\|PubMed:7935836, ECO:0000269\|PubMed:9465032}.
Ptm:		Ubiquitinated: when eIF4E levels are low, hypophosphorylated form is ubiquitinated by the BCR(KLHL25) complex, leading to its degradation and serving as a homeostatic mechanism to maintain translation and prevent eIF4E inhibition when eIF4E levels are low. Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E. {ECO:0000269\|PubMed:22578813}.
Similarity:		Belongs to the eIF4E-binding protein family. {ECO:0000305}.