UniProt functional annotation for P06730



	UniProt functional annotation for P06730

UniProt code: P06730.

Organism: Homo sapiens (Human).

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

Function: Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures (PubMed:16271312, PubMed:22578813). In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm (PubMed:24335285). Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap (By similarity). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation (PubMed:24335285). May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity). {ECO:0000250|UniProtKB:P63073, ECO:0000250|UniProtKB:P63074, ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:24335285}.

Subunit: eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions (PubMed:11408474, PubMed:11879179, PubMed:16271312, PubMed:17631896). It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3 (PubMed:8521827, PubMed:11408474, PubMed:11879179, PubMed:12975586). EIF4E is also known to interact with other partners (PubMed:8521827, PubMed:11408474, PubMed:11879179, PubMed:12975586). Interacts with EIF4ENIF1/4E-T; promotes recruitment to P-bodies and import into the nucleus (PubMed:10856257, PubMed:16157702, PubMed:23991149, PubMed:24335285, PubMed:28487484). Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:8521827, PubMed:16271312, PubMed:21661078, PubMed:24207126, PubMed:25533957, PubMed:25702871). Interacts mutually exclusive with EIF4A1 or EIF4A2 (PubMed:11408474). Interacts with NGDN and PIWIL2 (By similarity). Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1 (By similarity). Interacts directly with CYFIP1 (By similarity). Interacts with CLOCK (By similarity). Binds to MKNK2 in nucleus (PubMed:12897141). Interacts with LIMD1, WTIP and AJUBA (PubMed:20616046). Interacts with APOBEC3G in an RNA-dependent manner (PubMed:16699599). Interacts with LARP1 (PubMed:20430826). Interacts with METTL3 (PubMed:27117702). Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex (PubMed:29358667). Interacts with DDX3X; interaction is direct and in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability and is required for the repression of cap-dependent translation and the increase of IRES- mediated translation (PubMed:17667941, PubMed:21883093, PubMed:28733330). DDX3X competes with EIF4G1 for interaction with EIF4E (PubMed:17667941, PubMed:21883093). {ECO:0000250|UniProtKB:P63073, ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:11408474, ECO:0000269|PubMed:11879179, ECO:0000269|PubMed:12897141, ECO:0000269|PubMed:12975586, ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:16699599, ECO:0000269|PubMed:17631896, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:20430826, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:21661078, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:23991149, ECO:0000269|PubMed:24207126, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:25533957, ECO:0000269|PubMed:25702871, ECO:0000269|PubMed:27117702, ECO:0000269|PubMed:28487484, ECO:0000269|PubMed:28733330, ECO:0000269|PubMed:29358667, ECO:0000269|PubMed:8521827}.

Subunit: (Microbial infection) Interacts with Lassa virus Z protein. {ECO:0000269|PubMed:20212144}.

Subcellular location: Cytoplasm, P-body {ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:25923732}. Cytoplasm {ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:21883093}. Cytoplasm, Stress granule {ECO:0000269|PubMed:21883093}. Nucleus {ECO:0000269|PubMed:10856257}. Note=Interaction with EIF4ENIF1/4E-T is required for localization to processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285, PubMed:25923732). Imported in the nucleus via interaction with EIF4ENIF1/4E-T via a piggy-back mechanism (PubMed:10856257). {ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:25923732}.

Ptm: Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex. {ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:3112145, ECO:0000269|PubMed:7590282, ECO:0000269|PubMed:7665584, ECO:0000269|PubMed:7782323, ECO:0000269|PubMed:8505316, ECO:0000269|PubMed:9878069}.

Mass spectrometry: Mass=24964.3; Method=Electrospray; Evidence={ECO:0000269|PubMed:17036047};

Mass spectrometry: Mass=24960; Method=Electrospray; Evidence={ECO:0000269|PubMed:17631896};

Disease: Autism 19 (AUTS19) [MIM:615091]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269|PubMed:19556253}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. A heterozygous single-nucleotide insertion has been found in families affected by autism. The variant results in increased promoter activity and is involved in disease pathogenesis through EIF4E deregulation (PubMed:19556253). {ECO:0000269|PubMed:19556253}.

Disease: Note=A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t(45)(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E (PubMed:19556253). {ECO:0000269|PubMed:19556253}.

Similarity: Belongs to the eukaryotic initiation factor 4E 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:		Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures (PubMed:16271312, PubMed:22578813). In addition to its role in translation initiation, also acts as a regulator of translation and stability in the cytoplasm (PubMed:24335285). Component of the CYFIP1-EIF4E-FMR1 complex which binds to the mRNA cap and mediates translational repression: in the complex, EIF4E mediates the binding to the mRNA cap (By similarity). Component of a multiprotein complex that sequesters and represses translation of proneurogenic factors during neurogenesis (By similarity). In P-bodies, component of a complex that mediates the storage of translationally inactive mRNAs in the cytoplasm and prevents their degradation (PubMed:24335285). May play an important role in spermatogenesis through translational regulation of stage-specific mRNAs during germ cell development (By similarity). {ECO:0000250\|UniProtKB:P63073, ECO:0000250\|UniProtKB:P63074, ECO:0000269\|PubMed:16271312, ECO:0000269\|PubMed:22578813, ECO:0000269\|PubMed:24335285}.


Subunit:		eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions (PubMed:11408474, PubMed:11879179, PubMed:16271312, PubMed:17631896). It is composed of at least EIF4A, EIF4E and EIF4G1/EIF4G3 (PubMed:8521827, PubMed:11408474, PubMed:11879179, PubMed:12975586). EIF4E is also known to interact with other partners (PubMed:8521827, PubMed:11408474, PubMed:11879179, PubMed:12975586). Interacts with EIF4ENIF1/4E-T; promotes recruitment to P-bodies and import into the nucleus (PubMed:10856257, PubMed:16157702, PubMed:23991149, PubMed:24335285, PubMed:28487484). Hypophosphorylated EIF4EBP1, EIF4EBP2 and EIF4EBP3 compete with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation (PubMed:8521827, PubMed:16271312, PubMed:21661078, PubMed:24207126, PubMed:25533957, PubMed:25702871). Interacts mutually exclusive with EIF4A1 or EIF4A2 (PubMed:11408474). Interacts with NGDN and PIWIL2 (By similarity). Component of the CYFIP1-EIF4E-FMR1 complex composed of CYFIP, EIF4E and FMR1 (By similarity). Interacts directly with CYFIP1 (By similarity). Interacts with CLOCK (By similarity). Binds to MKNK2 in nucleus (PubMed:12897141). Interacts with LIMD1, WTIP and AJUBA (PubMed:20616046). Interacts with APOBEC3G in an RNA-dependent manner (PubMed:16699599). Interacts with LARP1 (PubMed:20430826). Interacts with METTL3 (PubMed:27117702). Interacts with RBM24; this interaction prevents EIF4E from binding to p53/TP53 mRNA and inhibits the assembly of translation initiation complex (PubMed:29358667). Interacts with DDX3X; interaction is direct and in an RNA-independent manner; this interaction enhances EIF4E cap-binding ability and is required for the repression of cap-dependent translation and the increase of IRES- mediated translation (PubMed:17667941, PubMed:21883093, PubMed:28733330). DDX3X competes with EIF4G1 for interaction with EIF4E (PubMed:17667941, PubMed:21883093). {ECO:0000250\|UniProtKB:P63073, ECO:0000269\|PubMed:10856257, ECO:0000269\|PubMed:11408474, ECO:0000269\|PubMed:11879179, ECO:0000269\|PubMed:12897141, ECO:0000269\|PubMed:12975586, ECO:0000269\|PubMed:16157702, ECO:0000269\|PubMed:16271312, ECO:0000269\|PubMed:16699599, ECO:0000269\|PubMed:17631896, ECO:0000269\|PubMed:17667941, ECO:0000269\|PubMed:20430826, ECO:0000269\|PubMed:20616046, ECO:0000269\|PubMed:21661078, ECO:0000269\|PubMed:21883093, ECO:0000269\|PubMed:23991149, ECO:0000269\|PubMed:24207126, ECO:0000269\|PubMed:24335285, ECO:0000269\|PubMed:25533957, ECO:0000269\|PubMed:25702871, ECO:0000269\|PubMed:27117702, ECO:0000269\|PubMed:28487484, ECO:0000269\|PubMed:28733330, ECO:0000269\|PubMed:29358667, ECO:0000269\|PubMed:8521827}.
Subunit:		(Microbial infection) Interacts with Lassa virus Z protein. {ECO:0000269\|PubMed:20212144}.
Subcellular location:		Cytoplasm, P-body {ECO:0000269\|PubMed:16157702, ECO:0000269\|PubMed:20616046, ECO:0000269\|PubMed:24335285, ECO:0000269\|PubMed:25923732}. Cytoplasm {ECO:0000269\|PubMed:10856257, ECO:0000269\|PubMed:21883093}. Cytoplasm, Stress granule {ECO:0000269\|PubMed:21883093}. Nucleus {ECO:0000269\|PubMed:10856257}. Note=Interaction with EIF4ENIF1/4E-T is required for localization to processing bodies (P-bodies) (PubMed:16157702, PubMed:24335285, PubMed:25923732). Imported in the nucleus via interaction with EIF4ENIF1/4E-T via a piggy-back mechanism (PubMed:10856257). {ECO:0000269\|PubMed:10856257, ECO:0000269\|PubMed:16157702, ECO:0000269\|PubMed:24335285, ECO:0000269\|PubMed:25923732}.
Ptm:		Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex. {ECO:0000269\|PubMed:11154262, ECO:0000269\|PubMed:3112145, ECO:0000269\|PubMed:7590282, ECO:0000269\|PubMed:7665584, ECO:0000269\|PubMed:7782323, ECO:0000269\|PubMed:8505316, ECO:0000269\|PubMed:9878069}.
Mass spectrometry:		Mass=24964.3; Method=Electrospray; Evidence={ECO:0000269\|PubMed:17036047};
Mass spectrometry:		Mass=24960; Method=Electrospray; Evidence={ECO:0000269\|PubMed:17631896};
Disease:		Autism 19 (AUTS19) [MIM:615091]: A complex multifactorial, pervasive developmental disorder characterized by impairments in reciprocal social interaction and communication, restricted and stereotyped patterns of interests and activities, and the presence of developmental abnormalities by 3 years of age. Most individuals with autism also manifest moderate mental retardation. {ECO:0000269\|PubMed:19556253}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry. A heterozygous single-nucleotide insertion has been found in families affected by autism. The variant results in increased promoter activity and is involved in disease pathogenesis through EIF4E deregulation (PubMed:19556253). {ECO:0000269\|PubMed:19556253}.
Disease:		Note=A chromosomal aberration involving EIF4E has been found in a patient with classic autism. Translocation t(45)(q23q31.3). The breakpoint on chromosome 4 is located 56 kb downstream of EIF4E (PubMed:19556253). {ECO:0000269\|PubMed:19556253}.
Similarity:		Belongs to the eukaryotic initiation factor 4E family. {ECO:0000305}.