EIF4E
entrez
1977
canonical
uniprot
P06730
canonical
ensembl
ENSG00000151247
resolver
ensp
ENSP00000280892
resolver
ensp
ENSP00000389624
resolver
ensp
ENSP00000423977
resolver
ensp
ENSP00000425561
resolver
enst
ENST00000504432
resolver
genesymbol
EIF4E
resolver
genesymbol_syn
EIF4EL1
resolver
genesymbol_syn
EIF4F
resolver
hgnc
HGNC:3287
resolver
uniprot
B7Z6V1
resolver
uniprot
D6RBW1
resolver
uniprot
D6RCQ6
resolver
uniprot
Q32Q75
resolver
uniprot
Q96E95
resolver
uniprot
X5D7E3
resolver
uniprot_entry
D6RBW1_HUMAN
resolver
uniprot_entry
IF4E_HUMAN
resolver
uniprot_entry
Q32Q75_HUMAN
resolver
uniprot_entry
X5D7E3_HUMAN
resolver
uniprot_sec
B7Z6V1
resolver
uniprot_sec
D6RCQ6
resolver
uniprot_sec
Q96E95
resolver
amino_acid_sequence
MATVEPETTPTPNPPTTEEEKTESNQEVANPEHYIKHPLQNRWALWFFKNDKSKTWQANLRLISKFDTVEDFWALYNHIQLSSNLMPGCDYSLFKDGIEPMWEDEKNKRGGRWLITLNKQQRRSDLDRFWLETLLCLIGESFDDYSDDVCGAVVNVRAKGDKIAIWTTECENREAVTHIGRVYKERLGLPPKIVIGYQSHADTATKSGSTTKNRFVV
uniprot
proteins
disease_involvement
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 intellectual disability. {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}.
uniprot
proteins
function
FUNCTION: Acts in the cytoplasm to initiate and regulate protein synthesis and is required in the nucleus for export of a subset of mRNAs from the nucleus to the cytoplasm which promotes processes such as RNA capping, processing and splicing (PubMed:11606200, PubMed:22578813, PubMed:22684010, PubMed:24335285, PubMed:29987188). Component of the protein complex eIF4F, which is involved in the recognition of the mRNA cap, ATP-dependent unwinding of 5'-terminal secondary structure and recruitment of mRNA to the ribosome (By similarity). This protein recognizes and binds the 7-methylguanosine (m7G)-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). Together with EIF4G1, antagonizes the scanning promoted by EIF1-EIF4G1 and is required for TISU translation, a process where the TISU element recognition makes scanning unnecessary (PubMed:29987188). 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). As well as its roles in translation, also involved in mRNA nucleocytoplasmic transport (By similarity). Its role in mRNA export from the nucleus to the cytoplasm relies on its ability to bind the m7G cap of RNAs and on the presence of the 50-nucleotide EIF4E sensitivity element (4ESE) in the 3'UTR of sensitive transcripts (By similarity). Interaction with the 4ESE is mediated by LRPPRC which binds simultaneously to both EIF4E and the 4ESE, thereby acting as a platform for assembly for the RNA export complex (By similarity). EIF4E-dependent mRNA export is independent of ongoing protein or RNA synthesis and is also NFX1-independent but is XPO1-dependent with LRPPRC interacting with XPO1 to form an EIF4E-dependent mRNA export complex (By similarity). Alters the composition of the cytoplasmic face of the nuclear pore to promote RNA export by reducing RANBP2 expression, relocalizing nucleoporin NUP214 and increasing expression of RANBP1 and RNA export factors DDX19 and GLE1 (By similarity). Promotes the nuclear export of cyclin CCND1 mRNA (By similarity). Promotes the nuclear export of NOS2/iNOS mRNA (PubMed:23471078). Promotes the nuclear export of MDM2 mRNA (PubMed:22684010). Promotes the export of additional mRNAs, including others involved in the cell cycle (By similarity). In the nucleus, binds to capped splice factor-encoding mRNAs and stimulates their nuclear export to enhance splice factor production by increasing their cytoplasmic availability to the translation machinery (By similarity). May also regulate splicing through interaction with the spliceosome in an RNA and m7G cap-dependent manner (By similarity). Also binds to some pre-mRNAs and may play a role in their recruitment to the spliceosome (By similarity). Promotes steady-state capping of a subset of coding and non-coding RNAs by mediating nuclear export of capping machinery mRNAs including RNMT, RNGTT and RAMAC to enhance their translation (By similarity). Stimulates mRNA 3'-end processing by promoting the expression of several core cleavage complex factors required for mRNA cleavage and polyadenylation, and may also have a direct effect through its interaction with the CPSF3 cleavage enzyme (By similarity). Rescues cells from apoptosis by promoting activation of serine/threonine-protein kinase AKT1 through mRNA export of NBS1 which potentiates AKT1 phosphorylation and also through mRNA export of AKT1 effectors, allowing for increased production of these proteins (By similarity). {ECO:0000250|UniProtKB:P63073, ECO:0000250|UniProtKB:P63074, ECO:0000269|PubMed:11606200, ECO:0000269|PubMed:16271312, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22684010, ECO:0000269|PubMed:23471078, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:29987188}.
uniprot
proteins
mass_dalton
25097
uniprot
proteins
mutagenesis
MUTAGEN 53; /note="S->A,D: No effect on phosphorylation level nor incorporation into eIF4F complex."; /evidence="ECO:0000269|PubMed:7590282, ECO:0000269|PubMed:8505316"; MUTAGEN 53; /note="S->A: Does not affect ability to rescue growth of yeast lacking a functional EIF4E/CDC33 gene."; /evidence="ECO:0000269|PubMed:11606200"; MUTAGEN 56; /note="W->A: Impairs mRNA nuclear export. Reduces affinity for ribavirin."; /evidence="ECO:0000269|PubMed:15601771, ECO:0000269|PubMed:22684010"; MUTAGEN 73; /note="W->A: Abolishes binding to EIF4EBP1. Impairs interaction with DDX3X. Does not impair mRNA nuclear export. Does not affect affinity for ribavirin."; /evidence="ECO:0000269|PubMed:15601771, ECO:0000269|PubMed:17667941, ECO:0000269|PubMed:22578813, ECO:0000269|PubMed:22684010"; MUTAGEN 102; /note="W->L: Decrease in mRNA cap binding; when associated with A-105."; /evidence="ECO:0000269|PubMed:1672854"; MUTAGEN 103; /note="E->A: No effect."; /evidence="ECO:0000269|PubMed:1672854"; MUTAGEN 104; /note="D->A: No effect."; /evidence="ECO:0000269|PubMed:1672854"; MUTAGEN 105; /note="E->A: Decrease in mRNA cap binding; when associated with L-102."; /evidence="ECO:0000269|PubMed:1672854"; MUTAGEN 119; /note="K->A: Higher affinity for EIF4G1."; /evidence="ECO:0000269|PubMed:17036047"; MUTAGEN 209; /note="S->A: Abolishes resistance to cellular stress and DNA-damaging agents. Does not affect ability to rescue growth of yeast lacking a functional EIF4E/CDC33 gene."; /evidence="ECO:0000269|PubMed:11606200, ECO:0000269|PubMed:25923732"; MUTAGEN 209; /note="S->D: Phosphomimetic mutant; confers resistance to cellular stress and DNA-damaging agents. Does not affect ability to rescue growth of yeast lacking a functional EIF4E/CDC33 gene."; /evidence="ECO:0000269|PubMed:11606200, ECO:0000269|PubMed:25923732
uniprot
proteins
post_translational_modification
PTM: Phosphorylation increases the ability of the protein to bind to mRNA caps and to form the eIF4F complex (PubMed:11154262, PubMed:3112145, PubMed:7590282, PubMed:7782323, PubMed:8505316, PubMed:9878069). Phosphorylation also enhances its mRNA transport function (By similarity). Phosphorylation at Ser-209 is not essential for protein synthesis (PubMed:11606200, PubMed:12138083). {ECO:0000250|UniProtKB:P63073, ECO:0000269|PubMed:11154262, ECO:0000269|PubMed:11606200, ECO:0000269|PubMed:12138083, ECO:0000269|PubMed:3112145, ECO:0000269|PubMed:7590282, ECO:0000269|PubMed:7782323, ECO:0000269|PubMed:8505316, ECO:0000269|PubMed:9878069}.
uniprot
proteins
protein_family
Eukaryotic initiation factor 4E family
uniprot
proteins
pubmed
10648556
uniprot
proteins
pubmed
10856257
uniprot
proteins
pubmed
11154262
uniprot
proteins
pubmed
11408474
uniprot
proteins
pubmed
11423616
uniprot
proteins
pubmed
11500381
uniprot
proteins
pubmed
11575918
uniprot
proteins
pubmed
11606200
uniprot
proteins
pubmed
11879179
uniprot
proteins
pubmed
12138083
uniprot
proteins
pubmed
12554669
uniprot
proteins
pubmed
12897141
uniprot
proteins
pubmed
12975586
uniprot
proteins
pubmed
1384058
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15601771
uniprot
proteins
pubmed
15657436
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16157702
uniprot
proteins
pubmed
16271312
uniprot
proteins
pubmed
16341674
uniprot
proteins
pubmed
16699599
uniprot
proteins
pubmed
1672854
uniprot
proteins
pubmed
17036047
uniprot
proteins
pubmed
1736299
uniprot
proteins
pubmed
17631896
uniprot
proteins
pubmed
17667941
uniprot
proteins
pubmed
19262567
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19433856
uniprot
proteins
pubmed
19556253
uniprot
proteins
pubmed
1993647
uniprot
proteins
pubmed
20212144
uniprot
proteins
pubmed
20430826
uniprot
proteins
pubmed
20616046
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21661078
uniprot
proteins
pubmed
21883093
uniprot
proteins
pubmed
22578813
uniprot
proteins
pubmed
22684010
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23471078
uniprot
proteins
pubmed
23814182
uniprot
proteins
pubmed
23991149
uniprot
proteins
pubmed
24207126
uniprot
proteins
pubmed
24335285
uniprot
proteins
pubmed
25533957
uniprot
proteins
pubmed
25702871
uniprot
proteins
pubmed
25923732
uniprot
proteins
pubmed
27117702
uniprot
proteins
pubmed
28325843
uniprot
proteins
pubmed
28487484
uniprot
proteins
pubmed
28733330
uniprot
proteins
pubmed
29358667
uniprot
proteins
pubmed
29987188
uniprot
proteins
pubmed
31042468
uniprot
proteins
pubmed
3112145
uniprot
proteins
pubmed
31712417
uniprot
proteins
pubmed
3469651
uniprot
proteins
pubmed
36843541
uniprot
proteins
pubmed
40441874
uniprot
proteins
pubmed
7590282
uniprot
proteins
pubmed
7782323
uniprot
proteins
pubmed
8505316
uniprot
proteins
pubmed
8521827
uniprot
proteins
pubmed
9878069
uniprot
proteins
sequence_length
217
uniprot
proteins
subcellular_location
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:12554669, ECO:0000269|PubMed:1384058, ECO:0000269|PubMed:15657436, ECO:0000269|PubMed:21883093, ECO:0000269|PubMed:23471078, ECO:0000269|PubMed:36843541}. Cytoplasm, Stress granule {ECO:0000269|PubMed:21883093}. Nucleus {ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:11423616, ECO:0000269|PubMed:1384058, ECO:0000269|PubMed:23471078, ECO:0000269|PubMed:36843541}. Nucleus speckle {ECO:0000269|PubMed:10648556}. Nucleus, nuclear body {ECO:0000269|PubMed:12554669, ECO:0000269|PubMed:15657436}. 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). Sequestered in the nucleus by EIF4EBP1 and EIF4EBP2 (By similarity). {ECO:0000250|UniProtKB:P63073, ECO:0000269|PubMed:10856257, ECO:0000269|PubMed:16157702, ECO:0000269|PubMed:24335285, ECO:0000269|PubMed:25923732}.
uniprot
proteins