Reactome | UniProt:Q04637 EIF4G1

chain	chain:1-1599 initiator methionine:1
checksum	324088B60863DA34
comment	FUNCTION 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 (PubMed:29987188). Exists in two complexes, either with EIF1 or with EIF4E (mutually exclusive) (PubMed:29987188). Together with EIF1, is required for leaky scanning, in particular for avoiding cap-proximal start codon (PubMed:29987188). Together with EIF4E, antagonizes the scanning promoted by EIF1-EIF4G1 and locates the start codon (through a TISU element) without scanning (PubMed:29987188). As a member of the eIF4F complex, required for endoplasmic reticulum stress-induced ATF4 mRNA translation (PubMed:29062139).SUBUNIT eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least EIF4A, EIF4E (cap-binding) and EIF4G1/EIF4G3 (PubMed:7651417, PubMed:7935836, PubMed:9372926). Interacts with eIF3 complex, mutually exclusive with EIF4A1 or EIF4A2, EIF4E and through its N-terminus with PABPC1 (PubMed:10970864, PubMed:10996799, PubMed:12086624, PubMed:16698552, PubMed:7651417, PubMed:7935836, PubMed:9372926, PubMed:9857202). Interacts with EIF4E or with EIF1 (mutually exclusive) through a common binding site (PubMed:29987188). Interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2 (PubMed:11154262, PubMed:9878069). Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate EIF4E (PubMed:11154262, PubMed:9878069). Non-phosphorylated EIF4EBP1 competes 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). EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA (PubMed:10970864, PubMed:10996799, PubMed:12086624, PubMed:9857202). Interacts with EIF4E3 (By similarity). Interacts with CIRBP and MIF4GD (PubMed:10970864, PubMed:10996799, PubMed:16513844, PubMed:18025107). Interacts with RBM4 (PubMed:17284590). Interacts with HNRNPD/AUF1; the interaction requires RNA (PubMed:24423872). Interacts with DDX3X; the interaction requires RNA (PubMed:22872150). Interacts with DAZAP2 (PubMed:17984221).SUBUNIT (Microbial infection) Interacts with rotavirus A NSP3; in this interaction, NSP3 takes the place of PABPC1 thereby inducing shutoff of host protein synthesis.SUBUNIT (Microbial infection) Interacts with human adenovirus 5 protein 100K; this interaction promotes translational shunt in presence of polysomes containing viral tripartite leader mRNAs.SUBUNIT (Microbial infection) Interacts with viral genome-linked protein (via c-terminus); this interaction plays a role in the translation of viral proteins.INTERACTION Phosphorylated at multiple sites in vivo. Phosphorylation at Ser-1185 by PRKCA induces binding to MKNK1.PTM Following infection by certain enteroviruses, rhinoviruses and aphthoviruses, EIF4G1 is cleaved by the viral protease 2A, or the leader protease in the case of aphthoviruses. This shuts down the capped cellular mRNA transcription.DISEASE The disease is caused by variants affecting the gene represented in this entry.MISCELLANEOUS Produced by alternative initiation at Met-41 of isoform A.MISCELLANEOUS Produced by alternative initiation at Met-88 of isoform A.MISCELLANEOUS Produced by alternative initiation at Met-165 of isoform A.MISCELLANEOUS Produced by alternative initiation at Met-197 of isoform A.MISCELLANEOUS Produced by alternative splicing.MISCELLANEOUS Produced by alternative splicing.MISCELLANEOUS Produced by alternative splicing.SIMILARITY Belongs to the eukaryotic initiation factor 4G family.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Truncated N-terminus.SEQUENCE CAUTION Aberrant splicing.
crossReference	[DatabaseIdentifier:11644187] ENSEMBL:ENSP00000416255 [DatabaseIdentifier:12477191] RefSeq:NP_001181876.2 [DatabaseIdentifier:12477194] RefSeq:NP_937884.2 [DatabaseIdentifier:12477196] RefSeq:NP_937887.2 [DatabaseIdentifier:12477189] RefSeq:NP_001181875.2 [DatabaseIdentifier:12477192] RefSeq:NP_001278086.2 [DatabaseIdentifier:12477193] RefSeq:NP_004944.3 [DatabaseIdentifier:12477195] RefSeq:NP_937885.1 [DatabaseIdentifier:12477190] RefSeq:NP_886553.3 [DatabaseIdentifier:12291586] Pharos - Targets:Q04637 [DatabaseIdentifier:12274399] PRO:Q04637 [DatabaseIdentifier:12219316] PDB:5ZK5 [DatabaseIdentifier:12212301] PDB:4F02 [DatabaseIdentifier:12148738] PDB:8OZ0 [DatabaseIdentifier:12219312] PDB:1UG3 [DatabaseIdentifier:12219313] PDB:4AZA [DatabaseIdentifier:12219315] PDB:1LJ2 [DatabaseIdentifier:12209939] PDB:8HUJ [DatabaseIdentifier:12219319] PDB:2W97 [DatabaseIdentifier:12219310] PDB:5EIR [DatabaseIdentifier:12219318] PDB:5T46 [DatabaseIdentifier:12219317] PDB:8J7R [DatabaseIdentifier:12219311] PDB:5EI3 [DatabaseIdentifier:12148751] PDB:6ZMW [DatabaseIdentifier:12219314] PDB:5EHC [DatabaseIdentifier:12135785] Orphanet:EIF4G1 [DatabaseIdentifier:12131394] OpenTargets:ENSG00000114867 [DatabaseIdentifier:11846733] HPA:ENSG00000114867-EIF4G1 [DatabaseIdentifier:11809723] GlyGen:Q04637 [DatabaseIdentifier:11793744] GeneCards:EIF4G1 [DatabaseIdentifier:11766878] ENSEMBL:ENST00000342981 [DatabaseIdentifier:11766882] ENSEMBL:ENST00000352767 [DatabaseIdentifier:11766879] ENSEMBL:ENST00000350481 [DatabaseIdentifier:11766886] ENSEMBL:ENST00000414031 [DatabaseIdentifier:11766885] ENSEMBL:ENST00000424196 [DatabaseIdentifier:11766884] ENSEMBL:ENST00000392537 [DatabaseIdentifier:11766881] ENSEMBL:ENST00000382330 [DatabaseIdentifier:11766883] ENSEMBL:ENST00000346169 [DatabaseIdentifier:11766880] ENSEMBL:ENST00000434061 [DatabaseIdentifier:11523509] ENSEMBL:ENSG00000114867 [DatabaseIdentifier:11644179] ENSEMBL:ENSP00000338020 [DatabaseIdentifier:11644186] ENSEMBL:ENSP00000317600 [DatabaseIdentifier:11644180] ENSEMBL:ENSP00000376320 [DatabaseIdentifier:11644183] ENSEMBL:ENSP00000316879 [DatabaseIdentifier:11644184] ENSEMBL:ENSP00000391935 [DatabaseIdentifier:11644182] ENSEMBL:ENSP00000411826 [DatabaseIdentifier:11644181] ENSEMBL:ENSP00000343450 [DatabaseIdentifier:11644185] ENSEMBL:ENSP00000371767
databaseName	UniProt
dbId	72583
description	recommendedName: Eukaryotic translation initiation factor 4 gamma 1 shortName: eIF-4-gamma 1 shortName: eIF-4G 1 shortName: eIF-4G1 alternativeName: p220
displayName	UniProt:Q04637 EIF4G1
geneName	EIF4G1 EIF4F EIF4G EIF4GI
identifier	Q04637
isSequenceChanged	false
keyword	3D-structure Acetylation Alternative initiation Alternative splicing Cytoplasm Disease variant Host-virus interaction Initiation factor Methylation Neurodegeneration Nucleus Parkinson disease Parkinsonism Phosphoprotein Protein biosynthesis Proteomics identification Reference proteome RNA-binding Translation regulation Translational shunt
modified	[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	EIF4G1
physicalEntity	[EntityWithAccessionedSequence:R-HSA-72584] EIF4G1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-165762] p-S1108,S1148,S1192-EIF4G1 [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000114867] ENSEMBL:ENSG00000114867 EIF4G1 [ReferenceDNASequence:12717255] UCSC:Q04637 EIF4G1 [ReferenceDNASequence:12115855] OMIM:600495 EIF4G1 [ReferenceDNASequence:12101262] NCBI Gene:1981 EIF4G1 [ReferenceDNASequence:12017169] Monarch:1981 EIF4G1 [ReferenceDNASequence:11923816] KEGG:hsa:1981 EIF4G1 [ReferenceDNASequence:11825438] HGNC:3296 EIF4G1 [ReferenceDNASequence:11387380] BioGPS Gene:1981 EIF4G1 [ReferenceDNASequence:11396651] COSMIC - genes:EIF4G1 EIF4G1 [ReferenceDNASequence:11422326] CTD Gene:1981 EIF4G1 [ReferenceDNASequence:11433145] dbSNP Gene:1981 EIF4G1
referenceTranscript	[ReferenceRNASequence:12658697] RefSeq:NM_182917.4 EIF4G1 [ReferenceRNASequence:12658702] RefSeq:NM_198241.3 EIF4G1 [ReferenceRNASequence:12658698] RefSeq:NM_001194947.2 EIF4G1 [ReferenceRNASequence:12658701] RefSeq:NM_198242.3 EIF4G1 [ReferenceRNASequence:12658696] RefSeq:NM_001291157.2 EIF4G1 [ReferenceRNASequence:12658699] RefSeq:NM_198244.3 EIF4G1 [ReferenceRNASequence:12658700] RefSeq:NM_001194946.2 EIF4G1 [ReferenceRNASequence:12658703] RefSeq:NM_004953.4 EIF4G1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	IF4G1_HUMAN D3DNT2 D3DNT4 D3DNT5 E9PFM1 G5E9S1 O43177 O95066 Q5HYG0 Q6ZN21 Q8N102
sequenceLength	1599
species	[Species:48887] Homo sapiens
stId	uniprot:Q04637
url	http://purl.uniprot.org/uniprot/Q04637

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-72584] EIF4G1 [cytosol] [EntityWithAccessionedSequence:R-HSA-165762] p-S1108,S1148,S1192-EIF4G1 [cytosol]
(referenceSequence)	[ModifiedResidue:165763] O-phospho-L-serine at 1147 [ModifiedResidue:165760] O-phospho-L-serine at 1231 [ModifiedResidue:165764] O-phospho-L-serine at 1185
(interactor)	[UndirectedInteraction:11130075] UniProt:Q9BUB5 <-> UniProt:Q04637 (IntAct) [UndirectedInteraction:11149705] UniProt:P13569 <-> UniProt:Q04637 (IntAct) [UndirectedInteraction:11168091] UniProt:Q09161 <-> UniProt:Q04637 (IntAct) [UndirectedInteraction:11181181] UniProt:P62280 <-> UniProt:Q04637 (IntAct) [UndirectedInteraction:11189351] UniProt:Q04637 <-> UniProt:P60842 (IntAct) [UndirectedInteraction:11189353] UniProt:Q04637 <-> UniProt:P06730 (IntAct) [UndirectedInteraction:11189355] UniProt:Q04637 <-> UniProt:P11940 (IntAct) [UndirectedInteraction:11189357] UniProt:Q04637 <-> UniProt:Q14240 (IntAct) [UndirectedInteraction:11189361] UniProt:Q04637 <-> UniProt:Q9BWF3-1 (IntAct) [UndirectedInteraction:11189365] UniProt:Q04637 <-> UniProt:Q9UGR2 (IntAct) [UndirectedInteraction:11189367] UniProt:Q04637 <-> UniProt:P23116 (IntAct) [UndirectedInteraction:11189369] UniProt:Q04637 <-> UniProt:P55884 (IntAct) [UndirectedInteraction:11189371] UniProt:Q04637 <-> UniProt:O00571 (IntAct) [UndirectedInteraction:11189373] UniProt:Q04637 <-> UniProt:P61981 (IntAct) [UndirectedInteraction:11189375] UniProt:Q04637 <-> UniProt:Q13347 (IntAct) [UndirectedInteraction:11189377] UniProt:Q04637 <-> UniProt:P10636-8 (IntAct) [UndirectedInteraction:11189379] UniProt:Q04637 <-> UniProt:Q13112 (IntAct) [UndirectedInteraction:11189381] UniProt:Q04637 <-> ChEBI:50210 (IntAct) [UndirectedInteraction:11189383] UniProt:Q04637 <-> UniProt:Q06787 (IntAct) [UndirectedInteraction:11189385] UniProt:Q04637 <-> UniProt:P03372 (IntAct) [UndirectedInteraction:11189387] UniProt:Q04637 <-> UniProt:O75822 (IntAct) [UndirectedInteraction:11189389] UniProt:Q04637 <-> UniProt:Q14103-4 (IntAct) [UndirectedInteraction:11189393] UniProt:Q04637 <-> UniProt:Q9J0X9 (IntAct) [UndirectedInteraction:11189395] UniProt:Q04637 <-> UniProt:Q13283 (IntAct) [UndirectedInteraction:11189397] UniProt:Q04637 <-> UniProt:P06748 (IntAct) [UndirectedInteraction:11189399] UniProt:Q04637 <-> UniProt:P51116 (IntAct) [UndirectedInteraction:11189401] UniProt:Q04637 <-> UniProt:P26196 (IntAct) [UndirectedInteraction:11189405] UniProt:Q04637 <-> UniProt:Q00721 (IntAct)

UniProt:Q04637 EIF4G1 Show undefined attributes

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