ID:IF4G1_HUMAN DESCRIPTION: RecName: Full=Eukaryotic translation initiation factor 4 gamma 1; Short=eIF-4-gamma 1; Short=eIF-4G 1; Short=eIF-4G1; AltName: Full=p220; 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. 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 and EIF4G1/EIF4G3. Interacts with eIF3, mutually exclusive with EIF4A1 or EIFA2, EIF4E and through its N-terminus with PAPBC1. Interacts through its C-terminus with the serine/threonine kinases MKNK1, and with MKNK2. Appears to act as a scaffold protein, holding these enzymes in place to phosphorylate EIF4E. 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. EIF4G1/EIF4G3 interacts with PABPC1 to bring about circularization of the mRNA. Rapamycin can attenuate insulin stimulation mediated by FKBPs. Interacts with EIF4E3. Interacts with CIRBP and MIF4GD. Interacts with rotavirus A NSP3; in this interaction, NSP3 takes the place of PABPC1 thereby inducing shutoff of host protein synthesis. Interacts with RBM4. INTERACTION: P60842:EIF4A1; NbExp=7; IntAct=EBI-73711, EBI-73449; Q14240:EIF4A2; NbExp=3; IntAct=EBI-73711, EBI-73473; P06730:EIF4E; NbExp=2; IntAct=EBI-73711, EBI-73440; Q14103-4:HNRNPD; NbExp=3; IntAct=EBI-73711, EBI-432545; Q9BUB5:MKNK1; NbExp=2; IntAct=EBI-73711, EBI-73837; PTM: 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: Defects in EIF4G1 are the cause of Parkinson disease type 18 (PARK18) [MIM:614251]. An autosomal dominant, late-onset form of Parkinson disease. Parkinson disease is a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. SIMILARITY: Belongs to the eIF4G family. SIMILARITY: Contains 1 MI domain. SIMILARITY: Contains 1 MIF4G domain. SIMILARITY: Contains 1 W2 domain. SEQUENCE CAUTION: Sequence=AAC78444.1; Type=Erroneous initiation; Sequence=AAC82471.1; Type=Erroneous initiation; Sequence=BAA02185.1; Type=Frameshift; Positions=Several; Sequence=BAD18554.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q04637
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Biological Process: GO:0000184 nuclear-transcribed mRNA catabolic process, nonsense-mediated decay GO:0001662 behavioral fear response GO:0002191 cap-dependent translational initiation GO:0006412 translation GO:0006413 translational initiation GO:0006417 regulation of translation GO:0006446 regulation of translational initiation GO:0007005 mitochondrion organization GO:0008284 positive regulation of cell proliferation GO:0010507 negative regulation of autophagy GO:0010801 negative regulation of peptidyl-threonine phosphorylation GO:0010942 positive regulation of cell death GO:0016032 viral process GO:0030307 positive regulation of cell growth GO:0031669 cellular response to nutrient levels GO:0032270 positive regulation of cellular protein metabolic process GO:0032502 developmental process GO:0033138 positive regulation of peptidyl-serine phosphorylation GO:0034645 cellular macromolecule biosynthetic process GO:0043488 regulation of mRNA stability GO:0045666 positive regulation of neuron differentiation GO:0060964 regulation of gene silencing by miRNA GO:0080135 regulation of cellular response to stress GO:0097009 energy homeostasis GO:1900087 positive regulation of G1/S transition of mitotic cell cycle GO:1901215 negative regulation of neuron death GO:1905537 positive regulation of eukaryotic translation initiation factor 4F complex assembly GO:1905606 regulation of presynapse assembly GO:1905612 positive regulation of mRNA cap binding GO:1905618 positive regulation of miRNA mediated inhibition of translation GO:1905696 regulation of polysome binding
BC065256 - Homo sapiens eukaryotic translation initiation factor 4 gamma, 1, mRNA (cDNA clone IMAGE:6146899), partial cds. AK299763 - Homo sapiens cDNA FLJ56483 complete cds, highly similar to Eukaryotic translation initiation factor 4 gamma 1. AK096719 - Homo sapiens cDNA FLJ39400 fis, clone PLACE6011102, highly similar to EUKARYOTIC TRANSLATION INITIATION FACTOR 4 GAMMA. AK128378 - Homo sapiens cDNA FLJ46521 fis, clone THYMU3033759, moderately similar to Eukaryotic translation initiation factor 4 gamma. BX647812 - Homo sapiens mRNA; cDNA DKFZp686A1451 (from clone DKFZp686A1451). AL832754 - Homo sapiens mRNA; cDNA DKFZp686A2427 (from clone DKFZp686A2427). AK226160 - Homo sapiens mRNA for eukaryotic translation initiation factor 4 gamma, 1 isoform 1 variant, clone: sh03325. BC010688 - Homo sapiens eukaryotic translation initiation factor 4 gamma, 1, mRNA (cDNA clone IMAGE:3867218), with apparent retained intron. BC140892 - Homo sapiens eukaryotic translation initiation factor 4 gamma, 1, mRNA (cDNA clone MGC:176569 IMAGE:9021760), complete cds. BC140896 - Homo sapiens eukaryotic translation initiation factor 4 gamma, 1, mRNA (cDNA clone MGC:176573 IMAGE:9021764), complete cds. AK131407 - Homo sapiens cDNA FLJ16513 fis, clone MESAN2001770, highly similar to EUKARYOTIC TRANSLATION INITIATION FACTOR 4 GAMMA. AY082886 - Homo sapiens eukaryotic translation initiation factor 4GI (EIF4GI) mRNA, complete cds. AF281070 - Homo sapiens putative regulatory uORF and eukaryotic translation initiation factor 4G I (EIF4GI) mRNAs, complete cds. AF002815 - Human eucaryotic translation initiation factor 4G isoform 1 mRNA, partial cds. AB210013 - Homo sapiens mRNA for EIF4G1 variant protein, clone: fh17714. AB384368 - Synthetic construct DNA, clone: pF1KSDB0030, Homo sapiens EIF4G1 gene for eukaryotic translation initiation factor 4 gamma 1, complete cds, without stop codon, in Flexi system. AF002816 - Human eucaryotic translation initiation factor 4G isoform 2 mRNA, partial cds. AF104913 - Homo sapiens eukaryotic protein synthesis initiation factor mRNA, complete cds. AK294567 - Homo sapiens cDNA FLJ56479 complete cds, highly similar to Eukaryotic translation initiation factor 4 gamma 1. AK308319 - Homo sapiens cDNA, FLJ98267. D12686 - Homo sapiens mRNA for eukaryotic initiation factor 4 gamma, complete cds. JD175757 - Sequence 156781 from Patent EP1572962. BC082764 - Homo sapiens eukaryotic translation initiation factor 4 gamma, 1, mRNA (cDNA clone IMAGE:6580118). AJ001046 - Homo sapiens mRNA for eukaryotic initiation factor 4 gamma. BC007788 - Homo sapiens eukaryotic translation initiation factor 4 gamma, 1, mRNA (cDNA clone IMAGE:3611484), partial cds. BT007282 - Homo sapiens eukaryotic translation initiation factor 4 gamma, 1 mRNA, complete cds. AK098133 - Homo sapiens cDNA FLJ40814 fis, clone TRACH2010587, highly similar to EUKARYOTIC TRANSLATION INITIATION FACTOR 4 GAMMA. DL491731 - Novel nucleic acids. DL490311 - Novel nucleic acids. JD355037 - Sequence 336061 from Patent EP1572962. JD454150 - Sequence 435174 from Patent EP1572962. JD502902 - Sequence 483926 from Patent EP1572962. JD347052 - Sequence 328076 from Patent EP1572962. JD537199 - Sequence 518223 from Patent EP1572962. JD389435 - Sequence 370459 from Patent EP1572962. JD132726 - Sequence 113750 from Patent EP1572962. JD483497 - Sequence 464521 from Patent EP1572962. JD335961 - Sequence 316985 from Patent EP1572962.
Biochemical and Signaling Pathways
BioCarta from NCI Cancer Genome Anatomy Project h_mTORPathway - mTOR Signaling Pathway h_iresPathway - Internal Ribosome entry pathway h_eif4Pathway - Regulation of eIF4e and p70 S6 Kinase h_eifPathway - Eukaryotic protein translation
Reactome (by CSHL, EBI, and GO)
Protein Q04637 (Reactome details) participates in the following event(s):
R-HSA-72631 Formation of the cap-binding eIF4F complex R-HSA-165766 Phosphorylation and activation of eIF4G by activated S6K1 R-HSA-450551 AUF1 binds translation and heat shock proteins R-HSA-72619 eIF2:GTP is hydrolyzed, eIFs are released R-HSA-429955 CCR4-NOT complex deadenylates mRNA R-HSA-429992 PARN deadenylates mRNA R-HSA-72635 eIF4F binds to mRNP R-HSA-430021 PAN2-PAN3 complex partially deadenylates mRNA R-HSA-8941312 ZCCHC6, ZCCHC11 are mRNA uridyltransferases R-HSA-72621 Ribosomal scanning R-HSA-157849 Formation of translation initiation complexes containing mRNA that does not circularize R-HSA-72697 Start codon recognition R-HSA-156823 Association of phospho-L13a with GAIT element of Ceruloplasmin mRNA R-HSA-156808 Formation of translation initiation complexes yielding circularized Ceruloplasmin mRNA in a 'closed-loop' conformation R-HSA-927832 UPF1 binds an mRNP with a termination codon preceding an Exon Junction Complex R-HSA-927789 Formation of UPF1:eRF3 complex on mRNA with a premature termination codon and no Exon Junction Complex R-HSA-1678842 Competitive inhibition of translation initiation by ISGylated 4EHP R-HSA-927889 SMG1 phosphorylates UPF1 (enhanced by Exon Junction Complex) R-HSA-72662 Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43S R-HSA-166208 mTORC1-mediated signalling R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA R-HSA-9010553 Regulation of expression of SLITs and ROBOs R-HSA-72706 GTP hydrolysis and joining of the 60S ribosomal subunit R-HSA-429947 Deadenylation of mRNA R-HSA-975957 Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC) R-HSA-72737 Cap-dependent Translation Initiation R-HSA-165159 mTOR signalling R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-376176 Signaling by ROBO receptors R-HSA-429914 Deadenylation-dependent mRNA decay R-HSA-927802 Nonsense-Mediated Decay (NMD) R-HSA-72702 Ribosomal scanning and start codon recognition R-HSA-72649 Translation initiation complex formation R-HSA-156827 L13a-mediated translation R-HSA-975956 Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC) R-HSA-1169408 ISG15 antiviral mechanism R-HSA-72613 Eukaryotic Translation Initiation R-HSA-162582 Signal Transduction R-HSA-8953854 Metabolism of RNA R-HSA-422475 Axon guidance R-HSA-1169410 Antiviral mechanism by IFN-stimulated genes R-HSA-72766 Translation R-HSA-1266738 Developmental Biology R-HSA-913531 Interferon Signaling R-HSA-392499 Metabolism of proteins R-HSA-1280215 Cytokine Signaling in Immune system R-HSA-168256 Immune System
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
