Eukaryotic translation initiation (Homo sapiens)

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85, 1413415, 185, 14, 262210, 23171110, 231325181, 7, 16, 187, 16, 272, 7, 9, 12, 16...3, 7, 16, 21, 277, 14, 16, 20, 24...1cytosolRPS2 RPS5 RPL18 RPS13 GDP EIF1AX RPS14 40S ribosomalcomplexEIF3G RPL24 RPL24 RPS14 RPS3A EIF4A1 RPL17 RPL32 RPLP1 RPL38 RPL4 RPL37 EIF3C EIF3G RPL36A RPL26 RPL11 RPL39 RPS6 RPS12 RPL19 EIF3B RPS27 RPS9 RPS27 5S rRNA EIF5EIF3H EIF4A1 RPS14 EIF5B RPL10 RPS5 RPL28 RPL23A RPL38 EIF4G1 EIF3G FAU RPL7A RPL13 RPL13A RPL36 EIF3D RPS12 RPL3L RPS24 GTP RPS27A(77-156) RPS29 Met-tRNAi RPL30 48S complexEIF2S3 RPL18A Met-tRNAi RPLP0 EIF3D RPL35 EIF2S1 RPS12 RPS4Y1 RPS9 RPL37 RPS8 EIF3H RPL10A RPL17 RPS29 18S rRNA EIF3I RPS4Y1 GTP RPS3 RPL11 PiEIF2S1 RPL13A EIF1AX RPL22 EIF2S2 RPS13 RPL27 RPS20 EIF2S2 RPS15A RPS25 EIF2S1 RPS5 EIF4H RPS21 RPS15A RPL32 EIF2B2 RPL35A RPL3L RPS10 RPL23 RPL24 FAU RPS13 18S rRNA RPS12 RPL37A RPS3A EIF4G1 RPS27 RPL15 RPL29 RPS10 EIF1AXEIF3B RPS21 RPS9 RPL30 RPSA RPL10A EIF4B RPL37A EIF3K GTP RPS19 RPL35 RPL12 EIF3H FAU Met-tRNAi RPL13 EIF2S1 eIF4A subunitscomplex60S ribosomalcomplexRPS9 RPS8 RPS4X EIF4B RPS25 RPS18 ATPRPS8 EIF2S1 5S rRNA RPL18 RPS7 EIF3H EIF2S2 RPLP2 EIF3F RPL7A GTPRPL23 RPL36 18S rRNA RPS8 RPS11 RPS3A EIF1AX RPL37A RPS11 RPS27 RPL10A EIF3I EIF2S3 RPL24 RPS23 RPL11 EIF3E EIF3E RPS26 5S rRNA EIF4A2 RPS3A EIF2S2 EIF4BRPL41 RPS25 EIF2S1 RPL11 RPS6 RPS20 EIF4A1 RPLP0 RPS23 RPS18 RPS15A EIF3C RPL26 EIF5RPL10 80S:Met-tRNAi:mRNARPS5 EIF2S1 EIF3F RPS20 RPL40 RPS12 RPS24 RPS4Y1 RPL4 RPS4X RPLP1 FAU EIF2B5 EIF2S2 FAU RPS17 RPS3 RPL17 EIF4A2 RPL26L1 RPL18 EIF3I FAU RPL34 RPS28 RPL13ARPL21 RPL18A RPS10 RPL39 EIF3J Met-tRNAi RPS4Y1 RPL9 RPL23 EIF1AX Ceruloplasmin mRNA RPL40 RPL34 RPS3A RPS3 RPS16 RPS14 RPS25 EIF4A1 EIF4A1 RPL37A RPS6 RPS15A RPL37 RPL17 RPL40 RPS15 RPS15 RPL28 RPS19 GDPEIF2S3 RPL35 EIF2S1:EIF2S2:EIF2S3RPS15 EIF2S1 EIF2S1 RPS9 RPS10 EIF4E RPL34 RPL36A EIF4A2 EIF3K EIF4A1 RPS9 Met-tRNAi RPS8 RPS2 RPS18 eIF1RPS4Y1 RPS27A(77-156) PABPC1RPS23 RPS11 RPS21 RPS6 RPS12 RPS4Y1 RPL7A RPS3 RPS2 RPL22 RPS23 28S rRNA RPL19 RPS16 EIF3G FAU RPL15 RPL31 RPL27 RPL3 RPL3L RPL6 EIF5RPS11 RPS3 5.8S rRNA RPL36A RPSA EIF3B RPL11 EIF2B3 RPS21 EIF4H RPL6 EIF2B4 RPL28 RPS28 eIF1EIF5B RNA-binding protein in RNP (ribonucleoprotein) complexes ADPMet-tRNAi RPL22 5S rRNA RPL24 EIF3J RPL9 EIF3J RPL9 EIF3H RPL6 RPL12 RPL35 RPLP2 RPS3 RPL26L1 RPL3 RPL9 RPS4X EIF2B3 RPL23 RPL21 RPS24 RPLP0 40S:eIF3:eIF1A5.8S rRNA FAU RPS2 RPS19 RPL38 GTP EIF3I RPL38 RPS23 RPL26L1 RPLP0 RPL4 EIF3F RPL19 RPL14 RPS4X RPS19 EIF4G1 EIF3A RPS12 43S:CeruloplasminmRNA:eIF4F:eIF4B:eIF4H:PABPEIF3F RPS16 RPL7A RPS7 RPL19 RPL5 RPSA RPS15A RPL31 RPS27 EIF3F RPS3A eIF3 subunitscomplexRPL27 RPL3 RPS10 RPL32 EIF3E RPS21 RPL28 RPS10 80S:Met-tRNAi:mRNA:eIF5B:GTPRPS14 RPS7 RPL30 EIF3C RPS11 RPL39 RPL14 RPL34 GTP RPL26 RPS15 RPS13 RPS16 RPL6 EIF3A RPS6 RPL4 28S rRNA RPL8 RPS7 EIF4B RPS4Y1 EIF3E RPS7 RPL15 EIF4H EIF2B1 5.8S rRNA 28S rRNA RPL14 RPS15A EIF2S2 RPL3 RPS5 RPS21 EIF4B RPS24 RPS11 RPS12 EIF4G1 RPL8 GDP eIF2:GTPRPL30 EIF1AXRPS20 RPS23 RPS2 EIF4G1 RPS27 RPL7 RPS26 RPS27A(77-156) EIF1AX RPS12 RPS24 EIF3I RPL35 RPS23 RPS4Y1 RPS9 RPL5 EIF3C RPL7 PiATPRPL26L1 RPS13 RPS3 RPL29 60s ribosomalcomplex lackingL13a subuniteIF2:GDP: eIF2BRPS13 RPS18 RPL15 EIF4E EIF4H EIF4A2 RPS27A(77-156) RPL36A RPS27A(77-156) RPS27 RPS4X RPS14 RPS25 RPL36 RPS21 RNA-binding protein in RNP (ribonucleoprotein) complexes eIF5B:GDPRPS3A ternary complexEIF2S2 EIF3K EIF4H18S rRNA RPL10A RPL29 EIF3A RPS20 RPS28 RPS12 RPL22 EIF3B PABPC1 RPS26 RPS19 RPS3 GTP RPL5 RPS2 18S rRNA 28S rRNA RPS14 EIF3D RPL27 CeruloplasminmRNA:eIF4F:eIF4B:eIF4HEIF2S2 RPL36A GTPEIF2S2 RPL8 RPL13A EIF4E RPL31 Ceruloplasmin mRNA Ceruloplasmin mRNA RPL10 RPS2 RPS11 18S rRNA RPL7 RPS3 EIF3C RPL41 Ceruloplasmin mRNA RPS6 EIF3F RPL5 RPS10 EIF4A2 RPSA Ceruloplasmin mRNA RPL23A EIF3J RPL36 PABPC1 RPL35A RPS26 RPL27A 5S rRNA EIF3G FAU RPS29 EIF1AXRPS7 phospho-L13aassociated wth the 3' UTR GAIT elementof ceruloplasminmRNA within thetranslationinitiation complexRPS7 Ceruloplasmin mRNA RPS15 GTP RPL37A RPL27A RPL27 EIF4B RPSA RPS20 RPL31 EIF3B EIF3H EIF4A2 RPS21 RPS19 EIF2S1 RPL10 RPS19 RPS29 RPL18 RPSA RPL27A RPS18 RPS4X RPL12 RPSA RPL26 EIF2S3 EIF4A1 RPS29 EIF4EBP1 RPL36 RPS4X ATPRPS14 p-RPL13AEIF3K RPL6 RPS4X Ceruloplasmin mRNA RPS5 RPS28 PieIF4F:mRNPEIF4EEIF2S3 RPL17 RPS17 18S rRNA RPS25 EIF4G1RPS20 RPS12 RPS8 EIF2S3 RPS14 RPS28 EIF2S1 RPS24 RPL13 RPL3 EIF3G RPS9 5.8S rRNA RPL8 RPS3A EIF4E RPS15 RPS25 EIF3I RPL18A EIF2S1 RPS27 RPS3A RPL41 EIF4A1 RPS6 RPS15 EIF2B4 EIF3I EIF2S3 RPS19 EIF3B RPS5 RPS9 RPL26L1 RPS24 Met-tRNAi EIF3D RPS8 RPS6 eIF2B subunitscomplexRPS29 43S complexRPS13 RPS18 RPL18A eIF5B:GTPRPL29 EIF1AX EIF2S3 RPS29 RPS16 RPS27 RPS5 RPL8 RNA-binding proteinin RNP(ribonucleoprotein)complexesRPS8 EIF4E mRNPEIF4G1 RPL10 EIF3A RPS5 EIF3J RPS27 EIF4G1 RPS28 EIF4A2 RPS21 EIF3B EIF2B2 RPS16 RPS15 28S rRNA RPS15 18S rRNA RPS17 RPS2 RPS6 EIF4E RPL37 RPL32 RPS26 mRNA:eIF4F:eIF4B:eIF4HMet-tRNAi EIF3D RPS7 FAU RPL10A RPL40 RPS28 EIF2B1 FAU RPLP2 RPL18A RPLP0 RPL5 EIF4H RPL21 RPS4X RPS18 RPS4Y1 RPS16 RPS4Y1 RPS4X RPL12 EIF3D Ceruloplasmin mRNA RPLP1 RPS15A RPS11 EIF4B RPS27A(77-156) PiRPS24 EIF2B5 RPS10 RPS25 RPS13 43S:mRNA:eIF4F:eIF4B:eIF4HCeruloplasmin mRNA RPS15 RPL19 RPS21 RPL40 EIF2S3 EIF4EBP1RPS29 ADPEIF4E EIF3D RPS24 RPS16 RPS24 RPS5 EIF4E p-RPL13A RPS25 RPL21 RPL41 RPL13 RPS27A(77-156) Met-tRNAiRPL30 EIF3C RPL12 RPS15A 5.8S rRNA EIF3A EIF3F RPS16 RPS15 RPL3L EIF3J RPS29 RPS3 RPL28 RPS11 EIF1AXRPS15A RPL3L RPS27 EIF3J RPL37 RPS18 RPS26 RPS15A RPS29 RPS20 RPS17 RPS9 EIF2S2 EIF4A2 EIF4A1 EIF2S3 RPS8 RPL39 RPL38 RPS17 RPSA RPS28 RPL35A RPS28 RPS17 RPS25 RPS27A(77-156) RPLP2 RPS17 RPL7 EIF3E EIF4E RPS3A RPL14 eIF4E:4E-BPRPS18 RPS11 RPS25 RPS3A EIF3K RPL23A RPL35A RPS10 RPS19 RPS29 RPS20 RPS2 RPL27A RPS13 RPS23 RPL4 Ceruloplasmin mRNA GTP RPS6 RPS21 EIF3C EIF3K EIF2S1:EIF2S2:EIF2S3RPL13 RPS7 RPS27A(77-156) RPS27A(77-156) RPS8 EIF4G1 RPL27A EIF2S3 RPS23 RPS28 18S rRNA RPS7 eIF2:GTPEIF5B RPS19 80S ribosomeGDP RPS17 RPL29 RPL18 Ceruloplasmin mRNA RPL23 RPS10 RPSA RPL9 RPS27A(77-156) Met-tRNAi EIF4H eIF2:GDPRPS17 RPS19 RPS18 RPS8 RPS2 RPL23A EIF3G RPSA 40S:Met-tRNAi:mRNARPS14 EIF3E RPS14 RPL34 EIF3H EIF3A RPL35A RPL22 RPS13 RPL31 GTP RPS16 RPS4X RPS28 18S rRNA EIF3A EIF3E L13a kinaseeIF4FRPSA RPS20 RPS17 RPL21 RPS17 RPLP1 RPS26 RPL15 RPS26 RPS4Y1 RPS3 RPL7A RPL41 RPL39 RPS5 EIF3K RPS18 RPS10 RPL32 EIF4A2 RPL14 RPS26 RPS20 RPL7 EIF2S2 RPL13A RPS6 GTP RPS26 EIF2S3 RPS13 RPS26 RPS23 RPS24 RPS11 RPS15A RPS2 18S rRNA RPS23 RPL23A RPS7 RPS9 RPL26 EIF2S2 RPLP1 RPLP2 RPS16 6, 286, 286, 286, 286, 286, 286, 286, 286, 286, 28


Description

Initiation of translation in the majority of eukaryotic cellular mRNAs depends on the 5'-cap (m7GpppN) and involves ribosomal scanning of the 5' untranslated region (5'-UTR) for an initiating AUG start codon. Therefore, this mechanism is often called cap-dependent translation initiation. Proximity to the cap, as well as the nucleotides surrounding an AUG codon, influence the efficiency of the start site recognition during the scanning process. However, if the recognition site is poor enough, scanning ribosomal subunits will ignore and skip potential starting AUGs, a phenomenon called leaky scanning. Leaky scanning allows a single mRNA to encode several proteins that differ in their amino-termini. Merrick (2010) provides an overview of this process and hghlights several features of it that remain incompletely understood.

Several eukaryotic cell and viral mRNAs initiate translation by an alternative mechanism that involves internal initiation rather than ribosomal scanning. These mRNAs contain complex nucleotide sequences, called internal ribosomal entry sites, where ribosomes bind in a cap-independent manner and start translation at the closest downstream AUG codon.

Initiation on several viral and cellular mRNAs is cap-independent and is mediated by binding of the ribosome to internal ribosome entry site (IRES) elements. These elements are often found in characteristically long structured regions on the 5'-UTR of an mRNA that may or may not have regulatory upstream open reading frames (uORFs). Both of these features on the 5'-end of the mRNA hinder ribosomal scanning, and thus promote a cap-independent translation initiation mechanism. IRESs act as specific translational enhancers that allow translation initiation to occur in response to specific stimuli and under the control of different trans-acting factors, as for example when cap-dependent protein synthesis is shut off during viral infection. Such regulatory elements have been identified in the mRNAs of growth factors, protooncogenes, angiogenesis factors, and apoptosis regulators, which are translated under a variety of stress conditions, including hypoxia, serum deprivation, irradiation and apoptosis. Thus, cap-independent translational control might have evolved to regulate cellular responses in acute but transient stress conditions that would otherwise lead to cell death, while the same mechanism is of major importance for viral mRNAs to bypass the shutting-off of host protein synthesis after infection. Encephalomyocarditis virus (EMCV) and hepatitis C virus exemplify two distinct mechanisms of IRES-mediated initiation. In contrast to cap-dependent initiation, the eIF4A and eIF4G subunits of eIF4F bind immediately upstream of the EMCV initiation codon and promote binding of a 43S complex. Accordingly, EMCV initiation does not involve scanning and does not require eIF1, eIF1A, and the eIF4E subunit of eIF4F. Nonetheless, initiation on some EMCV-like IRESs requires additional non-canonical initiation factors, which alter IRES conformation and promote binding of eIF4A/eIF4G. Initiation on the hepatitis C virus IRES is simpler: a 43S complex containing only eIF2 and eIF3 binds directly to the initiation codon as a result of specific interaction of the IRES and the 40S subunit.

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Bibliography

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  1. Pause A, Belsham GJ, Gingras AC, Donzé O, Lin TA, Lawrence JC, Sonenberg N.; ''Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function.''; PubMed Europe PMC Scholia
  2. Sampath P, Mazumder B, Seshadri V, Fox PL.; ''Transcript-selective translational silencing by gamma interferon is directed by a novel structural element in the ceruloplasmin mRNA 3' untranslated region.''; PubMed Europe PMC Scholia
  3. Pestova TV, Borukhov SI, Hellen CU.; ''Eukaryotic ribosomes require initiation factors 1 and 1A to locate initiation codons.''; PubMed Europe PMC Scholia
  4. Mazumder B, Sampath P, Seshadri V, Maitra RK, DiCorleto PE, Fox PL.; ''Regulated release of L13a from the 60S ribosomal subunit as a mechanism of transcript-specific translational control.''; PubMed Europe PMC Scholia
  5. Grifo JA, Tahara SM, Morgan MA, Shatkin AJ, Merrick WC.; ''New initiation factor activity required for globin mRNA translation.''; PubMed Europe PMC Scholia
  6. Safer B, Adams SL, Anderson WF, Merrick WC.; ''Binding of MET-TRNAf and GTP to homogeneous initiation factor MP.''; PubMed Europe PMC Scholia
  7. Pestova TV, Shatsky IN, Hellen CU.; ''Functional dissection of eukaryotic initiation factor 4F: the 4A subunit and the central domain of the 4G subunit are sufficient to mediate internal entry of 43S preinitiation complexes.''; PubMed Europe PMC Scholia
  8. Merrick WC.; ''Eukaryotic protein synthesis: still a mystery.''; PubMed Europe PMC Scholia
  9. Kozak M.; ''Evaluation of the "scanning model" for initiation of protein synthesis in eucaryotes.''; PubMed Europe PMC Scholia
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  11. Trachsel H, Erni B, Schreier MH, Staehelin T.; ''Initiation of mammalian protein synthesis. II. The assembly of the initiation complex with purified initiation factors.''; PubMed Europe PMC Scholia
  12. Rowlands AG, Panniers R, Henshaw EC.; ''The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2.''; PubMed Europe PMC Scholia
  13. Iost I, Dreyfus M, Linder P.; ''Ded1p, a DEAD-box protein required for translation initiation in Saccharomyces cerevisiae, is an RNA helicase.''; PubMed Europe PMC Scholia
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  16. Sonenberg N, Rupprecht KM, Hecht SM, Shatkin AJ.; ''Eukaryotic mRNA cap binding protein: purification by affinity chromatography on sepharose-coupled m7GDP.''; PubMed Europe PMC Scholia
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  18. Merrick WC, Kemper WM, Anderson WF.; ''Purification and characterization of homogeneous initiation factor M2A from rabbit reticulocytes.''; PubMed Europe PMC Scholia
  19. Asano K, Clayton J, Shalev A, Hinnebusch AG.; ''A multifactor complex of eukaryotic initiation factors, eIF1, eIF2, eIF3, eIF5, and initiator tRNA(Met) is an important translation initiation intermediate in vivo.''; PubMed Europe PMC Scholia
  20. Peterson DT, Merrick WC, Safer B.; ''Binding and release of radiolabeled eukaryotic initiation factors 2 and 3 during 80 S initiation complex formation.''; PubMed Europe PMC Scholia
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  26. Pestova TV, Lomakin IB, Lee JH, Choi SK, Dever TE, Hellen CU.; ''The joining of ribosomal subunits in eukaryotes requires eIF5B.''; PubMed Europe PMC Scholia
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  28. Majumdar R, Bandyopadhyay A, Maitra U.; ''Mammalian translation initiation factor eIF1 functions with eIF1A and eIF3 in the formation of a stable 40 S preinitiation complex.''; PubMed Europe PMC Scholia
  29. Dholakia JN, Wahba AJ.; ''Mechanism of the nucleotide exchange reaction in eukaryotic polypeptide chain initiation. Characterization of the guanine nucleotide exchange factor as a GTP-binding protein.''; PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128373view17:49, 3 February 2024Ash iyerFixing error (check)
128372view17:45, 3 February 2024Ash iyeridentifier added
128371view17:43, 3 February 2024Ash iyereif1 identifier added.
128323view00:28, 1 February 2024EweitzOntology Term : 'translation pathway' added !
117720view12:33, 22 May 2021EweitzModified title
114979view16:50, 25 January 2021ReactomeTeamReactome version 75
113423view11:49, 2 November 2020ReactomeTeamReactome version 74
112625view16:00, 9 October 2020ReactomeTeamReactome version 73
101541view11:40, 1 November 2018ReactomeTeamreactome version 66
101076view21:23, 31 October 2018ReactomeTeamreactome version 65
100606view19:57, 31 October 2018ReactomeTeamreactome version 64
100157view16:42, 31 October 2018ReactomeTeamreactome version 63
99707view15:11, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99288view12:46, 31 October 2018ReactomeTeamreactome version 62
93969view13:48, 16 August 2017ReactomeTeamreactome version 61
93568view11:27, 9 August 2017ReactomeTeamreactome version 61
86670view09:23, 11 July 2016ReactomeTeamreactome version 56
83337view10:49, 18 November 2015ReactomeTeamVersion54
76969view08:25, 17 July 2014ReactomeTeamFixed remaining interactions
76674view12:04, 16 July 2014ReactomeTeamFixed remaining interactions
76136view13:23, 11 June 2014AnweshaRe-fixing comment source
75707view11:05, 10 June 2014ReactomeTeamReactome 48 Update
75062view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74706view08:46, 30 April 2014ReactomeTeamReactome46
45250view18:36, 7 October 2011AlexanderPicoOntology Term : 'translation initiation pathway' added !
42035view21:51, 4 March 2011MaintBotAutomatic update
39838view05:52, 21 January 2011MaintBotNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
18S rRNA ProteinX03205 (EMBL)
28S rRNA ProteinM11167 (EMBL)
40S ribosomal complexComplexR-HSA-72392 (Reactome)
40S:Met-tRNAi:mRNAComplexR-HSA-72508 (Reactome)
40S:eIF3:eIF1AComplexR-HSA-72570 (Reactome)
43S complexComplexR-HSA-72571 (Reactome)
43S:

Ceruloplasmin

mRNA:eIF4F:eIF4B:eIF4H:PABP
ComplexR-HSA-156804 (Reactome)
43S:mRNA:eIF4F:eIF4B:eIF4HComplexR-HSA-72592 (Reactome)
48S complexComplexR-HSA-72594 (Reactome)
5.8S rRNA ProteinJ01866 (EMBL)
5S rRNA ProteinV00589 (EMBL)
60S ribosomal complexComplexR-HSA-72499 (Reactome)
60s ribosomal

complex lacking

L13a subunit
ComplexR-HSA-156817 (Reactome)
80S ribosomeComplexR-HSA-72500 (Reactome)
80S:Met-tRNAi:mRNA:eIF5B:GTPComplexR-HSA-72504 (Reactome)
80S:Met-tRNAi:mRNAComplexR-HSA-72505 (Reactome)
ADPMetaboliteCHEBI:16761 (ChEBI)
ATPMetaboliteCHEBI:15422 (ChEBI)
Ceruloplasmin mRNA:eIF4F:eIF4B:eIF4HComplexR-HSA-156809 (Reactome)
Ceruloplasmin mRNA ProteinM13699 (EMBL)
EIF1AX ProteinP47813 (Uniprot-TrEMBL)
EIF1AXProteinP47813 (Uniprot-TrEMBL)
EIF2B1 ProteinQ14232 (Uniprot-TrEMBL)
EIF2B2 ProteinP49770 (Uniprot-TrEMBL)
EIF2B3 ProteinQ9NR50 (Uniprot-TrEMBL)
EIF2B4 ProteinQ9UI10 (Uniprot-TrEMBL)
EIF2B5 ProteinQ13144 (Uniprot-TrEMBL)
EIF2S1 ProteinP05198 (Uniprot-TrEMBL)
EIF2S1:EIF2S2:EIF2S3ComplexR-HSA-72515 (Reactome)
EIF2S2 ProteinP20042 (Uniprot-TrEMBL)
EIF2S3 ProteinP41091 (Uniprot-TrEMBL)
EIF3A ProteinQ14152 (Uniprot-TrEMBL)
EIF3B ProteinP55884 (Uniprot-TrEMBL)
EIF3C ProteinQ99613 (Uniprot-TrEMBL)
EIF3D ProteinO15371 (Uniprot-TrEMBL)
EIF3E ProteinP60228 (Uniprot-TrEMBL)
EIF3F ProteinO00303 (Uniprot-TrEMBL)
EIF3G ProteinO75821 (Uniprot-TrEMBL)
EIF3H ProteinO15372 (Uniprot-TrEMBL)
EIF3I ProteinQ13347 (Uniprot-TrEMBL)
EIF3J ProteinO75822 (Uniprot-TrEMBL)
EIF3K ProteinQ9UBQ5 (Uniprot-TrEMBL)
EIF4A1 ProteinP60842 (Uniprot-TrEMBL)
EIF4A2 ProteinQ14240 (Uniprot-TrEMBL)
EIF4B ProteinP23588 (Uniprot-TrEMBL)
EIF4BProteinP23588 (Uniprot-TrEMBL)
EIF4E ProteinP06730 (Uniprot-TrEMBL)
EIF4EBP1 ProteinQ13541 (Uniprot-TrEMBL)
EIF4EBP1ProteinQ13541 (Uniprot-TrEMBL)
EIF4EProteinP06730 (Uniprot-TrEMBL)
EIF4G1 ProteinQ04637 (Uniprot-TrEMBL)
EIF4G1ProteinQ04637 (Uniprot-TrEMBL)
EIF4H ProteinQ15056 (Uniprot-TrEMBL)
EIF4HProteinQ15056 (Uniprot-TrEMBL)
EIF5B ProteinO60841 (Uniprot-TrEMBL)
EIF5ProteinP55010 (Uniprot-TrEMBL)
FAU ProteinP62861 (Uniprot-TrEMBL)
GDP MetaboliteCHEBI:17552 (ChEBI)
GDPMetaboliteCHEBI:17552 (ChEBI)
GTP MetaboliteCHEBI:15996 (ChEBI)
GTPMetaboliteCHEBI:15996 (ChEBI)
L13a kinaseR-HSA-170641 (Reactome)
Met-tRNAi R-NUL-72393 (Reactome)
Met-tRNAiR-NUL-72393 (Reactome)
PABPC1 ProteinP11940 (Uniprot-TrEMBL)
PABPC1ProteinP11940 (Uniprot-TrEMBL)
PiMetaboliteCHEBI:18367 (ChEBI)
RNA-binding protein

in RNP (ribonucleoprotein)

complexes
R-NUL-72595 (Reactome)
RNA-binding protein in RNP (ribonucleoprotein) complexes R-NUL-72595 (Reactome)
RPL10 ProteinP27635 (Uniprot-TrEMBL)
RPL10A ProteinP62906 (Uniprot-TrEMBL)
RPL11 ProteinP62913 (Uniprot-TrEMBL)
RPL12 ProteinP30050 (Uniprot-TrEMBL)
RPL13 ProteinP26373 (Uniprot-TrEMBL)
RPL13A ProteinP40429 (Uniprot-TrEMBL)
RPL13AProteinP40429 (Uniprot-TrEMBL)
RPL14 ProteinP50914 (Uniprot-TrEMBL)
RPL15 ProteinP61313 (Uniprot-TrEMBL)
RPL17 ProteinP18621 (Uniprot-TrEMBL)
RPL18 ProteinQ07020 (Uniprot-TrEMBL)
RPL18A ProteinQ02543 (Uniprot-TrEMBL)
RPL19 ProteinP84098 (Uniprot-TrEMBL)
RPL21 ProteinP46778 (Uniprot-TrEMBL)
RPL22 ProteinP35268 (Uniprot-TrEMBL)
RPL23 ProteinP62829 (Uniprot-TrEMBL)
RPL23A ProteinP62750 (Uniprot-TrEMBL)
RPL24 ProteinP83731 (Uniprot-TrEMBL)
RPL26 ProteinP61254 (Uniprot-TrEMBL)
RPL26L1 ProteinQ9UNX3 (Uniprot-TrEMBL)
RPL27 ProteinP61353 (Uniprot-TrEMBL)
RPL27A ProteinP46776 (Uniprot-TrEMBL)
RPL28 ProteinP46779 (Uniprot-TrEMBL)
RPL29 ProteinP47914 (Uniprot-TrEMBL)
RPL3 ProteinP39023 (Uniprot-TrEMBL)
RPL30 ProteinP62888 (Uniprot-TrEMBL)
RPL31 ProteinP62899 (Uniprot-TrEMBL)
RPL32 ProteinP62910 (Uniprot-TrEMBL)
RPL34 ProteinP49207 (Uniprot-TrEMBL)
RPL35 ProteinP42766 (Uniprot-TrEMBL)
RPL35A ProteinP18077 (Uniprot-TrEMBL)
RPL36 ProteinQ9Y3U8 (Uniprot-TrEMBL)
RPL36A ProteinP83881 (Uniprot-TrEMBL)
RPL37 ProteinP61927 (Uniprot-TrEMBL)
RPL37A ProteinP61513 (Uniprot-TrEMBL)
RPL38 ProteinP63173 (Uniprot-TrEMBL)
RPL39 ProteinP62891 (Uniprot-TrEMBL)
RPL3L ProteinQ92901 (Uniprot-TrEMBL)
RPL4 ProteinP36578 (Uniprot-TrEMBL)
RPL40 ProteinP62987 (Uniprot-TrEMBL)
RPL41 ProteinP62945 (Uniprot-TrEMBL)
RPL5 ProteinP46777 (Uniprot-TrEMBL)
RPL6 ProteinQ02878 (Uniprot-TrEMBL)
RPL7 ProteinP18124 (Uniprot-TrEMBL)
RPL7A ProteinP62424 (Uniprot-TrEMBL)
RPL8 ProteinP62917 (Uniprot-TrEMBL)
RPL9 ProteinP32969 (Uniprot-TrEMBL)
RPLP0 ProteinP05388 (Uniprot-TrEMBL)
RPLP1 ProteinP05386 (Uniprot-TrEMBL)
RPLP2 ProteinP05387 (Uniprot-TrEMBL)
RPS10 ProteinP46783 (Uniprot-TrEMBL)
RPS11 ProteinP62280 (Uniprot-TrEMBL)
RPS12 ProteinP25398 (Uniprot-TrEMBL)
RPS13 ProteinP62277 (Uniprot-TrEMBL)
RPS14 ProteinP62263 (Uniprot-TrEMBL)
RPS15 ProteinP62841 (Uniprot-TrEMBL)
RPS15A ProteinP62244 (Uniprot-TrEMBL)
RPS16 ProteinP62249 (Uniprot-TrEMBL)
RPS17 ProteinP08708 (Uniprot-TrEMBL)
RPS18 ProteinP62269 (Uniprot-TrEMBL)
RPS19 ProteinP39019 (Uniprot-TrEMBL)
RPS2 ProteinP15880 (Uniprot-TrEMBL)
RPS20 ProteinP60866 (Uniprot-TrEMBL)
RPS21 ProteinP63220 (Uniprot-TrEMBL)
RPS23 ProteinP62266 (Uniprot-TrEMBL)
RPS24 ProteinP62847 (Uniprot-TrEMBL)
RPS25 ProteinP62851 (Uniprot-TrEMBL)
RPS26 ProteinP62854 (Uniprot-TrEMBL)
RPS27 ProteinP42677 (Uniprot-TrEMBL)
RPS27A(77-156) ProteinP62979 (Uniprot-TrEMBL)
RPS28 ProteinP62857 (Uniprot-TrEMBL)
RPS29 ProteinP62273 (Uniprot-TrEMBL)
RPS3 ProteinP23396 (Uniprot-TrEMBL)
RPS3A ProteinP61247 (Uniprot-TrEMBL)
RPS4X ProteinP62701 (Uniprot-TrEMBL)
RPS4Y1 ProteinP22090 (Uniprot-TrEMBL)
RPS5 ProteinP46782 (Uniprot-TrEMBL)
RPS6 ProteinP62753 (Uniprot-TrEMBL)
RPS7 ProteinP62081 (Uniprot-TrEMBL)
RPS8 ProteinP62241 (Uniprot-TrEMBL)
RPS9 ProteinP46781 (Uniprot-TrEMBL)
RPSA ProteinP08865 (Uniprot-TrEMBL)
eIF1R-NUL-72617 (Reactome)
eIF2:GDP: eIF2BComplexR-HSA-72529 (Reactome)
eIF2:GDPComplexR-HSA-72530 (Reactome)
eIF2:GTPComplexR-HSA-72531 (Reactome)
eIF2B subunits complexComplexR-HSA-72526 (Reactome)
eIF3 subunits complexComplexR-HSA-72555 (Reactome)
eIF4A subunits complexComplexR-HSA-72576 (Reactome)
eIF4E:4E-BPComplexR-HSA-72581 (Reactome)
eIF4F:mRNPComplexR-HSA-72597 (Reactome)
eIF4FComplexR-HSA-72587 (Reactome)
eIF5B:GDPComplexR-HSA-72502 (Reactome)
eIF5B:GTPComplexR-HSA-72503 (Reactome)
mRNA:eIF4F:eIF4B:eIF4HComplexR-HSA-72593 (Reactome)
mRNPComplexR-HSA-72596 (Reactome)
p-RPL13A ProteinP40429 (Uniprot-TrEMBL)
p-RPL13AProteinP40429 (Uniprot-TrEMBL)
phospho-L13a

associated wth the 3' UTR GAIT element of ceruloplasmin mRNA within the translation

initiation complex
ComplexR-HSA-156824 (Reactome)
ternary complexComplexR-HSA-72532 (Reactome)

Annotated Interactions

View all...
SourceTargetTypeDatabase referenceComment
40S ribosomal complexArrowR-HSA-72673 (Reactome)
40S ribosomal complexR-HSA-72676 (Reactome)
40S:Met-tRNAi:mRNAArrowR-HSA-72619 (Reactome)
40S:Met-tRNAi:mRNAR-HSA-72672 (Reactome)
40S:eIF3:eIF1AArrowR-HSA-72676 (Reactome)
40S:eIF3:eIF1AR-HSA-72691 (Reactome)
43S complexArrowR-HSA-72691 (Reactome)
43S complexR-HSA-156808 (Reactome)
43S complexR-HSA-157849 (Reactome)
43S:

Ceruloplasmin

mRNA:eIF4F:eIF4B:eIF4H:PABP
ArrowR-HSA-156808 (Reactome)
43S:

Ceruloplasmin

mRNA:eIF4F:eIF4B:eIF4H:PABP
R-HSA-156823 (Reactome)
43S:mRNA:eIF4F:eIF4B:eIF4HArrowR-HSA-157849 (Reactome)
43S:mRNA:eIF4F:eIF4B:eIF4HR-HSA-72621 (Reactome)
48S complexArrowR-HSA-72621 (Reactome)
48S complexArrowR-HSA-72697 (Reactome)
48S complexR-HSA-72619 (Reactome)
48S complexR-HSA-72697 (Reactome)
60S ribosomal complexArrowR-HSA-72673 (Reactome)
60S ribosomal complexR-HSA-156826 (Reactome)
60S ribosomal complexR-HSA-72672 (Reactome)
60s ribosomal

complex lacking

L13a subunit
ArrowR-HSA-156826 (Reactome)
80S ribosomeR-HSA-72673 (Reactome)
80S:Met-tRNAi:mRNA:eIF5B:GTPArrowR-HSA-72672 (Reactome)
80S:Met-tRNAi:mRNA:eIF5B:GTPR-HSA-72671 (Reactome)
80S:Met-tRNAi:mRNAArrowR-HSA-72671 (Reactome)
ADPArrowR-HSA-72621 (Reactome)
ADPArrowR-HSA-72647 (Reactome)
ATPArrowR-HSA-72621 (Reactome)
ATPR-HSA-72621 (Reactome)
ATPR-HSA-72647 (Reactome)
Ceruloplasmin mRNA:eIF4F:eIF4B:eIF4HR-HSA-156808 (Reactome)
EIF1AXArrowR-HSA-156808 (Reactome)
EIF1AXArrowR-HSA-157849 (Reactome)
EIF1AXArrowR-HSA-72619 (Reactome)
EIF1AXArrowR-HSA-72673 (Reactome)
EIF1AXArrowR-HSA-72697 (Reactome)
EIF1AXR-HSA-156808 (Reactome)
EIF1AXR-HSA-157849 (Reactome)
EIF1AXR-HSA-72673 (Reactome)
EIF1AXR-HSA-72676 (Reactome)
EIF1AXR-HSA-72697 (Reactome)
EIF2S1:EIF2S2:EIF2S3ArrowR-HSA-72697 (Reactome)
EIF2S1:EIF2S2:EIF2S3R-HSA-72663 (Reactome)
EIF2S1:EIF2S2:EIF2S3R-HSA-72697 (Reactome)
EIF4BArrowR-HSA-72619 (Reactome)
EIF4BR-HSA-72647 (Reactome)
EIF4Bmim-catalysisR-HSA-72647 (Reactome)
EIF4EArrowR-HSA-72619 (Reactome)
EIF4EArrowR-HSA-72622 (Reactome)
EIF4EBP1ArrowR-HSA-72622 (Reactome)
EIF4ER-HSA-72631 (Reactome)
EIF4G1ArrowR-HSA-72619 (Reactome)
EIF4G1R-HSA-72631 (Reactome)
EIF4HArrowR-HSA-72619 (Reactome)
EIF4HR-HSA-72647 (Reactome)
EIF4Hmim-catalysisR-HSA-72647 (Reactome)
EIF5ArrowR-HSA-72619 (Reactome)
EIF5ArrowR-HSA-72697 (Reactome)
EIF5R-HSA-72619 (Reactome)
EIF5R-HSA-72697 (Reactome)
GDPArrowR-HSA-72722 (Reactome)
GTPArrowR-HSA-72669 (Reactome)
GTPR-HSA-72663 (Reactome)
GTPR-HSA-72722 (Reactome)
L13a kinasemim-catalysisR-HSA-156832 (Reactome)
Met-tRNAiR-HSA-72669 (Reactome)
PABPC1R-HSA-156808 (Reactome)
PiArrowR-HSA-72619 (Reactome)
PiArrowR-HSA-72621 (Reactome)
PiArrowR-HSA-72647 (Reactome)
PiArrowR-HSA-72671 (Reactome)
R-HSA-156808 (Reactome) The precise order of events leading to the circularization of poly (A) mRNA during translation initiation is unknown. Here the association of PABP with the poly (A) mRNA and the association of PABP with eIF4F are represented as occuring simultaneously after formation of the initiation complex. However, it is also possible that these interactions occur during the formation of the translation initiation complex. The binding of eIF4F to the cap and binding of PABP to the poly (A) tail, for example, may occur at the same time. In fact, the eIF4G-PABP interaction helps eIF4F to bind tighter to the cap (Borman et al. 2000.) In addition, eIF4B and eIF4H bind more transiently to the mRNA and may not be part of an initial complex in which PABP has not yet touched eIF4G.
R-HSA-156823 (Reactome) Although the mechanism through which L13a prevents translation initiation has not been determined, Mazumder et al. (2003) have described four alternatives. L13a could (1) inhibit the function of eIF4F, (2) block the recruitment of the 43S preinitiation complex, (3) prevent scanning of the 43S complex to the initiation codon, or 4) interfere with joining of the 60S ribosomal subunit.
R-HSA-156826 (Reactome) The L13a subunit of the 60s ribosome is phosphorylated about 16 hours after INF gamma induction by an unknown kinase. At this time, L13a is also released from the 60s subunit (Mazumder et al.,2003). It is unclear, however, whether phosphorylation occurs before or after the release of L13a. Here, phosphorylation is shown as occurring after release.
R-HSA-156832 (Reactome) The L13a subunit of the 60s ribosome is phosphorylated about 16 hours after INF gamma induction by an unknown kinase. At this time, L13a is also released from the 60s subunit (Mazumder et al.,2003). It is unclear, however, whether phosphorylation occurs before or after the release of L13a. Here, phosphorylation is shown as occurring after release.
R-HSA-157849 (Reactome) The translation initiation complex forms when the 43S complex binds the mRNA that is associated with eIF4F, eIF4B and eIF4H. eIF4G in the eIF4F complex can directly contact eIF3 in the 43S complex. eIF1A is necessary for the formation of this complex.
R-HSA-72619 (Reactome) Once the Met-tRNAi has recognized the AUG, eIF2-bound GTP is hydrolyzed. The reaction is catalyzed by eIF5 (or eIF5B) and is thought to cause dissociation of all other initiation factors and allow joining of the large 60S ribosomal subunit. Release of the initiation factors from 40S leaves the Met-tRNAi in the ribosomal P-site base-paired to the start codon on the mRNA.
R-HSA-72621 (Reactome) The mRNA-bound ribosomal complex moves along the 5'-untranslated region (5'-UTR) of the mRNA from its initial site to the initiation codon to form a 48S complex, in which the initiation codon (AUG) is base paired to the anticodon of the Met-tRNAi. It is not known whether eIF4A (or another ATPase, such as DED1) facilitates scanning by melting mRNA secondary structures or by actively propelling the ribosome.
R-HSA-72622 (Reactome) eIF4E gets released from the inactive eIF4E:4EBP complex.
R-HSA-72631 (Reactome) eIF4A interacts with eIF4G, and eIF4E interacts with the amino-terminal domain of eIF4G to form the cap-binding complex eIF4F.
R-HSA-72635 (Reactome) The factor eIF4E within the eIF4F (cap-binding) complex directly binds the 5'-cap on eukaryotic mRNAs. Note that the mRNA is in complex with cytoplasmic proteins constituting an mRNP complex.
R-HSA-72647 (Reactome) The DEAD-box RNA helicase eIF4A, together with the RNA-binding proteins eIF4B or eIF4H, is thought to unwind RNA secondary structures near the 5'-end of the mRNA and in the presence of ATP.
R-HSA-72663 (Reactome) Activation of eIF2 through direct binding of GTP.
R-HSA-72669 (Reactome) The ternary complex forms upon binding of the initiator methionyl-tRNA to the active eIF2:GTP complex.
R-HSA-72670 (Reactome) Inactive eIF2:GDP binds eIF2B to form an eIF2:GDP:eIF2B intermediate.
R-HSA-72671 (Reactome) Once the 60S subunit joins the translation initiation complex, eIF5B hydrolyzes its GTP and is released from the now 80S monosome. The fully assembled 80s ribosome is now ready to start elongation of the polypeptide chain.
R-HSA-72672 (Reactome) Joining of the 60S subunit to form the 80S ribosome is catalyzed by the presence of GTP-bound eIF5B.
R-HSA-72673 (Reactome) 80S monosomes dissociate into 40S and 60S ribosomal subunits. eIF1A promotes this dissociation.
R-HSA-72676 (Reactome) eIF3 and eIF1A bind to the 40S ribosomal subunit.
R-HSA-72691 (Reactome) The ternary complex (Met-tRNAi:eIF2:GTP) binds to the complex formed by the 40S subunit, eIF3 and eIF1A, to form the 43S complex. eIF1A promotes binding of the ternary complex to the 40S subunit within 43S. The initiator methionyl-tRNA from the ternary complex is positioned at the ribosomal P site.
R-HSA-72697 (Reactome) The AUG initiation codon in the mRNA is recognized by base pairing with the anticodon of the Met-tRNAi. This reaction requires eIF1, eIF1A, eIF2 and eIF5.
R-HSA-72722 (Reactome) eIF2B is a guanine nucleotide releasing factor that is required to cause GDP release so that a new GTP molecule can bind and activate eIF2, so that it can be reused.
RNA-binding protein

in RNP (ribonucleoprotein)

complexes
ArrowR-HSA-72647 (Reactome)
RPL13AArrowR-HSA-156826 (Reactome)
RPL13AR-HSA-156832 (Reactome)
eIF1ArrowR-HSA-72697 (Reactome)
eIF1R-HSA-72619 (Reactome)
eIF1R-HSA-72697 (Reactome)
eIF1mim-catalysisR-HSA-72621 (Reactome)
eIF1mim-catalysisR-HSA-72697 (Reactome)
eIF2:GDP: eIF2BArrowR-HSA-72670 (Reactome)
eIF2:GDP: eIF2BR-HSA-72722 (Reactome)
eIF2:GDPArrowR-HSA-72619 (Reactome)
eIF2:GDPR-HSA-72670 (Reactome)
eIF2:GTPArrowR-HSA-72663 (Reactome)
eIF2:GTPArrowR-HSA-72722 (Reactome)
eIF2:GTPR-HSA-72669 (Reactome)
eIF2B subunits complexArrowR-HSA-72722 (Reactome)
eIF2B subunits complexR-HSA-72670 (Reactome)
eIF2B subunits complexmim-catalysisR-HSA-72722 (Reactome)
eIF3 subunits complexArrowR-HSA-72619 (Reactome)
eIF3 subunits complexR-HSA-72676 (Reactome)
eIF4A subunits complexArrowR-HSA-72619 (Reactome)
eIF4A subunits complexArrowR-HSA-72647 (Reactome)
eIF4A subunits complexR-HSA-72631 (Reactome)
eIF4A subunits complexR-HSA-72647 (Reactome)
eIF4A subunits complexmim-catalysisR-HSA-72647 (Reactome)
eIF4E:4E-BPR-HSA-72622 (Reactome)
eIF4F:mRNPArrowR-HSA-72635 (Reactome)
eIF4F:mRNPR-HSA-72647 (Reactome)
eIF4FArrowR-HSA-72631 (Reactome)
eIF4FR-HSA-72635 (Reactome)
eIF5B:GDPArrowR-HSA-72671 (Reactome)
eIF5B:GTPR-HSA-72672 (Reactome)
mRNA:eIF4F:eIF4B:eIF4HArrowR-HSA-72647 (Reactome)
mRNA:eIF4F:eIF4B:eIF4HR-HSA-157849 (Reactome)
mRNPR-HSA-72635 (Reactome)
p-RPL13AArrowR-HSA-156832 (Reactome)
p-RPL13AR-HSA-156823 (Reactome)
phospho-L13a

associated wth the 3' UTR GAIT element of ceruloplasmin mRNA within the translation

initiation complex
ArrowR-HSA-156823 (Reactome)
ternary complexArrowR-HSA-72669 (Reactome)
ternary complexR-HSA-72691 (Reactome)

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