SRP-dependent cotranslational protein targeting to membrane (Homo sapiens)

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5, 11, 162, 10, 142, 168cytosolendoplasmic reticulum lumenSEC61B 28S rRNA 7SL RNA (ENST00000410707) SSR2 RPLP0 RPL40 RPS18 RPS10 RPL15 RPS29 RPLP1 RPL37 SSR1 nascent polypeptide with signal sequence RPL10L RPS16 RPL13A RPS19 RPL28 RPL37A SEC61B RPL19 RPS4Y2 RPLP2 SRP:polypeptide+signal:ribosomeCeruloplasmin mRNA RPS3A RPS24 RPS23 SRPR RPLP0 RPS6 RPS17 RPL24 RPL36A RPL35A RPL29 RPL38 RPL19 RPL36AL RPS20 RPLP2 RPL27 RPL38 5S rRNA RPS4X RPL35A RPN1 RPS9 RPL39 RPS12 RPL6 RPL10A RPL41 RPLP2 RPS16 RPL28 RPS4Y1 7SL RNA (ENST00000410687) 18S rRNA RPL41 RPL40 nascent polypeptide with signal sequence RPS4Y1 RPSA SRP54 FAU RPS8 DDOST nascent polypeptide with signal sequence RPS28 RPL4 RPL27 RPS13 RPL6 RPS19 RPL29 RPS24 RPL13 RPS17 RPS4Y2 RPL8 RPL13 RPS15A DDOST RPL37 RPL36AL RPS12 Ceruloplasmin mRNA RPL10A 28S rRNA RPL32 RPL3 RPS29 RPS10 SRP19 RPS13 SRP68 Translocon:TRAPRPS4Y1 SRPR RPL18 RPS6 SRP14 RPL40 RPS6 RPL3 RPS27L Ceruloplasmin mRNA RPL35 RPS28 RPL36A RPS27 RPL7 RPS20 RPL22L1 RPL18A RPS24 RPL23A RPL27 RPL7A RPL32 RPL14 RPL8 SRP72 SRP54 RPL30 SEC61G RPS25 RPSA RPL27A RPS4Y1 Ceruloplasmin mRNA RPS26 SSR3 RPL27A RPS25 RPS26 5S rRNA RPL29 RPS27L Ceruloplasmin mRNA SRP72 RPL3L RPL41 RPL31 RPL12 RPS8 RPL7 RPL38 RPL7 RPL3L RPLP2 RPL35 RPL22 RPL12 5S rRNA RPS15 RPL14 RPS10 cleaved nascent polypeptide RPL5 RPS27A(77-156) 5.8S rRNA RPS10 5S rRNA RPN2 nascent polypeptide with signal sequence RPS27L RPL3L RPL35 SRP14 Ceruloplasmin mRNA RPL23 RPL22 5.8S rRNA RPLP1 RPL24 RPL9 RPL17 RPL11 RPL17 RPL12 RPL36AL SEC61A2 RPL32 RPS4X mRNARPL13 RPL14 RPL15 RPL18 RPLP1 RPL39L RPL13 18S rRNA SSR3 RPL9 RPL35A 5.8S rRNA RPLP0 RPS13 SSR3 SEC11C RPS27A(77-156) RPL21 RPL35 RPL18A RPS3A RPL23A RPS21 RPL19 RPS13 RPL26 RPS9 RPS14 SSR4 RPS2 RPS28 RPL3 RPS23 RPL36A FAU RPL10A RPS29 RPL38 SRP14 SEC61A1 RPL13 SSR1 RPL23 RPL5 RPL12 RPL22L1 RPL34 RPS7 RPL3L RPL30 RPS7 28S rRNA RPL21 RPL10 RPL29 80S ribosomeSPCS3 RPL36AL Signal RecognitionParticleRPS23 RPL10A RPL10A RPS20 RPL32 RPL30 RPS18 RPL21 RPL23 RPL39 RPS4X RPL23A RPL37A RPS29 RPL10L RPL10 SEC11A RPL26 RPS17 18S rRNA RPL41 RPL11 RPS8 RPS15 RPL24 RPL39 SRP68 RPL9 RPL18 RPS4Y1 RPL26 RPL23A RPL18A RPS11 FAU RPS27L RPS14 RPS19 RPS27 RPL39 RPS24 SSR2 RPL15 SEC61B RPL38 SSR1 RPLP2 RPS25 RPL8 RPS14 RPS20 RPL17 RPL21 signal peptideRPS14 RPS11 RPL31 RPS16 RPL21 RPL5 RPL5 SRP9 RPS3 RPL22L1 7SL RNA (ENST00000410707) RPL22 RPL7 RPS5 RPS7 RPL30 RPL21 RPL35A RPL36AL 5.8S rRNA SSR4 SEC61A1 RPL36 SRP19 RPS15 RPSA RPL34 RPL26 RPL14 7SL RNA (ENST00000410687) SRP54 RPL18A RPLP1 RPS20 RPL10L RPS24 RPL27A RPL13A TRAM1 RPL31 RPL11 RPS12 RPLP0 RPL19 7SL RNA (ENST00000410707) RPL10L RPS23 RPL37A SSR2 RPS25 RPL11 RPS7 RPS9 7SL RNA (ENST00000410687) RPN2 RPS23 RPL14 RPL27A RPL7A RPS26 RPL26L1 RPS13 RPL5 RPL30 RPS5 FAU RPL12 RPL10 RPS7 RPS27 RPS4Y2 RPLP1 DDOST RPS28 RPL4 RPS9 RPL36A SRPRB RPL13 RPL9 RPS3 RPL27 RPS17 RPS4Y2 RPN1 RPL12 RPL8 RPL13A RPL18 RPL10 18S rRNA cleavedpolypeptide:TransloconRPS15A polypeptide+signal:TransloconRPS29 RPL27A RPS14 RPL10 RPL13A RPL18A RPL19 RPL37A RPS8 RPL6 RPL7 RPL4 RPL28 RPL26 RPL34 RPS29 RPLP1 RPS15A RPL24 RPL3L RPS5 RPL36AL RPS2 SRP receptorRPS12 SEC61G RPL7A RPL3L ribosome:mRNA:polypeptide+signalRPL18A RPSA RPS8 RPS18 18S rRNA RPL35 RPL31 RPS2 RPL29 RPL10A RPS3A RPL26L1 RPS21 RPL17 RPL22 RPS3A RPL27A RPL26L1 RPL18 RPL24 RPL32 RPL17 RPS3A RPS15A SSR4 RPS16 RPS9 RPN1 RPS15A RPL26L1 RPL28 RPL6 RPS11 RPS23 RPL27 RPL22L1 5S rRNA RPS13 FAU RPS20 RPL13A RPL23 RPS5 RPS6 RPS17 RPS2 RPS21 SEC61A2 RPLP0 RPL39L RPS27L SRP9 RPS3 RPL15 RPL34 RPS16 RPS6 TRAM1 RPL39L 28S rRNA RPL22 SRPreceptor:SRP:ribosome:polypeptide+signalRPL35A 28S rRNA RPS15 RPL40 RPL34 RPSA RPL15 RPS15A RPL23 RPL7A RPL37 RPLP2 RPL36 RPL37A 5.8S rRNA RPL39 RPL3 RPS4X TRAM1 RPL19 RPLP0 RPL36 RPL41 RPS27 RPL9 RPS27A(77-156) RPS9 RPL36 RPL6 28S rRNA RPL17 RPL29 RPS27 SRP19 SEC61A2 RPS5 18S rRNA RPL37A RPS6 SPCS1 FAU RPS27A(77-156) RPL36 RPL39 RPS27L RPS10 RPL30 RPS26 SRPRB RPS3A RPS19 RPS18 RPN2 RPS26 RPL10 RPL39L RPL23 5S rRNA RPSA RPL6 RPS12 RPL22L1 RPL36 RPS25 SEC61G RPS12 RPL37 RPL4 RPL13A RPL35 RPL26L1 RPS16 RPS4Y1 RPL28 RPL36A RPS18 RPS3 RPS11 RPL41 RPL40 RPS2 RPL22 RPL38 RPL28 RPL9 RPL26L1 RPL14 RPS28 RPS11 RPS2 SPCS2 RPS15 RPS27 RPL37 SRP72 RPL31 RPL39L RPS3 RPS19 RPL24 RPL4 RPL8 RPL3 RPS3 5.8S rRNA RPL34 RPS28 RPL23A RPS27A(77-156) RPL4 RPS10 RPS21 RPS26 RPS17 Signal PeptidaseRPL7A RPL7A RPL35A RPS7 RPL3 RPS18 RPS4X RPL8 RPL11 RPS11 RPS14 RPS21 RPL10L RPS19 RPL22L1 RPL26 RPS4X RPS8 RPS24 RPL18 RPL27 RPS25 RPL32 RPS4Y2 SRP68 RPL11 RPL10L SRP9 RPS15 RPL31 RPS21 RPS4Y2 SEC61A1 RPL15 RPL7 RPS5 RPL5 RPL40 RPL37 RPL23A RPL39L RPS27A(77-156) RPL36A 141, 3, 4, 6, 7, 9...


The process for translation of a protein destined for the endoplasmic reticulum (ER) branches from the canonical cytoslic translation process at the point when a nascent polypeptide containing a hydrophobic signal sequence is exposed on the surface of the cytosolic ribosome:mRNA:peptide complex. The signal sequence mediates the interaction of this complex with a cytosolic signal recognition particle (SRP) to form a complex which in turn docks with an SRP receptor complex on the ER membrane. There the ribosome complex is transferred from the SRP complex to a translocon complex embedded in the ER membrane and reoriented so that the nascent polypeptide protrudes through a pore in the translocon into the ER lumen. Translation, which had been halted by SRP binding, now resumes, the signal peptide is cleaved from the polypeptide, and elongation proceeds, with the growing polypeptide oriented into the ER lumen. View original pathway at:Reactome.


Pathway is converted from Reactome ID: 1799339
Reactome version: 66
Reactome Author 
Reactome Author: May, Bruce, Gopinathrao, G

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  1. Yin J, Iakhiaeva E, Menichelli E, Zwieb C.; ''Identification of the RNA binding regions of SRP68/72 and SRP72 by systematic mutagenesis of human SRP RNA.''; PubMed Europe PMC
  2. Dodson G, Steiner D.; ''The role of assembly in insulin's biosynthesis.''; PubMed Europe PMC
  3. Yin J, Yang CH, Zwieb C.; ''Assembly of the human signal recognition particle (SRP): overlap of regions required for binding of protein SRP54 and assembly control.''; PubMed Europe PMC
  4. Egea PF, Stroud RM, Walter P.; ''Targeting proteins to membranes: structure of the signal recognition particle.''; PubMed Europe PMC
  5. Lakkaraju AK, Mary C, Scherrer A, Johnson AE, Strub K.; ''SRP keeps polypeptides translocation-competent by slowing translation to match limiting ER-targeting sites.''; PubMed Europe PMC
  6. Menichelli E, Isel C, Oubridge C, Nagai K.; ''Protein-induced conformational changes of RNA during the assembly of human signal recognition particle.''; PubMed Europe PMC
  7. Iakhiaeva E, Hinck CS, Hinck AP, Zwieb C.; ''Characterization of the SRP68/72 interface of human signal recognition particle by systematic site-directed mutagenesis.''; PubMed Europe PMC
  8. Merrick WC.; ''Eukaryotic protein synthesis: still a mystery.''; PubMed Europe PMC
  9. Zwieb C.; ''Recognition of a tetranucleotide loop of signal recognition particle RNA by protein SRP19.''; PubMed Europe PMC
  10. Skach WR.; ''The expanding role of the ER translocon in membrane protein folding.''; PubMed Europe PMC
  11. Römisch K, Miller FW, Dobberstein B, High S.; ''Human autoantibodies against the 54 kDa protein of the signal recognition particle block function at multiple stages.''; PubMed Europe PMC
  12. Hsu K, Chang DY, Maraia RJ.; ''Human signal recognition particle (SRP) Alu-associated protein also binds Alu interspersed repeat sequence RNAs. Characterization of human SRP9.''; PubMed Europe PMC
  13. Gowda K, Clemons WM, Zwieb C, Black SD.; ''Expression, purification, and crystallography of the conserved methionine-rich domain of human signal recognition particle 54 kDa protein.''; PubMed Europe PMC
  14. Potter MD, Nicchitta CV.; ''Endoplasmic reticulum-bound ribosomes reside in stable association with the translocon following termination of protein synthesis.''; PubMed Europe PMC
  15. Rose MA, Weeks KM.; ''Visualizing induced fit in early assembly of the human signal recognition particle.''; PubMed Europe PMC
  16. Nagai K, Oubridge C, Kuglstatter A, Menichelli E, Isel C, Jovine L.; ''Structure, function and evolution of the signal recognition particle.''; PubMed Europe PMC
  17. Kuglstatter A, Oubridge C, Nagai K.; ''Induced structural changes of 7SL RNA during the assembly of human signal recognition particle.''; PubMed Europe PMC


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101356view11:24, 1 November 2018ReactomeTeamreactome version 66
100894view20:59, 31 October 2018ReactomeTeamreactome version 65
100435view19:33, 31 October 2018ReactomeTeamreactome version 64
99984view16:17, 31 October 2018ReactomeTeamreactome version 63
99538view14:52, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
99173view12:42, 31 October 2018ReactomeTeamreactome version 62
93920view13:44, 16 August 2017ReactomeTeamreactome version 61
93498view11:25, 9 August 2017ReactomeTeamreactome version 61
88426view12:03, 5 August 2016FehrhartOntology Term : 'mRNA nuclear export pathway' added !
86593view09:21, 11 July 2016ReactomeTeamreactome version 56
83340view10:50, 18 November 2015ReactomeTeamVersion54
81493view13:01, 21 August 2015ReactomeTeamVersion53
76970view08:25, 17 July 2014ReactomeTeamFixed remaining interactions
76675view12:04, 16 July 2014ReactomeTeamFixed remaining interactions
76003view10:06, 11 June 2014ReactomeTeamRe-fixing comment source
75709view11:05, 10 June 2014ReactomeTeamReactome 48 Update
75063view13:57, 8 May 2014AnweshaFixing comment source for displaying WikiPathways description
74707view08:46, 30 April 2014ReactomeTeamNew pathway

External references


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NameTypeDatabase referenceComment
18S rRNA ProteinX03205 (EMBL)
28S rRNA ProteinM11167 (EMBL)
5.8S rRNA ProteinJ01866 (EMBL)
5S rRNA ProteinV00589 (EMBL)
7SL RNA (ENST00000410687) ProteinENST00000410687 (Ensembl)
7SL RNA (ENST00000410707) ProteinENST00000410707 (Ensembl)
80S ribosomeComplexR-HSA-72500 (Reactome)
Ceruloplasmin mRNA ProteinM13699 (EMBL)
DDOST ProteinP39656 (Uniprot-TrEMBL)
FAU ProteinP62861 (Uniprot-TrEMBL)
RPL10 ProteinP27635 (Uniprot-TrEMBL)
RPL10A ProteinP62906 (Uniprot-TrEMBL)
RPL10L ProteinQ96L21 (Uniprot-TrEMBL)
RPL11 ProteinP62913 (Uniprot-TrEMBL)
RPL12 ProteinP30050 (Uniprot-TrEMBL)
RPL13 ProteinP26373 (Uniprot-TrEMBL)
RPL13A ProteinP40429 (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)
RPL22L1 ProteinQ6P5R6 (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)
RPL36AL ProteinQ969Q0 (Uniprot-TrEMBL)
RPL37 ProteinP61927 (Uniprot-TrEMBL)
RPL37A ProteinP61513 (Uniprot-TrEMBL)
RPL38 ProteinP63173 (Uniprot-TrEMBL)
RPL39 ProteinP62891 (Uniprot-TrEMBL)
RPL39L ProteinQ96EH5 (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)
RPN1 ProteinP04843 (Uniprot-TrEMBL)
RPN2 ProteinP04844 (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)
RPS27L ProteinQ71UM5 (Uniprot-TrEMBL)