SRP9 is the 9 kDa subunit of the signal recognition particle (SRP), the cytosolic ribonucleoprotein that mediates co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER). SRP comprises a single 7SL RNA (~300 nucleotides) and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72). SRP9 binds the SRP RNA as an obligate heterodimer with SRP14, and together with the Alu portion of the SRP RNA forms the Alu domain at one end of the particle. This Alu domain is the elongation-arrest module of SRP. When SRP binds a ribosome translating a signal sequence, the SRP9/SRP14 heterodimer reaches into the ribosomal elongation-factor binding site and transiently pauses (arrests) translation elongation, giving SRP time to deliver the ribosome-nascent chain complex to the ER membrane SRP receptor. SRP9 is an RNA-binding protein rather than a GTPase (the GTPases of the pathway are SRP54 and the SRP-receptor subunits). It functions in the cytoplasm/cytosol; SRP9/SRP14 transit the nucleolus during SRP assembly.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006614 SRP-dependent cotranslational protein targeting to membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of SRP9's defining biological process. As part of SRP, SRP9 (via the Alu/elongation-arrest domain) contributes to SRP-dependent co-translational targeting of proteins to the ER membrane. Conserved across the SRP9 family. Reason: Core biological process; SRP9 is an SRP subunit essential to co-translational ER targeting. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt mediates the cotranslational targeting |
| GO:0005786 signal recognition particle, endoplasmic reticulum targeting | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of SRP9 as a constitutive subunit of the signal recognition particle. Conserved and directly established. Reason: Core cellular component; SRP9 is one of the six SRP protein subunits. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt consists of a 7SL RNA molecule of 300 nucleotides and six protein |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of the cytoplasmic localization from the UniProt subcellular location. SRP functions in the cytoplasm targeting nascent chains to the ER. Reason: Correct compartment; SRP acts in the cytoplasm. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005829 cytosol | IEA GO_REF:0000117 | ACCEPT | Summary: ARBA machine-learning electronic annotation of cytosolic localization, consistent with the cytoplasmic site of SRP function. Reason: Correct compartment; consistent with UniProt cytoplasm and Reactome cytosol. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0006614 SRP-dependent cotranslational protein targeting to membrane | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based electronic assignment of the core SRP-dependent co-translational targeting process. Reason: Correct core process; redundant with IBA/NAS evidence. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt mediates the cotranslational targeting |
| GO:0008312 7S RNA binding | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of SRP RNA (7S/7SL) binding. SRP9 binds the SRP 7SL RNA as part of the SRP9/SRP14 Alu-domain heterodimer; this RNA-binding is its core molecular function. Reason: Core molecular function; SRP9 (with SRP14) binds the Alu portion of the SRP RNA. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt The complex of SRP9 and SRP14 is required for SRP |
| GO:0045900 negative regulation of translational elongation | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of the elongation-arrest function. The SRP9/SRP14 Alu domain transiently arrests translation elongation by reaching into the ribosomal elongation-factor binding site. This is the defining SRP9-specific contribution to SRP function. Reason: Core biological process; SRP9 is part of the Alu/elongation-arrest domain that negatively regulates elongation. Supporting Evidence: PMID:34208095 SRP9 and SRP14 function in elongation arrest |
| GO:0048500 signal recognition particle | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of SRP complex membership (general SRP term). SRP9 is a constitutive subunit. Reason: Core cellular component; redundant with the more specific GO:0005786. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt Component of the signal recognition particle (SRP) complex |
| GO:0005515 protein binding | IPI PMID:25910212 Widespread macromolecular interaction perturbations in human... | KEEP AS NON CORE | Summary: High-throughput interactome screen; the captured partner (ACTN2) is unrelated to SRP9's function. Bare protein binding is uninformative. Reason: Incidental high-throughput interaction; bare protein binding is uninformative. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; P35609: ACTN2 |
| GO:0005515 protein binding | IPI PMID:28514442 Architecture of the human interactome defines protein commun... | KEEP AS NON CORE | Summary: Human interactome study capturing the functionally central SRP9-SRP14 (P37108) Alu-heterodimer interaction. Biologically meaningful but the bare protein binding term is uninformative. Reason: Records the real SRP14 heterodimer interaction, but bare protein binding is uninformative; the informative MF is captured by GO:0008312 and complex membership by GO:0005786. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; P37108: SRP14 |
| GO:0005515 protein binding | IPI PMID:30021884 Histone Interaction Landscapes Visualized by Crosslinking Ma... | KEEP AS NON CORE | Summary: Crosslinking-MS interactome capturing the SRP9-SRP14 (P37108) interaction. Bare protein binding is uninformative. Reason: Records the real SRP14 interaction; bare protein binding is uninformative. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; P37108: SRP14 |
| GO:0005515 protein binding | IPI PMID:32296183 A reference map of the human binary protein interactome. | KEEP AS NON CORE | Summary: HuRI binary interactome capturing the SRP9-SRP14 (P37108) interaction. Bare protein binding is uninformative. Reason: Records the real SRP14 interaction; bare protein binding is uninformative. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; P37108: SRP14 |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | KEEP AS NON CORE | Summary: Neurodegenerative-disease interactome mapping; captured partners (CDHR3, DPP9, RYBP) are unrelated to SRP9's function. Bare protein binding is uninformative. Reason: Incidental high-throughput interactions; bare protein binding is uninformative. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; Q6ZTQ4: CDHR3 |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | KEEP AS NON CORE | Summary: Proteome-scale interactome capturing the SRP9-SRP14 (P37108) interaction. Bare protein binding is uninformative. Reason: Records the real SRP14 interaction; bare protein binding is uninformative. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; P37108: SRP14 |
| GO:0005515 protein binding | IPI PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... | KEEP AS NON CORE | Summary: OpenCell endogenous-tagging interactome capturing the SRP9-SRP14 (P37108) interaction. Bare protein binding is uninformative. Reason: Records the real SRP14 interaction; bare protein binding is uninformative. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; P37108: SRP14 |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | KEEP AS NON CORE | Summary: Multimodal cell map capturing the SRP9-SRP14 (P37108) interaction. Bare protein binding is uninformative. Reason: Records the real SRP14 interaction; bare protein binding is uninformative. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt P49458; P37108: SRP14 |
| GO:0005786 signal recognition particle, endoplasmic reticulum targeting | NAS PMID:34208095 SRPassing Co-translational Targeting: The Role of the Signal... | ACCEPT | Summary: ComplexPortal NAS assertion of SRP complex membership, from the SRP review describing the SRP9/SRP14 Alu domain. Reason: Core cellular component; SRP9 is an SRP subunit. Supporting Evidence: PMID:34208095 Alu domain |
| GO:0006617 SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition | NAS PMID:34208095 SRPassing Co-translational Targeting: The Role of the Signal... | KEEP AS NON CORE | Summary: ComplexPortal NAS (complex-level) annotation of signal-sequence recognition. Signal-sequence recognition is performed by the SRP54 subunit of the SRP, not directly by SRP9, whose specific role is elongation arrest within the Alu domain. The term applies at the SRP complex level of which SRP9 is part. Reason: Complex-level NAS annotation; signal-sequence recognition is the SRP54 function, while SRP9's direct contribution is elongation arrest. Supporting Evidence: PMID:34208095 signal sequence |
| GO:0005515 protein binding | IPI PMID:24965446 Host factors that interact with the pestivirus N-terminal pr... | KEEP AS NON CORE | Summary: SRP9 co-purifies with the pestivirus Npro ribonucleoprotein complex; an incidental ribosomal/RNP capture from a viral interactome study. Bare protein binding is uninformative. Reason: Incidental viral RNP co-purification; bare protein binding is uninformative. Supporting Evidence: PMID:24965446 components of the ribonucleoprotein complex |
| GO:0005829 cytosol | TAS Reactome:R-HSA-1799332 | ACCEPT | Summary: Reactome curation of cytosolic localization, consistent with SRP's cytoplasmic site of action. Reason: Correct compartment; redundant with UniProt cytoplasm. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm. |
| GO:0005786 signal recognition particle, endoplasmic reticulum targeting | NAS PMID:17154533 Compartmentalization directs assembly of the signal recognit... | ACCEPT | Summary: NAS assertion of SRP complex membership from a study on compartmentalized SRP assembly. Reason: Core cellular component; SRP9 is an SRP subunit. Supporting Evidence: PMID:17154533 Compartmentalization directs assembly of the signal recognition particle |
| GO:0003723 RNA binding | TAS PMID:7730321 Human signal recognition particle (SRP) Alu-associated prote... | ACCEPT | Summary: SRP9 (with SRP14) is the Alu RNA-binding protein that binds the Alu region of 7SL RNA. RNA binding is correct but is the general parent of the more specific 7S RNA binding. Reason: Correct molecular function; the more specific GO:0008312 (7S RNA binding) better captures SRP9's role. Supporting Evidence: PMID:7730321 regulates translational elongation of |
| GO:0005047 signal recognition particle binding | TAS PMID:7730321 Human signal recognition particle (SRP) Alu-associated prote... | KEEP AS NON CORE | Summary: Annotation of SRP9 binding the signal recognition particle. SRP9 is itself a constitutive subunit of SRP rather than an external SRP-binding factor, so this is redundant with its part_of SRP membership. Reason: SRP9 is part of SRP (captured by GO:0005786); describing it as SRP-binding is redundant and not the informative core MF. Supporting Evidence: file:human/SRP9/SRP9-uniprot.txt consists of a 7SL RNA molecule of 300 nucleotides and six protein |
| GO:0005785 signal recognition particle receptor complex | TAS PMID:7730321 Human signal recognition particle (SRP) Alu-associated prote... | MARK AS OVER ANNOTATED | Summary: SRP9 is annotated as part of the signal recognition particle receptor (SR) complex. This is incorrect; PMID:7730321 characterizes SRP9 as a component of the SRP (the Alu RNA-binding protein), not of the SRP receptor (SRalpha/SRbeta) complex. This appears to be an SRP-versus-SRP-receptor curation confusion. Reason: SRP9 is a subunit of SRP, not of the SRP receptor complex; the cited paper concerns SRP9 within SRP, so this CC is a mis-/over-annotation. Supporting Evidence: PMID:7730321 regulates translational elongation of |
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Download this section (compressed HTML)Q: How strictly required is SRP9/SRP14-mediated elongation arrest for productive ER targeting in mammalian cells, given that some substrates may be targeted without efficient arrest?
Q: Do the Alu-RNA-binding activities of SRP9/SRP14 toward Alu-derived transcripts (scAlu/scB1) have any regulatory role distinct from canonical SRP function?
Experiment: Reconstitute SRP with wild-type versus RNA-binding-deficient SRP9 to quantify the contribution of the SRP9/SRP14 Alu domain to elongation arrest and targeting efficiency on defined nascent-chain substrates.
Experiment: Use selective ribosome profiling in cells depleted of SRP9 to measure genome-wide effects on co-translational ER targeting and elongation pausing of signal-sequence-bearing mRNAs.
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