SRP9

UniProt ID: P49458
Organism: Homo sapiens
Review Status: COMPLETE
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Gene Description

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.

Existing Annotations Review

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

Core Functions

RNA-binding subunit that, as an obligate heterodimer with SRP14, binds the Alu portion of the SRP 7SL RNA to form the Alu (elongation-arrest) domain of the signal recognition particle.

Supporting Evidence:
  • file:human/SRP9/SRP9-uniprot.txt
    The complex of SRP9 and SRP14 is required for SRP
  • PMID:34208095
    SRP9 and SRP14 function in elongation arrest
  • PMID:26585389
    We defined a minimal Alu RNA sufficient for effective retrotransposition and determined a high-resolution structure of its complex with the SRP9/14 proteins.

Part of the SRP Alu domain that transiently arrests translation elongation at the ribosomal elongation-factor site, pausing the nascent chain while SRP-dependent co-translational targeting delivers the ribosome to the ER membrane.

Supporting Evidence:
  • PMID:34208095
    SRP9 and SRP14 function in elongation arrest
  • PMID:26585389
    The RNA adopts a compact, closed conformation that matches the envelope of the SRP Alu domain in the ribosomal translation elongation factor-binding site.

References

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Suggested Questions for Experts

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?

Suggested Experiments

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.

Deep Research

Falcon

(SRP9-deep-research-falcon.md)

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πŸ“š Additional Documentation

Notes

(SRP9-notes.md)

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Pn Notes

(SRP9-pn-notes.md)

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πŸ“„ View Raw YAML

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