SRP19 is the 19 kDa protein 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 consists of a single 7SL RNA (~300 nucleotides) and six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72). SRP19 binds directly to the SRP 7SL RNA and is the key assembly factor of the S domain: it is intrinsically disordered when free and folds upon RNA binding, clamping the apical tetraloops of helices 6 and 8 and thereby remodeling the asymmetric internal loop of helix 8 to create the binding site for the signal-sequence-recognition GTPase SRP54. SRP54 can only bind the SRP RNA after SRP19 has bound (ordered, SRP54-late assembly), so SRP19 is required for incorporation of SRP54 and for productive SRP assembly. SRP19 is an RNA-binding/scaffolding protein, not a GTPase. The mature particle functions in the cytoplasm, but SRP partially assembles in the nucleus/nucleolus, and SRP19 is actively imported into the nucleus by importin 8 and transportin.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005786 signal recognition particle, endoplasmic reticulum targeting | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of SRP19 as a constitutive subunit of the signal recognition particle. Conserved and directly demonstrated. Reason: Core cellular component; SRP19 is one of the six SRP protein subunits. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt consists of a 7SL RNA molecule of 300 nucleotides and 6 protein |
| GO:0008312 7S RNA binding | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of SRP19's core molecular function, binding the SRP 7SL RNA. SRP19 binds directly to 7SL RNA and scaffolds S-domain assembly. Conserved across the SRP19 family. Reason: Core molecular function; SRP19 binds the SRP 7SL RNA, supported by IDA. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt Binds directly to 7SL RNA |
| GO:0006617 SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition | IBA GO_REF:0000033 | ACCEPT | Summary: Phylogenetic annotation of SRP19's role in SRP-dependent co-translational targeting. SRP19 enables SRP54 incorporation, and SRP54 performs signal-sequence recognition; SRP19 is part of the complex performing this process. Reason: Core biological process; SRP19 is required for assembly of the signal-sequence-recognizing SRP54 into SRP. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt Mediates |
| GO:0005654 nucleoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of nucleoplasm localization. SRP19 is imported into the nucleus and SRP partially assembles in the nucleus/nucleolus; this is an assembly compartment, not the core ER-targeting site of action. Reason: Real assembly-stage localization, but not the defining cytoplasmic ER-targeting site of action. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt Nucleus, |
| GO:0005730 nucleolus | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: Electronic transfer of nucleolar localization, where SRP partially assembles. An assembly compartment rather than the core ER-targeting site. Reason: Real assembly-stage localization, secondary to the cytoplasmic site of SRP function. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt Nucleus, nucleolus |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | ACCEPT | Summary: Electronic transfer of the cytoplasmic localization, the site where mature SRP functions in ER targeting. Consistent with experimental EXP evidence. Reason: Correct core compartment; SRP acts in the cytoplasm. Supporting Evidence: file:human/SRP19/SRP19-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/TAS evidence. Supporting Evidence: file:human/SRP19/SRP19-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, SRP19's core molecular function. Reason: Correct core molecular function; redundant with IDA evidence. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt Binds directly to 7SL RNA |
| GO:0048500 signal recognition particle | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro-based annotation of SRP complex membership (general SRP term). Reason: Core cellular component; redundant with the more specific GO:0005786. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt Component of the signal recognition particle (SRP) complex |
| 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 SRP19-SRP68 (Q9UHB9) interaction within the SRP S domain. Biologically meaningful but the bare protein binding term is uninformative. Reason: Records the real SRP68 interaction, but bare protein binding is uninformative; covered by SRP complex membership and 7S RNA binding. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt P09132; Q9UHB9: SRP68 |
| 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 SRP19-SRP68 (Q9UHB9) interaction. Bare protein binding is uninformative. Reason: Records the real SRP68 interaction; bare protein binding is uninformative. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt P09132; Q9UHB9: SRP68 |
| 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, which notes SRP19 functions to stabilize the 7SL structure. Reason: Core cellular component; SRP19 is an SRP subunit. Supporting Evidence: PMID:34208095 SRP19 functions to stabilize the 7SL structure |
| GO:0006617 SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition | NAS PMID:34208095 SRPassing Co-translational Targeting: The Role of the Signal... | ACCEPT | Summary: ComplexPortal NAS annotation of SRP19's role in the signal-sequence-recognition step. SRP19 enables SRP54 incorporation; signal-sequence recognition is performed by SRP54 within the SRP of which SRP19 is part. Reason: Core biological process at the complex level; SRP19 is required for assembly of the signal-sequence-recognizing SRP54. Supporting Evidence: PMID:34208095 SRP19 functions to stabilize the 7SL structure |
| GO:0005829 cytosol | IDA GO_REF:0000052 | ACCEPT | Summary: HPA immunofluorescence cytosolic localization, consistent with the cytoplasmic site of SRP function. Reason: Correct core compartment; SRP acts in the cytosol. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| 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 HPA/UniProt evidence. Supporting Evidence: file:human/SRP19/SRP19-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm |
| GO:0005737 cytoplasm | EXP PMID:10618370 Signal recognition particle components in the nucleolus. | ACCEPT | Summary: Direct experimental cytoplasmic localization of SRP19, alongside its nucleolar localization during SRP assembly. Reason: Correct core compartment; experimentally demonstrated. Supporting Evidence: PMID:10618370 prominent nucleolar localization |
| GO:0005737 cytoplasm | EXP PMID:11682607 Signal recognition particle protein 19 is imported into the ... | ACCEPT | Summary: Direct experimental cytoplasmic localization of SRP19 from the nuclear-import study, which also documents nuclear/nucleolar pools. Reason: Correct core compartment; experimentally demonstrated. Supporting Evidence: PMID:11682607 imported into the nucleus |
| GO:0003723 RNA binding | IPI PMID:17434535 A threefold RNA-protein interface in the signal recognition ... | ACCEPT | Summary: SRP19 binds the SRP RNA; RNA binding is the general parent of the more specific 7S RNA binding. This DisProt annotation reflects SRP19's disorder-to-order RNA-binding transition. Reason: Correct molecular function; the more specific GO:0008312 (7S RNA binding) better captures SRP19's role. Supporting Evidence: PMID:17434535 SRP19 protein is unstructured |
| GO:0008312 7S RNA binding | IDA PMID:27899666 Structures of human SRP72 complexes provide insights into SR... | ACCEPT | Summary: Direct structural evidence that SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA, preparing helix 8 for SRP54 binding. Core SRP RNA-binding molecular function. Reason: Core molecular function with direct structural (IDA) support. Supporting Evidence: PMID:27899666 SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA |
| GO:0043022 ribosome binding | IDA PMID:27899666 Structures of human SRP72 complexes provide insights into SR... | KEEP AS NON CORE | Summary: SRP19 contributes to the SRP complex's ribosome interaction; the study concerns SRP RNA remodeling and ribosome binding, in which SRP19 clamps the RNA. The contributes_to qualifier appropriately reflects that ribosome binding is a complex-level activity. Reason: Complex-level activity to which SRP19 contributes (contributes_to); SRP19's defining MF is SRP RNA binding. Supporting Evidence: PMID:27899666 5f-loop involved in ribosome binding |
| GO:0048500 signal recognition particle | IDA PMID:27899666 Structures of human SRP72 complexes provide insights into SR... | ACCEPT | Summary: Direct structural evidence placing SRP19 within the SRP complex. Reason: Core cellular component; structurally demonstrated. Supporting Evidence: PMID:27899666 SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA |
| GO:0003723 RNA binding | HDA PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-bi... | ACCEPT | Summary: High-throughput mRNA-interactome capture detecting SRP19 as an RNA-binding protein. Correct but generic parent of 7S RNA binding. Reason: Correct general molecular function; the specific GO:0008312 better captures SRP19's SRP RNA binding. Supporting Evidence: PMID:22658674 Insights into RNA biology from an atlas of mammalian mRNA-binding proteins |
| GO:0005786 signal recognition particle, endoplasmic reticulum targeting | IDA PMID:18089836 A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydro... | ACCEPT | Summary: Drug-target screen identifying SRP as the target of TAS-103; the compound disrupts SRP complex formation and reduces SRP14 and SRP19, detecting SRP19 as part of the SRP complex. Reason: Core cellular component; SRP19 is detected as part of the SRP complex. Supporting Evidence: PMID:18089836 disrupts SRP complex formation |
| GO:0008312 7S RNA binding | IDA PMID:17434535 A threefold RNA-protein interface in the signal recognition ... | ACCEPT | Summary: Direct evidence that SRP19 folds upon binding SRP RNA, forming a threefold RNA-protein interface that gates SRP54 binding. Core SRP RNA-binding molecular function. Reason: Core molecular function with direct (IDA) support. Supporting Evidence: PMID:17434535 SRP19 protein is unstructured |
| GO:0005730 nucleolus | IDA PMID:10618370 Signal recognition particle components in the nucleolus. | KEEP AS NON CORE | Summary: Direct evidence that GFP-SRP19 displays prominent nucleolar localization, reflecting the nuclear/nucleolar stage of SRP assembly. An assembly compartment rather than the core ER-targeting site. Reason: Real assembly-stage localization; not the defining cytoplasmic site of SRP function. Supporting Evidence: PMID:10618370 prominent nucleolar localization |
| GO:0005786 signal recognition particle, endoplasmic reticulum targeting | TAS PMID:1678319 Identification of deletion mutations and three new genes at ... | ACCEPT | Summary: TAS annotation of SRP membership from the positional-cloning paper that mapped SRP19 near the APC locus and found one gene identical to SRP19, the 19 kDa SRP component. Reason: Core cellular component; SRP19 is an SRP subunit. The cited paper correctly identifies SRP19 as the SRP 19 kDa component. Supporting Evidence: PMID:1678319 identical to SRP19 |
| GO:0006613 cotranslational protein targeting to membrane | TAS PMID:1678319 Identification of deletion mutations and three new genes at ... | ACCEPT | Summary: TAS annotation of the (older parent) co-translational protein targeting process for SRP19 as an SRP component. Reason: Correct biological process; the SRP-dependent child terms better specify SRP19's role. Supporting Evidence: PMID:1678319 identical to SRP19 |
Loading supporting content…
Download this section (compressed HTML)Q: What is the functional significance of the nuclear/nucleolar SRP19 pool and its active import, given that mature SRP acts in the cytoplasm?
Q: Do the alternative SRP19 isoforms differ in RNA-binding or SRP54-recruitment activity?
Experiment: Reconstitute SRP assembly with wild-type versus RNA-clamp-deficient SRP19 mutants to quantify the requirement for SRP19 in SRP54 incorporation and signal-sequence-dependent targeting.
Experiment: Track SRP19 nucleocytoplasmic shuttling and SRP assembly state in cells with impaired importin-8/transportin import to test whether nuclear assembly contributes to functional SRP biogenesis.
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)