Existing Annotations Review

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

Core Functions

SRP RNA-binding scaffolding subunit that binds the SRP 7SL RNA, clamping helices 6 and 8 and remodeling helix 8 to create the SRP54 binding site, thereby enabling ordered assembly of the SRP S domain.

Molecular Function:

7S RNA binding

Directly Involved In:

SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition

In Complex:

signal recognition particle, endoplasmic reticulum targeting

Supporting Evidence:

PMID:27899666
SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA
PMID:12086622
SRP19 clamps the tetraloops of two branched helices (helices 6 and 8) and allows them to interact side by side.
file:human/SRP19/SRP19-uniprot.txt
Binds directly to 7SL RNA

Required assembly factor for incorporation of the signal-sequence-recognition GTPase SRP54 into the SRP, gating productive SRP assembly for co-translational ER targeting.

Molecular Function:

7S RNA binding

Directly Involved In:

SRP-dependent cotranslational protein targeting to membrane

In Complex:

signal recognition particle

Supporting Evidence:

file:human/SRP19/SRP19-uniprot.txt
Mediates
PMID:17434535
SRP19 protein is unstructured
PMID:12086622
In Archaea and Eukarya, SRP19 binds to 7SL RNA and promotes the incorporation of SRP54, which contains the binding sites for GTP, the signal peptide, and the membrane-bound SRP receptor.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping

GO_REF:0000052

Gene Ontology annotation based on curation of immunofluorescence data

PMID:10618370

Signal recognition particle components in the nucleolus.

SRP19 binds SRP RNA independently and must bind before SRP54, effecting a conformational change promoting SRP54 binding; GFP-SRP19 shows prominent nucleolar plus cytoplasmic localization.

PMID:11682607

Signal recognition particle protein 19 is imported into the nucleus by importin 8 (RanBP8) and transportin.

SRP19 is efficiently imported into the nucleus by importin 8 and transportin; a significant endogenous pool is nuclear/nucleolar.

PMID:1678319

Identification of deletion mutations and three new genes at the familial polyposis locus.

Positional cloning at the APC/polyposis locus identified a gene identical to SRP19, the 19 kDa component of the ribosomal signal recognition particle.

PMID:17434535

A threefold RNA-protein interface in the signal recognition particle gates native complex assembly.

SRP19 is unstructured when free and folds into a compact core plus two extended RNA-binding loops upon binding SRP RNA; SRP54 subsequently binds the assembled SRP19-RNA complex.

PMID:18089836

A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads.

SRP is the target of TAS-103; the compound disrupts SRP complex formation and reduces the amount of SRP14 and SRP19, detecting SRP19 within the SRP complex.

PMID:22658674

Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.

PMID:27899666

Structures of human SRP72 complexes provide insights into SRP RNA remodeling and ribosome interaction.

SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA, preparing the asymmetric loop of helix 8 for SRP54 binding; SRP72-RBD remodels the 5f-loop involved in ribosome binding.

PMID:33961781

Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.

PMID:34208095

SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection.

SRP19 functions to stabilize the 7SL RNA structure within SRP; SRP consists of Alu and S domains with six proteins and 7SL RNA.

PMID:35271311

OpenCell: Endogenous tagging for the cartography of human cellular organization.

Reactome:R-HSA-1799332

Reactome: Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)

PMID:12086622

Crystal structure of SRP19 in complex with the S domain of SRP RNA and its implication for the assembly of the signal recognition particle.

Crystal structure of SRP19 bound to the S-domain of SRP RNA shows SRP19 clamps the tetraloops of helices 6 and 8 (helix 6 acting as a splint), pre-organizing the SRP54-binding site on helix 8; unlike bacterial systems, human SRP54 cannot bind SRP RNA before SRP19, establishing SRP19 as an upstream eukaryotic assembly factor.

PMID:38858088

The nucleolar phase of signal recognition particle assembly.

GFP-SRP19 accumulates in nucleoli and co-localizes with nucleolar markers; nucleolar disruption (low-dose actinomycin D, uL18/RPL5 depletion) relocalizes SRP19, and SRP proteins associate with many nucleolar/ribosome-biogenesis factors, supporting a bona fide nucleolar phase of SRP assembly.

PMID:35754847

Signal Recognition Particle in Human Diseases.

Reviews SRP-related human disease; SRP19 is among the SRP autoantigens (anti-SRP19, anti-SRP54, anti-SRP72, anti-7SL) recognized in immune-mediated necrotizing myopathy (IMNM)/anti-SRP myositis.

file:human/SRP19/SRP19-uniprot.txt

UniProt entry P09132 (SRP19_HUMAN), Signal recognition particle 19 kDa protein

SRP19 is a subunit of the SRP ribonucleoprotein (7SL RNA + six proteins); binds directly to 7SL RNA and mediates binding of SRP54 to the SRP complex; cytoplasmic with nuclear/nucleolar assembly pools.

Suggested Experiments

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.

Deep Research

Falcon

(SRP19-deep-research-falcon.md)

Research report: Human SRP19 (UniProt P09132) functional annotation Falcon Edison Scientific Literature 24 citations 2 artifacts 2026-06-12T02:29:09.188063

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000013 The requested figures showing GFP-SRP19 localization, the effects of nucleolar disruption, and quantitative plots are provided: - * (image/png)

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You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
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We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.

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We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.

Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.

Research report: Human SRP19 (UniProt P09132) functional annotation

0. Target verification (gene/protein identity)

The literature retrieved here consistently defines SRP19 as the signal recognition particle 19 kDa protein, an RNA-binding subunit of the mammalian signal recognition particle (SRP) that binds 7SL RNA and promotes assembly of the SRP S-domain, enabling SRP54 incorporation—matching the UniProt P09132 description and SRP19-family/domain context. (oubridge2002crystalstructureof pages 1-2, faoro2021noncanonicalfunctionsand pages 3-4, issa2024thenucleolarphase pages 1-2)

1. Key concepts and definitions (current understanding)

1.1 What is SRP19?

SRP19 is a single-domain RNA-binding protein that is part of the S domain of the mammalian SRP ribonucleoprotein (RNP). Reviews describe SRP19 as an αβ-fold protein with βαββα topology, emphasizing its role as an RNA-binding structural component rather than an enzyme. (Faoro & Ataide, 2021-05; https://doi.org/10.3389/fmolb.2021.679584) (faoro2021noncanonicalfunctionsand pages 3-4)

1.2 What is the SRP pathway and where does SRP19 fit?

The mammalian SRP is a cytosolic RNP that co-translationally targets nascent secreted and membrane proteins to the endoplasmic reticulum (ER) by recognizing signal sequences on ribosome–nascent chain complexes and delivering them to the ER via the SRP receptor/translocon system. SRP19’s specific role is primarily in SRP assembly and S-domain architecture, which enables downstream SRP functions in targeting. (faoro2021noncanonicalfunctionsand pages 3-4, kellogg2023unravelingsrpbiogenesis pages 35-40)

1.3 Molecular function: SRP19 is an SRP RNA assembly factor within the mature complex

A key structural model derived from a crystal structure of SRP19 in complex with the S domain RNA (representing the S domain of human 7SL RNA) shows that SRP19 binds SRP RNA and clamps key RNA helices: SRP19 “clamps the tetraloops of two branched helices (helices 6 and 8)” and helix 6 functions as a “splint,” partially pre-organizing the SRP54-binding site on helix 8. (Oubridge et al., 2002-06; https://doi.org/10.1016/S1097-2765(02)00530-0) (oubridge2002crystalstructureof pages 1-2)

Functionally, this creates a eukaryote-specific assembly dependency: in contrast to bacterial SRP systems (where the SRP54 homolog can bind SRP RNA without SRP19), human SRP54 is unable to bind 7SL RNA without prior SRP19 binding, placing SRP19 upstream in hierarchical SRP assembly. (Oubridge et al., 2002-06; https://doi.org/10.1016/S1097-2765(02)00530-0) (oubridge2002crystalstructureof pages 1-2)

2. SRP19 complex membership, interactions, and pathway placement

2.1 Core SRP composition

A 2024 study explicitly describes mammalian SRP as consisting of 7SL RNA plus six proteins (SRP9, SRP14, SRP19, SRP54, SRP68, SRP72) and uses SRP19 as a bait/marker for SRP interactome analyses, supporting that SRP19 is a canonical core SRP subunit. (Issa et al., 2024-06; https://doi.org/10.26508/lsa.202402614) (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 8-9)

2.2 Assembly logic: SRP19 shapes the S domain to recruit SRP54

Reviews summarize that SRP19 binds the GGAG tetraloop at the tip of helix 6 in 7SL RNA and clamps helices 6 and 8, inducing the “closed” S-domain structure that supports productive SRP assembly. (Faoro & Ataide, 2021-05; https://doi.org/10.3389/fmolb.2021.679584) (faoro2021noncanonicalfunctionsand pages 3-4)

3. Subcellular localization and SRP biogenesis route

3.1 Nuclear/nucleolar assembly phase followed by cytoplasmic maturation

Recent synthesis of SRP biogenesis emphasizes that (i) most SRP proteins are translated in the cytoplasm, (ii) several are imported into the nucleus, and (iii) SRP19 assembles with 7SL RNA first in the nucleolus, producing a pre-SRP that is exported, after which SRP54 is attached to complete SRP maturation. (Kellogg, 2023; pages describing import/export and nucleolar first assembly) (kellogg2023unravelingsrpbiogenesis pages 35-40)

3.2 2024 primary evidence: SRP19 nucleolar accumulation and nucleolus-dependence

Issa et al. (2024) provide direct imaging and perturbation evidence that SRP biogenesis occurs partly in the nucleolus and that SRP19 participates in this phase. They show GFP-SRP19 accumulating in nucleoli and co-localizing with nucleolar markers, and they report that nucleolar disruption alters SRP19 distribution. (Issa et al., 2024-06; https://doi.org/10.26508/lsa.202402614) (issa2024thenucleolarphase pages 8-9, issa2024thenucleolarphase media 3dc4c0c3)

In the same study, inhibition of nucleolar transcription by low-dose actinomycin D is associated with relocalization of GFP-SRP19 into more compact nucleolar structures, and depletion of a ribosomal component (uL18/RPL5) disrupts nucleolar structure and alters GFP-SRP19 localization, supporting that SRP19’s nucleolar localization is functionally coupled to nucleolar integrity. (issa2024thenucleolarphase media 3dc4c0c3, issa2024thenucleolarphase media d5a9ef09)

4. Recent developments and latest research (prioritizing 2023–2024)

4.1 Nucleolar phase of SRP assembly (2024)

The principal 2024 advance in the retrieved corpus is the quantitative proteomics and cell-biology demonstration that SRP proteins (including SRP19) associate with “scores” of nucleolar proteins involved in ribosome biogenesis and that an intact nucleolus is required for correct SRP protein localization and efficient SRP production. (Issa et al., 2024-06; https://doi.org/10.26508/lsa.202402614) (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 8-9)

4.2 SRP subunit homeostasis and SRP19 dependence on other SRP components (2023)

A 2023 SRP biogenesis/quality-control synthesis reports that SRP19 and SRP54 protein levels are attenuated by loss of other SRP subunits, and that SRP54 depletion disrupts ribosome association of SRP19 (along with other SRP proteins), consistent with SRP19 being structurally integrated into SRP–ribosome interactions and SRP integrity. (kellogg2023unravelingsrpbiogenesis pages 111-116)

4.3 SRP19 in pathogen/host context (2024)

In a 2024 PLOS Pathogens study of flavivirus-driven ER remodeling, viral proteins are reported to interact with SRP components, including an interaction involving viral NS4B and SRP19; this is presented as part of a viral strategy to rewire ER-localized translation and translocation machinery. (Wong et al., 2024-12; https://doi.org/10.1371/journal.ppat.1012766) (kellogg2023unravelingsrpbiogenesis pages 46-51)

5. Current applications and real-world implementations

5.1 Clinical diagnostics: anti-SRP antibody testing in immune-mediated necrotizing myopathy

A major real-world implementation relevant to SRP19 is clinical testing for anti-SRP autoantibodies in immune-mediated necrotizing myopathy (IMNM). A disease-focused review lists four SRP-associated autoantibody specificities linked to necrotizing myopathy: anti-SRP19, anti-SRP54, anti-SRP72, and anti-7SL RNA. (Kellogg et al., 2022-06; https://doi.org/10.3389/fgene.2022.898083) (kellogg2022signalrecognitionparticle pages 2-4)

6. Expert opinions and analysis (authoritative sources)

A key expert-level interpretation from structural biology is that SRP19 is not simply a passive subunit, but an RNA-architecture organizer whose binding “preorganizes” the SRP54 site on 7SL RNA, thereby enforcing hierarchical assembly in eukaryotes. (Oubridge et al., 2002-06; https://doi.org/10.1016/S1097-2765(02)00530-0) (oubridge2002crystalstructureof pages 1-2)

Complementary expert synthesis emphasizes that mammalian SRP components—including SRP19—also have noncanonical or disease-linked associations, motivating closer study of SRP subunits as disease modifiers or therapeutic targets, even though SRP19’s best-supported “primary” function remains SRP RNP assembly. (Faoro & Ataide, 2021-05; https://doi.org/10.3389/fmolb.2021.679584) (faoro2021noncanonicalfunctionsand pages 3-4)

7. Quantitative statistics and data points from recent studies/reviews

7.1 Autoimmune myopathy prevalence/incidence

IMNM is reported to account for 17–45% of idiopathic inflammatory myopathy (IIM) patients, and IIM incidence is reported as approximately 2 per 100,000. (Kellogg et al., 2022-06; https://doi.org/10.3389/fgene.2022.898083) (kellogg2022signalrecognitionparticle pages 2-4)

7.2 SRP-dependent transcript set size

A 2023 SRP biogenesis/quality-control synthesis reports that ~500 genes have been identified as SRP-dependent via DeepRNAseq, providing an approximate scale of SRP pathway substrate scope (though not specific to SRP19 alone). (kellogg2023unravelingsrpbiogenesis pages 111-116)

7.3 Quantitative imaging evidence for SRP19 in nuclear bodies

Issa et al. (2024) include quantitative counting of nuclear body association (Cajal bodies) for GFP-tagged SRP proteins, including SRP19, and provide microscopy panels documenting SRP19 nucleolar localization patterns under perturbation. (Issa et al., 2024-06; https://doi.org/10.26508/lsa.202402614) (issa2024thenucleolarphase media 3dc4c0c3, issa2024thenucleolarphase media 392a1c04)

8. Summary for functional annotation

SRP19 (human; UniProt P09132) is best annotated as an SRP RNA-binding assembly factor/structural subunit of the mammalian SRP S domain, whose primary molecular function is to bind the S-domain region of 7SL RNA, clamp and remodel RNA helices (notably helices 6 and 8), and thereby enable SRP54 incorporation and formation of a functional SRP competent for co-translational targeting to the ER. Its cellular lifecycle includes a significant nucleolar assembly phase (supported by 2024 imaging and perturbation evidence) followed by cytoplasmic function in SRP-mediated targeting on translating ribosomes. (oubridge2002crystalstructureof pages 1-2, faoro2021noncanonicalfunctionsand pages 3-4, kellogg2023unravelingsrpbiogenesis pages 35-40, issa2024thenucleolarphase media 3dc4c0c3)

Evidence map table

Topic	Key points for functional annotation	Representative evidence (paper + year + main method/result)	URL	Citation id placeholders
Identity	Human SRP19 corresponds to signal recognition particle 19 kDa protein, a canonical eukaryotic SRP subunit in the S domain of the SRP ribonucleoprotein; distinct from bacterial systems that lack a true SRP19 counterpart.	Althoff et al., 1994, NAR: comparative/evolutionary analysis placed SRP19 among small mammalian SRP proteins and noted lack of a bacterial counterpart with equivalent binding behavior; Faoro & Ataide, 2021: review defines mammalian SRP as 7SL RNA plus SRP9/14/19/54/68/72.	https://doi.org/10.1093/nar/22.11.1933 ; https://doi.org/10.3389/fmolb.2021.679584	(althoff1994molecularevolutionof pages 6-7, althoff1994molecularevolutionof pages 7-8, faoro2021noncanonicalfunctionsand pages 3-4)
Domains	SRP19 is a single-domain RNA-binding protein of the αβ fold / βαββα topology; functionally specialized for 7SL RNA recognition rather than enzymatic catalysis.	Faoro & Ataide, 2021: summarizes structural class and fold of SRP19 from prior structural work, emphasizing RNA-binding architecture.	https://doi.org/10.3389/fmolb.2021.679584	(faoro2021noncanonicalfunctionsand pages 3-4)
Complex membership	SRP19 is one of the six protein subunits of mammalian SRP and resides in the S domain with SRP54, SRP68, SRP72 on the 7SL RNA scaffold.	Issa et al., 2024: defines core mammalian SRP composition and studies tagged SRP19 in SRP biogenesis; Kellogg 2023: places SRP19 in the S domain assembled on 7SL RNA.	https://doi.org/10.26508/lsa.202402614	(issa2024thenucleolarphase pages 1-2, kellogg2023unravelingsrpbiogenesis pages 35-40, kellogg2023unravelingsrpbiogenesis pages 40-43)
Molecular function	Primary function is RNA-structure remodeling during SRP assembly: SRP19 binds the GGAG tetraloop of helix 6 in 7SL RNA, clamps helices 6 and 8, and induces the closed S-domain conformation needed for productive SRP formation.	Oubridge et al., 2002, Mol Cell: crystal structure of SRP19–S-domain RNA complex showed SRP19 clamps tetraloops of helices 6 and 8 and preorganizes the SRP54-binding site; Faoro & Ataide, 2021: review summarizes this RNA-binding mechanism.	https://doi.org/10.1016/S1097-2765(02)00530-0 ; https://doi.org/10.3389/fmolb.2021.679584	(oubridge2002crystalstructureof pages 1-2, faoro2021noncanonicalfunctionsand pages 3-4)
Assembly role	SRP19 is essential for eukaryotic SRP assembly because human SRP54 cannot bind 7SL RNA efficiently before SRP19 binds; thus SRP19 acts as an upstream assembly factor within the mature complex.	Oubridge et al., 2002: structural/biochemical interpretation explicitly states prior SRP19 binding is required for human SRP54 incorporation; Kellogg 2023: depletion predicted to alter the SRP54 interface and compromise SRP integrity.	https://doi.org/10.1016/S1097-2765(02)00530-0	(oubridge2002crystalstructureof pages 1-2, kellogg2023unravelingsrpbiogenesis pages 43-46, kellogg2023unravelingsrpbiogenesis pages 111-116)
Pathway context	SRP19 participates in the co-translational protein-targeting pathway to the ER, indirectly enabling signal-sequence recognition and SRP receptor engagement by building the correct S-domain architecture. It is not an enzyme and does not transport substrate directly; its role is structural/assembly-related in the SRP pathway.	Faoro & Ataide, 2021: reviews S-domain function in signal-sequence recognition and receptor interaction; Kellogg 2023: SRP co-translationally targets secretory/membrane proteins to ER and protects some mRNAs from degradation.	https://doi.org/10.3389/fmolb.2021.679584	(faoro2021noncanonicalfunctionsand pages 3-4, kellogg2023unravelingsrpbiogenesis pages 35-40)
Localization / biogenesis route	SRP19 is synthesized in the cytoplasm, imported to the nucleus, and assembles with 7SL RNA first in the nucleolus; pre-SRP is then exported, with final maturation completed in the cytoplasm. Mature SRP functions in the cytosol on translating ribosomes targeting to the ER membrane.	Kellogg 2023: review/preprint describes SRP19 nuclear import and first nucleolar assembly step with 7SL RNA; Issa et al., 2024: microscopy/proteomics show GFP-SRP19 nucleolar accumulation and dependence on nucleolar integrity.	https://doi.org/10.26508/lsa.202402614	(kellogg2023unravelingsrpbiogenesis pages 35-40, issa2024thenucleolarphase pages 8-9, issa2024thenucleolarphase pages 1-2)
Recent 2024 development: nucleolar phase	New evidence strengthens the model that SRP biogenesis partly occurs in the nucleolus and that SRP19 transiently accumulates there; nucleolar disruption alters SRP19 localization, supporting a bona fide nucleolar assembly phase.	Issa et al., 2024: inducible GFP-SRP19 U2OS cell lines, quantitative proteomics, IP/WB, and perturbations (low-dose actinomycin D; uL18 depletion) demonstrated nucleolar accumulation and relocalization of SRP19 when nucleolar structure/function is perturbed.	https://doi.org/10.26508/lsa.202402614	(issa2024thenucleolarphase pages 8-9, issa2024thenucleolarphase media 3dc4c0c3, issa2024thenucleolarphase media d5a9ef09)
Recent 2023 development: SRP homeostasis	SRP19 abundance depends on other SRP subunits; loss of partner subunits reduces SRP19 protein and disrupts SRP–ribosome association, indicating coordinated SRP quality control/homeostasis.	Kellogg 2023: HeLa-cell work reports SRP19 and SRP54 protein attenuation after loss of other SRP subunits and disrupted ribosome association involving SRP19 in SRP54-depleted cells.	https://doi.org/10.3389/fgene.2022.898083	(kellogg2023unravelingsrpbiogenesis pages 111-116)
Disease links: autoimmunity	SRP19 is a recognized autoantigen in immune-mediated necrotizing myopathy (IMNM) / anti-SRP myositis; anti-SRP19 antibodies are reported among the pathogenic anti-SRP specificities.	Kellogg et al., 2022: review lists anti-SRP19 among four SRP-targeted antibodies associated with necrotizing myopathy; Julien et al., 2024 and Kellogg 2023 further discuss anti-SRP antibodies in IMNM.	https://doi.org/10.3389/fgene.2022.898083 ; https://doi.org/10.3390/antib13010012	(kellogg2022signalrecognitionparticle pages 2-4, kellogg2023unravelingsrpbiogenesis pages 40-43, kellogg2023unravelingsrpbiogenesis pages 43-46)
Disease links: other human relevance	SRP19 has been implicated in cancer-related biology and may be perturbed in infection-related ER remodeling; these are secondary/noncanonical associations compared with its canonical SRP assembly role.	Kellogg et al., 2022: review notes SRP19 with SRP54/SRP68 can attenuate p53 in cervical cancer; Wong et al., 2024 reports viral NS4B interaction with SRP19 during flaviviral ER-specific remodeling (host-pathway rewiring rather than core SRP19 function).	https://doi.org/10.3389/fgene.2022.898083 ; https://doi.org/10.1371/journal.ppat.1012766	(kellogg2022signalrecognitionparticle pages 2-4, kellogg2023unravelingsrpbiogenesis pages 46-51)
Quantitative stats	Recent literature provides several useful quantitative anchors: anti-SRP antibodies occur in 17–45% of IMNM patients; idiopathic inflammatory myopathy incidence is about 2 per 100,000; SRP dependency has been assigned to ~500 genes by DeepRNAseq; Issa et al. report SRP19 interactome validation using SILAC and microscopy-based counting of Cajal body association.	Kellogg et al., 2022: prevalence/incidence figures for IMNM/IIM; Kellogg 2023: ~500 SRP-dependent genes; Issa et al., 2024: SILAC-based interactome and microscopy quantification of SRP19-positive nuclear bodies.	https://doi.org/10.3389/fgene.2022.898083 ; https://doi.org/10.26508/lsa.202402614	(kellogg2022signalrecognitionparticle pages 2-4, kellogg2023unravelingsrpbiogenesis pages 111-116, issa2024thenucleolarphase pages 8-9, issa2024thenucleolarphase media 3dc4c0c3)

Table: This table summarizes the identity, function, assembly role, localization, disease links, and recent developments for human SRP19 (UniProt P09132). It is designed as a compact evidence map for functional annotation, with representative sources and citation placeholders tied to available context IDs.

References (URLs and publication dates)

Key sources used in this report:
- Oubridge C. et al. “Crystal structure of SRP19 in complex with the S domain of SRP RNA…” 2002-06. Molecular Cell. https://doi.org/10.1016/S1097-2765(02)00530-0 (oubridge2002crystalstructureof pages 1-2)
- Faoro C., Ataide S.F. “Noncanonical Functions and Cellular Dynamics of the Mammalian SRP Components” 2021-05. Frontiers in Molecular Biosciences. https://doi.org/10.3389/fmolb.2021.679584 (faoro2021noncanonicalfunctionsand pages 3-4)
- Issa A. et al. “The nucleolar phase of signal recognition particle assembly” 2024-06. Life Science Alliance. https://doi.org/10.26508/lsa.202402614 (issa2024thenucleolarphase pages 1-2, issa2024thenucleolarphase pages 8-9, issa2024thenucleolarphase media 3dc4c0c3)
- Kellogg M.K. et al. “Signal Recognition Particle in Human Diseases” 2022-06. Frontiers in Genetics. https://doi.org/10.3389/fgene.2022.898083 (kellogg2022signalrecognitionparticle pages 2-4)
- Wong H.H. et al. “Flaviviruses induce ER-specific remodelling of protein synthesis” 2024-12. PLOS Pathogens. https://doi.org/10.1371/journal.ppat.1012766 (kellogg2023unravelingsrpbiogenesis pages 46-51)
- Althoff S. et al. “Molecular evolution of SRP cycle components…” 1994-06. Nucleic Acids Research. https://doi.org/10.1093/nar/22.11.1933 (althoff1994molecularevolutionof pages 6-7, althoff1994molecularevolutionof pages 7-8)

References

(oubridge2002crystalstructureof pages 1-2): Chris Oubridge, Andreas Kuglstatter, Luca Jovine, and Kiyoshi Nagai. Crystal structure of srp19 in complex with the s domain of srp rna and its implication for the assembly of the signal recognition particle. Molecular cell, 9 6:1251-61, Jun 2002. URL: https://doi.org/10.1016/s1097-2765(02)00530-0, doi:10.1016/s1097-2765(02)00530-0. This article has 87 citations and is from a highest quality peer-reviewed journal.
(faoro2021noncanonicalfunctionsand pages 3-4): Camilla Faoro and Sandro F. Ataide. Noncanonical functions and cellular dynamics of the mammalian signal recognition particle components. Frontiers in Molecular Biosciences, May 2021. URL: https://doi.org/10.3389/fmolb.2021.679584, doi:10.3389/fmolb.2021.679584. This article has 32 citations.
(issa2024thenucleolarphase pages 1-2): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.
(kellogg2023unravelingsrpbiogenesis pages 35-40): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(issa2024thenucleolarphase pages 8-9): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.
(issa2024thenucleolarphase media 3dc4c0c3): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.
(issa2024thenucleolarphase media d5a9ef09): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.
(kellogg2023unravelingsrpbiogenesis pages 111-116): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(kellogg2023unravelingsrpbiogenesis pages 46-51): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(kellogg2022signalrecognitionparticle pages 2-4): Morgana K. Kellogg, Elena B. Tikhonova, and Andrey L. Karamyshev. Signal recognition particle in human diseases. Frontiers in Genetics, Jun 2022. URL: https://doi.org/10.3389/fgene.2022.898083, doi:10.3389/fgene.2022.898083. This article has 30 citations and is from a peer-reviewed journal.
(issa2024thenucleolarphase media 392a1c04): Amani Issa, Florence Schlotter, Justine Flayac, Jing Chen, Ludivine Wacheul, Manon Philippe, Lucas Sardini, Lalia Mostefa, Franck Vandermoere, Edouard Bertrand, Céline Verheggen, Denis LJ Lafontaine, and Séverine Massenet. The nucleolar phase of signal recognition particle assembly. Life Science Alliance, 7:e202402614, Jun 2024. URL: https://doi.org/10.26508/lsa.202402614, doi:10.26508/lsa.202402614. This article has 8 citations and is from a peer-reviewed journal.
(althoff1994molecularevolutionof pages 6-7): Steven Althoff, David Selinger, and Jo Ann Wise. Molecular evolution of srp cycle components: functional implications. Nucleic acids research, 22 11:1933-47, Jun 1994. URL: https://doi.org/10.1093/nar/22.11.1933, doi:10.1093/nar/22.11.1933. This article has 118 citations and is from a highest quality peer-reviewed journal.
(althoff1994molecularevolutionof pages 7-8): Steven Althoff, David Selinger, and Jo Ann Wise. Molecular evolution of srp cycle components: functional implications. Nucleic acids research, 22 11:1933-47, Jun 1994. URL: https://doi.org/10.1093/nar/22.11.1933, doi:10.1093/nar/22.11.1933. This article has 118 citations and is from a highest quality peer-reviewed journal.
(kellogg2023unravelingsrpbiogenesis pages 40-43): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.
(kellogg2023unravelingsrpbiogenesis pages 43-46): MK Kellogg. Unraveling srp biogenesis and quality control: implications for human disease pathogenesis. Unknown journal, 2023.

Artifacts

Edison artifact artifact-00

Citations

faoro2021noncanonicalfunctionsand pages 3-4
oubridge2002crystalstructureof pages 1-2
kellogg2023unravelingsrpbiogenesis pages 35-40
kellogg2023unravelingsrpbiogenesis pages 111-116
kellogg2023unravelingsrpbiogenesis pages 46-51
kellogg2022signalrecognitionparticle pages 2-4
issa2024thenucleolarphase pages 1-2
issa2024thenucleolarphase pages 8-9
althoff1994molecularevolutionof pages 6-7
althoff1994molecularevolutionof pages 7-8
kellogg2023unravelingsrpbiogenesis pages 40-43
kellogg2023unravelingsrpbiogenesis pages 43-46
https://doi.org/10.3389/fmolb.2021.679584
https://doi.org/10.1016/S1097-2765(02
https://doi.org/10.26508/lsa.202402614
https://doi.org/10.1371/journal.ppat.1012766
https://doi.org/10.3389/fgene.2022.898083
https://doi.org/10.1093/nar/22.11.1933
https://doi.org/10.3390/antib13010012
https://doi.org/10.1016/s1097-2765(02
https://doi.org/10.3389/fmolb.2021.679584,
https://doi.org/10.26508/lsa.202402614,
https://doi.org/10.3389/fgene.2022.898083,
https://doi.org/10.1093/nar/22.11.1933,

📚 Additional Documentation

Notes

(SRP19-notes.md)

SRP19 (P09132, human) review notes

Identity and overview

UniProt P09132, SRP19_HUMAN, "Signal recognition particle 19 kDa protein", 144 aa, HGNC:11300, gene on chromosome 5.
Member of the SRP19 family [file:human/SRP19/SRP19-uniprot.txt "Belongs to the SRP19 family"].
Component of the signal recognition particle (SRP), a ribonucleoprotein that mediates cotranslational targeting of secretory/membrane proteins to the ER [file:human/SRP19/SRP19-uniprot.txt "Component of the signal recognition particle (SRP) complex, a ribonucleoprotein complex that mediates the cotranslational targeting of secretory and membrane proteins to the endoplasmic reticulum (ER)"].
SRP19 binds directly to 7SL (SRP) RNA and mediates binding of SRP54 to the SRP complex [file:human/SRP19/SRP19-uniprot.txt "Binds directly to 7SL RNA (By similarity). Mediates binding of SRP54 to the SRP complex (By similarity)."].

Core molecular function: SRP RNA binding / scaffolding required for SRP54 recruitment (S-domain assembly)

SRP19 is a scaffolding protein that clamps helices 6 and 8 of SRP RNA, and this prepares the asymmetric loop of helix 8 for SRP54 binding PMID:27899666 PMID:27899666.
In vitro reconstitution shows SRP19 must bind SRP RNA before SRP54 can bind ("SRP54-late" assembly), effecting a conformational change in the RNA that promotes SRP54 binding PMID:10618370 PMID:10618370.
SRP19 is unstructured when free and folds (compact core + two extended RNA-binding loops) upon SRP RNA binding; SRP54 then binds the preformed SRP19-RNA complex forming a threefold RNA-protein interface PMID:17434535.
SRP19 binds SRP RNA independently of other SRP proteins PMID:10618370.
This is an RNA-binding/scaffolding function, NOT a GTPase. The GTPase of SRP is SRP54 (and the SRP receptor SRalpha); SRP19 is not a GTPase. PMID:27899666

GO term mapping

7S RNA binding (GO:0008312) is the most specific MF term for the SRP RNA-binding activity, directly supported by IDA in PMID:27899666 (CAFA) and PMID:17434535. RNA binding (GO:0003723) is the parent; HDA (PMID:22658674 mRNA interactome capture) and DisProt IPI (PMID:17434535) annotations are to this generic parent.
signal recognition particle / SRP, ER targeting (GO:0048500, GO:0005786) — SRP19 is a constitutive subunit of the 6-protein + 7SL RNA SRP [file:human/SRP19/SRP19-uniprot.txt "Component of a signal recognition particle complex that consists of a 7SL RNA molecule of 300 nucleotides and 6 protein subunits: SRP72, SRP68, SRP54, SRP19, SRP14 and SRP9"].
SRP-dependent cotranslational protein targeting to membrane (GO:0006614) and the signal-sequence-recognition child (GO:0006617) and the older parent cotranslational protein targeting to membrane (GO:0006613) — all correct BP annotations.

Subcellular location

Cytoplasm / cytosol (site of SRP function) [file:human/SRP19/SRP19-uniprot.txt "SUBCELLULAR LOCATION: Cytoplasm"]. Experimental cytoplasm annotations from PMID:10618370 and PMID:11682607.
Nucleus, nucleolus and nucleoplasm — SRP partially assembles in the nucleus/nucleolus; GFP-SRP19 shows prominent nucleolar plus nucleoplasmic localization PMID:10618370 PMID:10618370. SRP19 is actively imported to the nucleus by importin 8 and transportin PMID:11682607 PMID:11682607.
Nucleus/nucleolus are real but represent the assembly compartment, not the core ER-targeting site of action; keep as non-core localizations.

ribosome binding (GO:0043022, contributes_to, IDA PMID:27899666)

SRP72-RBD remodels the 5f-loop "involved in ribosome binding" and the paper concerns SRP RNA remodeling/ribosome interaction; SRP19 is one component clamping the RNA. SRP as a whole binds ribosomes. The contributes_to qualifier is appropriate (SRP19 contributes to the complex's ribosome binding). Keep as non-core. PMID:27899666

protein binding (GO:0005515) IPI annotations

PMID:33961781 (BioPlex / Huttlin dual proteome-scale network) and PMID:35271311 (OpenCell endogenous tagging) — both have WITH=UniProtKB:Q9UHB9 (SRP68). These capture the SRP19-SRP68 interaction within the SRP S domain. UniProt records this IntAct interaction: [file:human/SRP19/SRP19-uniprot.txt "P09132; Q9UHB9: SRP68; NbExp=6"]. Bare protein binding is uninformative per curation guidelines; keep as non-core (genuine interaction, but covered by SRP complex membership).

PMID:1678319 (familial polyposis locus)

This is the original positional cloning paper that mapped SRP19 near the APC locus on chromosome 5; one of the new genes "contained sequence identical to SRP19, the gene coding for the 19 kd component of the ribosomal signal recognition particle" PMID:1678319. Used as the TAS source for SRP membership (GO:0005786) and cotranslational targeting (GO:0006613). The annotations are correct (SRP membership / cotranslational targeting), even though the paper's primary topic is the APC polyposis locus.

PMID:18089836 (TAS-103 drug target screen) — IDA for SRP membership (GO:0005786)

This drug-target paper found SRP as the target of TAS-103; it identified the SRP54 subunit as the binding protein, and showed TAS-103 disrupts SRP complex formation and reduces the amount of SRP14 and SRP19 PMID:18089836. SRP19 is detected as part of the SRP complex here; supports SRP membership (part_of GO:0005786). Per guidelines (do not REMOVE an IDA just because the abstract foregrounds SRP54), accept the SRP-membership annotation.

PMID:34208095 (review, ComplexPortal NAS source)

Review stating SRP19 functions to stabilize the 7SL structure: PMID:34208095. SRP is a six-protein + 7SL RNA complex with Alu and S domains; SRP19 binds in the S domain. Supports SRP membership and cotranslational targeting BP.

Summary of core vs non-core

CORE MF: 7S RNA binding (GO:0008312) — SRP RNA binding/scaffolding required for SRP54 recruitment and S-domain assembly.
CORE complex: signal recognition particle (GO:0048500 / GO:0005786, part_of).
CORE BP: SRP-dependent cotranslational protein targeting to membrane (GO:0006614 and children GO:0006617/GO:0006613).
Non-core: generic RNA binding (GO:0003723, parent of 7S RNA binding); ribosome binding (contributes_to, complex-level); protein binding (IPI to SRP68); nucleus/nucleolus/nucleoplasm/cytoplasm localizations (assembly + steady-state compartments, not the defining ER-targeting site).
No GTPase function (SRP19 is not a GTPase).

Falcon deep-research findings (incorporated 2026-06)

Foundational structure of the SRP19 RNA clamp: crystal structure of SRP19 bound to the S-domain of SRP RNA shows SRP19 clamps the tetraloops of helices 6 and 8 (helix 6 acting as a "splint") and pre-organizes the SRP54-binding site on helix 8 PMID:12086622. Added (HIGH) and used to strengthen the core 7S-RNA-binding/scaffolding core_function.
Eukaryote-specific assembly hierarchy: unlike bacterial systems, human SRP54 cannot bind 7SL RNA before SRP19, placing SRP19 upstream as the assembly factor that gates SRP54 incorporation PMID:12086622. Added to the SRP54-incorporation core_function supported_by.
Nucleolar assembly phase: GFP-SRP19 accumulates in nucleoli and co-localizes with nucleolar markers; nucleolar disruption (low-dose actinomycin D; uL18/RPL5 depletion) relocalizes SRP19, and SRP proteins associate with many nucleolar/ribosome-biogenesis factors PMID:38858088. Added (MEDIUM); reinforces the existing non-core nucleolar/nucleoplasm assembly localizations (already supported by PMID:10618370, PMID:11682607).
Disease/autoantigen context: SRP19 is among the SRP autoantigens (anti-SRP19, anti-SRP54, anti-SRP72, anti-7SL) recognized in immune-mediated necrotizing myopathy (IMNM)/anti-SRP myositis PMID:35754847. Added (LOW); not a core molecular-function source.
The Falcon "kellogg2023unravelingsrpbiogenesis" source is a 2023 thesis/dissertation ("Unknown journal"); its claims (SRP19 abundance depends on other SRP subunits; SRP54 depletion disrupts SRP19 ribosome association; ~500 SRP-dependent genes) are not separately PMID-resolvable, so notes-only (not added).
A Falcon-cited flavivirus NS4B-SRP19 interaction (attributed to Wong et al. 2024 PLOS Pathogens, but the citation key actually points to the Kellogg thesis) could not be verified on PubMed; not added.

Pn Notes

(SRP19-pn-notes.md)

SRP19 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: P09132
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-11
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/SRP19/SRP19-ai-review.yaml
AIGR review HTML: missing - genes/human/SRP19/SRP19-ai-review.html
Gene notes: present - genes/human/SRP19/SRP19-notes.md
GOA TSV: present - genes/human/SRP19/SRP19-goa.tsv
UniProt record: present - genes/human/SRP19/SRP19-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/SRP19.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/SRP19.md
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv

Deep Research Files

genes/human/SRP19/SRP19-deep-research-falcon.md

AIGR Review Snapshot

Description: 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.
Existing/core annotation action counts: ACCEPT: 21; KEEP_AS_NON_CORE: 6

PN Consistency Summary

Consistency: Strong and mutually consistent. Deep research, review YAML, and PN annotation all describe SRP19 as the 19 kDa SRP subunit that binds 7SL RNA (clamping helices 6/8), gating SRP54 incorporation and S-domain assembly. The PN "SRP component" label and GO:0006614 mapping match the review's core BP (GO:0006614 IEA, ACCEPT; plus the signal-sequence-recognition child GO:0006617). No contradictions.
PN story / NEW pressure: PN asserts only the canonical SRP cotranslational-targeting role, already captured (GO:0006614, GO:0006617, GO:0008312 7S RNA binding, GO:0005786 SRP membership). Nuclear/nucleolar assembly localizations (GO:0005730/0005654, kept non-core) and the disease/autoantigen context (PMID:35754847) are in the review but outside the PN story. Conclusion: already captured (no NEW pressure).
Evidence alignment: PN dossier lists no reference titles; alignment via projected-term provenance. Review's core support (PMID:27899666 SRP72/19 RNA-remodeling structures; PMID:12086622 SRP19 helix-6/8 clamp; PMID:10618370 ordered SRP54-late assembly; PMID:34208095 SRP review) all encode the SRP cotranslational-targeting biology the PN maps to. No divergence.
Verdict: Fully consistent; PN already captured, review more granular (adds 7S RNA binding and signal-sequence-recognition child). No edits warranted.

Full Consistency Review

UniProt: P09132 · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE
PN placement: ER proteostasis|Protein transport|Signal recognition particle component ; PN-node mapping: group=mapped scope=ok_for_propagation_to_go→GO:0006614 (SRP-dependent cotranslational protein targeting to membrane); class Protein transport=mapped→GO:0015031; branch=no_mapping.
Consistency: Strong and mutually consistent. Deep research, review YAML, and PN annotation all describe SRP19 as the 19 kDa SRP subunit that binds 7SL RNA (clamping helices 6/8), gating SRP54 incorporation and S-domain assembly. The PN "SRP component" label and GO:0006614 mapping match the review's core BP (GO:0006614 IEA, ACCEPT; plus the signal-sequence-recognition child GO:0006617). No contradictions.
PN story / NEW pressure: PN asserts only the canonical SRP cotranslational-targeting role, already captured (GO:0006614, GO:0006617, GO:0008312 7S RNA binding, GO:0005786 SRP membership). Nuclear/nucleolar assembly localizations (GO:0005730/0005654, kept non-core) and the disease/autoantigen context (PMID:35754847) are in the review but outside the PN story. Conclusion: already captured (no NEW pressure).
Mapping strategy: No change needed. GO:0006614 (goa_status already_in_goa_exact) is present and ACCEPTed — exact projection, not broader than the review. The class-level GO:0015031 is a broad class target, not asserted of SRP19 specifically.
Evidence alignment: PN dossier lists no reference titles; alignment via projected-term provenance. Review's core support (PMID:27899666 SRP72/19 RNA-remodeling structures; PMID:12086622 SRP19 helix-6/8 clamp; PMID:10618370 ordered SRP54-late assembly; PMID:34208095 SRP review) all encode the SRP cotranslational-targeting biology the PN maps to. No divergence.
Verdict: Fully consistent; PN already captured, review more granular (adds 7S RNA binding and signal-sequence-recognition child). No edits warranted.

PN Dossier Context

review_batch: proteostasis-batch-2026-06-11
review_yaml: genes/human/SRP19/SRP19-ai-review.yaml
PN workbook rows: 1

PN row 1: ER proteostasis | Protein transport | Signal recognition particle component

UniProt: P09132
In branches: ER
PN-node mapping records (path + ancestors):
- [group] ER proteostasis|Protein transport|Signal recognition particle component
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006614 SRP-dependent cotranslational protein targeting to membrane]
  rationale: This PN group captures core signal-recognition-particle machinery used to direct translating ribosome-nascent chain complexes to the ER membrane. The group is machinery-centric rather than process-equivalent, so it propagates to the GO targeting process.
- [class] ER proteostasis|Protein transport
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0015031 protein transport]
  rationale: The PN ER Protein transport class groups ER-targeting and ER-insertion pathways. GO protein transport is the appropriate propagation target, while the source class remains ER-specific and broader than any single GO transport subtype.
- [branch] ER proteostasis
  status=no_mapping scope= GO=[]
  rationale: Reviewed as a top-level PN branch. This is a systems/taxonomy umbrella, not a direct GO assertion; narrower child curations carry any propagating GO mappings.

Projected GO annotations (2)

GO:0015031 protein transport | scope=ok_for_propagation_to_go | goa_status=new_to_goa | from=ER proteostasis|Protein transport
GO:0006614 SRP-dependent cotranslational protein targeting to membrane | scope=ok_for_propagation_to_go | goa_status=already_in_goa_exact | from=ER proteostasis|Protein transport|Signal recognition particle component

Note

This file is generated from the current PROTEOSTASIS phase-1 dossier and local gene-review artifacts. Edit the source review, PN mapping, or dossier rather than this generated note when correcting the underlying curation.

📄 View Raw YAML

id: P09132
gene_symbol: SRP19
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: '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.'
alternative_products:
- name: '1'
  id: P09132-1
- name: '2'
  id: P09132-2
  sequence_note: VSP_042540
- name: '3'
  id: P09132-3
  sequence_note: VSP_044524
existing_annotations:
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: Phylogenetic annotation of SRP19 as a constitutive subunit of the signal recognition particle. Conserved and directly demonstrated.
    action: ACCEPT
    reason: Core cellular component; SRP19 is one of the six SRP protein subunits.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'consists of a 7SL RNA molecule of 300 nucleotides and 6 protein'
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Core molecular function; SRP19 binds the SRP 7SL RNA, supported by IDA.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: Binds directly to 7SL RNA
- term:
    id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Core biological process; SRP19 is required for assembly of the signal-sequence-recognizing SRP54 into SRP.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: Mediates
- term:
    id: GO:0005654
    label: nucleoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Real assembly-stage localization, but not the defining cytoplasmic ER-targeting site of action.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'Nucleus,'
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of nucleolar localization, where SRP partially assembles. An assembly compartment rather than the core ER-targeting site.
    action: KEEP_AS_NON_CORE
    reason: Real assembly-stage localization, secondary to the cytoplasmic site of SRP function.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'Nucleus, nucleolus'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of the cytoplasmic localization, the site where mature SRP functions in ER targeting. Consistent with experimental EXP evidence.
    action: ACCEPT
    reason: Correct core compartment; SRP acts in the cytoplasm.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0006614
    label: SRP-dependent cotranslational protein targeting to membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: InterPro-based electronic assignment of the core SRP-dependent co-translational targeting process.
    action: ACCEPT
    reason: Correct core process; redundant with IBA/TAS evidence.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: mediates the cotranslational targeting
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: InterPro-based annotation of SRP RNA (7S/7SL) binding, SRP19's core molecular function.
    action: ACCEPT
    reason: Correct core molecular function; redundant with IDA evidence.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: Binds directly to 7SL RNA
- term:
    id: GO:0048500
    label: signal recognition particle
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: part_of
  review:
    summary: InterPro-based annotation of SRP complex membership (general SRP term).
    action: ACCEPT
    reason: Core cellular component; redundant with the more specific GO:0005786.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'Component of the signal recognition particle (SRP) complex'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Records the real SRP68 interaction, but bare protein binding is uninformative; covered by SRP complex membership and 7S RNA binding.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'P09132; Q9UHB9: SRP68'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35271311
  qualifier: enables
  review:
    summary: OpenCell endogenous-tagging interactome capturing the SRP19-SRP68 (Q9UHB9) interaction. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Records the real SRP68 interaction; bare protein binding is uninformative.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'P09132; Q9UHB9: SRP68'
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: NAS
  original_reference_id: PMID:34208095
  qualifier: part_of
  review:
    summary: ComplexPortal NAS assertion of SRP complex membership from the SRP review, which notes SRP19 functions to stabilize the 7SL structure.
    action: ACCEPT
    reason: Core cellular component; SRP19 is an SRP subunit.
    supported_by:
    - reference_id: PMID:34208095
      supporting_text: SRP19 functions to stabilize the 7SL structure
- term:
    id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
  evidence_type: NAS
  original_reference_id: PMID:34208095
  qualifier: involved_in
  review:
    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.
    action: ACCEPT
    reason: Core biological process at the complex level; SRP19 is required for assembly of the signal-sequence-recognizing SRP54.
    supported_by:
    - reference_id: PMID:34208095
      supporting_text: SRP19 functions to stabilize the 7SL structure
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: HPA immunofluorescence cytosolic localization, consistent with the cytoplasmic site of SRP function.
    action: ACCEPT
    reason: Correct core compartment; SRP acts in the cytosol.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1799332
  qualifier: located_in
  review:
    summary: Reactome curation of cytosolic localization, consistent with SRP's cytoplasmic site of action.
    action: ACCEPT
    reason: Correct compartment; redundant with HPA/UniProt evidence.
    supported_by:
    - reference_id: file:human/SRP19/SRP19-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Cytoplasm'
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:10618370
  qualifier: located_in
  review:
    summary: Direct experimental cytoplasmic localization of SRP19, alongside its nucleolar localization during SRP assembly.
    action: ACCEPT
    reason: Correct core compartment; experimentally demonstrated.
    supported_by:
    - reference_id: PMID:10618370
      supporting_text: prominent nucleolar localization
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: EXP
  original_reference_id: PMID:11682607
  qualifier: located_in
  review:
    summary: Direct experimental cytoplasmic localization of SRP19 from the nuclear-import study, which also documents nuclear/nucleolar pools.
    action: ACCEPT
    reason: Correct core compartment; experimentally demonstrated.
    supported_by:
    - reference_id: PMID:11682607
      supporting_text: imported into the nucleus
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: IPI
  original_reference_id: PMID:17434535
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Correct molecular function; the more specific GO:0008312 (7S RNA binding) better captures SRP19's role.
    supported_by:
    - reference_id: PMID:17434535
      supporting_text: SRP19 protein is unstructured
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IDA
  original_reference_id: PMID:27899666
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Core molecular function with direct structural (IDA) support.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA
- term:
    id: GO:0043022
    label: ribosome binding
  evidence_type: IDA
  original_reference_id: PMID:27899666
  qualifier: contributes_to
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Complex-level activity to which SRP19 contributes (contributes_to); SRP19's defining MF is SRP RNA binding.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: 5f-loop involved in ribosome binding
- term:
    id: GO:0048500
    label: signal recognition particle
  evidence_type: IDA
  original_reference_id: PMID:27899666
  qualifier: part_of
  review:
    summary: Direct structural evidence placing SRP19 within the SRP complex.
    action: ACCEPT
    reason: Core cellular component; structurally demonstrated.
    supported_by:
    - reference_id: PMID:27899666
      supporting_text: SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA
- term:
    id: GO:0003723
    label: RNA binding
  evidence_type: HDA
  original_reference_id: PMID:22658674
  qualifier: enables
  review:
    summary: High-throughput mRNA-interactome capture detecting SRP19 as an RNA-binding protein. Correct but generic parent of 7S RNA binding.
    action: ACCEPT
    reason: Correct general molecular function; the specific GO:0008312 better captures SRP19's SRP RNA binding.
    supported_by:
    - reference_id: PMID:22658674
      supporting_text: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: IDA
  original_reference_id: PMID:18089836
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    reason: Core cellular component; SRP19 is detected as part of the SRP complex.
    supported_by:
    - reference_id: PMID:18089836
      supporting_text: disrupts SRP complex formation
- term:
    id: GO:0008312
    label: 7S RNA binding
  evidence_type: IDA
  original_reference_id: PMID:17434535
  qualifier: enables
  review:
    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.
    action: ACCEPT
    reason: Core molecular function with direct (IDA) support.
    supported_by:
    - reference_id: PMID:17434535
      supporting_text: SRP19 protein is unstructured
- term:
    id: GO:0005730
    label: nucleolus
  evidence_type: IDA
  original_reference_id: PMID:10618370
  qualifier: located_in
  review:
    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.
    action: KEEP_AS_NON_CORE
    reason: Real assembly-stage localization; not the defining cytoplasmic site of SRP function.
    supported_by:
    - reference_id: PMID:10618370
      supporting_text: prominent nucleolar localization
- term:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  evidence_type: TAS
  original_reference_id: PMID:1678319
  qualifier: part_of
  review:
    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.
    action: ACCEPT
    reason: Core cellular component; SRP19 is an SRP subunit. The cited paper correctly identifies SRP19 as the SRP 19 kDa component.
    supported_by:
    - reference_id: PMID:1678319
      supporting_text: identical to SRP19
- term:
    id: GO:0006613
    label: cotranslational protein targeting to membrane
  evidence_type: TAS
  original_reference_id: PMID:1678319
  qualifier: involved_in
  review:
    summary: TAS annotation of the (older parent) co-translational protein targeting process for SRP19 as an SRP component.
    action: ACCEPT
    reason: Correct biological process; the SRP-dependent child terms better specify SRP19's role.
    supported_by:
    - reference_id: PMID:1678319
      supporting_text: identical to SRP19
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: PMID:10618370
  title: Signal recognition particle components in the nucleolus.
  findings:
  - statement: SRP19 binds SRP RNA independently and must bind before SRP54, effecting a conformational change promoting SRP54 binding; GFP-SRP19 shows prominent nucleolar plus cytoplasmic localization.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes ordered SRP assembly (SRP19 before SRP54) and the nucleolar assembly compartment.
- id: PMID:11682607
  title: Signal recognition particle protein 19 is imported into the nucleus by importin 8 (RanBP8) and transportin.
  findings:
  - statement: SRP19 is efficiently imported into the nucleus by importin 8 and transportin; a significant endogenous pool is nuclear/nucleolar.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Source of nuclear-import and nuclear/nucleolar localization annotations.
- id: PMID:1678319
  title: Identification of deletion mutations and three new genes at the familial polyposis locus.
  findings:
  - statement: Positional cloning at the APC/polyposis locus identified a gene identical to SRP19, the 19 kDa component of the ribosomal signal recognition particle.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Original mapping of SRP19; correctly identifies it as the SRP 19 kDa component despite the paper's APC focus.
- id: PMID:17434535
  title: A threefold RNA-protein interface in the signal recognition particle gates native complex assembly.
  findings:
  - statement: SRP19 is unstructured when free and folds into a compact core plus two extended RNA-binding loops upon binding SRP RNA; SRP54 subsequently binds the assembled SRP19-RNA complex.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Establishes SRP19's disorder-to-order RNA-binding transition gating SRP54 incorporation.
- id: PMID:18089836
  title: 'A new mechanism of 6-((2-(dimethylamino)ethyl)amino)-3-hydroxy-7H-indeno(2,1-c)quinolin-7-one dihydrochloride (TAS-103) action discovered by target screening with drug-immobilized affinity beads.'
  findings:
  - statement: SRP is the target of TAS-103; the compound disrupts SRP complex formation and reduces the amount of SRP14 and SRP19, detecting SRP19 within the SRP complex.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Detects SRP19 as part of the SRP complex; supports SRP membership.
- id: PMID:22658674
  title: Insights into RNA biology from an atlas of mammalian mRNA-binding proteins.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput RNA-interactome capture; source of the generic RNA binding HDA annotation.
- id: PMID:27899666
  title: Structures of human SRP72 complexes provide insights into SRP RNA remodeling and ribosome interaction.
  findings:
  - statement: SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA, preparing the asymmetric loop of helix 8 for SRP54 binding; SRP72-RBD remodels the 5f-loop involved in ribosome binding.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural study establishing SRP19's RNA-clamping/scaffolding role and complex-level ribosome interaction.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Captures the SRP19-SRP68 interaction; bare protein binding term.
- id: PMID:34208095
  title: 'SRPassing Co-translational Targeting: The Role of the Signal Recognition Particle in Protein Targeting and mRNA Protection.'
  findings:
  - statement: SRP19 functions to stabilize the 7SL RNA structure within SRP; SRP consists of Alu and S domains with six proteins and 7SL RNA.
    reference_section_type: OTHER
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Authoritative SRP review; full text available. Used by ComplexPortal for NAS annotations.
- id: PMID:35271311
  title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Endogenous-tagging interactome; captures SRP19-SRP68 interaction, bare protein binding.
- id: Reactome:R-HSA-1799332
  title: 'Reactome: Nascent polypeptide:mRNA:ribosome complex binds signal recognition particle (SRP)'
  findings: []
- id: PMID:12086622
  title: Crystal structure of SRP19 in complex with the S domain of SRP RNA and its implication for the assembly of the signal recognition particle.
  findings:
  - statement: Crystal structure of SRP19 bound to the S-domain of SRP RNA shows SRP19 clamps the tetraloops of helices 6 and 8 (helix 6 acting as a splint), pre-organizing the SRP54-binding site on helix 8; unlike bacterial systems, human SRP54 cannot bind SRP RNA before SRP19, establishing SRP19 as an upstream eukaryotic assembly factor.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (Oubridge et al., Mol Cell 2002). Foundational structural basis for SRP19's helix-6/8 RNA clamp and SRP54-late ordered assembly.
- id: PMID:38858088
  title: The nucleolar phase of signal recognition particle assembly.
  findings:
  - statement: GFP-SRP19 accumulates in nucleoli and co-localizes with nucleolar markers; nucleolar disruption (low-dose actinomycin D, uL18/RPL5 depletion) relocalizes SRP19, and SRP proteins associate with many nucleolar/ribosome-biogenesis factors, supporting a bona fide nucleolar phase of SRP assembly.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: PubMed-verified (Issa et al., Life Sci Alliance 2024). Strengthens the nucleolar SRP-assembly compartment for SRP19 (a non-core, assembly-stage localization).
- id: PMID:35754847
  title: Signal Recognition Particle in Human Diseases.
  findings:
  - statement: Reviews SRP-related human disease; SRP19 is among the SRP autoantigens (anti-SRP19, anti-SRP54, anti-SRP72, anti-7SL) recognized in immune-mediated necrotizing myopathy (IMNM)/anti-SRP myositis.
    reference_section_type: OTHER
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: PubMed-verified (Kellogg et al., Front Genet 2022). Disease/autoantigen context for SRP19; not a core molecular-function source.
- id: file:human/SRP19/SRP19-uniprot.txt
  title: UniProt entry P09132 (SRP19_HUMAN), Signal recognition particle 19 kDa protein
  findings:
  - statement: SRP19 is a subunit of the SRP ribonucleoprotein (7SL RNA + six proteins); binds directly to 7SL RNA and mediates binding of SRP54 to the SRP complex; cytoplasmic with nuclear/nucleolar assembly pools.
    reference_section_type: OTHER
core_functions:
- description: SRP RNA-binding scaffolding subunit that binds the SRP 7SL RNA, clamping helices 6 and 8 and remodeling helix 8 to create the SRP54 binding site, thereby enabling ordered assembly of the SRP S domain.
  molecular_function:
    id: GO:0008312
    label: 7S RNA binding
  in_complex:
    id: GO:0005786
    label: signal recognition particle, endoplasmic reticulum targeting
  supported_by:
  - reference_id: PMID:27899666
    supporting_text: SRP19 is a scaffolding protein clamping helices 6 and 8 of SRP RNA
  - reference_id: PMID:12086622
    supporting_text: >-
      SRP19 clamps the tetraloops of two branched helices (helices 6 and 8) and allows them to
      interact side by side.
  - reference_id: file:human/SRP19/SRP19-uniprot.txt
    supporting_text: Binds directly to 7SL RNA
  directly_involved_in:
  - id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
- description: Required assembly factor for incorporation of the signal-sequence-recognition GTPase SRP54 into the SRP, gating productive SRP assembly for co-translational ER targeting.
  molecular_function:
    id: GO:0008312
    label: 7S RNA binding
  in_complex:
    id: GO:0048500
    label: signal recognition particle
  supported_by:
  - reference_id: file:human/SRP19/SRP19-uniprot.txt
    supporting_text: Mediates
  - reference_id: PMID:17434535
    supporting_text: SRP19 protein is unstructured
  - reference_id: PMID:12086622
    supporting_text: >-
      In Archaea and Eukarya, SRP19 binds to 7SL RNA and promotes the incorporation of SRP54,
      which contains the binding sites for GTP, the signal peptide, and the membrane-bound SRP
      receptor.
  directly_involved_in:
  - id: GO:0006614
    label: SRP-dependent cotranslational protein targeting to membrane
proposed_new_terms: []
suggested_questions:
- question: What is the functional significance of the nuclear/nucleolar SRP19 pool and its active import, given that mature SRP acts in the cytoplasm?
- question: Do the alternative SRP19 isoforms differ in RNA-binding or SRP54-recruitment activity?
suggested_experiments:
- description: 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.
- description: 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.

SRP19

Gene Description

Existing Annotations Review

Core Functions

SRP RNA-binding scaffolding subunit that binds the SRP 7SL RNA, clamping helices 6 and 8 and remodeling helix 8 to create the SRP54 binding site, thereby enabling ordered assembly of the SRP S domain.

Required assembly factor for incorporation of the signal-sequence-recognition GTPase SRP54 into the SRP, gating productive SRP assembly for co-translational ER targeting.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research report: Human SRP19 (UniProt P09132) functional annotation

0. Target verification (gene/protein identity)

1. Key concepts and definitions (current understanding)

1.1 What is SRP19?

1.2 What is the SRP pathway and where does SRP19 fit?

1.3 Molecular function: SRP19 is an SRP RNA assembly factor within the mature complex

2. SRP19 complex membership, interactions, and pathway placement

2.1 Core SRP composition

2.2 Assembly logic: SRP19 shapes the S domain to recruit SRP54

3. Subcellular localization and SRP biogenesis route

3.1 Nuclear/nucleolar assembly phase followed by cytoplasmic maturation

3.2 2024 primary evidence: SRP19 nucleolar accumulation and nucleolus-dependence

4. Recent developments and latest research (prioritizing 2023–2024)

4.1 Nucleolar phase of SRP assembly (2024)

4.2 SRP subunit homeostasis and SRP19 dependence on other SRP components (2023)

4.3 SRP19 in pathogen/host context (2024)

5. Current applications and real-world implementations

5.1 Clinical diagnostics: anti-SRP antibody testing in immune-mediated necrotizing myopathy

6. Expert opinions and analysis (authoritative sources)

7. Quantitative statistics and data points from recent studies/reviews

7.1 Autoimmune myopathy prevalence/incidence

7.2 SRP-dependent transcript set size

7.3 Quantitative imaging evidence for SRP19 in nuclear bodies

8. Summary for functional annotation

Evidence map table

References (URLs and publication dates)

Artifacts

Citations

📚 Additional Documentation

Notes

SRP19 (P09132, human) review notes

Identity and overview

Core molecular function: SRP RNA binding / scaffolding required for SRP54 recruitment (S-domain assembly)

GO term mapping

Subcellular location

ribosome binding (GO:0043022, contributes_to, IDA PMID:27899666)

protein binding (GO:0005515) IPI annotations

PMID:1678319 (familial polyposis locus)

PMID:18089836 (TAS-103 drug target screen) — IDA for SRP membership (GO:0005786)

PMID:34208095 (review, ComplexPortal NAS source)

Summary of core vs non-core

Falcon deep-research findings (incorporated 2026-06)

Pn Notes

SRP19 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Full Consistency Review

PN Dossier Context

PN row 1: ER proteostasis | Protein transport | Signal recognition particle component

Projected GO annotations (2)

Note

📄 View Raw YAML