Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005785 signal recognition particle receptor complex	IBA GO_REF:0000033	ACCEPT	Summary: SRPRB is the beta subunit of the heterodimeric SRP receptor; phylogenetic assignment of SR-complex membership is consistent with direct structural and biochemical evidence. Core structural identity. Reason: SRP receptor complex membership is the core cellular-component identity of SRPRB; SRPRB heterodimerizes with SRPRA. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt Component of the signal recognition particle (SRP) complex receptor (SR)
GO:0045047 protein targeting to ER	IBA GO_REF:0000033	ACCEPT	Summary: As part of the SRP receptor, SRPRB participates in targeting nascent secretory/membrane proteins to the ER. Core biological process. Reason: Core SR-mediated process; the SRP receptor ensures correct targeting of nascent proteins to the ER membrane. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt the correct targeting of the nascent secretory proteins to the
GO:0005525 GTP binding	IEA GO_REF:0000002	ACCEPT	Summary: SRPRB is a small GTPase of the Ras superfamily (Arf/Sar1-related) with conserved GTP-binding motifs; GTP binding and hydrolysis drive the SRP-targeting cycle. Core molecular function. Reason: Core molecular function; SRPRB binds GTP (structure solved in the Mg2+-GTP-bound state) and its GTPase activity regulates targeting. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt GTP-binding PMID:29567807 PMID:34020957
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: Electronic transfer of the ER membrane subcellular location from UniProt; the correct and core compartment for the membrane-anchored SR-beta subunit. Reason: Correct core location; SRPRB is a single-pass ER membrane protein. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005515 protein binding	IPI PMID:16169070 A human protein-protein interaction network: a resource for ...	KEEP AS NON CORE	Summary: High-throughput protein-protein interaction capture. SRPRB's functionally informative interaction is with SRPRA (the SR heterodimer), but bare protein binding is uninformative. Reason: Real but the bare protein binding term is uninformative per curation guidelines; the SR-complex term captures the informative content. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt Heterodimer with SRPRA
GO:0005515 protein binding	IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling...	KEEP AS NON CORE	Summary: BioPlex affinity-MS interactome capture. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt Heterodimer with SRPRA
GO:0005515 protein binding	IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func...	KEEP AS NON CORE	Summary: Multimodal cell-map interactome capture. Bare protein binding is uninformative. Reason: High-throughput interaction; bare protein binding is uninformative and not core. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt Heterodimer with SRPRA
GO:0005785 signal recognition particle receptor complex	EXP PMID:16439358 The structure of the mammalian signal recognition particle (...	ACCEPT	Summary: Crystal structure of mammalian SR-beta in complex with the SRalpha (SRPRA) binding domain (SRX); direct experimental evidence that SRPRB is part of the heterodimeric SRP receptor. Core structural identity. Reason: Experimentally demonstrated core SR membership; SRPRB-SRPRA heterodimer structure. Supporting Evidence: PMID:16439358 The SR is a heterodimeric complex assembled by the two GTPases SRalpha and SRbeta
GO:0006617 SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition	NAS PMID:16439358 The structure of the mammalian signal recognition particle (...	ACCEPT	Summary: SRPRB, as part of the SR, participates in SRP-dependent cotranslational targeting of nascent chains to the ER membrane. Core biological process. Reason: Core SR-mediated process; the SRP receptor mediates SRP-dependent cotranslational targeting at the ER. Supporting Evidence: PMID:16439358 co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum
GO:0016020 membrane	NAS PMID:16439358 The structure of the mammalian signal recognition particle (...	KEEP AS NON CORE	Summary: The SR is membrane-anchored via SRPRB; a generic membrane localization that is a parent of the specific ER membrane term. Reason: Correct but generic; the ER membrane term captures the informative localization. Supporting Evidence: PMID:16439358 which is membrane-anchored
GO:0005789 endoplasmic reticulum membrane	ISS GO_REF:0000024	ACCEPT	Summary: Curator ISS transfer of ER membrane localization from an ortholog; the correct and core compartment for SRPRB. Reason: Correct core location; redundant with other ER membrane evidence. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0016020 membrane	IDA PMID:22375059 Different effects of Sec61α, Sec62 and Sec63 depletion on tr...	KEEP AS NON CORE	Summary: Direct evidence of membrane localization from a study of Sec61/Sec62/Sec63-dependent ER translocation; a generic membrane term, parent of ER membrane. Reason: Correct but generic; the ER membrane term captures the informative localization. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005789 endoplasmic reticulum membrane	TAS Reactome:R-HSA-1791060	ACCEPT	Summary: Reactome TAS annotation of ER membrane localization for SRPRB, consistent with the core compartment. Reason: Correct core location; consistent with experimental and ISS evidence. Supporting Evidence: file:human/SRPRB/SRPRB-uniprot.txt SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
GO:0005881 cytoplasmic microtubule	IDA PMID:23264731 MTR120/KIAA1383, a novel microtubule-associated protein, pro...	REMOVE	Summary: Wrong-gene citation. PMID:23264731 characterizes MTR120/KIAA1383 as a microtubule-associated protein; the now-cached full text never mentions or assays SRPRB (no occurrence of SRPRB / SR-beta / SRP receptor). SRPRB is an ER-membrane GTPase, for which a cytoplasmic microtubule localization is biologically implausible. Reason: The full text of PMID:23264731 is now available and confirms the paper is entirely about MTR120/KIAA1383 and does not assay SRPRB, so this GO:0005881 IDA is a wrong-gene mis-attribution. This matches the sibling SERP1 review, where the same PMID:23264731 cytoplasmic-microtubule annotation was REMOVED after full-text confirmation; previously this row was held UNDECIDED only because the full text was unavailable. Supporting Evidence: PMID:23264731 a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis
GO:0005737 cytoplasm	IDA PMID:19664239 Subcellular localization of APMCF1 and its biological signif...	KEEP AS NON CORE	Summary: GFP-APMCF1 (SRPRB) overexpression showed a generally cytoplasmic distribution in COS-7 cells. A diffuse cytoplasmic signal is consistent with an ER-membrane protein (the ER is in the cytoplasm), but cytoplasm is imprecise relative to the ER membrane and the signal derives from overexpression of a GFP fusion. Reason: Plausible but imprecise (and overexpression-based); the informative core localization is the ER membrane. Supporting Evidence: PMID:19664239 EGFP-APMCF1 was generally localized in the cytoplasm of COS-7 cell

Core Functions

Membrane-anchored beta subunit of the heterodimeric signal recognition particle (SRP) receptor; a Ras-superfamily GTPase that, together with SRPRA, docks the SRP-ribosome-nascent chain complex at the ER membrane to enable SRP-dependent cotranslational protein targeting.

Molecular Function:

GTP binding

Directly Involved In:

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

Cellular Locations:

endoplasmic reticulum membrane

In Complex:

signal recognition particle receptor complex

Supporting Evidence:

file:human/SRPRB/SRPRB-uniprot.txt
Component of the signal recognition particle (SRP) complex receptor (SR)
PMID:16439358
The SR is a heterodimeric complex assembled by the two GTPases SRalpha and SRbeta
PMID:29567807
PMID:37643813

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000024

Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity

GO_REF:0000033

Annotation inferences using phylogenetic trees

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:16169070

A human protein-protein interaction network: a resource for annotating the proteome.

PMID:16439358

The structure of the mammalian signal recognition particle (SRP) receptor as prototype for the interaction of small GTPases with Longin domains.

The SR is a heterodimeric complex of the two GTPases SRalpha and SRbeta, membrane-anchored; crystal structure of mammalian SRbeta in the Mg2+-GTP-bound state in complex with the SRalpha (SRX) binding domain.

PMID:19664239

Subcellular localization of APMCF1 and its biological significance of expression pattern in normal and malignant human tissues.

EGFP-APMCF1 (SRPRB) overexpressed in COS-7 cells localized generally to the cytoplasm.

PMID:22375059

Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells.

PMID:23264731

MTR120/KIAA1383, a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis.

Characterizes MTR120/KIAA1383 as a microtubule-associated protein promoting microtubule stability and cytokinesis.

PMID:33961781

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

PMID:40205054

Multimodal cell maps as a foundation for structural and functional genomics.

Reactome:R-HSA-1791060

Expression of SRPRB (SRP Receptor subunit beta)

PMID:29567807

Structure of a prehandover mammalian ribosomal SRP·SRP receptor targeting complex.

Cryo-EM structure of the mammalian translating ribosome with SRP and SRP receptor in a prehandover conformation; GTP-bound SRbeta and eukaryote-specific SRP/SR proteins form a large assembly at the distal SRP RNA site, and SRP/SR GTP hydrolysis is delayed at this stage to allow signal-sequence handover.

PMID:34020957

Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational protein translocation into the ER.

Structural, biochemical and single-molecule analyses show eukaryotic SRP-mediated targeting requires sequential GTPase-driven compaction of the SRP receptor (SRalpha/SRbeta) and conformational rearrangements that couple the SRP/SR GTPase cycle to protein translocation.

PMID:37643813

Examining SRP pathway function in mRNA localization to the endoplasmic reticulum.

CRISPR/Cas9 knockout of SRPRB (SRbeta) in mammalian cells profoundly destabilizes SRalpha (proteasome-sensitive) and redistributes residual SRalpha to the cytosol, yet steady-state ER mRNA localization is largely unaltered, uncoupling ER mRNA localization from SRP receptor expression.

PMID:36921042

Signal recognition particle receptor-β (SR-β) coordinates cotranslational N-glycosylation.

SRbeta (SRPRB) is required for assembly of an N-glycosylation-competent translocon; perturbing the SRbeta GTP-binding site (mutation or guanine-analog probes) causes hypoglycosylation and reduces SRbeta association with the oligosaccharyltransferase (OST) complex without disrupting SRalpha-SRbeta association, revealing a function coordinating ER translation with N-glycosylation.

Suggested Experiments

Experiment: Use endogenous tagging plus proximity labeling and super-resolution microscopy to test whether SRPRB localizes to microtubules under any condition, distinguishing genuine localization from overexpression or co-purification artifacts.

Experiment: Reconstitute SRP-dependent targeting with wild-type and GTPase-dead SRPRB to quantify the role of SRPRB GTP hydrolysis in receptor recycling and nascent-chain delivery to Sec61.

Deep Research

Falcon

(SRPRB-deep-research-falcon.md)

Research Report: Human **SRPRB** (SRP receptor subunit beta; SRβ) — Functional Annotation Falcon Edison Scientific Literature 26 citations 2 artifacts 2026-06-12T02:40:47.530108

Edison artifact artifact-00 (text/markdown)

## Context ID: pqac-00000018 The mechanistic diagram in Figure 4E illustrates how SR-β (SRPRB) coordinates cotranslational N-glycosylation. It shows that SR-β f (image/png)

The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.

You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.

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.

We are interested in where in or outside the cell the gene product carries out its function.

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 SRPRB (SRP receptor subunit beta; SRβ) — Functional Annotation

1. Target identity verification (mandatory)

The gene symbol SRPRB in Homo sapiens encodes Signal Recognition Particle (SRP) receptor subunit beta (SRβ), an integral endoplasmic reticulum (ER) membrane protein and the membrane-anchoring subunit of the heterodimeric SRP receptor (SRα/SRβ). This matches the UniProt Q9Y5M8 description provided (SRP receptor subunit beta; SR-β; APMCF1). Experimental work describing SRβ as the transmembrane GTPase subunit that anchors SRα to the ER and binds GTP specifically is consistent with the expected domain/family assignment (P-loop NTPase/small GTPase-like). (miller1995thebetasubunit pages 1-2, miller1995thebetasubunit pages 6-7)

A recent human genetics/cell biology study explicitly refers to SRPRB as encoding the “membrane anchoring subunit” of the SRP receptor, with CRISPR knockout of SRPRB disrupting SRα stability and ER localization—directly aligning the symbol SRPRB with the SRβ protein identity in human cells. (child2023examiningsrppathway pages 2-4)

2. Key concepts and current understanding

2.1 The SRP pathway and the SRP receptor (SR)

The SRP pathway mediates cotranslational targeting of a large fraction of secretory and membrane proteins to the ER. In this process, SRP binds emerging signal sequences on ribosome–nascent chain complexes and delivers them to the ER-localized SRP receptor (SR), enabling transfer to the protein translocation machinery (e.g., Sec61). The SRP receptor is a heterodimer of SRα (peripheral membrane GTPase) and SRβ (integral membrane GTPase). (miller1995thebetasubunit pages 1-2)

2.2 Definition: SRPRB/SRβ molecular role

SRβ is best understood as:
- An ER membrane anchor for SRα (maintaining SRα at the ER surface). (miller1995thebetasubunit pages 1-2, child2023examiningsrppathway pages 2-4)
- A GTP-binding transmembrane small GTPase with canonical GTPase motifs in its cytosolic domain. (miller1995thebetasubunit pages 6-7, miller1995thebetasubunit pages 7-9)
- A structural/mechanistic component of the targeting complex that helps organize the SRP–SR GTPase cycle on the ribosome and (as shown recently) helps coordinate downstream ER cotranslational processing events such as N-glycosylation. (kobayashi2018structureofa pages 1-3, phoomak2023signalrecognitionparticle pages 1-2)

3. Protein features, domains, and subcellular localization

3.1 Membrane topology and ER localization

Classic biochemical characterization established SRβ as an integral membrane protein with a single signal-anchor transmembrane segment (no cleaved signal peptide) and a cytosolic GTPase domain, consistent with function on the cytosolic face of the ER where ribosomes dock. (miller1995thebetasubunit pages 6-7, miller1995thebetasubunit pages 5-6)

3.2 GTPase family assignment

SRβ belongs to the GTPase superfamily and forms a distinct subgroup distantly related to ARF/Sar1-like small GTPases; it binds GTP specifically in UV crosslinking assays, supporting its functional classification as a GTP-binding protein. (miller1995thebetasubunit pages 1-2, miller1995thebetasubunit pages 7-9)

4. Molecular function in pathways: SRP receptor cycle, targeting, and translocation

SRα behaves as a peripheral membrane protein, and SRβ mediates stable membrane association of SRα. This anchoring is not merely structural: SRβ’s nucleotide-binding domain suggested (even in early work) an additional regulated role in targeting/translocation. (miller1995thebetasubunit pages 1-2, miller1995thebetasubunit pages 6-7)

Direct evidence in human cells shows that loss of SRPRB (SRβ) destabilizes SRα and causes cytosolic redistribution of residual SRα, while re-expression of SRβ restores SRα abundance and ER localization. (child2023examiningsrppathway pages 2-4)

4.2 Structural and mechanistic role during cotranslational targeting (2018–2021 mechanistic framework)

A cryo-EM structure of a prehandover mammalian ribosomal SRP·SR targeting complex places SRβ as an ER-integrated, eukaryote-specific SRP receptor component with GTP bound. In this structure, the SRα NG domain contacts the SRβ-bound GTP, and SRβ (together with SRP68 elements) helps form a platform that docks/stabilizes the NG heterodimer at the distal SRP RNA site to enable subsequent handover steps. (kobayashi2018structureofa pages 1-3)

Follow-on mechanistic work supports a model in which SRP-mediated targeting requires sequential conformational rearrangements driven by the SRP/SR GTPase cycle, including receptor compaction and GTPase rearrangement to transition from cargo recognition near the ribosome exit tunnel to a distal state compatible with translocon engagement. In this framework, SRβ is part of the membrane-proximal SR architecture that enables these rearrangements at the ER. (lee2021receptorcompactionand pages 1-2, lee2021receptorcompactionand pages 2-3)

5. Recent developments (prioritizing 2023–2024)

5.1 2023: SRβ coordinates cotranslational N-glycosylation by promoting a glycosylation-competent translocon

A 2023 Science Advances study provided direct evidence for a previously underappreciated function of SRβ: SRβ is required for assembly of an N-glycosylation–competent translocon and thereby coordinates cotranslational translation/translocation with N-glycosylation. Perturbation of SRβ’s GTP-binding site (mutation) or small-molecule guanine analog probes produced a hypoglycosylation phenotype without disrupting SRα–SRβ association, but reduced SRβ association with the oligosaccharyltransferase (OST) complex, linking SRβ activity to OST recruitment/engagement. (phoomak2023signalrecognitionparticle pages 1-2)

A mechanistic schematic from the same study summarizes this model: SRβ promotes recruitment/assembly of OST with the ribosome–Sec61 translocon to create a glycosylation-competent supercomplex, whereas SRβ perturbation prevents proper OST engagement and results in hypoglycosylation. (phoomak2023signalrecognitionparticle media 4ab7387b)

5.2 2023: SRPRB knockout and ER mRNA localization

A 2023 RNA study used CRISPR/Cas9 to generate SRPRB knockout lines and found that, although SRβ loss profoundly destabilizes SRα, steady-state ER localization patterns of mRNAs were largely unaltered in their assays, arguing that ER mRNA localization can be uncoupled from SRP receptor expression under tested conditions. This refines (and complicates) common assumptions that SR is strictly required for ER mRNA localization. (child2023examiningsrppathway pages 2-4)

5.3 2024: SRPRB appears mainly in association/omics contexts rather than established mechanistic disease biology

In 2024 literature retrieved here, SRPRB often appears in gene signatures (e.g., cancer prognostic models, extracellular vesicle proteomics, epigenetic review examples) rather than as a deeply validated causal driver; these contexts can be hypothesis-generating but typically do not supersede the experimentally defined SRβ function in ER targeting and cotranslational processing. (OpenTargets Search: -SRPRB)

6. Quantitative statistics and data from recent studies

6.1 Quantitative phenotypes from SRPRB knockout (2023)

In SRPRB knockout cells, mutant SRPRB transcript levels were reported at ~50–80% of parental and showed reduced engagement with heavy polysomes (shift from fractions 13–18 to fractions 8–10), consistent with nonsense-mediated decay/translation effects. Proteasome inhibition (MG132) for 16 hours increased SRα levels in SRβ-deficient cells, supporting proteasome-mediated SRα turnover when SRβ is absent. (child2023examiningsrppathway pages 2-4)

6.2 Quantitative glycoproteomics and screening statistics (2023)

In the SRβ–glycosylation coordination study:
- A high-throughput screen of 361,103 small molecules identified guanine analog activity (including 6-thioguanine) associated with glycosylation defects. (phoomak2023signalrecognitionparticle pages 1-2)
- Glycoproteomic analysis identified 796 acceptor sequons; 244 showed >25% reduction in glycan occupancy and 95 showed >50% reduction after treatment. (phoomak2023signalrecognitionparticle pages 2-3)
- Comparison with a direct OST inhibitor (NGI-1) suggested only partial overlap: among 617 sequons quantified in both datasets, only ~50% of strongly affected sites by one condition matched the other, consistent with a mechanism distinct from simple OST inhibition and implicating cotranslational/translocon coordination. (phoomak2023signalrecognitionparticle pages 2-3)

7. Current applications and real-world implementations

7.1 Chemical biology and pathway probing of cotranslational processing

The 2023 identification of guanine-analog probes that induce SRβ-linked hypoglycosylation provides a practical chemical perturbation strategy to interrogate how cotranslational targeting interfaces with glycosylation and translocon assembly. This is directly applicable to studies of secretory pathway quality control and glycoprotein biogenesis. (phoomak2023signalrecognitionparticle pages 1-2, phoomak2023signalrecognitionparticle pages 2-3)

7.2 Functional genomics models to dissect ER targeting and mRNA localization

SRPRB knockout cell lines (and complementary SRα suppression approaches) provide real-world cellular systems for separating SR-dependent protein targeting functions from SR-independent ER mRNA localization phenomena, enabling mechanistic dissection of ER-associated translation biology. (child2023examiningsrppathway pages 2-4)

7.3 Disease association resources (hypothesis generation)

Open Targets lists modest associations between SRPRB and several disease terms (e.g., neurodegenerative disease) derived largely from functional screening evidence (CRISPRi/CRISPRa survival screens). These data are useful for hypothesis generation and prioritization but should be interpreted cautiously because they do not, by themselves, establish SRPRB as a well-validated monogenic disease gene or therapeutic target. (OpenTargets Search: -SRPRB)

8. Expert synthesis and analysis (evidence-weighted)

Core, highest-confidence function: SRPRB encodes SRβ, an ER-integrated GTP-binding receptor subunit essential for stable SRα association with the ER and for canonical SRP-mediated cotranslational targeting. This is supported by foundational biochemical work and reinforced by direct human knockout phenotypes. (miller1995thebetasubunit pages 1-2, child2023examiningsrppathway pages 2-4)
Mechanistic refinement from structures: Cryo-EM places SRβ as an organizing element in eukaryotic targeting intermediates; GTP-bound SRβ interacts with SRα domain architecture to stabilize/dock the SRP–SR NG heterodimer for handover steps, with evidence that SRβ may not hydrolyze GTP in at least one prehandover conformation. (kobayashi2018structureofa pages 1-3)
Major 2023 advance: SRβ is not only an anchor; it can coordinate assembly of a glycosylation-competent translocon by modulating association with OST, providing a direct mechanistic bridge between targeting and a key cotranslational modification (N-glycosylation). This expands functional annotation of SRPRB into cotranslational processing beyond simple targeting. (phoomak2023signalrecognitionparticle pages 1-2, phoomak2023signalrecognitionparticle media 4ab7387b)
Limits of current evidence: Many 2024 mentions of SRPRB occur in omics signatures or association resources; these do not yet replace direct mechanistic studies as the basis for functional annotation. (OpenTargets Search: -SRPRB)

9. Summary table

Category	Evidence summary	Key citations (pqac IDs)	Publication(s) + date + URL
Identity	Human SRPRB matches UniProt Q9Y5M8 and encodes signal recognition particle receptor subunit beta (SRβ), also called the membrane-anchoring subunit of the heterodimeric SRP receptor. Loss of SRPRB destabilizes SRα and redistributes residual SRα to the cytosol, confirming the specific SRα/SRβ receptor identity in human cells.	(miller1995thebetasubunit pages 1-2, child2023examiningsrppathway pages 2-4)	Miller et al., J Cell Biol (Feb 1995), https://doi.org/10.1083/jcb.128.3.273; Child et al., RNA (Aug 2023), https://doi.org/10.1261/rna.079643.123
Domains	SRβ is an integral membrane small GTPase with a single transmembrane signal-anchor and a cytosolic GTP-binding domain containing canonical GTPase motifs; it defines a distinct SRβ subfamily related to ARF/Sar1-like small GTPases. Structural work further places a GTP molecule bound to SRβ within the mammalian targeting complex.	(miller1995thebetasubunit pages 6-7, miller1995thebetasubunit pages 7-9, kobayashi2018structureofa pages 7-9)	Miller et al., J Cell Biol (Feb 1995), https://doi.org/10.1083/jcb.128.3.273; Kobayashi et al., Science (Apr 2018), https://doi.org/10.1126/science.aar7924
Localization	SRβ localizes to the endoplasmic reticulum membrane as the membrane-integrated subunit of the SRP receptor, with its GTPase domain on the cytosolic face. Complementation of SRPRB knockout restores SRα localization to the ER, reinforcing ER residency of the functional complex.	(miller1995thebetasubunit pages 6-7, miller1995thebetasubunit pages 5-6, child2023examiningsrppathway pages 2-4)	Miller et al., J Cell Biol (Feb 1995), https://doi.org/10.1083/jcb.128.3.273; Child et al., RNA (Aug 2023), https://doi.org/10.1261/rna.079643.123
Complexes/partners	Major partners are SRα (SRPRA), SRP54/SRP, the ribosome-nascent chain complex, and functionally the Sec61 translocon. Recent work adds the oligosaccharyltransferase (OST) complex as an SRβ-associated partner needed for a glycosylation-competent translocon. Cryo-EM places SRβ together with SRP68 in a platform that docks the NG heterodimer at the distal SRP RNA site.	(phoomak2023signalrecognitionparticle pages 1-2, kobayashi2018structureofa pages 1-3, kobayashi2018structureofa pages 3-5, phoomak2023signalrecognitionparticle media 4ab7387b)	Kobayashi et al., Science (Apr 2018), https://doi.org/10.1126/science.aar7924; Phoomak et al., Sci Adv (Mar 2023), https://doi.org/10.1126/sciadv.ade8079
Core molecular function	SRβ’s core role is to anchor and organize the SRP receptor at the ER during co-translational targeting of secretory and membrane proteins. Beyond anchoring, its GTP-bound state contributes to assembly/stabilization of the targeting complex and, in 2023 work, to coordination of cotranslational N-glycosylation by promoting OST engagement with the translocon.	(miller1995thebetasubunit pages 1-2, kobayashi2018structureofa pages 1-3, phoomak2023signalrecognitionparticle pages 1-2)	Miller et al., J Cell Biol (Feb 1995), https://doi.org/10.1083/jcb.128.3.273; Kobayashi et al., Science (Apr 2018), https://doi.org/10.1126/science.aar7924; Phoomak et al., Sci Adv (Mar 2023), https://doi.org/10.1126/sciadv.ade8079
Key mechanistic insights	Early biochemical work showed specific GTP binding by SRβ and proposed that its nucleotide state could regulate targeting/translocation. Cryo-EM and single-molecule work later showed that eukaryotic targeting requires SR compaction and GTPase-driven rearrangements; GTP-bound SRβ contacts the SRα NG/SRX architecture and provides a eukaryote-specific stabilizing effect that helps dock the targeting complex for signal-sequence handover. Notably, the 2018 structure suggested SRβ may remain GTP-bound without hydrolysis in that prehandover state.	(miller1995thebetasubunit pages 7-9, kobayashi2018structureofa pages 1-3, kobayashi2018structureofa pages 3-5, lee2021receptorcompactionand pages 1-2, lee2021receptorcompactionand pages 2-3)	Miller et al., J Cell Biol (Feb 1995), https://doi.org/10.1083/jcb.128.3.273; Kobayashi et al., Science (Apr 2018), https://doi.org/10.1126/science.aar7924; Lee et al., Sci Adv (May 2021), https://doi.org/10.1126/sciadv.abg0942
Phenotypes/perturbations	SRPRB knockout in human cells causes profound destabilization of SRα, proteasome-sensitive SRα loss, and cytosolic redistribution of residual SRα, but surprisingly leaves bulk steady-state ER/cytosol mRNA partitioning largely unchanged. Chemical or mutational perturbation of the SRβ GTP-binding site causes an N-glycosylation-deficient phenotype and reduces SRβ association with OST without disrupting SRα-SRβ association.	(child2023examiningsrppathway pages 2-4, phoomak2023signalrecognitionparticle pages 1-2)	Child et al., RNA (Aug 2023), https://doi.org/10.1261/rna.079643.123; Phoomak et al., Sci Adv (Mar 2023), https://doi.org/10.1126/sciadv.ade8079
Recent (2023-2024) developments	In 2023, SRPRB was shown to have a previously underappreciated role in assembling an N-glycosylation-competent translocon and coordinating cotranslational N-glycosylation, expanding its function beyond receptor anchoring. Also in 2023, human SRPRB knockout experiments challenged simple models that ER mRNA localization is strictly SR-dependent. In 2024, SRPRB appears mainly in omics/association contexts rather than as a directly validated disease gene; Open Targets lists modest disease associations largely derived from functional screening evidence rather than gene-specific mechanistic human pathology.	(child2023examiningsrppathway pages 2-4, phoomak2023signalrecognitionparticle pages 1-2, phoomak2023signalrecognitionparticle pages 2-3, OpenTargets Search: -SRPRB)	Child et al., RNA (Aug 2023), https://doi.org/10.1261/rna.079643.123; Phoomak et al., Sci Adv (Mar 2023), https://doi.org/10.1126/sciadv.ade8079; Open Targets context (accessed via tool context)
Quantitative data points	Reported quantitative findings include: SRPRB KO transcripts at ~50–80% of parental with mutant mRNAs shifted from heavy polysomes fractions 13–18 to fractions 8–10; MG132 for 16 h increased SRα levels in KO cells. In the glycosylation study, a 361,103-compound screen identified 6-thioguanine; treatment effects were seen with 10 μM compounds and ~6 h onset; among 796 sequons, 244 showed >25% occupancy loss and 95 showed >50% loss; among 617 shared sequons, only ~50% overlapped with NGI-1-sensitive sites.	(child2023examiningsrppathway pages 2-4, phoomak2023signalrecognitionparticle pages 1-2, phoomak2023signalrecognitionparticle pages 2-3)	Child et al., RNA (Aug 2023), https://doi.org/10.1261/rna.079643.123; Phoomak et al., Sci Adv (Mar 2023), https://doi.org/10.1126/sciadv.ade8079
OpenTargets association context	Open Targets lists low-to-moderate association scores between SRPRB and several diseases (for example neurodegenerative disease score 0.5463) based on 5 evidence items tied to CRISPRi/CRISPRa survival screens (literature PMID 34031600). These are useful hypothesis-generating links but do not currently establish SRPRB as a well-validated monogenic disease gene.	(OpenTargets Search: -SRPRB)	Open Targets platform context for SRPRB associations (tool-derived evidence context)

Table: This table summarizes the best-supported functional annotation for human SRPRB/SRβ, integrating classic biochemistry, structural studies, and recent 2023 findings. It is useful for distinguishing the core ER-targeting role of SRβ from newer evidence linking it to cotranslational N-glycosylation and from weaker disease-association signals.

Key source URLs (with publication dates)

Miller et al., Journal of Cell Biology (Feb 1995): https://doi.org/10.1083/jcb.128.3.273 (miller1995thebetasubunit pages 1-2)
Kobayashi et al., Science (Apr 2018): https://doi.org/10.1126/science.aar7924 (kobayashi2018structureofa pages 1-3)
Lee et al., Science Advances (May 2021): https://doi.org/10.1126/sciadv.abg0942 (lee2021receptorcompactionand pages 1-2)
Child et al., RNA (Aug 2023): https://doi.org/10.1261/rna.079643.123 (child2023examiningsrppathway pages 2-4)
Phoomak et al., Science Advances (Mar 2023): https://doi.org/10.1126/sciadv.ade8079 (phoomak2023signalrecognitionparticle pages 1-2)
Open Targets SRPRB associations (tool-derived context): evidence summarized in (OpenTargets Search: -SRPRB)

References

(miller1995thebetasubunit pages 1-2): Joshua D. Miller, S. Tajima, L. Lauffer, and P. Walter. The beta subunit of the signal recognition particle receptor is a transmembrane gtpase that anchors the alpha subunit, a peripheral membrane gtpase, to the endoplasmic reticulum membrane. The Journal of cell biology, 128:273-282, Feb 1995. URL: https://doi.org/10.1083/jcb.128.3.273, doi:10.1083/jcb.128.3.273. This article has 167 citations.
(miller1995thebetasubunit pages 6-7): Joshua D. Miller, S. Tajima, L. Lauffer, and P. Walter. The beta subunit of the signal recognition particle receptor is a transmembrane gtpase that anchors the alpha subunit, a peripheral membrane gtpase, to the endoplasmic reticulum membrane. The Journal of cell biology, 128:273-282, Feb 1995. URL: https://doi.org/10.1083/jcb.128.3.273, doi:10.1083/jcb.128.3.273. This article has 167 citations.
(child2023examiningsrppathway pages 2-4): Jessica R. Child, Alex C. Hofler, Qiang Chen, Brenda H. Yang, JohnCarlo Kristofich, Tianli Zheng, Molly M. Hannigan, Andrew L. Elles, David W. Reid, and Christopher V. Nicchitta. Examining srp pathway function in mrna localization to the endoplasmic reticulum. RNA, 29:1703-1724, Aug 2023. URL: https://doi.org/10.1261/rna.079643.123, doi:10.1261/rna.079643.123. This article has 13 citations and is from a domain leading peer-reviewed journal.
(miller1995thebetasubunit pages 7-9): Joshua D. Miller, S. Tajima, L. Lauffer, and P. Walter. The beta subunit of the signal recognition particle receptor is a transmembrane gtpase that anchors the alpha subunit, a peripheral membrane gtpase, to the endoplasmic reticulum membrane. The Journal of cell biology, 128:273-282, Feb 1995. URL: https://doi.org/10.1083/jcb.128.3.273, doi:10.1083/jcb.128.3.273. This article has 167 citations.
(kobayashi2018structureofa pages 1-3): Kan Kobayashi, Ahmad Jomaa, Jae Ho Lee, Sowmya Chandrasekar, Daniel Boehringer, Shu-ou Shan, and Nenad Ban. Structure of a prehandover mammalian ribosomal srp·srp receptor targeting complex. Science, 360:323-327, Apr 2018. URL: https://doi.org/10.1126/science.aar7924, doi:10.1126/science.aar7924. This article has 74 citations and is from a highest quality peer-reviewed journal.
(phoomak2023signalrecognitionparticle pages 1-2): Chatchai Phoomak, Natalie Rinis, Marta Baro, Shiteshu Shrimal, Daniel Bennett, Scott A. Shaffer, Mark Lehrman, Reid Gilmore, and Joseph N. Contessa. Signal recognition particle receptor-β (sr-β) coordinates cotranslational n-glycosylation. Science Advances, Mar 2023. URL: https://doi.org/10.1126/sciadv.ade8079, doi:10.1126/sciadv.ade8079. This article has 6 citations and is from a highest quality peer-reviewed journal.
(miller1995thebetasubunit pages 5-6): Joshua D. Miller, S. Tajima, L. Lauffer, and P. Walter. The beta subunit of the signal recognition particle receptor is a transmembrane gtpase that anchors the alpha subunit, a peripheral membrane gtpase, to the endoplasmic reticulum membrane. The Journal of cell biology, 128:273-282, Feb 1995. URL: https://doi.org/10.1083/jcb.128.3.273, doi:10.1083/jcb.128.3.273. This article has 167 citations.
(lee2021receptorcompactionand pages 1-2): Jae Ho Lee, Ahmad Jomaa, SangYoon Chung, Yu-Hsien Hwang Fu, Ruilin Qian, Xuemeng Sun, Hao-Hsuan Hsieh, Sowmya Chandrasekar, Xiaotian Bi, Simone Mattei, Daniel Boehringer, Shimon Weiss, Nenad Ban, and Shu-ou Shan. Receptor compaction and gtpase rearrangement drive srp-mediated cotranslational protein translocation into the er. May 2021. URL: https://doi.org/10.1126/sciadv.abg0942, doi:10.1126/sciadv.abg0942. This article has 27 citations and is from a highest quality peer-reviewed journal.
(lee2021receptorcompactionand pages 2-3): Jae Ho Lee, Ahmad Jomaa, SangYoon Chung, Yu-Hsien Hwang Fu, Ruilin Qian, Xuemeng Sun, Hao-Hsuan Hsieh, Sowmya Chandrasekar, Xiaotian Bi, Simone Mattei, Daniel Boehringer, Shimon Weiss, Nenad Ban, and Shu-ou Shan. Receptor compaction and gtpase rearrangement drive srp-mediated cotranslational protein translocation into the er. May 2021. URL: https://doi.org/10.1126/sciadv.abg0942, doi:10.1126/sciadv.abg0942. This article has 27 citations and is from a highest quality peer-reviewed journal.
(phoomak2023signalrecognitionparticle media 4ab7387b): Chatchai Phoomak, Natalie Rinis, Marta Baro, Shiteshu Shrimal, Daniel Bennett, Scott A. Shaffer, Mark Lehrman, Reid Gilmore, and Joseph N. Contessa. Signal recognition particle receptor-β (sr-β) coordinates cotranslational n-glycosylation. Science Advances, Mar 2023. URL: https://doi.org/10.1126/sciadv.ade8079, doi:10.1126/sciadv.ade8079. This article has 6 citations and is from a highest quality peer-reviewed journal.
(OpenTargets Search: -SRPRB): Open Targets Query (-SRPRB, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(phoomak2023signalrecognitionparticle pages 2-3): Chatchai Phoomak, Natalie Rinis, Marta Baro, Shiteshu Shrimal, Daniel Bennett, Scott A. Shaffer, Mark Lehrman, Reid Gilmore, and Joseph N. Contessa. Signal recognition particle receptor-β (sr-β) coordinates cotranslational n-glycosylation. Science Advances, Mar 2023. URL: https://doi.org/10.1126/sciadv.ade8079, doi:10.1126/sciadv.ade8079. This article has 6 citations and is from a highest quality peer-reviewed journal.
(kobayashi2018structureofa pages 7-9): Kan Kobayashi, Ahmad Jomaa, Jae Ho Lee, Sowmya Chandrasekar, Daniel Boehringer, Shu-ou Shan, and Nenad Ban. Structure of a prehandover mammalian ribosomal srp·srp receptor targeting complex. Science, 360:323-327, Apr 2018. URL: https://doi.org/10.1126/science.aar7924, doi:10.1126/science.aar7924. This article has 74 citations and is from a highest quality peer-reviewed journal.
(kobayashi2018structureofa pages 3-5): Kan Kobayashi, Ahmad Jomaa, Jae Ho Lee, Sowmya Chandrasekar, Daniel Boehringer, Shu-ou Shan, and Nenad Ban. Structure of a prehandover mammalian ribosomal srp·srp receptor targeting complex. Science, 360:323-327, Apr 2018. URL: https://doi.org/10.1126/science.aar7924, doi:10.1126/science.aar7924. This article has 74 citations and is from a highest quality peer-reviewed journal.

Artifacts

Edison artifact artifact-00

Citations

child2023examiningsrppathway pages 2-4
miller1995thebetasubunit pages 1-2
kobayashi2018structureofa pages 1-3
phoomak2023signalrecognitionparticle pages 1-2
phoomak2023signalrecognitionparticle pages 2-3
lee2021receptorcompactionand pages 1-2
miller1995thebetasubunit pages 6-7
miller1995thebetasubunit pages 7-9
miller1995thebetasubunit pages 5-6
lee2021receptorcompactionand pages 2-3
kobayashi2018structureofa pages 7-9
kobayashi2018structureofa pages 3-5
https://doi.org/10.1083/jcb.128.3.273;
https://doi.org/10.1261/rna.079643.123
https://doi.org/10.1126/science.aar7924
https://doi.org/10.1126/science.aar7924;
https://doi.org/10.1126/sciadv.ade8079
https://doi.org/10.1126/sciadv.abg0942
https://doi.org/10.1261/rna.079643.123;
https://doi.org/10.1126/sciadv.ade8079;
https://doi.org/10.1083/jcb.128.3.273
https://doi.org/10.1083/jcb.128.3.273,
https://doi.org/10.1261/rna.079643.123,
https://doi.org/10.1126/science.aar7924,
https://doi.org/10.1126/sciadv.ade8079,
https://doi.org/10.1126/sciadv.abg0942,

📚 Additional Documentation

Notes

(SRPRB-notes.md)

SRPRB (Q9Y5M8) review notes

Identity / overview

SRPRB is the beta subunit of the signal recognition particle receptor (SR), a heterodimeric ER-membrane
complex (SRalpha = SRPRA + SRbeta = SRPRB). SRbeta is a small Ras-superfamily GTPase (closely related to
Arf/Sar1) that is membrane-anchored via a single N-terminal transmembrane helix and tethers the
soluble SRalpha to the ER membrane. The SR docks the SRP-ribosome-nascent chain complex at the ER so
that cotranslational translocation through the Sec61 channel can proceed. Also known as APMCF1.

UniProt FUNCTION: "Component of the signal recognition particle (SRP) complex receptor (SR)";
"Ensures, in conjunction with the SRP complex, the correct targeting of the nascent secretory proteins
to the endoplasmic reticulum membrane system"; "May mediate the membrane association of SR"
[file:human/SRPRB/SRPRB-uniprot.txt].
SUBUNIT: "Heterodimer with SRPRA" [file:human/SRPRB/SRPRB-uniprot.txt].
SUBCELLULAR LOCATION: "Endoplasmic reticulum membrane ... Single-pass membrane protein"
[file:human/SRPRB/SRPRB-uniprot.txt].
GTPase: TRANSMEM 37-57; GTP BINDING sites at 71-79, 92-95, 120, 248; KW GTP-binding, Nucleotide-binding.
BRENDA 3.6.5.4. Belongs to the SRP receptor beta subunit family.

Key functional evidence

Structure of mammalian SR: PMID:16439358 "The structure of the mammalian signal recognition particle
(SRP) receptor as prototype for the interaction of small GTPases with Longin domains" — "The SR is a
heterodimeric complex assembled by the two GTPases SRalpha and SRbeta, which is membrane-anchored";
"2.45-A structure of mammalian SRbeta in its Mg2+ GTP-bound state in complex with the minimal binding
domain of SRalpha"; "SRbeta is a member of the Ras-GTPase superfamily closely related to Arf and Sar1"
PMID:16439358.
Cryo-EM of SRP-RNC-SR: PMID:34020957 (PDB 7NFX) "Receptor compaction and GTPase rearrangement drive
SRP-mediated cotranslational protein translocation into the ER" (in uniprot reference list; not cached).

Annotation review decisions

Core MF: GTP binding (GO:0005525) — SRbeta is a GTPase; this is its core molecular activity.
Core CC: signal recognition particle receptor complex (GO:0005785); endoplasmic reticulum membrane
(GO:0005789).
Core BP: protein targeting to ER (GO:0045047) / SRP-dependent cotranslational targeting, signal sequence
recognition (GO:0006617).
GO:0016020 membrane (NAS/IDA): SRPRB is an ER-membrane protein; "membrane" is a correct but generic
parent of ER membrane. KEEP_AS_NON_CORE (generic).
GO:0005881 cytoplasmic microtubule (IDA, PMID:23264731): the cited paper is about MTR120/KIAA1383, a
microtubule-associated protein, and characterizes microtubule biology; it does not establish SRPRB as a
microtubule component. SRPRB is an ER-membrane GTPase, not a microtubule protein. This appears to be a
mis-attributed/over-extended localization. Cannot verify SRPRB involvement from the cached abstract.
-> UNDECIDED (per guidelines: do not REMOVE an experimental annotation on incomplete evidence; flag
inconsistency). Biologically implausible as a core function.
GO:0005737 cytoplasm (IDA, PMID:19664239): APMCF1 = SRPRB alias; GFP-APMCF1 subcellular localization
study. A diffuse cytoplasmic signal is plausible for an ER-membrane protein (ER is cytoplasmic). KEEP
as non-core (the ER membrane is the informative location).
protein binding (GO:0005515) IPI rows: high-throughput interactome captures (PMID:16169070,
PMID:33961781, PMID:40205054); the informative SRPRA interaction is captured by the SR-complex term.
KEEP_AS_NON_CORE per guidelines.

Disease

No clearly established Mendelian disease for SRPRB (gene MIM 616883; phenotype not assigned in UniProt).

Falcon deep-research findings (incorporated 2026-06)

Cryo-EM of the prehandover mammalian ribosome-SRP-SR complex shows GTP-bound SRbeta (SRPRB) and eukaryote-specific SRP/SR proteins forming a large assembly at the distal SRP RNA site, with SRP/SR GTP hydrolysis delayed at this stage to permit signal-sequence handover PMID:29567807. Added to GTP binding (GO:0005525) and SR-complex core_function supported_by.
Eukaryotic SRP-mediated targeting requires sequential GTPase-driven compaction of the SR (SRalpha/SRbeta) and conformational rearrangements coupling the SRP/SR GTPase cycle to translocation; SRP54 SCN mutations uncouple the cycle from translocation PMID:34020957. Added to GTP binding supported_by.
Human SRPRB CRISPR knockout profoundly destabilizes SRalpha (proteasome-sensitive) and redistributes residual SRalpha to the cytosol, while steady-state ER mRNA localization is largely unaltered (uncoupling ER mRNA localization from SR expression) PMID:37643813. Added to SR-complex core_function supported_by; direct human loss-of-function evidence for the SRbeta anchoring role.
New SRbeta function beyond anchoring: SRbeta is required to assemble an N-glycosylation-competent translocon; perturbing its GTP-binding site causes hypoglycosylation and reduces SRbeta-OST association without disrupting SRalpha-SRbeta binding PMID:36921042. Candidate for a future MF/BP annotation (cotranslational N-glycosylation coordination); reference added (relevance HIGH).
Foundational Miller et al. 1995 (J Cell Biol) characterizing SRbeta as a transmembrane GTPase anchoring SRalpha is consistent with the review but predates the 2020-2025 scope; not added (PMID not separately resolved here).

Pn Notes

(SRPRB-pn-notes.md)

SRPRB PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: PN consistency rereview against local AIGR review and available deep-research artifacts
UniProt: Q9Y5M8
AIGR review status: COMPLETE
Review batch: proteostasis-batch-2026-06-11
Batch change status: added

Source Files Checked

AIGR review YAML: present - genes/human/SRPRB/SRPRB-ai-review.yaml
AIGR review HTML: missing - genes/human/SRPRB/SRPRB-ai-review.html
Gene notes: present - genes/human/SRPRB/SRPRB-notes.md
GOA TSV: present - genes/human/SRPRB/SRPRB-goa.tsv
UniProt record: present - genes/human/SRPRB/SRPRB-uniprot.txt
PN dossier: projects/PROTEOSTASIS/reports/phase1_dossiers/SRPRB.md
PN consistency section: projects/PROTEOSTASIS/reports/phase1_dossiers/_sections/SRPRB.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/SRPRB/SRPRB-deep-research-falcon.md

AIGR Review Snapshot

Description: SRPRB (signal recognition particle receptor subunit beta, SR-beta; also APMCF1) is a 271 aa single-pass ER membrane protein and a small Ras-superfamily GTPase closely related to Arf and Sar1. It is the membrane-anchored beta subunit of the heterodimeric signal recognition particle (SRP) receptor (SR), assembling with the soluble alpha subunit SRPRA via a Longin-domain interface and tethering SRPRA to the ER membrane. The SRP receptor docks the SRP-ribosome-nascent chain complex at the ER so that signal-sequence-bearing nascent secretory and membrane proteins are delivered to the Sec61 translocon for cotranslational translocation and insertion. SRP-dependent targeting is driven by a GTPase cycle in which the SR (SRPRA and SRPRB) and the SRP54 GTPase reciprocally activate one another; GTP binding and hydrolysis by SRPRB regulate ribosome-nascent chain handover and receptor recycling. SRPRB is broadly expressed and localizes to the ER membrane.
Existing/core annotation action counts: ACCEPT: 8; KEEP_AS_NON_CORE: 6; REMOVE: 1

PN Consistency Summary

Consistency: Largely consistent. Deep research, review YAML, and PN annotation agree SRPRB is the membrane-anchored beta subunit of the SRP receptor (a Ras/Arf/Sar1-family GTPase) that docks the SRP-RNC complex at the ER. PN "SRP receptor subunit"→GO:0006614 matches the review's core BP (GO:0045047 protein targeting to ER + GO:0006617 signal-sequence-recognition child, ACCEPT; goa_status here is entailed_by_goa_closure, correctly reflecting that SRPRB's GOA carries GO:0045047/0006617 rather than GO:0006614 directly). One internal review flag: GO:0005881 cytoplasmic microtubule (IDA, PMID:23264731) — re-examined below.
PN story / NEW pressure: PN asserts only the canonical SR docking role in cotranslational targeting, already captured (GO:0045047, GO:0006617, GO:0005785 SR complex, GO:0005525 GTP binding, GO:0005789 ER membrane). A genuinely novel SRbeta function — coordinating cotranslational N-glycosylation via OST engagement (PMID:36921042) — is in the review references but is not the PN story; nearest GO term GO:0180058 (verified real, OST-centric) is not a clean fit. Conclusion: already captured for the PN node (no NEW pressure on the mapping).
Evidence alignment: PN dossier lists no reference titles; alignment via projected-term provenance. Review's core support (PMID:16439358 SR-beta/SRalpha Longin structure; PMID:29567807 prehandover cryo-EM; PMID:34020957 SR compaction/GTPase; PMID:37643813 SRPRB KO stabilizes SRalpha) all encode SR docking biology. MTR120 re-examination: the cached full text of PMID:23264731 (now available) is entirely about MTR120/KIAA1383, a 120 kDa MT-associated protein found in an ORFeome localization screen; SRPRB (Q9Y5M8, 271 aa ER GTPase) is never mentioned or assayed. The GO:0005881 cytoplasmic-microtubule IDA on SRPRB is a definitive mis-attribution (wrong protein), not merely unverifiable — the review's UNDECIDED was conservative only because full text was unavailable; it now is.
Verdict: Consistent for the PN node; PN already captured. One warranted edit: with full text confirming PMID:23264731 does not assay SRPRB, the cytoplasmic-microtubule annotation should move from UNDECIDED to MARK_AS_OVER_ANNOTATED (wrong-gene citation; correctness → WRONG_IDENTIFIER).

Full Consistency Review

UniProt: Q9Y5M8 · batch: proteostasis-batch-2026-06-11 · review status: COMPLETE
PN placement: ER proteostasis|Protein transport|SRP receptor subunit ; 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: Largely consistent. Deep research, review YAML, and PN annotation agree SRPRB is the membrane-anchored beta subunit of the SRP receptor (a Ras/Arf/Sar1-family GTPase) that docks the SRP-RNC complex at the ER. PN "SRP receptor subunit"→GO:0006614 matches the review's core BP (GO:0045047 protein targeting to ER + GO:0006617 signal-sequence-recognition child, ACCEPT; goa_status here is entailed_by_goa_closure, correctly reflecting that SRPRB's GOA carries GO:0045047/0006617 rather than GO:0006614 directly). One internal review flag: GO:0005881 cytoplasmic microtubule (IDA, PMID:23264731) — re-examined below.
PN story / NEW pressure: PN asserts only the canonical SR docking role in cotranslational targeting, already captured (GO:0045047, GO:0006617, GO:0005785 SR complex, GO:0005525 GTP binding, GO:0005789 ER membrane). A genuinely novel SRbeta function — coordinating cotranslational N-glycosylation via OST engagement (PMID:36921042) — is in the review references but is not the PN story; nearest GO term GO:0180058 (verified real, OST-centric) is not a clean fit. Conclusion: already captured for the PN node (no NEW pressure on the mapping).
Mapping strategy: No change needed. GO:0006614 closure-entailed projection is consistent with the review's accepted GO:0045047/0006617 (both descend the same ER-targeting branch); not broader than the review in a problematic way. Class-level GO:0015031 is a broad class target, not asserted of SRPRB.
Evidence alignment: PN dossier lists no reference titles; alignment via projected-term provenance. Review's core support (PMID:16439358 SR-beta/SRalpha Longin structure; PMID:29567807 prehandover cryo-EM; PMID:34020957 SR compaction/GTPase; PMID:37643813 SRPRB KO stabilizes SRalpha) all encode SR docking biology. MTR120 re-examination: the cached full text of PMID:23264731 (now available) is entirely about MTR120/KIAA1383, a 120 kDa MT-associated protein found in an ORFeome localization screen; SRPRB (Q9Y5M8, 271 aa ER GTPase) is never mentioned or assayed. The GO:0005881 cytoplasmic-microtubule IDA on SRPRB is a definitive mis-attribution (wrong protein), not merely unverifiable — the review's UNDECIDED was conservative only because full text was unavailable; it now is.
Verdict: Consistent for the PN node; PN already captured. One warranted edit: with full text confirming PMID:23264731 does not assay SRPRB, the cytoplasmic-microtubule annotation should move from UNDECIDED to MARK_AS_OVER_ANNOTATED (wrong-gene citation; correctness → WRONG_IDENTIFIER).

PN Dossier Context

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

PN row 1: ER proteostasis | Protein transport | SRP receptor subunit

UniProt: Q9Y5M8
In branches: ER
PN-node mapping records (path + ancestors):
- [group] ER proteostasis|Protein transport|SRP receptor subunit
  status=mapped scope=ok_for_propagation_to_go GO=[GO:0006614 SRP-dependent cotranslational protein targeting to membrane]
  rationale: SRP receptor subunits participate in docking the SRP-ribosome complex to the ER membrane during cotranslational targeting. Mapping to the GO SRP-dependent targeting process is appropriate at propagation scope.
- [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=entailed_by_goa_closure | from=ER proteostasis|Protein transport|SRP receptor subunit

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: Q9Y5M8
gene_symbol: SRPRB
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: SRPRB (signal recognition particle receptor subunit beta, SR-beta; also APMCF1) is a 271 aa single-pass ER membrane protein and a small Ras-superfamily GTPase closely related to Arf and Sar1. It is the membrane-anchored beta subunit of the heterodimeric signal recognition particle (SRP) receptor (SR), assembling with the soluble alpha subunit SRPRA via a Longin-domain interface and tethering SRPRA to the ER membrane. The SRP receptor docks the SRP-ribosome-nascent chain complex at the ER so that signal-sequence-bearing nascent secretory and membrane proteins are delivered to the Sec61 translocon for cotranslational translocation and insertion. SRP-dependent targeting is driven by a GTPase cycle in which the SR (SRPRA and SRPRB) and the SRP54 GTPase reciprocally activate one another; GTP binding and hydrolysis by SRPRB regulate ribosome-nascent chain handover and receptor recycling. SRPRB is broadly expressed and localizes to the ER membrane.
existing_annotations:
- term:
    id: GO:0005785
    label: signal recognition particle receptor complex
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: part_of
  review:
    summary: SRPRB is the beta subunit of the heterodimeric SRP receptor; phylogenetic assignment of SR-complex membership is consistent with direct structural and biochemical evidence. Core structural identity.
    action: ACCEPT
    reason: SRP receptor complex membership is the core cellular-component identity of SRPRB; SRPRB heterodimerizes with SRPRA.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Component of the signal recognition particle (SRP) complex receptor (SR)
- term:
    id: GO:0045047
    label: protein targeting to ER
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: involved_in
  review:
    summary: As part of the SRP receptor, SRPRB participates in targeting nascent secretory/membrane proteins to the ER. Core biological process.
    action: ACCEPT
    reason: Core SR-mediated process; the SRP receptor ensures correct targeting of nascent proteins to the ER membrane.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: the correct targeting of the nascent secretory proteins to the
- term:
    id: GO:0005525
    label: GTP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: SRPRB is a small GTPase of the Ras superfamily (Arf/Sar1-related) with conserved GTP-binding motifs; GTP binding and hydrolysis drive the SRP-targeting cycle. Core molecular function.
    action: ACCEPT
    reason: Core molecular function; SRPRB binds GTP (structure solved in the Mg2+-GTP-bound state) and its GTPase activity regulates targeting.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: GTP-binding
    - reference_id: PMID:29567807
    - reference_id: PMID:34020957
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: Electronic transfer of the ER membrane subcellular location from UniProt; the correct and core compartment for the membrane-anchored SR-beta subunit.
    action: ACCEPT
    reason: Correct core location; SRPRB is a single-pass ER membrane protein.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:16169070
  qualifier: enables
  review:
    summary: High-throughput protein-protein interaction capture. SRPRB's functionally informative interaction is with SRPRA (the SR heterodimer), but bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: Real but the bare protein binding term is uninformative per curation guidelines; the SR-complex term captures the informative content.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Heterodimer with SRPRA
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:33961781
  qualifier: enables
  review:
    summary: BioPlex affinity-MS interactome capture. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Heterodimer with SRPRA
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:40205054
  qualifier: enables
  review:
    summary: Multimodal cell-map interactome capture. Bare protein binding is uninformative.
    action: KEEP_AS_NON_CORE
    reason: High-throughput interaction; bare protein binding is uninformative and not core.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: Heterodimer with SRPRA
- term:
    id: GO:0005785
    label: signal recognition particle receptor complex
  evidence_type: EXP
  original_reference_id: PMID:16439358
  qualifier: part_of
  review:
    summary: Crystal structure of mammalian SR-beta in complex with the SRalpha (SRPRA) binding domain (SRX); direct experimental evidence that SRPRB is part of the heterodimeric SRP receptor. Core structural identity.
    action: ACCEPT
    reason: Experimentally demonstrated core SR membership; SRPRB-SRPRA heterodimer structure.
    supported_by:
    - reference_id: PMID:16439358
      supporting_text: The SR is a heterodimeric complex assembled by the two GTPases SRalpha and SRbeta
- term:
    id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
  evidence_type: NAS
  original_reference_id: PMID:16439358
  qualifier: involved_in
  review:
    summary: SRPRB, as part of the SR, participates in SRP-dependent cotranslational targeting of nascent chains to the ER membrane. Core biological process.
    action: ACCEPT
    reason: Core SR-mediated process; the SRP receptor mediates SRP-dependent cotranslational targeting at the ER.
    supported_by:
    - reference_id: PMID:16439358
      supporting_text: co-translational targeting of secretory and membrane proteins to the endoplasmic reticulum
- term:
    id: GO:0016020
    label: membrane
  evidence_type: NAS
  original_reference_id: PMID:16439358
  qualifier: located_in
  review:
    summary: The SR is membrane-anchored via SRPRB; a generic membrane localization that is a parent of the specific ER membrane term.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the ER membrane term captures the informative localization.
    supported_by:
    - reference_id: PMID:16439358
      supporting_text: which is membrane-anchored
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: located_in
  review:
    summary: Curator ISS transfer of ER membrane localization from an ortholog; the correct and core compartment for SRPRB.
    action: ACCEPT
    reason: Correct core location; redundant with other ER membrane evidence.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IDA
  original_reference_id: PMID:22375059
  qualifier: located_in
  review:
    summary: Direct evidence of membrane localization from a study of Sec61/Sec62/Sec63-dependent ER translocation; a generic membrane term, parent of ER membrane.
    action: KEEP_AS_NON_CORE
    reason: Correct but generic; the ER membrane term captures the informative localization.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1791060
  qualifier: located_in
  review:
    summary: Reactome TAS annotation of ER membrane localization for SRPRB, consistent with the core compartment.
    action: ACCEPT
    reason: Correct core location; consistent with experimental and ISS evidence.
    supported_by:
    - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
      supporting_text: 'SUBCELLULAR LOCATION: Endoplasmic reticulum membrane'
- term:
    id: GO:0005881
    label: cytoplasmic microtubule
  evidence_type: IDA
  original_reference_id: PMID:23264731
  qualifier: located_in
  review:
    summary: Wrong-gene citation. PMID:23264731 characterizes MTR120/KIAA1383 as a microtubule-associated protein; the now-cached full text never mentions or assays SRPRB (no occurrence of SRPRB / SR-beta / SRP receptor). SRPRB is an ER-membrane GTPase, for which a cytoplasmic microtubule localization is biologically implausible.
    action: REMOVE
    reason: The full text of PMID:23264731 is now available and confirms the paper is entirely about MTR120/KIAA1383 and does not assay SRPRB, so this GO:0005881 IDA is a wrong-gene mis-attribution. This matches the sibling SERP1 review, where the same PMID:23264731 cytoplasmic-microtubule annotation was REMOVED after full-text confirmation; previously this row was held UNDECIDED only because the full text was unavailable.
    supported_by:
    - reference_id: PMID:23264731
      supporting_text: a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:19664239
  qualifier: located_in
  review:
    summary: GFP-APMCF1 (SRPRB) overexpression showed a generally cytoplasmic distribution in COS-7 cells. A diffuse cytoplasmic signal is consistent with an ER-membrane protein (the ER is in the cytoplasm), but cytoplasm is imprecise relative to the ER membrane and the signal derives from overexpression of a GFP fusion.
    action: KEEP_AS_NON_CORE
    reason: Plausible but imprecise (and overexpression-based); the informative core localization is the ER membrane.
    supported_by:
    - reference_id: PMID:19664239
      supporting_text: EGFP-APMCF1 was generally localized in the cytoplasm of COS-7 cell
core_functions:
- description: Membrane-anchored beta subunit of the heterodimeric signal recognition particle (SRP) receptor; a Ras-superfamily GTPase that, together with SRPRA, docks the SRP-ribosome-nascent chain complex at the ER membrane to enable SRP-dependent cotranslational protein targeting.
  molecular_function:
    id: GO:0005525
    label: GTP binding
  in_complex:
    id: GO:0005785
    label: signal recognition particle receptor complex
  locations:
  - id: GO:0005789
    label: endoplasmic reticulum membrane
  supported_by:
  - reference_id: file:human/SRPRB/SRPRB-uniprot.txt
    supporting_text: Component of the signal recognition particle (SRP) complex receptor (SR)
  - reference_id: PMID:16439358
    supporting_text: The SR is a heterodimeric complex assembled by the two GTPases SRalpha and SRbeta
  - reference_id: PMID:29567807
  - reference_id: PMID:37643813
  directly_involved_in:
  - id: GO:0045047
    label: protein targeting to ER
  - id: GO:0006617
    label: SRP-dependent cotranslational protein targeting to membrane, signal sequence recognition
proposed_new_terms: []
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
  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, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: PMID:16169070
  title: 'A human protein-protein interaction network: a resource for annotating the proteome.'
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: High-throughput interactome; source of an IPI protein-binding annotation.
- id: PMID:16439358
  title: The structure of the mammalian signal recognition particle (SRP) receptor as prototype for the interaction of small GTPases with Longin domains.
  findings:
  - statement: The SR is a heterodimeric complex of the two GTPases SRalpha and SRbeta, membrane-anchored; crystal structure of mammalian SRbeta in the Mg2+-GTP-bound state in complex with the SRalpha (SRX) binding domain.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: Structural basis for the SRPRB-SRPRA heterodimer and SRPRB GTPase identity; source of SR-complex membership and targeting annotations.
- id: PMID:19664239
  title: Subcellular localization of APMCF1 and its biological significance of expression pattern in normal and malignant human tissues.
  findings:
  - statement: EGFP-APMCF1 (SRPRB) overexpressed in COS-7 cells localized generally to the cytoplasm.
    reference_section_type: RESULTS
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Overexpression GFP-fusion localization study under the APMCF1 alias; diffuse cytoplasmic signal consistent with an ER-membrane protein.
- id: PMID:22375059
  title: Different effects of Sec61α, Sec62 and Sec63 depletion on transport of polypeptides into the endoplasmic reticulum of mammalian cells.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: Study of Sec61/62/63-dependent ER translocation; source of a generic membrane localization for SRPRB.
- id: PMID:23264731
  title: MTR120/KIAA1383, a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis.
  findings:
  - statement: Characterizes MTR120/KIAA1383 as a microtubule-associated protein promoting microtubule stability and cytokinesis.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: NONE
    correctness: WRONG_IDENTIFIER
    review_notes: Full text (now cached, full_text_available) is entirely about MTR120/KIAA1383 and never mentions or assays SRPRB (no occurrence of SRPRB / SR-beta / SRP receptor). The GO:0005881 cytoplasmic-microtubule IDA citing this paper is a wrong-gene mis-attribution and has been REMOVED, consistent with the sibling SERP1 review.
- id: PMID:33961781
  title: Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: BioPlex affinity-MS interactome; source of an IPI protein-binding annotation.
- id: PMID:40205054
  title: Multimodal cell maps as a foundation for structural and functional genomics.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Multimodal cell-map interactome; source of an IPI protein-binding annotation.
- id: Reactome:R-HSA-1791060
  title: Expression of SRPRB (SRP Receptor subunit beta)
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: Reactome record; source of a TAS ER membrane localization for SRPRB.
- id: PMID:29567807
  title: "Structure of a prehandover mammalian ribosomal SRP\xB7SRP receptor targeting\
    \ complex."
  findings:
  - statement: Cryo-EM structure of the mammalian translating ribosome with SRP and SRP receptor in a prehandover conformation; GTP-bound SRbeta and eukaryote-specific SRP/SR proteins form a large assembly at the distal SRP RNA site, and SRP/SR GTP hydrolysis is delayed at this stage to allow signal-sequence handover.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:29567807; Science 2018). Structural basis for GTP-bound SRbeta in the targeting complex and delayed GTP hydrolysis during handover; directly informs SRPRB GTPase function and SR-complex role. Not cached; no verbatim supporting_text added.
- id: PMID:34020957
  title: Receptor compaction and GTPase rearrangement drive SRP-mediated cotranslational
    protein translocation into the ER.
  findings:
  - statement: Structural, biochemical and single-molecule analyses show eukaryotic SRP-mediated targeting requires sequential GTPase-driven compaction of the SRP receptor (SRalpha/SRbeta) and conformational rearrangements that couple the SRP/SR GTPase cycle to protein translocation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:34020957; Sci Adv 2021). Mechanistic model of SR compaction and GTPase rearrangement during targeting; supports SRPRB GTP-binding/hydrolysis role in the receptor cycle. Not cached; no verbatim supporting_text added.
- id: PMID:37643813
  title: Examining SRP pathway function in mRNA localization to the endoplasmic reticulum.
  findings:
  - statement: CRISPR/Cas9 knockout of SRPRB (SRbeta) in mammalian cells profoundly destabilizes SRalpha (proteasome-sensitive) and redistributes residual SRalpha to the cytosol, yet steady-state ER mRNA localization is largely unaltered, uncoupling ER mRNA localization from SRP receptor expression.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:37643813; RNA 2023). Direct human SRPRB knockout evidence that SRbeta stabilizes SRalpha at the ER; refines models of SR-dependent mRNA localization. Not cached; no verbatim supporting_text added.
- id: PMID:36921042
  title: "Signal recognition particle receptor-β (SR-β) coordinates cotranslational\
    \ N-glycosylation."
  findings:
  - statement: SRbeta (SRPRB) is required for assembly of an N-glycosylation-competent translocon; perturbing the SRbeta GTP-binding site (mutation or guanine-analog probes) causes hypoglycosylation and reduces SRbeta association with the oligosaccharyltransferase (OST) complex without disrupting SRalpha-SRbeta association, revealing a function coordinating ER translation with N-glycosylation.
    reference_section_type: ABSTRACT
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: PubMed-verified (PMID:36921042; Sci Adv 2023). Newly described SRbeta function beyond receptor anchoring (coordinating cotranslational N-glycosylation via OST engagement, GTP-dependent). Not cached; no verbatim supporting_text added.
suggested_questions:
- question: Is the reported cytoplasmic-microtubule localization of SRPRB a genuine secondary localization or a mis-attribution from the MTR120 study, and does SRPRB have any verified function outside the SRP receptor?
- question: How do the GTPase cycles of SRPRB, SRPRA, and SRP54 coordinate ribosome-nascent chain handover to the Sec61 translocon, and what is the specific catalytic contribution of SRPRB GTP hydrolysis?
suggested_experiments:
- description: Use endogenous tagging plus proximity labeling and super-resolution microscopy to test whether SRPRB localizes to microtubules under any condition, distinguishing genuine localization from overexpression or co-purification artifacts.
- description: Reconstitute SRP-dependent targeting with wild-type and GTPase-dead SRPRB to quantify the role of SRPRB GTP hydrolysis in receptor recycling and nascent-chain delivery to Sec61.

SRPRB

Gene Description

Existing Annotations Review

Core Functions

Membrane-anchored beta subunit of the heterodimeric signal recognition particle (SRP) receptor; a Ras-superfamily GTPase that, together with SRPRA, docks the SRP-ribosome-nascent chain complex at the ER membrane to enable SRP-dependent cotranslational protein targeting.

References

Suggested Questions for Experts

Suggested Experiments

Deep Research

Falcon

Research Report: Human SRPRB (SRP receptor subunit beta; SRβ) — Functional Annotation

1. Target identity verification (mandatory)

2. Key concepts and current understanding

2.1 The SRP pathway and the SRP receptor (SR)

2.2 Definition: SRPRB/SRβ molecular role

3. Protein features, domains, and subcellular localization

3.1 Membrane topology and ER localization

3.2 GTPase family assignment

4. Molecular function in pathways: SRP receptor cycle, targeting, and translocation

4.1 SRβ as the membrane-anchoring subunit for SRα

4.2 Structural and mechanistic role during cotranslational targeting (2018–2021 mechanistic framework)

5. Recent developments (prioritizing 2023–2024)

5.1 2023: SRβ coordinates cotranslational N-glycosylation by promoting a glycosylation-competent translocon

5.2 2023: SRPRB knockout and ER mRNA localization

5.3 2024: SRPRB appears mainly in association/omics contexts rather than established mechanistic disease biology

6. Quantitative statistics and data from recent studies

6.1 Quantitative phenotypes from SRPRB knockout (2023)

6.2 Quantitative glycoproteomics and screening statistics (2023)

7. Current applications and real-world implementations

7.1 Chemical biology and pathway probing of cotranslational processing

7.2 Functional genomics models to dissect ER targeting and mRNA localization

7.3 Disease association resources (hypothesis generation)

8. Expert synthesis and analysis (evidence-weighted)

9. Summary table

Key source URLs (with publication dates)

Artifacts

Citations

📚 Additional Documentation

Notes

SRPRB (Q9Y5M8) review notes

Identity / overview

Key functional evidence

Annotation review decisions

Disease

Falcon deep-research findings (incorporated 2026-06)

Pn Notes

SRPRB 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 | SRP receptor subunit

Projected GO annotations (2)

Note

📄 View Raw YAML