| 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. | (pqac-00000001, pqac-00000002) | 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. | (pqac-00000003, pqac-00000010, pqac-00000011) | 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. | (pqac-00000003, pqac-00000007, pqac-00000002) | 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. | (pqac-00000005, pqac-00000009, pqac-00000012, pqac-00000018) | 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. | (pqac-00000001, pqac-00000009, pqac-00000016) | 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. | (pqac-00000010, pqac-00000009, pqac-00000012, pqac-00000013, pqac-00000014) | 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. | (pqac-00000015, pqac-00000016) | 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. | (pqac-00000015, pqac-00000016, pqac-00000017, pqac-00000008) | 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. | (pqac-00000015, pqac-00000016, pqac-00000017) | 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. | (pqac-00000008) | 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.*