SERP1 (stress-associated endoplasmic reticulum protein 1, also RAMP4, ribosome-attached/associated membrane protein 4) is a small (66 aa) single-pass endoplasmic reticulum membrane protein that associates with the Sec61 translocon. It is induced by ER stress and hypoxia and binds nascent membrane and secretory proteins during their translocation into the ER, protecting these still-unfolded substrates from degradation while ER stress persists and then facilitating their N-glycosylation after stress resolves, including modulating which N-glycosylation sites are used. Through these activities SERP1 contributes to the endoplasmic reticulum unfolded protein response and to the biogenesis and quality control of membrane proteins at the translocon. It physically associates with components of the Sec61 complex (SEC61A1, SEC61B) and calnexin.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005783
endoplasmic reticulum
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: SERP1 acts at the ER (translocon) where it stabilizes nascent membrane proteins; the phylogenetic active-site assignment is correct. 2024 cryo-EM (PMID:38896445) directly shows RAMP4/SERP1 intercalated into the Sec61 lateral gate, confirming its translocon-associated site of action.
Reason: Core site of action; SERP1 is a translocon-associated ER membrane protein.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Interacts with target proteins during their translocation into the lumen of the endoplasmic reticulum
|
|
GO:0030968
endoplasmic reticulum unfolded protein response
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: SERP1 is stress-induced and acts during ER stress to protect nascent membrane proteins, placing it in the ER unfolded protein response; the phylogenetic assignment is well supported.
Reason: Core biological process; SERP1 (stress-associated ER protein) functions during ER stress to protect translocating substrates.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Protects unfolded target proteins against degradation during ER stress
|
|
GO:0005783
endoplasmic reticulum
|
IEA
GO_REF:0000002 |
ACCEPT |
Summary: InterPro-based ER localization, consistent with experimental and orthology evidence.
Reason: Correct core localization.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Endoplasmic reticulum membrane
|
|
GO:0005789
endoplasmic reticulum membrane
|
IEA
GO_REF:0000044 |
ACCEPT |
Summary: SERP1 is a single-pass ER membrane protein; the subcellular-location-based annotation is correct.
Reason: Core localization, consistent with the single-pass ER membrane topology.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane
|
|
GO:0016020
membrane
|
IEA
GO_REF:0000044 |
KEEP AS NON CORE |
Summary: Generic membrane localization, a parent of the more informative ER membrane term.
Reason: Correct but uninformative; the specific GO:0005789 (ER membrane) better captures SERP1 localization.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-
|
|
GO:0005515
protein binding
|
IPI
PMID:25416956 A proteome-scale map of the human interactome network. |
KEEP AS NON CORE |
Summary: Proteome-scale interactome capture of a SERP1 interaction (TMEM79); a real interaction but the bare protein binding term is uninformative.
Reason: High-throughput interactome capture; bare protein binding is uninformative per curation guidelines.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Q9Y6X1; Q9BSE2: TMEM79
|
|
GO:0005515
protein binding
|
IPI
PMID:32296183 A reference map of the human binary protein interactome. |
KEEP AS NON CORE |
Summary: HuRI binary-interactome screen capturing SERP1 binding to a large set of membrane and secretory proteins; these are consistent with SERP1's translocon-substrate-stabilizing role but the bare protein binding term is uninformative.
Reason: Many partners are nascent membrane-protein substrates consistent with SERP1's function, but bare protein binding is uninformative per guidelines.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Q9Y6X1; Q9BY50: SEC11C
|
|
GO:0005789
endoplasmic reticulum membrane
|
ISS
GO_REF:0000024 |
ACCEPT |
Summary: Sequence-similarity transfer of ER membrane localization from the mouse ortholog; consistent with stronger evidence.
Reason: Correct core localization, redundant with IEA/TAS evidence.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane
|
|
GO:0016020
membrane
|
ISS
GO_REF:0000024 |
KEEP AS NON CORE |
Summary: Sequence-similarity transfer of generic membrane localization; a parent of ER membrane.
Reason: Correct but uninformative; the specific GO:0005789 (ER membrane) better captures SERP1 localization.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-
|
|
GO:0005881
cytoplasmic microtubule
|
IDA
PMID:23264731 MTR120/KIAA1383, a novel microtubule-associated protein, pro... |
REMOVE |
Summary: The cited paper characterizes MTR120/KIAA1383, an unrelated ~120 kDa microtubule-associated protein, and contains no data on SERP1/RAMP4. SERP1 is a 66 aa single-pass ER membrane protein, for which a cytoplasmic-microtubule localization is biologically implausible. This annotation is a mis-attribution.
Reason: The full text of PMID:23264731 is available and is entirely about MTR120/KIAA1383 with no mention of SERP1/RAMP4; the cytoplasmic-microtubule localization is inconsistent with SERP1's established ER membrane localization and topology. This is a demonstrable wrong-gene mis-attribution, not a second-guessing of supporting evidence.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-1791167 |
ACCEPT |
Summary: Reactome curation of SERP1 ER membrane localization (SERP1/RAMP4 expression context).
Reason: Correct core localization; redundant with experimental/orthology evidence.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane
|
|
GO:0005829
cytosol
|
TAS
Reactome:R-HSA-9609921 |
KEEP AS NON CORE |
Summary: Reactome cytosol annotation arising from a tail-anchored-protein (SGTA) pathway context; SERP1 is an ER membrane protein with a cytosol-facing portion, but cytosol is not its primary compartment.
Reason: The primary localization is the ER membrane; the cytosol annotation reflects a pathway context (TA-protein targeting) and the cytosol-facing topology rather than a core localization.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane
|
|
GO:0005783
endoplasmic reticulum
|
TAS
PMID:10601334 Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ri... |
ACCEPT |
Summary: The defining SERP1/RAMP4 study localizes the protein to the ER, where it acts during stress.
Reason: Core localization, from the primary characterization of SERP1.
Supporting Evidence:
PMID:10601334
stabilizes membrane proteins during stress and facilitates subsequent glycosylation
|
|
GO:0005840
ribosome
|
TAS
PMID:10601334 Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ri... |
KEEP AS NON CORE |
Summary: SERP1 is also named RAMP4 (ribosome-associated/attached membrane protein 4) for its association with ribosome-translocon junctions at the ER; the ribosome term is broad relative to this translocon-associated context.
Reason: Reflects the RAMP4 ribosome/translocon association, but the bare ribosome term is a coarse descriptor of its translocon-associated localization; the core compartment is the ER membrane.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
Interacts with SEC61B, SEC61A1 and the SEC61 complex
|
|
GO:0007009
plasma membrane organization
|
TAS
PMID:10601334 Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ri... |
KEEP AS NON CORE |
Summary: By stabilizing nascent membrane proteins during stress, SERP1 indirectly influences the surface expression of membrane proteins; this is a downstream consequence rather than a core function.
Reason: Indirect, downstream effect of SERP1's translocon-substrate stabilization; not a core function.
Supporting Evidence:
PMID:10601334
stabilizes membrane proteins during stress
|
|
GO:0009101
glycoprotein biosynthetic process
|
TAS
PMID:10601334 Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ri... |
KEEP AS NON CORE |
Summary: SERP1 facilitates N-glycosylation of its target proteins after termination of ER stress and may modulate which N-glycosylation sites are used; a real but modulatory/secondary role.
Reason: Supported by the primary study and UniProt, but a downstream/modulatory effect on glycosylation rather than the core stabilization function.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
May facilitate glycosylation of target proteins after termination of ER stress
|
|
GO:0036211
protein modification process
|
TAS
PMID:10601334 Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ri... |
KEEP AS NON CORE |
Summary: Very general process term (parent of glycosylation), derived from SERP1's role in facilitating glycosylation of its targets.
Reason: Overly general; the more specific GO:0009101 (glycoprotein biosynthetic process) captures the relevant activity, and even that is secondary.
Supporting Evidence:
file:human/SERP1/SERP1-uniprot.txt
May facilitate glycosylation of target proteins after termination of ER stress
|
Q: Does SERP1/RAMP4 protect nascent substrates by physically shielding them at the translocon, by recruiting chaperones such as calnexin, or by slowing translocation, and is this selective for particular substrate classes?
Q: How does SERP1 modulate N-glycosylation site usage on its targets after ER stress resolves?
Experiment: Site-specific proximity proteomics (e.g., split-BioID at the Sec61 translocon) under ER stress to define the SERP1-dependent nascent-substrate interactome and its dynamics through stress and recovery.
Experiment: Glycoproteomic comparison of SERP1 wild-type versus knockout cells before and after ER stress to test the proposed stabilization and N-glycosylation-site-modulation functions on defined substrates.
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.
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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.
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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.
Human SERP1 (UniProt Q9Y6X1), also known as RAMP4 (ribosome-attached membrane protein 4), is a small tail-anchored ER membrane protein that associates tightly with ribosomeβSec61 translocon complexes. Recent structural work (2024) supports a direct mechanistic role in modulating Sec61 channel gating by intercalating into the Sec61 lateral gate, widening the pore and contributing to a more hydrophilic lumenal funnelβfeatures consistent with SERP1βs established connection to ER stress adaptation and proteostasis. (lewis2024structuralanalysisof pages 1-2, lewis2024structuralanalysisof pages 4-6)
A compact evidence map with key claims, quantitative data, and URLs is provided below.
| Topic | Key evidence/claim | Quantitative details | Primary sources |
|---|---|---|---|
| Identity / localization | SERP1 is the same protein as RAMP4 and is a small tail-anchored endoplasmic reticulum (ER) membrane protein associated with ribosome-bound Sec61 translocon complexes in human cells. Structural work places it at the ER ribosomeβtranslocon interface rather than as a soluble stress factor (lewis2024structuralanalysisof pages 1-2, lewis2024structuralanalysisof pages 4-6, lewis2024structuralanalysisof pages 28-29). | Human RAMP4 sequence shown in structural study; TMD length ~25 aa; occupancy enriched in non-MPT RTCs (see quantitative row) (lewis2024structuralanalysisof pages 4-6, lewis2024structuralanalysisof pages 6-8). | Lewis 2024 eLife. https://doi.org/10.1101/2023.12.22.572959; Gemmer & FΓΆrster 2020 Journal of Cell Science. https://doi.org/10.1242/jcs.231340 |
| Structure & mechanism | 2024 cryo-EM/AF2 analysis shows RAMP4 has a ribosome-binding domain plus a kinked transmembrane helix that intercalates into Sec61βs lateral gate, widens the pore, and helps form a more hydrophilic lumenal funnel without displacing the plug helix. Authors propose RAMP4 can stabilize an open-but-plugged Sec61 state and may act as a surrogate signal peptide after substrate SP release (lewis2024structuralanalysisof pages 4-6, lewis2024structuralanalysisof pages 9-11, lewis2024structuralanalysisof pages 1-2, lewis2024structuralanalysisof pages 28-29). | TMD kink ~40Β° at a conserved glycine; RAMP4 present in ~81% of non-MPT RTCs; ~85% of Sec61β’TRAPβ’OSTA RTCs and ~53% of Sec61β’TRAP RTCs (lewis2024structuralanalysisof pages 6-8, lewis2024structuralanalysisof pages 4-6). | Lewis 2024 eLife. https://doi.org/10.1101/2023.12.22.572959 |
| ER stress regulation | SERP1/RAMP4 is stress inducible and functionally linked to ER proteostasis. In cell/animal injury and infection models, increased SERP1 accompanies ER stress, whereas SERP1 overexpression dampens ER-stress markers and apoptosis/inflammation, supporting a protective role during ER stress (tian2019adenguevirus pages 1-3, cai2022serp1reducesinchoate pages 3-5). | DENV-2 infection/replicon: SERP1 expression increased 34.5-fold; acute hepatic injury study reported LPS-induced SERP1 increase and reduction of GRP78/GRP94/CHOP with SERP1 overexpression; in liver study, Torin1 not used here, but 4-PBA-like protective effect noted (tian2019adenguevirus pages 1-3, cai2022serp1reducesinchoate pages 3-5). | Tian 2019 Viruses. https://doi.org/10.3390/v11090787; Cai 2022 Molecular Medicine Reports. https://doi.org/10.3892/mmr.2022.12709 |
| Interacting partners | SERP1/RAMP4 interacts with Sec61Ξ± and Sec61Ξ² and directly contacts the ribosome. Structural mapping places its ribosome-binding domain against 28S rRNA helices and ribosomal proteins, while functional virology work identified interaction with DENV-2 NS4B, linking SERP1 to ER-associated viral replication biology (lewis2024structuralanalysisof pages 4-6, tian2019adenguevirus pages 1-3). | Ribosome contacts include 28S rRNA helices 47, 57, 59 and proteins eL19, eL22, eL31; DENV-2 NS4B overexpression alleviated SERP1-mediated inhibition of replication (lewis2024structuralanalysisof pages 4-6, tian2019adenguevirus pages 1-3). | Lewis 2024 eLife. https://doi.org/10.1101/2023.12.22.572959; Tian 2019 Viruses. https://doi.org/10.3390/v11090787 |
| ER-phagy reporter applications | SERP1/RAMP4 is used as an ER-targeting module in reticulophagy/ER-phagy reporters. Tandem fluorescent SERP1/RAMP4 reporters exploit acid-sensitive GFP loss with retained mCherry/RFP signal after ER fragments reach lysosomes, enabling imaging- or flow-based ER-phagy readouts; 2024 methodological work also highlights caveats from reporter overexpression and recommends knock-in/endogenous-tagging strategies for in vivo use (sang2024visualizingerphagyand pages 2-3, liu2025theepsteinbarrvirus pages 9-10, sang2024visualizingerphagyand pages 1-2, sang2024visualizingerphagyand pages 22-25). | Keima excitation shift ~440 nm to ~586 nm in acidic lysosomes; Torin1 induction example 100 nM for 4 h; quantification used 20β30 cells/condition; readout is red-only puncta or GFP loss relative to mCherry (sang2024visualizingerphagyand pages 2-3, sang2024visualizingerphagyand pages 22-25). | Sang 2024 Journal of Cell Biology. https://doi.org/10.1083/jcb.202408061; Liu 2025 Autophagy. https://doi.org/10.1080/15548627.2024.2440846 |
| Disease / biomarker associations | SERP1 has emerging disease relevance mainly through expression- and signature-based evidence rather than established causal clinical genetics in this corpus. It appears in a 12-gene ER-stress prognostic signature for pancreatic cancer and is described as a risk-associated factor; Open Targets also lists weaker literature/animal-model/genetic-association links to neoplasm, liver disease, drug allergy, dystonia 33, and Marinesco-SjΓΆgren syndrome (chen2023arisksignature pages 3-6, OpenTargets Search: -SERP1, chen2023arisksignature pages 12-13, chen2023arisksignature pages 8-12, chen2023arisksignature pages 6-8). | Pancreatic cancer model coefficient for SERP1: 0.496637586; signature AUC ~0.79; low- vs high-risk survival difference p < 0.0001; multivariate HR = 3.613, p < 0.001 for risk level (chen2023arisksignature pages 6-8). | Chen 2023 Frontiers in Molecular Biosciences. https://doi.org/10.3389/fmolb.2023.1298077; Open Targets Platform evidence summary (OpenTargets Search: -SERP1) |
| Quantitative stats | Available quantitative evidence consistently supports a translocon-centered, stress-responsive role. Structurally, RAMP4 is abundant in non-MPT RTCs; functionally, perturbing SERP1 changes viral replication and prognostic models; assay literature provides explicit doses/timings for reporter use (lewis2024structuralanalysisof pages 6-8, tian2019adenguevirus pages 1-3, chen2023arisksignature pages 6-8, sang2024visualizingerphagyand pages 22-25). | RTC occupancy: ~85% Sec61β’TRAPβ’OSTA, ~53% Sec61β’TRAP, ~81% non-MPT RTCs; DENV-2: SERP1 induction 34.5-fold, viral yields reduced ~37-fold by overexpression, increased ~3.4-fold after shRNA knockdown and ~16-fold after knockout; ER-phagy assay: Torin1 100 nM, 4 h, 20β30 cells/condition (lewis2024structuralanalysisof pages 6-8, tian2019adenguevirus pages 1-3, sang2024visualizingerphagyand pages 22-25). | Lewis 2024 eLife. https://doi.org/10.1101/2023.12.22.572959; Tian 2019 Viruses. https://doi.org/10.3390/v11090787; Chen 2023 Frontiers in Molecular Biosciences. https://doi.org/10.3389/fmolb.2023.1298077; Sang 2024 Journal of Cell Biology. https://doi.org/10.1083/jcb.202408061 |
Table: This table summarizes functional annotation evidence for human SERP1/RAMP4 (UniProt Q9Y6X1), including localization, mechanism, stress biology, applications, disease associations, and key quantitative findings. It is useful as a traceable, citation-linked overview of the strongest gathered evidence.
The target gene SERP1 corresponds to the ER protein commonly called RAMP4, and the literature retrieved here explicitly uses βSERP1 (RAMP4)β as a unified identity. (tian2019adenguevirus pages 1-3, lewis2024structuralanalysisof pages 1-2)
SERP1/RAMP4 is described as a tail-anchored ER membrane protein. A 2024 cryo-EM/structure-prediction analysis resolves distinct architectural features: a ribosome-binding domain (RBD) connected through a linker to a kinked transmembrane domain (TMD) that engages the Sec61 lateral gate. (lewis2024structuralanalysisof pages 4-6)
The best-supported primary function from mechanistic evidence is that SERP1/RAMP4 acts as a translocon-associated factor that directly modulates Sec61 channel conformation and therefore influences co-translational translocation and membrane protein/secretory protein biogenesis at the ER. (lewis2024structuralanalysisof pages 4-6, lewis2024structuralanalysisof pages 1-2)
SERP1/RAMP4 is associated with ribosome-bound ER translocon complexes. Reviews and structural work identify it among βribosome-associated membrane proteins (RAMPs)β recovered from ER microsomes and linked to Sec61-containing assemblies. (gemmer2020aclearerpicture pages 2-3, lewis2024structuralanalysisof pages 1-2)
Major 2024 advance (Lewis et al., eLife, May 2024): RAMP4 is frequently observed intercalated into Sec61βs lateral gate, and this configuration widens the Sec61 pore and contributes to a more hydrophilic pore interior. (lewis2024structuralanalysisof pages 1-2)
Mechanistic details include:
- The RBD contacts the ribosome (28S rRNA helices and ribosomal proteins), and the TMD occupies the lateral gate. (lewis2024structuralanalysisof pages 4-6)
- The pore ring is widened, while the plug helix can remain present (open-but-plugged conformation). (lewis2024structuralanalysisof pages 4-6, lewis2024structuralanalysisof pages 28-29)
- Quantitative occupancy in native ribosomeβtranslocon complexes (RTCs): ~85% of Sec61β’TRAPβ’OSTA RTCs and ~53% of Sec61β’TRAP RTCs contain RAMP4, corresponding to ~81% of non-MPT RTCs. (lewis2024structuralanalysisof pages 6-8)
Expert interpretation (from the authorsβ mechanistic hypotheses): the structure supports the idea that RAMP4 can function as a regulatory translocon component, potentially including a βsurrogate signal peptideβ role that stabilizes an open channel state after substrate signal peptide dissociation. (lewis2024structuralanalysisof pages 9-11)
In a DENV-2 infection/replicon system, SERP1 mRNA showed a 34.5-fold induction in Huh7.5 cells under viral conditions that impose ER stress. (tian2019adenguevirus pages 1-3)
In an acute hepatic injury model (LPS/D-GalN in vivo; LPS in hepatocytes), SERP1 expression increased alongside ER stress markers, and SERP1 overexpression reduced ER stress markers (GRP78/GRP94/CHOP) and decreased apoptosis/inflammation readouts. (cai2022serp1reducesinchoate pages 3-5)
Functional virology work reports SERP1/RAMP4 interacts with Sec61Ξ± and Sec61Ξ², supporting a direct relationship to the Sec61 translocation machinery. (tian2019adenguevirus pages 1-3)
Lewis et al. (2024; eLife; publication month May 2024) provide the most direct mechanistic update: RAMP4 is physically located within the Sec61 lateral gate in a large fraction of RTCs, and the model predicts effects on pore hydrophilicity and gating states. URL: https://doi.org/10.1101/2023.12.22.572959 (lewis2024structuralanalysisof pages 1-2, lewis2024structuralanalysisof pages 4-6)
A 2024 Journal of Cell Biology methods-focused study emphasizes how ER-phagy reporters are interpreted and flags caveats of RAMP4 overexpression, motivating knock-in/endogenous-tagging approaches for in vivo work. It cites RAMP4-based reporters (e.g., GFP-mCherry-RAMP4; RAMP4-Keima) and explains their readouts. URL: https://doi.org/10.1083/jcb.202408061 (sang2024visualizingerphagyand pages 2-3)
A 2023 pancreatic cancer study includes SERP1 in a 12-gene ER-stress-associated risk score; the risk formula includes a SERP1 coefficient (0.496637586 Γ SERP1) and reports predictive performance (AUC ~0.79) for the composite signature, with strong risk-group survival differences (p < 0.0001). URL: https://doi.org/10.3389/fmolb.2023.1298077 (chen2023arisksignature pages 6-8)
SERP1/RAMP4 is used as an ER-targeting module in dual fluorescence reporters that quantify ER-to-lysosome flux via pH-dependent GFP loss relative to mCherry/RFP.
Examples of implemented designs:
- A Dox-regulated stable HCT116 line expressing an in-frame SERP1/RAMP4βeGFPβmCherry fusion reporter; interpretation: ER insertion yields dual signal; lysosomal delivery yields loss of GFP relative to mCherry. (liu2025theepsteinbarrvirus pages 9-10)
- RAMP4-based and related ratiometric reporter strategies described for ER-phagy flux estimation, including Keima-based excitation shift (~440 nm to ~586 nm) and tandem FP βred-only punctaβ scoring. (sang2024visualizingerphagyand pages 2-3)
Practical assay parameters reported in 2024 methods include Torin1 100 nM for 4 h to induce autophagy/ER-phagy, and quantification approaches using lysosomal colocalization and ImageJ, with 20β30 cells per condition in one described analysis. (sang2024visualizingerphagyand pages 22-25)
SERP1 is used as one feature in multi-gene ER-stress signatures for prognosis stratification in pancreatic cancer, suggesting potential application as a component of composite biomarkers (rather than a standalone validated clinical biomarker based on this corpus). (chen2023arisksignature pages 6-8, chen2023arisksignature pages 3-6)
Open Targets lists SERP1 associations with disease terms including neoplasm, liver disease, drug allergy, dystonia 33, and Marinesco-SjΓΆgren syndrome, with evidence types including literature, animal model, and genetic association (source-dependent). This indicates heterogeneous, generally low-to-moderate strength associations in the platform snapshot retrieved here. (OpenTargets Search: -SERP1)
In the pancreatic cancer study, SERP1 contributes to a multi-gene risk score associated with overall survival, but the same work also notes SERP1 alone was not significantly differentially expressed in one tumor-vs-normal comparison figure, illustrating that its importance may be multivariate/context-specific. (chen2023arisksignature pages 3-6, chen2023arisksignature pages 6-8)
References
(lewis2024structuralanalysisof pages 1-2): Aaron J. O. Lewis, Frank Zhong, Robert J. Keenan, and Ramanujan S. Hegde. Structural analysis of the dynamic ribosome-translocon complex. eLife, May 2024. URL: https://doi.org/10.1101/2023.12.22.572959, doi:10.1101/2023.12.22.572959. This article has 23 citations and is from a domain leading peer-reviewed journal.
(lewis2024structuralanalysisof pages 4-6): Aaron J. O. Lewis, Frank Zhong, Robert J. Keenan, and Ramanujan S. Hegde. Structural analysis of the dynamic ribosome-translocon complex. eLife, May 2024. URL: https://doi.org/10.1101/2023.12.22.572959, doi:10.1101/2023.12.22.572959. This article has 23 citations and is from a domain leading peer-reviewed journal.
(lewis2024structuralanalysisof pages 28-29): Aaron J. O. Lewis, Frank Zhong, Robert J. Keenan, and Ramanujan S. Hegde. Structural analysis of the dynamic ribosome-translocon complex. eLife, May 2024. URL: https://doi.org/10.1101/2023.12.22.572959, doi:10.1101/2023.12.22.572959. This article has 23 citations and is from a domain leading peer-reviewed journal.
(lewis2024structuralanalysisof pages 6-8): Aaron J. O. Lewis, Frank Zhong, Robert J. Keenan, and Ramanujan S. Hegde. Structural analysis of the dynamic ribosome-translocon complex. eLife, May 2024. URL: https://doi.org/10.1101/2023.12.22.572959, doi:10.1101/2023.12.22.572959. This article has 23 citations and is from a domain leading peer-reviewed journal.
(lewis2024structuralanalysisof pages 9-11): Aaron J. O. Lewis, Frank Zhong, Robert J. Keenan, and Ramanujan S. Hegde. Structural analysis of the dynamic ribosome-translocon complex. eLife, May 2024. URL: https://doi.org/10.1101/2023.12.22.572959, doi:10.1101/2023.12.22.572959. This article has 23 citations and is from a domain leading peer-reviewed journal.
(tian2019adenguevirus pages 1-3): Jia-Ni Tian, Chi-Chen Yang, Chiu-Kai Chuang, Ming-Han Tsai, Ren-Huang Wu, Chiung-Tong Chen, and Andrew Yueh. A dengue virus type 2 (denv-2) ns4b-interacting host factor, serp1, reduces denv-2 production by suppressing viral rna replication. Viruses, 11:787, Aug 2019. URL: https://doi.org/10.3390/v11090787, doi:10.3390/v11090787. This article has 19 citations.
(cai2022serp1reducesinchoate pages 3-5): Jie Cai, Zhenhua Sun, Lili Zhang, and Hongrui Xu. Serp1 reduces inchoate acute hepatic injury through regulation of endoplasmic reticulum stress via the gsk3Ξ²/Ξ²-catenin/tcf/lef signaling pathway. Molecular Medicine Reports, Apr 2022. URL: https://doi.org/10.3892/mmr.2022.12709, doi:10.3892/mmr.2022.12709. This article has 7 citations and is from a peer-reviewed journal.
(sang2024visualizingerphagyand pages 2-3): Yongjuan Sang, Boran Li, Tinglin Su, Hanyu Zhan, Yue Xiong, Zhiming Huang, Changjing Wang, Xiaoxia Cong, Mengjie Du, Yang Wu, Hang Yu, Xi Yang, Kezhi Ding, Xuhua Wang, Xiaolong Miao, Weihua Gong, Liang Wang, Jingwei Zhao, Yiting Zhou, Wei Liu, Xinyang Hu, and Qiming Sun. Visualizing er-phagy and er architecture in vivo. The Journal of Cell Biology, Nov 2024. URL: https://doi.org/10.1083/jcb.202408061, doi:10.1083/jcb.202408061. This article has 10 citations.
(liu2025theepsteinbarrvirus pages 9-10): Jiangnan Liu, Noemi Nagy, Carlos Ayala-Torres, Solenne Bleuse, Francisco Aguilar-Alonso, Ola Larsson, and Maria G. Masucci. The epstein-barr virus deubiquitinase bplf1 regulates stress-induced ribosome ufmylation and reticulophagy. Autophagy, 21:996-1018, Jan 2025. URL: https://doi.org/10.1080/15548627.2024.2440846, doi:10.1080/15548627.2024.2440846. This article has 8 citations and is from a domain leading peer-reviewed journal.
(sang2024visualizingerphagyand pages 1-2): Yongjuan Sang, Boran Li, Tinglin Su, Hanyu Zhan, Yue Xiong, Zhiming Huang, Changjing Wang, Xiaoxia Cong, Mengjie Du, Yang Wu, Hang Yu, Xi Yang, Kezhi Ding, Xuhua Wang, Xiaolong Miao, Weihua Gong, Liang Wang, Jingwei Zhao, Yiting Zhou, Wei Liu, Xinyang Hu, and Qiming Sun. Visualizing er-phagy and er architecture in vivo. The Journal of Cell Biology, Nov 2024. URL: https://doi.org/10.1083/jcb.202408061, doi:10.1083/jcb.202408061. This article has 10 citations.
(sang2024visualizingerphagyand pages 22-25): Yongjuan Sang, Boran Li, Tinglin Su, Hanyu Zhan, Yue Xiong, Zhiming Huang, Changjing Wang, Xiaoxia Cong, Mengjie Du, Yang Wu, Hang Yu, Xi Yang, Kezhi Ding, Xuhua Wang, Xiaolong Miao, Weihua Gong, Liang Wang, Jingwei Zhao, Yiting Zhou, Wei Liu, Xinyang Hu, and Qiming Sun. Visualizing er-phagy and er architecture in vivo. The Journal of Cell Biology, Nov 2024. URL: https://doi.org/10.1083/jcb.202408061, doi:10.1083/jcb.202408061. This article has 10 citations.
(chen2023arisksignature pages 3-6): Haofei Chen, Ning Xu, Jia Xu, Cheng Zhang, Xin Li, Hao Xu, Weixiong Zhu, Jinze Li, Daoming Liang, and Wence Zhou. A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer. Frontiers in Molecular Biosciences, Nov 2023. URL: https://doi.org/10.3389/fmolb.2023.1298077, doi:10.3389/fmolb.2023.1298077. This article has 5 citations.
(OpenTargets Search: -SERP1): Open Targets Query (-SERP1, 5 results). Buniello, A. et al. (2025). Open Targets Platform: facilitating therapeutic hypotheses building in drug discovery. Nucleic Acids Research.
(chen2023arisksignature pages 12-13): Haofei Chen, Ning Xu, Jia Xu, Cheng Zhang, Xin Li, Hao Xu, Weixiong Zhu, Jinze Li, Daoming Liang, and Wence Zhou. A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer. Frontiers in Molecular Biosciences, Nov 2023. URL: https://doi.org/10.3389/fmolb.2023.1298077, doi:10.3389/fmolb.2023.1298077. This article has 5 citations.
(chen2023arisksignature pages 8-12): Haofei Chen, Ning Xu, Jia Xu, Cheng Zhang, Xin Li, Hao Xu, Weixiong Zhu, Jinze Li, Daoming Liang, and Wence Zhou. A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer. Frontiers in Molecular Biosciences, Nov 2023. URL: https://doi.org/10.3389/fmolb.2023.1298077, doi:10.3389/fmolb.2023.1298077. This article has 5 citations.
(chen2023arisksignature pages 6-8): Haofei Chen, Ning Xu, Jia Xu, Cheng Zhang, Xin Li, Hao Xu, Weixiong Zhu, Jinze Li, Daoming Liang, and Wence Zhou. A risk signature based on endoplasmic reticulum stress-associated genes predicts prognosis and immunity in pancreatic cancer. Frontiers in Molecular Biosciences, Nov 2023. URL: https://doi.org/10.3389/fmolb.2023.1298077, doi:10.3389/fmolb.2023.1298077. This article has 5 citations.
(gemmer2020aclearerpicture pages 2-3): Max Gemmer and Friedrich FΓΆrster. A clearer picture of the er translocon complex. Journal of Cell Science, Feb 2020. URL: https://doi.org/10.1242/jcs.231340, doi:10.1242/jcs.231340. This article has 144 citations and is from a domain leading peer-reviewed journal.
UniProt: Q9Y6X1 (SERP1_HUMAN), 66 aa; AltName "Ribosome-attached membrane protein 4" (RAMP4). Single-pass ER membrane protein (TM 39-59), small tail-anchored-like topology.
SERP1/RAMP4 is a stress-induced, Sec61-translocon-associated single-pass ER membrane protein that stabilizes and protects nascent membrane/secretory proteins during ER stress and facilitates their N-glycosylation after stress resolves; functions in the ER unfolded protein response.
ER proteostasis|Protein transport|SEC61 channel accessory protein ; PN-node mapping: group "SEC61 channel accessory protein"=no_mapping (broad category); parent class "Protein transport"=mapped/ok GO:0015031 protein transport; branch=no_mapping.new_to_goa. SERP1 is a translocon-associated substrate stabilizer/chaperone, not a transport carrier; it does not itself transport proteins. GO:0015031 over-reaches (TOMM20/HSPA8/RAB7A precedent: rejected as broader/unsupported). The group-level no_mapping decision is appropriate; the class-level GO:0015031 should not propagate to SERP1.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.
id: Q9Y6X1
gene_symbol: SERP1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: SERP1 (stress-associated endoplasmic reticulum protein 1, also RAMP4, ribosome-attached/associated membrane protein 4) is a small (66 aa) single-pass endoplasmic reticulum membrane protein that associates with the Sec61 translocon. It is induced by ER stress and hypoxia and binds nascent membrane and secretory proteins during their translocation into the ER, protecting these still-unfolded substrates from degradation while ER stress persists and then facilitating their N-glycosylation after stress resolves, including modulating which N-glycosylation sites are used. Through these activities SERP1 contributes to the endoplasmic reticulum unfolded protein response and to the biogenesis and quality control of membrane proteins at the translocon. It physically associates with components of the Sec61 complex (SEC61A1, SEC61B) and calnexin.
existing_annotations:
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: SERP1 acts at the ER (translocon) where it stabilizes nascent membrane proteins; the phylogenetic active-site assignment is correct. 2024 cryo-EM (PMID:38896445) directly shows RAMP4/SERP1 intercalated into the Sec61 lateral gate, confirming its translocon-associated site of action.
action: ACCEPT
reason: Core site of action; SERP1 is a translocon-associated ER membrane protein.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: Interacts with target proteins during their translocation into the lumen of the endoplasmic reticulum
- reference_id: PMID:38896445
- term:
id: GO:0030968
label: endoplasmic reticulum unfolded protein response
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: involved_in
review:
summary: SERP1 is stress-induced and acts during ER stress to protect nascent membrane proteins, placing it in the ER unfolded protein response; the phylogenetic assignment is well supported.
action: ACCEPT
reason: Core biological process; SERP1 (stress-associated ER protein) functions during ER stress to protect translocating substrates.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: Protects unfolded target proteins against degradation during ER stress
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: located_in
review:
summary: InterPro-based ER localization, consistent with experimental and orthology evidence.
action: ACCEPT
reason: Correct core localization.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: Endoplasmic reticulum membrane
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: SERP1 is a single-pass ER membrane protein; the subcellular-location-based annotation is correct.
action: ACCEPT
reason: Core localization, consistent with the single-pass ER membrane topology.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane'
- term:
id: GO:0016020
label: membrane
evidence_type: IEA
original_reference_id: GO_REF:0000044
qualifier: located_in
review:
summary: Generic membrane localization, a parent of the more informative ER membrane term.
action: KEEP_AS_NON_CORE
reason: Correct but uninformative; the specific GO:0005789 (ER membrane) better captures SERP1 localization.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:25416956
qualifier: enables
review:
summary: Proteome-scale interactome capture of a SERP1 interaction (TMEM79); a real interaction but the bare protein binding term is uninformative.
action: KEEP_AS_NON_CORE
reason: High-throughput interactome capture; bare protein binding is uninformative per curation guidelines.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Q9Y6X1; Q9BSE2: TMEM79'
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:32296183
qualifier: enables
review:
summary: HuRI binary-interactome screen capturing SERP1 binding to a large set of membrane and secretory proteins; these are consistent with SERP1's translocon-substrate-stabilizing role but the bare protein binding term is uninformative.
action: KEEP_AS_NON_CORE
reason: Many partners are nascent membrane-protein substrates consistent with SERP1's function, but bare protein binding is uninformative per guidelines.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Q9Y6X1; Q9BY50: SEC11C'
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: located_in
review:
summary: Sequence-similarity transfer of ER membrane localization from the mouse ortholog; consistent with stronger evidence.
action: ACCEPT
reason: Correct core localization, redundant with IEA/TAS evidence.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane'
- term:
id: GO:0016020
label: membrane
evidence_type: ISS
original_reference_id: GO_REF:0000024
qualifier: located_in
review:
summary: Sequence-similarity transfer of generic membrane localization; a parent of ER membrane.
action: KEEP_AS_NON_CORE
reason: Correct but uninformative; the specific GO:0005789 (ER membrane) better captures SERP1 localization.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-'
- term:
id: GO:0005881
label: cytoplasmic microtubule
evidence_type: IDA
original_reference_id: PMID:23264731
qualifier: located_in
review:
summary: The cited paper characterizes MTR120/KIAA1383, an unrelated ~120 kDa microtubule-associated protein, and contains no data on SERP1/RAMP4. SERP1 is a 66 aa single-pass ER membrane protein, for which a cytoplasmic-microtubule localization is biologically implausible. This annotation is a mis-attribution.
action: REMOVE
reason: The full text of PMID:23264731 is available and is entirely about MTR120/KIAA1383 with no mention of SERP1/RAMP4; the cytoplasmic-microtubule localization is inconsistent with SERP1's established ER membrane localization and topology. This is a demonstrable wrong-gene mis-attribution, not a second-guessing of supporting evidence.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane'
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1791167
qualifier: located_in
review:
summary: Reactome curation of SERP1 ER membrane localization (SERP1/RAMP4 expression context).
action: ACCEPT
reason: Correct core localization; redundant with experimental/orthology evidence.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane'
- term:
id: GO:0005829
label: cytosol
evidence_type: TAS
original_reference_id: Reactome:R-HSA-9609921
qualifier: located_in
review:
summary: Reactome cytosol annotation arising from a tail-anchored-protein (SGTA) pathway context; SERP1 is an ER membrane protein with a cytosol-facing portion, but cytosol is not its primary compartment.
action: KEEP_AS_NON_CORE
reason: The primary localization is the ER membrane; the cytosol annotation reflects a pathway context (TA-protein targeting) and the cytosol-facing topology rather than a core localization.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: 'Endoplasmic reticulum membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single-pass membrane'
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: TAS
original_reference_id: PMID:10601334
qualifier: located_in
review:
summary: The defining SERP1/RAMP4 study localizes the protein to the ER, where it acts during stress.
action: ACCEPT
reason: Core localization, from the primary characterization of SERP1.
supported_by:
- reference_id: PMID:10601334
supporting_text: stabilizes membrane proteins during stress and facilitates subsequent glycosylation
- term:
id: GO:0005840
label: ribosome
evidence_type: TAS
original_reference_id: PMID:10601334
qualifier: located_in
review:
summary: SERP1 is also named RAMP4 (ribosome-associated/attached membrane protein 4) for its association with ribosome-translocon junctions at the ER; the ribosome term is broad relative to this translocon-associated context.
action: KEEP_AS_NON_CORE
reason: Reflects the RAMP4 ribosome/translocon association, but the bare ribosome term is a coarse descriptor of its translocon-associated localization; the core compartment is the ER membrane.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: Interacts with SEC61B, SEC61A1 and the SEC61 complex
- term:
id: GO:0007009
label: plasma membrane organization
evidence_type: TAS
original_reference_id: PMID:10601334
qualifier: involved_in
review:
summary: By stabilizing nascent membrane proteins during stress, SERP1 indirectly influences the surface expression of membrane proteins; this is a downstream consequence rather than a core function.
action: KEEP_AS_NON_CORE
reason: Indirect, downstream effect of SERP1's translocon-substrate stabilization; not a core function.
supported_by:
- reference_id: PMID:10601334
supporting_text: stabilizes membrane proteins during stress
- term:
id: GO:0009101
label: glycoprotein biosynthetic process
evidence_type: TAS
original_reference_id: PMID:10601334
qualifier: involved_in
review:
summary: SERP1 facilitates N-glycosylation of its target proteins after termination of ER stress and may modulate which N-glycosylation sites are used; a real but modulatory/secondary role.
action: KEEP_AS_NON_CORE
reason: Supported by the primary study and UniProt, but a downstream/modulatory effect on glycosylation rather than the core stabilization function.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: May facilitate glycosylation of target proteins after termination of ER stress
- term:
id: GO:0036211
label: protein modification process
evidence_type: TAS
original_reference_id: PMID:10601334
qualifier: involved_in
review:
summary: Very general process term (parent of glycosylation), derived from SERP1's role in facilitating glycosylation of its targets.
action: KEEP_AS_NON_CORE
reason: Overly general; the more specific GO:0009101 (glycoprotein biosynthetic process) captures the relevant activity, and even that is secondary.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: May facilitate glycosylation of target proteins after termination of ER stress
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
findings: []
- id: PMID:10601334
title: Stress-associated endoplasmic reticulum protein 1 (SERP1)/Ribosome-associated membrane protein 4 (RAMP4) stabilizes membrane proteins during stress and facilitates subsequent glycosylation.
findings:
- statement: SERP1/RAMP4 is an ER-stress-induced, translocon-associated ER membrane protein that stabilizes nascent membrane proteins during stress and facilitates their glycosylation after stress.
reference_section_type: ABSTRACT
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: Defining characterization of SERP1/RAMP4; establishes the stress-induced translocon-associated stabilization and post-stress glycosylation roles.
- id: PMID:23264731
title: MTR120/KIAA1383, a novel microtubule-associated protein, promotes microtubule stability and ensures cytokinesis.
findings:
- statement: Characterizes MTR120/KIAA1383, an unrelated ~120 kDa microtubule-associated protein; the full text contains no data on SERP1/RAMP4.
reference_section_type: ABSTRACT
reference_review:
relevance: NONE
correctness: WRONG_IDENTIFIER
review_notes: Paper is entirely about MTR120/KIAA1383, not SERP1/RAMP4; the cytoplasmic-microtubule IDA annotation on SERP1 is a wrong-gene mis-attribution and is recommended for removal.
- id: PMID:25416956
title: A proteome-scale map of the human interactome network.
findings: []
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: High-throughput interactome; source of a bare protein binding annotation (TMEM79), not relevant to SERP1's core function.
- id: PMID:32296183
title: A reference map of the human binary protein interactome.
findings: []
reference_review:
relevance: LOW
correctness: VERIFIED
review_notes: HuRI binary-interactome map; source of many bare protein binding annotations, largely with membrane/secretory proteins consistent with SERP1's translocon role but individually uninformative.
- id: Reactome:R-HSA-1791167
title: Expression of SERP1 (RAMP4)
findings: []
- id: Reactome:R-HSA-9609921
title: SGTA binds Tail-anchored protein
findings: []
- id: file:human/SERP1/SERP1-uniprot.txt
title: UniProt entry Q9Y6X1 (SERP1_HUMAN), stress-associated endoplasmic reticulum protein 1 / RAMP4
findings:
- statement: Single-pass ER membrane protein that interacts with target proteins during ER translocation, protects unfolded targets against degradation during ER stress, and facilitates their glycosylation after stress; interacts with the SEC61 complex and calnexin.
reference_section_type: OTHER
- id: PMID:38896445
title: Structural analysis of the dynamic ribosome-translocon complex.
findings:
- statement: Cryo-EM of native ribosome-translocon complexes shows that a large proportion contain RAMP4 (SERP1) intercalated into the Sec61 lateral gate, widening the central pore and contributing to its hydrophilic interior; this places SERP1/RAMP4 as a structural, gating-modulating component of the Sec61 translocon.
reference_section_type: ABSTRACT
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified (Lewis, Zhong, Keenan, Hegde, eLife 2024; DOI 10.7554/eLife.95814). Direct structural evidence that RAMP4/SERP1 occupies the Sec61 lateral gate and widens the pore, supporting the translocon-associated, gating-modulating role. The Falcon report cited the bioRxiv preprint DOI (10.1101/2023.12.22.572959); this is the published eLife version. Not cached, so no verbatim supporting_text added to annotations.
- id: PMID:31461934
title: A Dengue Virus Type 2 (DENV-2) NS4B-Interacting Host Factor, SERP1, Reduces DENV-2 Production by Suppressing Viral RNA Replication.
findings:
- statement: SERP1 was identified as a DENV-2 NS4B-interacting host factor; SERP1 is strongly induced (~34.5-fold) under DENV-2-induced ER stress, and SERP1 overexpression suppresses DENV-2 RNA replication and viral yield, consistent with a protective ER-stress-associated role.
reference_section_type: ABSTRACT
reference_review:
relevance: HIGH
correctness: VERIFIED
review_notes: PubMed-verified (Tian et al., Viruses 2019; DOI 10.3390/v11090787). SERP1-specific experimental study (interaction, induction, knockdown/knockout). Establishes ER-stress inducibility and an antiviral/proteostasis-protective context; does not by itself ground a new GO annotation beyond the existing UPR/ER terms. Not cached.
- id: PMID:35419615
title: SERP1 reduces inchoate acute hepatic injury through regulation of endoplasmic reticulum stress via the GSK3beta/beta-catenin/TCF/LEF signaling pathway.
findings:
- statement: In acute hepatic injury models, SERP1 expression rises with ER stress, and SERP1 overexpression reduces ER-stress markers (GRP78/GRP94/CHOP), apoptosis, and inflammation, supporting a cytoprotective role during ER stress.
reference_section_type: ABSTRACT
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: PubMed-verified (Cai et al., Mol Med Rep 2022; DOI 10.3892/mmr.2022.12709). SERP1-specific overexpression study in a liver-injury context; supports a protective ER-stress role but is a downstream/physiological readout rather than direct evidence for a core molecular function. Not cached.
- id: PMID:32019826
title: A clearer picture of the ER translocon complex.
findings:
- statement: Review of the ER translocon; RAMP4/SERP1 is among the ribosome-associated membrane proteins recovered with Sec61-containing translocon fractions, supporting its translocon-associated localization.
reference_section_type: OTHER
reference_review:
relevance: MEDIUM
correctness: VERIFIED
review_notes: PubMed-verified (Gemmer & Forster, J Cell Sci 2020; DOI 10.1242/jcs.231340). Authoritative translocon review providing family-level context for RAMP4/SERP1 association with the Sec61 translocon. Not cached.
core_functions:
- description: Stress-induced, Sec61-translocon-associated ER membrane protein that binds and stabilizes nascent membrane and secretory proteins during ER stress, protecting them from premature degradation.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: Protects unfolded target proteins against degradation during ER stress
- reference_id: PMID:10601334
supporting_text: stabilizes membrane proteins during stress and facilitates subsequent glycosylation
locations:
- id: GO:0005789
label: endoplasmic reticulum membrane
directly_involved_in:
- id: GO:0030968
label: endoplasmic reticulum unfolded protein response
- description: Facilitates N-glycosylation of its target proteins after termination of ER stress and may modulate the use of N-glycosylation sites, coupling membrane-protein stabilization to subsequent maturation.
supported_by:
- reference_id: file:human/SERP1/SERP1-uniprot.txt
supporting_text: May facilitate glycosylation of target proteins after termination of ER stress
locations:
- id: GO:0005789
label: endoplasmic reticulum membrane
proposed_new_terms: []
suggested_questions:
- question: Does SERP1/RAMP4 protect nascent substrates by physically shielding them at the translocon, by recruiting chaperones such as calnexin, or by slowing translocation, and is this selective for particular substrate classes?
- question: How does SERP1 modulate N-glycosylation site usage on its targets after ER stress resolves?
suggested_experiments:
- description: Site-specific proximity proteomics (e.g., split-BioID at the Sec61 translocon) under ER stress to define the SERP1-dependent nascent-substrate interactome and its dynamics through stress and recovery.
- description: Glycoproteomic comparison of SERP1 wild-type versus knockout cells before and after ER stress to test the proposed stabilization and N-glycosylation-site-modulation functions on defined substrates.