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this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.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.
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 ribosome–Sec61 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 funnel—features consistent with SERP1’s 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 ribosome–translocon 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 & Förster 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 Sec61’s 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 ~40° at a conserved glycine; RAMP4 present in ~81% of non-MPT RTCs; ~85% of Sec61•TRAP•OSTA RTCs and ~53% of Sec61•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 Sec61α and Sec61β 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 20–30 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-Sjögren 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% Sec61•TRAP•OSTA, ~53% Sec61•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, 20–30 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 “SERP1 (RAMP4)” 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 “ribosome-associated membrane proteins (RAMPs)” 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 Sec61’s 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 ribosome–translocon complexes (RTCs): ~85% of Sec61•TRAP•OSTA RTCs and ~53% of Sec61•TRAP RTCs contain RAMP4, corresponding to ~81% of non-MPT RTCs. (lewis2024structuralanalysisof pages 6-8)
Expert interpretation (from the authors’ mechanistic hypotheses): the structure supports the idea that RAMP4 can function as a regulatory translocon component, potentially including a “surrogate signal peptide” 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 Sec61α and Sec61β, 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 × 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/RAMP4–eGFP–mCherry 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 “red-only puncta” 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 20–30 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-Sjögren 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 gsk3β/β-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 Förster. 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.