| 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 (pqac-00000000, pqac-00000002, pqac-00000007). | Human RAMP4 sequence shown in structural study; TMD length ~25 aa; occupancy enriched in non-MPT RTCs (see quantitative row) (pqac-00000002, pqac-00000015). | 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 (pqac-00000018, pqac-00000020, pqac-00000021, pqac-00000022). | 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 (pqac-00000015, pqac-00000017, pqac-00000019). | 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 (pqac-00000008, pqac-00000009). | 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 (pqac-00000008, pqac-00000009). | 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 (pqac-00000002, pqac-00000008, pqac-00000018). | Ribosome contacts include 28S rRNA helices 47, 57, 59 and proteins eL19, eL22, eL31; DENV-2 NS4B overexpression alleviated SERP1-mediated inhibition of replication (pqac-00000002, pqac-00000008). | 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 (pqac-00000011, pqac-00000012, pqac-00000030, pqac-00000031, pqac-00000032, pqac-00000033). | 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 (pqac-00000031, pqac-00000033). | 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 (pqac-00000024, pqac-00000025, pqac-00000026, pqac-00000027, pqac-00000029). | 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 (pqac-00000029). | Chen 2023 Frontiers in Molecular Biosciences. https://doi.org/10.3389/fmolb.2023.1298077; Open Targets Platform evidence summary (pqac-00000025) |
| 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 (pqac-00000015, pqac-00000016, pqac-00000029, pqac-00000033). | 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 (pqac-00000015, pqac-00000016, pqac-00000033). | 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.*