| Evidence type | What was shown | System/assay | Key quantitative findings (numbers) | Interpretation for SERP2 function/localization | Source (paper, year, URL) |
|---|---|---|---|---|---|
| Genetic association | Human **SERP2** was explicitly named **Stress-Associated Endoplasmic Reticulum Protein 2**; an intergenic SNP near SERP2 showed a female-specific asthma association, and the paper also noted prior associations of SERP2-region variants with lung function/COPD and female Alzheimer’s disease signals. | SNP-by-sex interaction GWAS and sex-stratified analysis in 23,323 Canadian adults from CLSA | 23,323 individuals analyzed; 49 SNPs with interaction *p* < 10^-5 screened; **3 female-specific SNPs** passed Bonferroni correction, including **rs9525931 near SERP2** (pqac-00000000) | Confirms the existence of human SERP2 as a distinct gene; current direct evidence is genetic/association-based rather than mechanistic, with the name implying ER association but not proving biochemical function. | Odimba et al., 2023, *Journal of Asthma and Allergy*, https://doi.org/10.2147/JAA.S404670 (pqac-00000000) |
| Structural/translocon (family context) | In recent cryo-EM interpretation, **RAMP4** localizes near the **Sec61 lateral gate** and was proposed to behave like a **fourth Sec61 subunit**, helping keep the channel open and tether the complex to ribosomes during membrane protein insertion. | Cryo-EM/structural interpretation of stalled ribosome–translocon intermediates, reviewed in eLife Insight | No explicit stoichiometric number beyond the proposal of a **"fourth subunit"**; structural intermediates captured open-gate states (pqac-00000020) | Supports a plausible **ER translocon-associated** role for the UniProt-defined SERP2/RAMP4-family protein, but this evidence is for **RAMP4 family context** and does **not explicitly map the studied RAMP4 species to SERP2/Q8N6R1**. | Vismpas & Förster, 2024, *eLife*, https://doi.org/10.7554/eLife.98548 (pqac-00000020) |
| Structural/translocon (family context) | Earlier translocon review summarized that **RAMP4/SERP1** was originally isolated among ribosome-associated membrane proteins and was unusually resistant to detergent/salt extraction with Sec61-associated material, but its exact stoichiometry/position was unresolved in older preparations. | Review of biochemical isolation and cryo-ET literature on mammalian ER translocons | No direct SERP2-specific numbers; key point is **detergent- and salt-resistant recovery** with translocon fractions (pqac-00000022) | Reinforces the inference that RAMP4-family proteins are **ER membrane/ribosome-translocon associated**; however, this remains **family-level context**, not direct evidence for human SERP2 specifically. | Gemmer & Förster, 2020, *Journal of Cell Science*, https://doi.org/10.1242/jcs.231340 (pqac-00000022) |
| Intramembrane proteolysis | **RAMP4-2** was experimentally tested as a **tail-anchored (TA) protein** and was the **only one among tested TA candidates** efficiently cleaved by **SPPL2c**; it also overlapped with SPPL2c in the ER. | HEK293/HeLa overexpression, Western blot cleavage assays, immunofluorescence colocalization | In the tested panel, **RAMP4-2** was the only candidate efficiently cleaved by SPPL2c; near-complete depletion was reported under assay conditions (pqac-00000004, pqac-00000005) | Provides the strongest functional/localization clue linked to the UniProt identity: if **RAMP4-2 corresponds to SERP2/Q8N6R1**, then SERP2 is likely an **ER-localized TA membrane protein** and a potential **SPPL2c/SPP substrate**. The limitation is that the retrieved paper text did **not explicitly map RAMP4-2 to SERP2/C13orf21/Q8N6R1**. | Niemeyer et al., 2019, *EMBO Reports*, https://doi.org/10.15252/embr.201846449 (pqac-00000004, pqac-00000005) |
| Intramembrane proteolysis / regulatory assay | **HA-RAMP4-2** was used as the readout substrate in SPPL2c inhibition studies; the paper explicitly referred to **RAMP4-2 as “stress-associated endoplasmic reticulum protein family member 2.”** | HEK-cell SPPL2c inhibition and co-immunoprecipitation assays using HA-RAMP4-2 substrate | Multiple assays quantified inhibition of **RAMP4-2** cleavage; exact effect sizes varied by mutant, but RAMP4-2 was the central substrate readout (pqac-00000006, pqac-00000013, pqac-00000014) | Supports the designation of **RAMP4-2 as an ER stress-associated family member 2**, consistent with the UniProt annotation for SERP2; still, the paper excerpt did **not** provide the direct human gene symbol/UniProt mapping. | Contreras et al., 2023, *Cellular and Molecular Life Sciences*, https://doi.org/10.1007/s00018-023-04823-7 (pqac-00000006, pqac-00000013, pqac-00000014) |
| Overall evidence quality / ambiguity | Retrieved literature repeatedly showed that **SERP2 is ambiguous** in the wider literature (e.g., viral/invertebrate “SERP-2” entries), while direct human SERP2 mechanistic studies were sparse; most mechanistic data came from **RAMP4/RAMP4-2 family literature** lacking explicit accession mapping. | Cross-literature verification across retrieved genetics, translocon, and protease papers | No direct number; key result is **absence of explicit SERP2↔RAMP4-2/Q8N6R1 mapping in retrieved primary texts** (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000006) | Best-supported conclusion is cautious: human **SERP2/Q8N6R1** is likely an **ER-associated RAMP4-family membrane protein**, probably **tail-anchored** and potentially linked to **translocon biology and intramembrane proteolysis**, but the direct literature base is limited. | Synthesis from retrieved evidence (pqac-00000000, pqac-00000001, pqac-00000002, pqac-00000003, pqac-00000006) |


*Table: This table summarizes the strongest retrieved evidence relevant to human SERP2/Q8N6R1 and separates direct human SERP2 findings from indirect RAMP4/RAMP4-2 family context. It is useful because the literature is sparse and symbol ambiguity makes careful evidence tracking essential.*