SERP2 (stress-associated endoplasmic reticulum protein 2, also RAMP4-2, ribosome-associated membrane protein RAMP4-2) is a small (65 aa) single-pass endoplasmic reticulum membrane protein of the RAMP4 family and a paralog of SERP1/RAMP4. Like SERP1, it associates with the Sec61 translocon and binds nascent membrane and secretory proteins during their translocation into the ER, protecting these still-unfolded substrates from degradation during ER stress and facilitating their N-glycosylation after stress resolves, including modulating which N-glycosylation sites are used. Through these activities SERP2 contributes to the endoplasmic reticulum unfolded protein response and to membrane-protein biogenesis at the translocon. It physically associates with components of the Sec61 complex (SEC61A1, SEC61B) and calnexin. Its function is established largely by orthology and paralogy, and it is less experimentally characterized than SERP1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005783 endoplasmic reticulum | IBA GO_REF:0000033 | ACCEPT | Summary: SERP2 acts at the ER (translocon) where, like its SERP1 paralog, it stabilizes nascent membrane proteins; the phylogenetic active-site assignment is correct. Reason: Core site of action; SERP2 is a translocon-associated ER membrane protein. Supporting Evidence: file:human/SERP2/SERP2-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: SERP2 is a stress-associated ER protein that acts during ER stress to protect nascent membrane proteins, placing it in the ER unfolded protein response. Reason: Core biological process; SERP2 functions during ER stress to protect translocating substrates. Supporting Evidence: file:human/SERP2/SERP2-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 orthology and phylogenetic evidence. Reason: Correct core localization. Supporting Evidence: file:human/SERP2/SERP2-uniprot.txt Interacts with SEC61B, SEC61A1 and the SEC61 complex |
| GO:0005789 endoplasmic reticulum membrane | IEA GO_REF:0000044 | ACCEPT | Summary: SERP2 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/SERP2/SERP2-uniprot.txt Membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single- |
| 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 SERP2 localization. Supporting Evidence: file:human/SERP2/SERP2-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 SERP2 interaction; 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/SERP2/SERP2-uniprot.txt Q8N6R1; Q8N6L0 |
| 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 SERP2 binding to a large set of membrane and secretory proteins; consistent with a translocon-substrate-stabilizing role but the bare protein binding term is uninformative. Reason: Many partners are membrane-protein substrates consistent with SERP2's function, but bare protein binding is uninformative per guidelines. Supporting Evidence: file:human/SERP2/SERP2-uniprot.txt Q8N6R1; Q13520: AQP6 |
| GO:0005789 endoplasmic reticulum membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Sequence-similarity transfer of ER membrane localization from the mouse ortholog; consistent with the RAMP4-family identity. Reason: Correct core localization, redundant with IEA evidence. Supporting Evidence: file:human/SERP2/SERP2-uniprot.txt Membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single- |
| 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 SERP2 localization. Supporting Evidence: file:human/SERP2/SERP2-uniprot.txt Membrane {ECO:0000250|UniProtKB:Q9R2C1}; Single- |
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Download this section (compressed HTML)Q: Is SERP2/RAMP4-2 functionally redundant with SERP1/RAMP4, or does it have distinct substrate preferences, tissue expression, or stress-response behavior?
Q: Which nascent membrane-protein substrates depend on SERP2 for stabilization or correct N-glycosylation during ER stress?
Experiment: Generate SERP2 single and SERP1/SERP2 double knockouts and assess membrane-protein stability, surface expression, and glycosylation under ER stress to test redundancy with SERP1.
Experiment: Proximity proteomics of SERP2 at the Sec61 translocon under basal and ER-stress conditions to define its substrate interactome and compare it with SERP1's.
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