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 |
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Download this section (compressed HTML)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.
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