SSR1 encodes Translocon-associated protein subunit alpha (TRAP-alpha), a single-pass type I ER membrane glycoprotein that is a core component of the heterotetrameric TRAP complex (TRAP-alpha/beta/gamma/delta, encoded by SSR1-4). The TRAP complex stably associates with the Sec61 protein-conducting channel and ribosomes at the ER membrane, facilitating co-translational translocation of secretory and membrane proteins, particularly those with weak or atypical signal peptides. TRAP-alpha features a large N-terminal luminal domain positioned beneath the Sec61 channel exit site and a single long transmembrane helix that contacts Sec61. The complex coordinates with the oligosaccharyltransferase (OST) to couple translocation with N-glycosylation. TRAP-alpha also participates in ER quality control and ERAD pathways.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005783
endoplasmic reticulum
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: IBA annotation for ER localization based on phylogenetic inference from PANTHER. TRAP-alpha is well-established as an ER-resident protein across eukaryotes. Recent cryo-EM structures confirm TRAP as a core ER translocon component [SSR1-deep-research-falcon.md].
Reason: Core localization annotation. TRAP-alpha is definitively an ER membrane protein. The IBA annotation is well-supported by extensive structural and biochemical evidence showing TRAP-alpha as a core component of the ER translocon complex [Pauwels et al. 2023; Karki et al. 2023; PMID:36697828].
Supporting Evidence:
PMID:8050590
The alpha-subunit of the TRAP complex (TRAP alpha) is a single-spanning membrane protein of the endoplasmic reticulum (ER) which is found in proximity of nascent polypeptide chains translocating across the membrane.
file:human/SSR1/SSR1-deep-research-falcon.md
model: Edison Scientific Literature
|
|
GO:0005789
endoplasmic reticulum membrane
|
IEA
GO_REF:0000120 |
ACCEPT |
Summary: IEA annotation based on InterPro TRAP_alpha domain and UniProt subcellular location annotation. This is the specific membrane localization.
Reason: Core localization annotation. TRAP-alpha is a single-pass type I membrane protein anchored in the ER membrane. UniProt confirms this topology with a luminal N-terminal domain and cytoplasmic C-terminus. Structural studies confirm ER membrane integration [PMID:36697828].
Supporting Evidence:
PMID:36697828
near-complete atomic model of the most abundant ER translocon variant comprising the protein-conducting channel SEC61, TRAP and the oligosaccharyltransferase complex A (OSTA) reveals specific interactions of TRAP with other translocon components
|
|
GO:0005515
protein binding
|
IPI
PMID:17380188 Simultaneous induction of the four subunits of the TRAP comp... |
MODIFY |
Summary: IPI annotation based on interaction with SERPINA1/alpha1-antitrypsin, calnexin (CANX), and SEC61B detected in the context of ER stress and ERAD studies.
Reason: While the protein binding annotation reflects genuine interactions, it is uninformative. The study shows TRAP complex involvement in ERAD and interaction with misfolded substrates like alpha1-antitrypsin NHK variant. A more specific term capturing the functional interaction would be appropriate.
Proposed replacements:
protein localization to ribosome-translocon complex
Supporting Evidence:
PMID:17380188
The TRAP complex bound preferentially to misfolded proteins rather than correctly folded wild-type substrates. Thus, the TRAP complex induced by the unfolded protein response pathway might discriminate ERAD substrates from correctly folded substrates, accelerating degradation.
|
|
GO:0005515
protein binding
|
IPI
PMID:22314232 Palmitoylated calnexin is a key component of the ribosome-tr... |
MODIFY |
Summary: IPI annotation for interaction with palmitoylated calnexin (CANX). The study demonstrates calnexin association with the ribosome-translocon complex including TRAP components.
Reason: The protein binding term is too generic. The interaction with calnexin is functionally significant - palmitoylated calnexin associates with the ribosome-translocon complex to facilitate glycoprotein folding. A more specific MF term should be used.
Proposed replacements:
protein localization to ribosome-translocon complex
Supporting Evidence:
PMID:22314232
Palmitoylation mediates the association of calnexin with the ribosome-translocon complex (RTC) leading to the formation of a supercomplex that recruits the actin cytoskeleton, leading to further stabilization of the assembly.
|
|
GO:0005515
protein binding
|
IPI
PMID:29568061 An AP-MS- and BioID-compatible MAC-tag enables comprehensive... |
MODIFY |
Summary: IPI annotation for interaction with calnexin detected by AP-MS and BioID proximity labeling methods.
Reason: High-throughput interaction study confirming calnexin-TRAP association. The generic protein binding term is uninformative - should be captured by more specific translocon-related terms.
Proposed replacements:
protein localization to ribosome-translocon complex
Supporting Evidence:
PMID:29568061
An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping of protein interactions and subcellular localizations.
|
|
GO:0005515
protein binding
|
IPI
PMID:35271311 OpenCell: Endogenous tagging for the cartography of human ce... |
MODIFY |
Summary: IPI annotation from OpenCell study detecting interactions with calnexin and SEC61B via endogenous tagging.
Reason: High-throughput proteomics confirming established TRAP complex interactions. The generic protein binding is uninformative for understanding function. These represent structural associations within the translocon complex.
Proposed replacements:
protein localization to ribosome-translocon complex
Supporting Evidence:
PMID:35271311
2022 Mar 11. OpenCell: Endogenous tagging for the cartography of human cellular organization.
|
|
GO:0005783
endoplasmic reticulum
|
IEA
GO_REF:0000107 |
ACCEPT |
Summary: IEA annotation transferred from mouse ortholog via Ensembl Compara.
Reason: Redundant with IBA annotation but correct. ER localization is core to TRAP-alpha function and well-conserved across mammals.
|
|
GO:0005783
endoplasmic reticulum
|
IDA
GO_REF:0000052 |
ACCEPT |
Summary: IDA annotation based on Human Protein Atlas immunofluorescence data.
Reason: Direct experimental evidence for ER localization. HPA immunofluorescence confirms ER residence of SSR1/TRAP-alpha.
|
|
GO:0005789
endoplasmic reticulum membrane
|
NAS
PMID:36697828 Visualization of translation and protein biogenesis at the E... |
ACCEPT |
Summary: NAS annotation from ComplexPortal based on cryo-ET structural study visualizing the SEC61-TRAP-OSTA translocon complex.
Reason: Core localization. The structural study provides near-atomic resolution of TRAP within the ER membrane translocon complex [Gemmer et al. 2023].
Supporting Evidence:
PMID:36697828
An AlphaFold-based model of TRAP could be fitted unambiguously into the SEC61-OSTA-TRAP translocon map, requiring only minor repositioning of single transmembrane helices
|
|
GO:0031204
post-translational protein targeting to membrane, translocation
|
NAS
PMID:36697828 Visualization of translation and protein biogenesis at the E... |
MODIFY |
Summary: NAS annotation from ComplexPortal. However, this term refers to post-translational translocation, whereas TRAP is primarily involved in co-translational translocation.
Reason: The term is inaccurate. TRAP/SSR1 is primarily involved in co-translational protein targeting, not post-translational. The structural study and all functional evidence show TRAP associating with translating ribosomes at the ER. Should be replaced with co-translational targeting term.
Proposed replacements:
cotranslational protein targeting to membrane
Supporting Evidence:
PMID:36697828
The dynamic ribosome-translocon complex, which resides at the endoplasmic reticulum (ER) membrane, produces a major fraction of the human proteome
|
|
GO:0005789
endoplasmic reticulum membrane
|
TAS
Reactome:R-HSA-1791164 |
ACCEPT |
Summary: TAS annotation from Reactome pathway "Expression of SSR1 (Trap alpha)" indicating ER membrane localization.
Reason: Core localization annotation. Reactome pathway information is consistent with established TRAP-alpha function.
|
|
GO:0005783
endoplasmic reticulum
|
TAS
PMID:8050590 The N-terminal region of the alpha-subunit of the TRAP compl... |
ACCEPT |
Summary: TAS annotation from original characterization paper describing TRAP-alpha as an ER protein.
Reason: Primary literature confirming ER localization. This paper established the widespread conservation of TRAP-alpha in eukaryotes.
Supporting Evidence:
PMID:8050590
The alpha-subunit of the TRAP complex (TRAP alpha) is a single-spanning membrane protein of the endoplasmic reticulum (ER) which is found in proximity of nascent polypeptide chains translocating across the membrane.
|
|
GO:0006613
cotranslational protein targeting to membrane
|
TAS
PMID:8050590 The N-terminal region of the alpha-subunit of the TRAP compl... |
ACCEPT |
Summary: TAS annotation indicating involvement in co-translational protein targeting based on the original characterization.
Reason: Core function annotation. TRAP-alpha is established as a component of the ribosome-translocon complex facilitating co-translational translocation of nascent polypeptides into the ER.
Supporting Evidence:
PMID:8050590
The alpha-subunit of the TRAP complex (TRAP alpha) is a single-spanning membrane protein of the endoplasmic reticulum (ER) which is found in proximity of nascent polypeptide chains translocating across the membrane.
|
|
GO:0008284
positive regulation of cell population proliferation
|
TAS
PMID:10437777 Translocon-associated protein alpha transcripts are induced ... |
KEEP AS NON CORE |
Summary: TAS annotation based on observation that TRAP-alpha transcripts are induced by GM-CSF and more abundant in growing vs quiescent cells.
Reason: This is a pleiotropic effect rather than a core function. The study shows TRAP-alpha mRNA is upregulated in proliferating cells stimulated by GM-CSF, but this reflects increased demand for protein secretion capacity rather than direct regulation of proliferation. TRAP-alpha's primary function is in protein translocation, not proliferation control.
Supporting Evidence:
PMID:10437777
Its messenger RNA was more abundant in growing cells than in either factor-deprived cells or quiescent cells
|
|
GO:0016020
membrane
|
TAS
PMID:8050590 The N-terminal region of the alpha-subunit of the TRAP compl... |
MARK AS OVER ANNOTATED |
Summary: TAS annotation for generic membrane localization.
Reason: Too general. GO:0005789 (endoplasmic reticulum membrane) is more specific and accurate for TRAP-alpha localization. This generic term adds no additional information.
Supporting Evidence:
PMID:8050590
The N-terminal region of the alpha-subunit of the TRAP complex has a conserved cluster of negative charges.
|
|
GO:0036503
ERAD pathway
|
TAS
PMID:17380188 Simultaneous induction of the four subunits of the TRAP comp... |
NEW |
Summary: Proposed new annotation based on evidence that TRAP complex participates in ERAD by preferentially binding misfolded proteins.
Reason: TRAP complex is induced by ER stress and preferentially binds misfolded proteins, facilitating their degradation via ERAD. This represents an additional function beyond co-translational translocation.
Supporting Evidence:
PMID:17380188
The TRAP complex bound preferentially to misfolded proteins rather than correctly folded wild-type substrates. Thus, the TRAP complex induced by the unfolded protein response pathway might discriminate ERAD substrates from correctly folded substrates, accelerating degradation.
|
Q: What is the precise mechanism by which TRAP-alpha recognizes and assists translocation of substrates with weak signal peptides?
Q: Does TRAP-alpha have substrate specificity or does it function equivalently for all translocon-dependent substrates?
Q: What is the functional significance of TRAP-alpha phosphorylation at Ser-268 during mitosis?
Experiment: Structure-function studies with TRAP-alpha luminal domain mutants to determine residues critical for nascent chain interaction
Experiment: Quantitative proteomics comparing translocation efficiency of defined substrates in TRAP-knockdown vs control cells
Experiment: Investigation of TRAP-alpha post-translational modifications and their regulation during cell cycle or ER stress
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.
Plan and verification
- Identity and nomenclature: The human SSR1 gene encodes TRAP-α (also called signal sequence receptor subunit α), a subunit of the heterotetrameric translocon-associated protein (TRAP) complex composed of SSR1–SSR4 (TRAP-α, -β, -γ, -δ) that binds the Sec61 translocon on the endoplasmic reticulum (ER) membrane (Pauwels et al., Science Advances, 3 Mar 2023, https://doi.org/10.1126/sciadv.adf0797) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3). The articles cited below use mammalian, including human, ribosome–Sec61–TRAP assemblies and explicitly identify the TRAP subunits by the SSR1–SSR4 nomenclature, satisfying organism and symbol verification (Pauwels 2023; Karki et al., EMBO Reports, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3, karki2023molecularviewof pages 1-2).
- Family/domains: Recent structures and reviews align with UniProt’s TRAP-α family assignment and domain features: a large luminal glycoprotein domain and a single long transmembrane helix for TRAP-α, as detailed below (Karki 2023; Russo 2020) (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2, russo2020understandingthemammalian pages 5-6).
Key concepts and definitions
- What is TRAP-α/SSR1? TRAP-α is the α subunit of the ER-resident TRAP complex that stably associates with the Sec61 protein-conducting channel and the ribosome, assisting co‑translational translocation of secretory and membrane proteins, especially those with weak or atypical signal peptides (Pauwels 2023; Russo 2020) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3, russo2020understandingthemammalian pages 5-6).
- Structure and domains: Cryo‑EM/ET reveals that TRAP-α contains a prominent luminal domain positioned directly beneath the Sec61α channel exit and a long, diagonal transmembrane helix that contacts Sec61 at the hinge/backside region; its luminal domain bears N‑glycosylation sites (e.g., Asn136, Asn191) and is poised for nascent chain interactions (Karki 2023, EMBO Reports, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5). In the assembled TRAP, a seven-helix membrane bundle forms from TRAP-γ’s four helices plus one C‑terminal helix each from TRAP-α/β/δ, positioning the luminal TRAP-α/β/δ “crescent” adjacent to Sec61 (Pauwels 2023, 3 Mar 2023, https://doi.org/10.1126/sciadv.adf0797) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3).
- Localization and topology: TRAP-α is an ER membrane single-pass type I membrane glycoprotein with a large luminal N‑terminal domain and a short cytosolic C‑terminus; its luminal mass sits under the Sec61 pore, while the C‑terminal cytosolic tail localizes near ribosomal proteins (Karki 2023) (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2).
Molecular function and pathways
- Co‑translational translocation: TRAP-α, within the TRAP complex, stabilizes the ribosome–Sec61 assembly and facilitates insertion/translocation of nascent polypeptides, particularly those with below‑average hydrophobicity or Gly/Pro‑rich signal peptides that would otherwise inefficiently open Sec61’s lateral gate (Pauwels 2023; Gemmer et al., Life Science Alliance, 12 Jun 2024, https://doi.org/10.26508/lsa.202302496) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3, gemmer2024exploringthemolecular pages 1-3). Karki 2023 further demonstrates in atomistic MD and cellular assays that TRAP strengthens ribosome anchoring and supports preproinsulin translocation, with TRAP-α perturbation impairing this pathway (Karki 2023, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 5-7, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5).
- Substrate specificity: Multiple recent studies converge that TRAP dependency correlates with weakly hydrophobic and Gly/Pro‑rich signal peptides; TRAP-α’s luminal proximity to the exit likely helps “ratchet” such sequences into the ER and prevent back‑sliding (Pauwels 2023; Gemmer 2024; Russo 2020) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3, gemmer2024exploringthemolecular pages 1-3, russo2020understandingthemammalian pages 5-6).
- Coordination with N‑glycosylation: TRAP’s luminal surface lies adjacent to the oligosaccharyltransferase (OST) active site; structures and modeling support a role for TRAP-α in positioning nascent chains for initial N‑linked glycosylation during co‑translational translocation (Pauwels 2023; Karki 2023) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3, karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2). This spatial coupling explains why defects in TRAP subunits can present with glycosylation abnormalities (Karki 2023) (karki2023molecularviewof pages 1-2).
- ER membrane remodeling: Cryo‑EM/MD indicates that Sec61/TRAP locally thins and curves the ER luminal leaflet, reduces local lipid order, and increases lipid flip‑flops; this remodeling likely tunes lateral‑gate dynamics to promote engagement of challenging signal sequences (Karki 2023, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 5-7, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5).
- ERQC/UPR connections: TRAP abundance and association with the ribosome–Sec61 assembly vary with translational state and ER stress, situating TRAP-α within ER quality control networks that influence substrate selection and processing; reviews emphasize TRAP integration with ERAD/UPR pathways (Gemmer 2024; Russo 2020) (gemmer2024exploringthemolecular pages 1-3, russo2020understandingthemammalian pages 5-6).
Recent developments (2023–2024)
- High-resolution architectures: Two 2023 cryo‑EM studies established the ribosome–Sec61–TRAP organization and details of TRAP-α placement and interfaces, including a seven‑TMH bundle incorporating the α/β/δ C‑terminal helices around TRAP-γ (Pauwels 2023, Science Advances, 3 Mar 2023, https://doi.org/10.1126/sciadv.adf0797) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3). Karki 2023 provided a ribosome‑bound Sec61/TRAP reconstruction with MD that explains how TRAP reshapes the ER membrane to aid translocation and highlighted TRAP-α’s role in preproinsulin biogenesis (EMBO Reports, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 5-7, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5).
- Native-membrane context: Cryo‑ET/subtomogram averaging in 2024 showed TRAP’s substoichiometric association with multipass translocons and higher abundance on non‑translating ribosome–MPTs; luminal TRAP contacts bridge to back‑of‑Sec61 factors, supporting a modular assembly that adapts to translational state (Gemmer 2024, 12 Jun 2024, https://doi.org/10.26508/lsa.202302496) (gemmer2024exploringthemolecular pages 1-3).
- Mechanistic implications: Together, these studies substantiate that TRAP-α’s luminal domain is spatially poised to influence nascent chain handling and N‑glycosylation, while its TM helix and complex interfaces modulate Sec61 conformation and the local membrane to expand the repertoire of efficiently translocated substrates (Pauwels 2023; Karki 2023) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3, karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5).
Current applications and real-world implementations
- Translocon inhibitors: Pauwels 2023 identified the cyclotriazadisulfonamide derivative CK147 as a Sec61 inhibitor that binds near the lumenal plug; resistance mutations cluster around the lateral gate/plug. This provides a structural foothold for rational design of translocon inhibitors with potential antiviral or anticancer applications (Science Advances, 3 Mar 2023, https://doi.org/10.1126/sciadv.adf0797) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3).
- Host dependency in viral infection: Genetic and mechanistic studies indicate that ER translocon modules (including TRAP subunits SSR1–SSR4) are host factors for flaviviruses; comprehensive CRISPR screens and recent reviews highlight reliance on the mammalian translocon for dengue/Zika replication and ER processes (Marceau et al., Nature, 22 Jun 2016, https://doi.org/10.1038/nature18631; Verhaegen & Vermeire, npj Viruses, 6 Jun 2024, https://doi.org/10.1038/s44298-024-00031-7) (, ). These insights motivate host-directed antiviral strategies targeting translocon/OST modules.
- Endocrine relevance: Building on 2021–2023 evidence that SSR1/TRAP‑α affects insulin biogenesis, recent mechanistic work indicates that TRAP-α supports preproinsulin translocation and early folding steps, linking TRAP function to glycemic control; this provides a conceptual framework for potential biomarkers/interventions in metabolic disease (Karki 2023, EMBO Reports, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 5-7, karki2023molecularviewof pages 1-2).
Expert perspectives and authoritative syntheses
- A focused review (Russo 2020) consolidates the view of TRAP (including TRAP‑α/SSR1) as a substrate‑selective facilitator in co‑translational translocation, located to couple with OST and influence ERQC/UPR, anticipating the detailed structural confirmations published in 2023–2024 (Open Biology, 20 May 2020, https://doi.org/10.1098/rsob.190244) (russo2020understandingthemammalian pages 5-6).
- A 2024 native-membrane structural analysis (Gemmer 2024) argues for dynamic association of TRAP with multipass translocons and variable stoichiometry depending on translation state, shaping current models of how accessory factors tune ER translocation in situ (Life Science Alliance, 12 Jun 2024, https://doi.org/10.26508/lsa.202302496) (gemmer2024exploringthemolecular pages 1-3).
- A 2024 virology review (Verhaegen & Vermeire) frames TRAP within the ER hub exploited across the flavivirus lifecycle and discusses ER‑targeting antiviral strategies, underscoring translational relevance (npj Viruses, 6 Jun 2024, https://doi.org/10.1038/s44298-024-00031-7) ().
Relevant statistics and data
- Structural resolutions and architecture: Pauwels 2023 resolved ribosome–Sec61–TRAP architecture and a seven‑helix TM bundle positioning luminal TRAP-α/β/δ; CK147 binding site mapped at the Sec61 plug/lateral gate region (Science Advances, 3 Mar 2023, https://doi.org/10.1126/sciadv.adf0797) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3). Karki 2023 provided a high‑resolution ribosome‑bound Sec61/TRAP map and multi‑microsecond MD showing local ER membrane thinning/curvature and lipid disorder increases near TRAP (EMBO Reports, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 5-7, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5).
- Translational-state dependence: Cryo‑ET indicates TRAP is substoichiometric within multipass translocons and most abundant in complexes with non‑translating ribosomes, implying regulated engagement with MPTs (Gemmer 2024, 12 Jun 2024, https://doi.org/10.26508/lsa.202302496) (gemmer2024exploringthemolecular pages 1-3).
- Substrate class: Across studies, TRAP dependence associates with signal peptides of lower hydrophobicity and higher Gly/Pro content, consistent with a role in enabling otherwise inefficient Sec61 gating and nascent chain handling (Pauwels 2023; Gemmer 2024; Russo 2020) (pauwels2023structuralinsightsinto pages 1-2, gemmer2024exploringthemolecular pages 1-3, russo2020understandingthemammalian pages 5-6).
Human disease links
- Congenital disorders of glycosylation (CDG): Germline mutations in TRAP subunits produce glycosylation phenotypes, mechanistically consistent with TRAP’s spatial coupling to OST and role in early translocation (Karki 2023, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 1-2).
- Infection biology: TRAP components are host dependency factors for dengue/Zika and related flaviviruses, with genetic screens and reviews implicating mammalian translocon function in viral RNA replication complexes (Marceau 2016, 22 Jun 2016, https://doi.org/10.1038/nature18631; Verhaegen 2024, 6 Jun 2024, https://doi.org/10.1038/s44298-024-00031-7) (, ).
- Endocrine/metabolic disease: TRAP‑α supports preproinsulin translocation; perturbation compromises insulin biogenesis and can contribute to ER stress in β cells, suggesting mechanistic ties to dysglycemia (Karki 2023, EMBO Reports, 20 Nov 2023, https://doi.org/10.15252/embr.202357910) (karki2023molecularviewof pages 5-7, karki2023molecularviewof pages 1-2).
Concise mechanistic model
- Topology: TRAP-α is a single-pass ER glycoprotein with a luminal N‑terminal domain and a diagonal TM helix packing against Sec61 (Karki 2023) (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 3-5).
- Assembly: In the ribosome–Sec61–TRAP supercomplex, TRAP-γ anchors to rRNA and rpL38 and packs with α/β/δ helices; TRAP‑α/β/δ luminal domains form a crescent under Sec61’s luminal exit (Pauwels 2023) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3).
- Function: TRAP-α helps stabilize the ribosome exit tunnel and modulates Sec61 gating within a locally remodeled ER membrane, enabling efficient co‑translational translocation and coupling to OST for N‑glycosylation—particularly benefitting substrates with weak/atypical signal peptides (Karki 2023; Pauwels 2023; Gemmer 2024) (karki2023molecularviewof pages 5-7, pauwels2023structuralinsightsinto pages 1-2, gemmer2024exploringthemolecular pages 1-3).
Embedded key sources (with URLs and dates)
| Year | Citation (first author et al., journal) | Topic focus | Key finding(s) relevant to SSR1/TRAP-α (citation) | URL | Publication date (month/year) |
|------:|----------------------------------------|-------------|--------------------------------------------------|-----|----------------------------|
| 2023 | Pauwels et al., Science Advances | Cryo-EM of ribosome–Sec61–TRAP; translocon inhibition | Defines heterotetrameric TRAP architecture; positions TRAP-α (SSR1) lumenal trimer adjacent to Sec61 exit and a TM helix contacting Sec61; identifies CK147 binding site on Sec61 (translocon inhibitor) (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3) | https://doi.org/10.1126/sciadv.adf0797 | Mar/2023 |
| 2023 | Karki et al., EMBO Reports | Cryo-EM/MD of Sec61/TRAP; membrane remodeling; preproinsulin dependence | Atomic/modeling view of Sec61–TRAP–ribosome showing TRAP-α lumenal domain below Sec61 exit, ribosome anchoring, and TRAP-driven local ER membrane thinning/curvature that facilitates insertion of weak signal peptides; TRAP-α required for efficient preproinsulin translocation (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 5-7) | https://doi.org/10.15252/embr.202357910 | Nov/2023 |
| 2024 | Gemmer et al., Life Science Alliance | Cryo-ET of multipass translocon in native ER membranes | Subtomogram averages reveal compositional variability of multipass translocon; TRAP associates substoichiometrically and is enriched in non-translating ribosome-bound MPTs; luminal TRAP contacts a back-of-Sec61 subunit, supporting TRAP-α role in SP handling and coordination with OST (gemmer2024exploringthemolecular pages 1-3) | https://doi.org/10.26508/lsa.202302496 | Jun/2024 |
| 2020 | Russo et al., Open Biology (review) | Review of mammalian TRAP functions; ERQC/UPR links | Synthesizes functional evidence that TRAP (including SSR1/TRAP‑α) is a substrate‑selective co‑translational facilitator for weak/hydrophilic signal peptides, influences topology/insertion, and is positioned to coordinate with OST and ER‑quality control (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.1098/rsob.190244 | May/2020 |
| 2017 | Pfeffer et al., Nature Communications | Molecular organization of the TRAP complex | Assigned positions of TRAP subunits within native translocon structures; established TRAP as integral Sec61 accessory that helps regulate signal peptide insertion and topology (see Pfeffer et al.; foundational architecture referenced in later cryo-EM work) (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.1038/ncomms14516 | Feb/2017 |
Table: Concise table of authoritative recent and foundational publications describing SSR1 (TRAP‑α) structure and function, with URLs, dates, and context‑ID citations for the evidence used.
Notes on symbol ambiguity
- The symbol SSR1 is used in oncology literature for unrelated targets; here, all cited structural and mechanistic works explicitly define SSR1 as TRAP‑α/signal sequence receptor subunit α in Homo sapiens and place it in the TRAP complex with SSR2–SSR4, consistent with UniProt P43307 (Pauwels 2023; Karki 2023) (pauwels2023structuralinsightsinto pages 1-2, karki2023molecularviewof pages 1-2).
References (with direct links and publication dates)
- Pauwels E. et al. Structural insights into TRAP association with ribosome–Sec61 complex and translocon inhibition by a CADA derivative. Science Advances. 3 Mar 2023. https://doi.org/10.1126/sciadv.adf0797 (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3).
- Karki S. et al. Molecular view of ER membrane remodeling by the Sec61/TRAP translocon. EMBO Reports. 20 Nov 2023. https://doi.org/10.15252/embr.202357910 (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 5-7, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5).
- Gemmer M. et al. Exploring the molecular composition of the multipass translocon in its native membrane environment. Life Science Alliance. 12 Jun 2024. https://doi.org/10.26508/lsa.202302496 (gemmer2024exploringthemolecular pages 1-3).
- Russo A. Understanding the mammalian TRAP complex function(s). Open Biology. 20 May 2020. https://doi.org/10.1098/rsob.190244 (russo2020understandingthemammalian pages 5-6).
- Verhaegen M., Vermeire K. The ER: a crucial cellular hub in flavivirus infection and potential target site for antiviral interventions. npj Viruses. 6 Jun 2024. https://doi.org/10.1038/s44298-024-00031-7 ().
- Marceau C.D. et al. Genetic dissection of Flaviviridae host factors through genome-scale CRISPR screens. Nature. 22 Jun 2016. https://doi.org/10.1038/nature18631 ().
References
(pauwels2023structuralinsightsinto pages 1-2): Eva Pauwels, Neesha R. Shewakramani, Brent De Wijngaert, Anita Camps, Becky Provinciael, Joren Stroobants, Kai-Uwe Kalies, Enno Hartmann, Piet Maes, Kurt Vermeire, and Kalyan Das. Structural insights into trap association with ribosome-sec61 complex and translocon inhibition by a cada derivative. Science Advances, Mar 2023. URL: https://doi.org/10.1126/sciadv.adf0797, doi:10.1126/sciadv.adf0797. This article has 36 citations and is from a highest quality peer-reviewed journal.
(pauwels2023structuralinsightsinto pages 2-3): Eva Pauwels, Neesha R. Shewakramani, Brent De Wijngaert, Anita Camps, Becky Provinciael, Joren Stroobants, Kai-Uwe Kalies, Enno Hartmann, Piet Maes, Kurt Vermeire, and Kalyan Das. Structural insights into trap association with ribosome-sec61 complex and translocon inhibition by a cada derivative. Science Advances, Mar 2023. URL: https://doi.org/10.1126/sciadv.adf0797, doi:10.1126/sciadv.adf0797. This article has 36 citations and is from a highest quality peer-reviewed journal.
(karki2023molecularviewof pages 1-2): Sudeep Karki, Matti Javanainen, Shahid Rehan, Dale Tranter, Juho Kellosalo, Juha T Huiskonen, Lotta Happonen, and Ville Paavilainen. Molecular view of
(karki2023molecularviewof pages 2-3): Sudeep Karki, Matti Javanainen, Shahid Rehan, Dale Tranter, Juho Kellosalo, Juha T Huiskonen, Lotta Happonen, and Ville Paavilainen. Molecular view of
(russo2020understandingthemammalian pages 5-6): Antonietta Russo. Understanding the mammalian trap complex function(s). Open Biology, 10:190244, May 2020. URL: https://doi.org/10.1098/rsob.190244, doi:10.1098/rsob.190244. This article has 28 citations and is from a peer-reviewed journal.
(karki2023molecularviewof pages 3-5): Sudeep Karki, Matti Javanainen, Shahid Rehan, Dale Tranter, Juho Kellosalo, Juha T Huiskonen, Lotta Happonen, and Ville Paavilainen. Molecular view of
(gemmer2024exploringthemolecular pages 1-3): Max Gemmer, Marten L. Chaillet, and Friedrich Förster. Exploring the molecular composition of the multipass translocon in its native membrane environment. Life Science Alliance, 7:e202302496, Jun 2024. URL: https://doi.org/10.26508/lsa.202302496, doi:10.26508/lsa.202302496. This article has 12 citations and is from a peer-reviewed journal.
(karki2023molecularviewof pages 5-7): Sudeep Karki, Matti Javanainen, Shahid Rehan, Dale Tranter, Juho Kellosalo, Juha T Huiskonen, Lotta Happonen, and Ville Paavilainen. Molecular view of
Full review is present and marked complete. The local review supports SSR1/TRAP-alpha as an ER membrane component of the translocon-associated protein complex, associated with Sec61 and ribosome-bound translocons during co-translational protein targeting/translocation. The review modifies broad or misleading protein binding and post-translational-translocation annotations toward GO:0140597 protein localization to ribosome-translocon complex and GO:0006613 cotranslational protein targeting to membrane. [file:human/SSR1/SSR1-ai-review.yaml; PMID:36697828]
PN curation conclusion: the PN placement under ER proteostasis > Protein transport > TRAP complex component is a strong positive control. Broad PN projection to GO:0015031 protein transport is entailed by the more specific local translocation annotations and should be treated as confirmatory rather than a novel gene-review change.
local_review_complete_not_phase1. PN placement: ER proteostasis > Protein transport > TRAP complex component. Main issue: Good example where PN context is compatible with existing ER targeting/translocation GO termsNo phase-1 dossier exists for this priority-only gene. This note preserves the current PROTEOSTASIS boundary or exception decision and should be superseded by a dossier section if the gene is promoted into a full phase-1 batch.
This file is generated from the current PROTEOSTASIS priority table, PN projection outputs, and local gene-review artifacts. Edit those source records rather than this generated note when correcting the underlying curation.
id: P43307
gene_symbol: SSR1
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:9606
label: Homo sapiens
description: SSR1 encodes Translocon-associated protein subunit alpha
(TRAP-alpha), a single-pass type I ER membrane glycoprotein that is a core
component of the heterotetrameric TRAP complex (TRAP-alpha/beta/gamma/delta,
encoded by SSR1-4). The TRAP complex stably associates with the Sec61
protein-conducting channel and ribosomes at the ER membrane, facilitating
co-translational translocation of secretory and membrane proteins,
particularly those with weak or atypical signal peptides. TRAP-alpha features
a large N-terminal luminal domain positioned beneath the Sec61 channel exit
site and a single long transmembrane helix that contacts Sec61. The complex
coordinates with the oligosaccharyltransferase (OST) to couple translocation
with N-glycosylation. TRAP-alpha also participates in ER quality control and
ERAD pathways.
existing_annotations:
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: IBA
original_reference_id: GO_REF:0000033
review:
summary: IBA annotation for ER localization based on phylogenetic
inference from PANTHER. TRAP-alpha is well-established as an ER-resident
protein across eukaryotes. Recent cryo-EM structures confirm TRAP as a
core ER translocon component [SSR1-deep-research-falcon.md].
action: ACCEPT
reason: Core localization annotation. TRAP-alpha is definitively an ER
membrane protein. The IBA annotation is well-supported by extensive
structural and biochemical evidence showing TRAP-alpha as a core
component of the ER translocon complex [Pauwels et al. 2023; Karki et
al. 2023; PMID:36697828].
supported_by:
- reference_id: PMID:8050590
supporting_text: "The alpha-subunit of the TRAP complex (TRAP alpha) is
a single-spanning membrane protein of the endoplasmic reticulum (ER) which
is found in proximity of nascent polypeptide chains translocating across
the membrane."
- reference_id: file:human/SSR1/SSR1-deep-research-falcon.md
supporting_text: 'model: Edison Scientific Literature'
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: IEA
original_reference_id: GO_REF:0000120
review:
summary: IEA annotation based on InterPro TRAP_alpha domain and UniProt
subcellular location annotation. This is the specific membrane
localization.
action: ACCEPT
reason: Core localization annotation. TRAP-alpha is a single-pass type I
membrane protein anchored in the ER membrane. UniProt confirms this
topology with a luminal N-terminal domain and cytoplasmic C-terminus.
Structural studies confirm ER membrane integration [PMID:36697828].
supported_by:
- reference_id: PMID:36697828
supporting_text: "near-complete atomic model of the most abundant ER translocon
variant comprising the protein-conducting channel SEC61, TRAP and the
oligosaccharyltransferase complex A (OSTA) reveals specific interactions
of TRAP with other translocon components"
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:17380188
review:
summary: IPI annotation based on interaction with
SERPINA1/alpha1-antitrypsin, calnexin (CANX), and SEC61B detected in the
context of ER stress and ERAD studies.
action: MODIFY
reason: While the protein binding annotation reflects genuine
interactions, it is uninformative. The study shows TRAP complex
involvement in ERAD and interaction with misfolded substrates like
alpha1-antitrypsin NHK variant. A more specific term capturing the
functional interaction would be appropriate.
proposed_replacement_terms:
- id: GO:0140597
label: protein localization to ribosome-translocon complex
additional_reference_ids:
- PMID:17380188
supported_by:
- reference_id: PMID:17380188
supporting_text: "The TRAP complex bound preferentially to misfolded proteins
rather than correctly folded wild-type substrates. Thus, the TRAP complex
induced by the unfolded protein response pathway might discriminate ERAD
substrates from correctly folded substrates, accelerating degradation."
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:22314232
review:
summary: IPI annotation for interaction with palmitoylated calnexin
(CANX). The study demonstrates calnexin association with the
ribosome-translocon complex including TRAP components.
action: MODIFY
reason: The protein binding term is too generic. The interaction with
calnexin is functionally significant - palmitoylated calnexin associates
with the ribosome-translocon complex to facilitate glycoprotein folding.
A more specific MF term should be used.
proposed_replacement_terms:
- id: GO:0140597
label: protein localization to ribosome-translocon complex
supported_by:
- reference_id: PMID:22314232
supporting_text: "Palmitoylation mediates the association of calnexin with
the ribosome-translocon complex (RTC) leading to the formation of a supercomplex
that recruits the actin cytoskeleton, leading to further stabilization
of the assembly."
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:29568061
review:
summary: IPI annotation for interaction with calnexin detected by AP-MS
and BioID proximity labeling methods.
action: MODIFY
reason: High-throughput interaction study confirming calnexin-TRAP
association. The generic protein binding term is uninformative - should
be captured by more specific translocon-related terms.
proposed_replacement_terms:
- id: GO:0140597
label: protein localization to ribosome-translocon complex
supported_by:
- reference_id: PMID:29568061
supporting_text: An AP-MS- and BioID-compatible MAC-tag enables
comprehensive mapping of protein interactions and subcellular
localizations.
- term:
id: GO:0005515
label: protein binding
evidence_type: IPI
original_reference_id: PMID:35271311
review:
summary: IPI annotation from OpenCell study detecting interactions with
calnexin and SEC61B via endogenous tagging.
action: MODIFY
reason: High-throughput proteomics confirming established TRAP complex
interactions. The generic protein binding is uninformative for
understanding function. These represent structural associations within
the translocon complex.
proposed_replacement_terms:
- id: GO:0140597
label: protein localization to ribosome-translocon complex
supported_by:
- reference_id: PMID:35271311
supporting_text: '2022 Mar 11. OpenCell: Endogenous tagging for the cartography
of human cellular organization.'
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: IEA
original_reference_id: GO_REF:0000107
review:
summary: IEA annotation transferred from mouse ortholog via Ensembl
Compara.
action: ACCEPT
reason: Redundant with IBA annotation but correct. ER localization is core
to TRAP-alpha function and well-conserved across mammals.
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: IDA
original_reference_id: GO_REF:0000052
review:
summary: IDA annotation based on Human Protein Atlas immunofluorescence
data.
action: ACCEPT
reason: Direct experimental evidence for ER localization. HPA
immunofluorescence confirms ER residence of SSR1/TRAP-alpha.
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: NAS
original_reference_id: PMID:36697828
review:
summary: NAS annotation from ComplexPortal based on cryo-ET structural
study visualizing the SEC61-TRAP-OSTA translocon complex.
action: ACCEPT
reason: Core localization. The structural study provides near-atomic
resolution of TRAP within the ER membrane translocon complex [Gemmer et
al. 2023].
supported_by:
- reference_id: PMID:36697828
supporting_text: "An AlphaFold-based model of TRAP could be fitted unambiguously
into the SEC61-OSTA-TRAP translocon map, requiring only minor repositioning
of single transmembrane helices"
- term:
id: GO:0031204
label: post-translational protein targeting to membrane, translocation
evidence_type: NAS
original_reference_id: PMID:36697828
review:
summary: NAS annotation from ComplexPortal. However, this term refers to
post-translational translocation, whereas TRAP is primarily involved in
co-translational translocation.
action: MODIFY
reason: The term is inaccurate. TRAP/SSR1 is primarily involved in
co-translational protein targeting, not post-translational. The
structural study and all functional evidence show TRAP associating with
translating ribosomes at the ER. Should be replaced with
co-translational targeting term.
proposed_replacement_terms:
- id: GO:0006613
label: cotranslational protein targeting to membrane
supported_by:
- reference_id: PMID:36697828
supporting_text: "The dynamic ribosome-translocon complex, which resides
at the endoplasmic reticulum (ER) membrane, produces a major fraction
of the human proteome"
- term:
id: GO:0005789
label: endoplasmic reticulum membrane
evidence_type: TAS
original_reference_id: Reactome:R-HSA-1791164
review:
summary: TAS annotation from Reactome pathway "Expression of SSR1 (Trap
alpha)" indicating ER membrane localization.
action: ACCEPT
reason: Core localization annotation. Reactome pathway information is
consistent with established TRAP-alpha function.
- term:
id: GO:0005783
label: endoplasmic reticulum
evidence_type: TAS
original_reference_id: PMID:8050590
review:
summary: TAS annotation from original characterization paper describing
TRAP-alpha as an ER protein.
action: ACCEPT
reason: Primary literature confirming ER localization. This paper
established the widespread conservation of TRAP-alpha in eukaryotes.
supported_by:
- reference_id: PMID:8050590
supporting_text: "The alpha-subunit of the TRAP complex (TRAP alpha) is
a single-spanning membrane protein of the endoplasmic reticulum (ER) which
is found in proximity of nascent polypeptide chains translocating across
the membrane."
- term:
id: GO:0006613
label: cotranslational protein targeting to membrane
evidence_type: TAS
original_reference_id: PMID:8050590
review:
summary: TAS annotation indicating involvement in co-translational protein
targeting based on the original characterization.
action: ACCEPT
reason: Core function annotation. TRAP-alpha is established as a component
of the ribosome-translocon complex facilitating co-translational
translocation of nascent polypeptides into the ER.
supported_by:
- reference_id: PMID:8050590
supporting_text: "The alpha-subunit of the TRAP complex (TRAP alpha) is
a single-spanning membrane protein of the endoplasmic reticulum (ER) which
is found in proximity of nascent polypeptide chains translocating across
the membrane."
- term:
id: GO:0008284
label: positive regulation of cell population proliferation
evidence_type: TAS
original_reference_id: PMID:10437777
review:
summary: TAS annotation based on observation that TRAP-alpha transcripts
are induced by GM-CSF and more abundant in growing vs quiescent cells.
action: KEEP_AS_NON_CORE
reason: This is a pleiotropic effect rather than a core function. The
study shows TRAP-alpha mRNA is upregulated in proliferating cells
stimulated by GM-CSF, but this reflects increased demand for protein
secretion capacity rather than direct regulation of proliferation.
TRAP-alpha's primary function is in protein translocation, not
proliferation control.
supported_by:
- reference_id: PMID:10437777
supporting_text: "Its messenger RNA was more abundant in growing cells than
in either factor-deprived cells or quiescent cells"
- term:
id: GO:0016020
label: membrane
evidence_type: TAS
original_reference_id: PMID:8050590
review:
summary: TAS annotation for generic membrane localization.
action: MARK_AS_OVER_ANNOTATED
reason: Too general. GO:0005789 (endoplasmic reticulum membrane) is more
specific and accurate for TRAP-alpha localization. This generic term
adds no additional information.
supported_by:
- reference_id: PMID:8050590
supporting_text: The N-terminal region of the alpha-subunit of the
TRAP complex has a conserved cluster of negative charges.
- term:
id: GO:0036503
label: ERAD pathway
evidence_type: TAS
original_reference_id: PMID:17380188
review:
summary: Proposed new annotation based on evidence that TRAP complex
participates in ERAD by preferentially binding misfolded proteins.
action: NEW
reason: TRAP complex is induced by ER stress and preferentially binds
misfolded proteins, facilitating their degradation via ERAD. This
represents an additional function beyond co-translational translocation.
supported_by:
- reference_id: PMID:17380188
supporting_text: "The TRAP complex bound preferentially to misfolded proteins
rather than correctly folded wild-type substrates. Thus, the TRAP complex
induced by the unfolded protein response pathway might discriminate ERAD
substrates from correctly folded substrates, accelerating degradation."
references:
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000052
title: Gene Ontology annotation based on curation of immunofluorescence data
findings: []
- id: GO_REF:0000107
title: Automatic transfer of experimentally verified manual GO annotation
data to orthologs using Ensembl Compara
findings: []
- id: GO_REF:0000120
title: Combined Automated Annotation using Multiple IEA Methods
findings: []
- id: PMID:8050590
title: The N-terminal region of the alpha-subunit of the TRAP complex has a
conserved cluster of negative charges.
findings:
- statement: TRAP-alpha is a single-spanning ER membrane protein found in
proximity to nascent polypeptides during translocation
- statement: Conservation across eukaryotes (human, fish, plants) with
preserved charge distribution and glycosylation sites
- id: PMID:10437777
title: Translocon-associated protein alpha transcripts are induced by
granulocyte-macrophage colony-stimulating factor and exhibit complex
alternative polyadenylation.
findings:
- statement: TRAP-alpha mRNA is upregulated by GM-CSF
- statement: Higher expression in proliferating vs quiescent cells
- statement: Gene located on chromosome 6
- id: PMID:17380188
title: Simultaneous induction of the four subunits of the TRAP complex by ER
stress accelerates ER degradation.
findings:
- statement: All four TRAP subunits induced by ER stress via
XBP1/IRE1alpha pathway
- statement: TRAP complex associates with ERAD substrates at late stage
- statement: Preferential binding to misfolded proteins over correctly
folded substrates
- statement: TRAP involved in ERAD pathway, not just nascent polypeptide
biosynthesis
- id: PMID:22314232
title: Palmitoylated calnexin is a key component of the ribosome-translocon
complex.
findings:
- statement: Palmitoylated calnexin associates with ribosome-translocon
complex (RTC) including TRAP
- statement: This supercomplex formation is essential for glycoprotein
folding
- id: PMID:29568061
title: An AP-MS- and BioID-compatible MAC-tag enables comprehensive mapping
of protein interactions and subcellular localizations.
findings:
- statement: Confirmed TRAP-alpha interaction with calnexin by proximity
labeling
- id: PMID:35271311
title: 'OpenCell: Endogenous tagging for the cartography of human cellular organization.'
findings:
- statement: High-throughput proteomics confirming SSR1 interactions with
calnexin and SEC61B
- id: PMID:36697828
title: Visualization of translation and protein biogenesis at the ER
membrane.
findings:
- statement: Near-atomic resolution cryo-ET structure of SEC61-TRAP-OSTA
translocon complex
- statement: TRAP present in both signal peptide and multipass translocon
variants
- statement: AlphaFold model of TRAP fits structural density
- statement: TRAP makes specific interactions with SEC61 and OSTA within
the translocon
- id: Reactome:R-HSA-1791164
title: Expression of SSR1 (Trap alpha)
findings:
- statement: Basic gene expression pathway for SSR1
- id: file:human/SSR1/SSR1-deep-research-falcon.md
title: Deep research review of SSR1
findings:
- statement: TRAP-alpha is the alpha subunit of the ER-resident TRAP
complex that stably associates with the Sec61 protein-conducting
channel and the ribosome
- statement: TRAP assists co-translational translocation of secretory and
membrane proteins, especially those with weak or atypical signal
peptides
- statement: Cryo-EM structures show TRAP-alpha contains a prominent
luminal domain positioned directly beneath the Sec61alpha channel exit
and a long, diagonal transmembrane helix
core_functions:
- description: Core component of the ribosome-translocon complex facilitating
co-translational translocation of nascent polypeptides
molecular_function:
id: GO:0005515
label: protein binding
directly_involved_in:
- id: GO:0006613
label: cotranslational protein targeting to membrane
- id: GO:0036503
label: ERAD pathway
locations:
- id: GO:0005789
label: endoplasmic reticulum membrane
supported_by:
- reference_id: PMID:36697828
supporting_text: "near-complete atomic model of the most abundant ER translocon
variant comprising the protein-conducting channel SEC61, TRAP and the oligosaccharyltransferase
complex A (OSTA) reveals specific interactions of TRAP with other translocon
components"
- reference_id: PMID:8050590
supporting_text: "The alpha-subunit of the TRAP complex (TRAP alpha) is a
single-spanning membrane protein of the endoplasmic reticulum (ER) which
is found in proximity of nascent polypeptide chains translocating across
the membrane."
proposed_new_terms: []
suggested_questions:
- question: What is the precise mechanism by which TRAP-alpha recognizes and
assists translocation of substrates with weak signal peptides?
- question: Does TRAP-alpha have substrate specificity or does it function
equivalently for all translocon-dependent substrates?
- question: What is the functional significance of TRAP-alpha phosphorylation
at Ser-268 during mitosis?
suggested_experiments:
- description: Structure-function studies with TRAP-alpha luminal domain
mutants to determine residues critical for nascent chain interaction
- description: Quantitative proteomics comparing translocation efficiency of
defined substrates in TRAP-knockdown vs control cells
- description: Investigation of TRAP-alpha post-translational modifications
and their regulation during cell cycle or ER stress