Proposed New Ontology Terms

TRAP complex

Definition: A heterotetrameric protein complex composed of TRAP-alpha (SSR1), TRAP-beta (SSR2), TRAP-gamma (SSR3), and TRAP-delta (SSR4) subunits that associates with the Sec61 translocon at the endoplasmic reticulum membrane. The TRAP complex facilitates co-translational protein translocation, particularly for substrates with weak or suboptimal signal peptides.

Justification: There is currently no specific GO term for the translocon-associated protein (TRAP) complex. This heterotetrameric complex (SSR1-4/TRAP-alpha,beta,gamma,delta) is distinct from the Sec61 translocon core and functions as a co-factor for protein translocation. A dedicated cellular component term would improve annotation precision for all TRAP subunit genes. Note that ComplexPortal CPX-8024 ("Translocon-associated protein complex") already captures this complex and is cited in the UniProt record; the GO request should reference CPX-8024 as supporting evidence for the complex's existence and composition.

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0005783 endoplasmic reticulum	IEA GO_REF:0000002	ACCEPT	Summary: This IEA annotation is derived from InterPro domain mapping (IPR008856 TRAP_beta). SSR2/TRAP-beta is well-established as an ER-resident protein. The protein is part of the TRAP complex that associates with the Sec61 translocon at the ER membrane [file:human/SSR2/SSR2-deep-research-falcon.md]. Reason: Accurate annotation. SSR2 is an integral ER membrane protein as part of the TRAP complex. The InterPro-based inference is consistent with extensive experimental evidence showing ER localization [PMID:7789174, PMID:36697828]. Supporting Evidence: PMID:7789174 We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene, which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane. file:human/SSR2/SSR2-deep-research-falcon.md [Deep research confirms] SSR2 encodes TRAP-beta (signal sequence receptor subunit beta) ... predominantly resides in the endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane	IEA GO_REF:0000044	ACCEPT	Summary: This IEA annotation is based on UniProt subcellular location vocabulary mapping. SSR2 is an integral ER membrane protein with a single transmembrane helix. UniProt records: "Endoplasmic reticulum membrane; Single-pass type I membrane protein." Reason: Accurate and well-supported annotation. SSR2/TRAP-beta has type I topology (N lumen, C cytosol) with a single transmembrane helix embedded in the ER membrane [file:human/SSR2/SSR2-deep-research-falcon.md]. Cryo-EM structures confirm this localization [PMID:36697828]. Supporting Evidence: PMID:36697828 An AlphaFold-based model of TRAP could be fitted unambiguously into the SEC61-OSTA-TRAP translocon map
GO:0016020 membrane	IEA GO_REF:0000002	MARK AS OVER ANNOTATED	Summary: This IEA annotation is derived from InterPro domain mapping. While correct that SSR2 is a membrane protein, this term is too general compared to the more specific GO:0005789 (endoplasmic reticulum membrane) annotation that is also present. Reason: GO:0005789 (endoplasmic reticulum membrane) is already annotated and is strictly more specific. GO:0016020 is redundant given that more precise localization information is captured by the ER-membrane term; best-practice curation flags such general terms as over-annotations when a specific child is present. Supporting Evidence: PMID:7789174 which codes for an endoplasmic reticulum (ER) membrane protein
GO:0005515 protein binding	IPI PMID:18724357 STING is an endoplasmic reticulum adaptor that facilitates i...	MARK AS OVER ANNOTATED	Summary: This IPI annotation is based on the interaction between SSR2/TRAP-beta and STING1, demonstrated by yeast two-hybrid screening and co-immunoprecipitation in PMID:18724357. The study identified SSR2 as a STING1 interactor and showed that TRAP-beta ablation reduced STING's ability to induce interferon-beta. Reason: The evidence for this IPI record is the STING1 interaction (WITH Q86WV6, PMID:18724357, yeast-two-hybrid plus co-IP). The interaction is experimentally real but its biological significance is uncertain; the paper frames it as the translocon potentially influencing STING-mediated innate signalling, not as a core SSR2 function. Substituting GO:0106138 (Sec61 translocon complex binding) as the replacement term would swap in a different molecular partner unsupported by this IPI evidence record. MARK_AS_OVER_ANNOTATED is the appropriate disposition: protein binding is non-informative and this specific STING1 interaction is peripheral to SSR2's core role. GO:0106138 is retained in core_functions, supported by structural co-complex evidence (PMID:36697828). Supporting Evidence: PMID:18724357 we screened an IFN-induced, human fibroblast yeast two-hybrid cDNA library using STING (amino acids 173-379) as a bait and repeatedly isolated Ssr2/TRAPbeta, a member of the TRAP complex comprising four subunits (alpha-delta) that facilitates translocation of proteins into the ER following translation PMID:18724357 we confirmed that TRAPbeta can indeed associate with endogenous STING in HEK 293 cells following co-immunoprecipitation experiments
GO:0106138 Sec61 translocon complex binding	IDA PMID:36697828 Visualization of translation and protein biogenesis at the E...	NEW	Summary: NEW annotation proposed to capture the direct physical association of SSR2/TRAP-beta with the Sec61 translocon, as demonstrated by cryo-electron tomography showing the near-complete atomic model of the SEC61-TRAP-OSTA complex. TRAP stably associates with Sec61 at the ER membrane. Reason: The cryo-ET study (PMID:36697828) directly visualizes the TRAP complex in stable association with Sec61 in native ER membranes, providing structural IDA-level evidence for Sec61 translocon complex binding. This is the core MF of SSR2 and should be annotated directly rather than inferred by remapping the STING1 IPI record. The co-IP data in PMID:18724357 (Sec61beta co-IP) provides additional biochemical support. Supporting Evidence: PMID:36697828 The 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:0005789 endoplasmic reticulum membrane	NAS PMID:36697828 Visualization of translation and protein biogenesis at the E...	ACCEPT	Summary: This NAS annotation is based on Gemmer et al. (2023), which used cryo-electron tomography to visualize the native ER translocon including the TRAP complex. The study provides near-complete atomic models of the SEC61-TRAP-OSTA complex at the ER membrane. Reason: This is an accurate annotation supported by high-resolution structural data. The cryo-ET study directly visualizes SSR2/TRAP-beta as an integral component of the ER membrane translocon complex [PMID:36697828]. Supporting Evidence: PMID:36697828 The 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:0031204 post-translational protein targeting to membrane, translocation	NAS PMID:36697828 Visualization of translation and protein biogenesis at the E...	REMOVE	Summary: This NAS annotation suggests SSR2/TRAP-beta is involved in post-translational protein translocation. However, the TRAP complex is primarily associated with co-translational translocation, assisting the Sec61 translocon during ribosome- associated protein synthesis and membrane insertion. Reason: GO:0031204 captures post-translational protein targeting, but the TRAP complex acts co-translationally (ribosome-bound Sec61 complexes). The correct sub-pathway term, GO:0006613 (cotranslational protein targeting to membrane), is already independently annotated from PMID:7789174. MODIFY to a term already present would produce a duplicate; REMOVE is the cleaner disposition for the incorrectly assigned sub-pathway term. Supporting Evidence: PMID:36697828 distinct polysomes bind to different ER translocons specialized in the synthesis of proteins with signal peptides or multipass transmembrane proteins with the translocon-associated protein complex (TRAP) present in both file:human/SSR2/SSR2-deep-research-falcon.md [Deep research confirms] TRAP is a heterotetramer of SSR1 (alpha), SSR2 (beta), SSR3 (gamma), SSR4 (delta) ... co-translational protein translocation
GO:0005783 endoplasmic reticulum	TAS PMID:7789174 Isolation and mapping of the human beta-signal sequence rece...	ACCEPT	Summary: This TAS annotation is based on the original cloning paper by Chinen et al. (1995) which identified SSR2 as encoding an ER membrane protein. The paper describes isolation of the human beta-signal sequence receptor gene. Reason: Accurate annotation with appropriate primary literature support. The paper explicitly describes SSR2 as encoding "an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane." Supporting Evidence: PMID:7789174 We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene, which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane.
GO:0006613 cotranslational protein targeting to membrane	TAS PMID:7789174 Isolation and mapping of the human beta-signal sequence rece...	ACCEPT	Summary: This TAS annotation captures the core function of SSR2/TRAP-beta in co-translational protein translocation. The TRAP complex associates with ribosome-Sec61 complexes and facilitates membrane targeting of nascent polypeptides, particularly those with weak or suboptimal signal peptides. Reason: This is a core function annotation. SSR2 as part of the TRAP complex is directly involved in co-translational protein translocation at the ER membrane. Recent cryo-EM studies confirm that TRAP is consistently present in the co-translational translocon and modulates Sec61 function for challenging substrates [PMID:36697828; file:human/SSR2/SSR2-deep-research-falcon.md]. Supporting Evidence: PMID:7789174 which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane
GO:0016020 membrane	TAS PMID:7789174 Isolation and mapping of the human beta-signal sequence rece...	MARK AS OVER ANNOTATED	Summary: This TAS annotation based on PMID:7789174 indicates SSR2 is a membrane protein. This is accurate but less specific than GO:0005789 (ER membrane) which is also annotated from the same reference. Reason: GO:0005789 (endoplasmic reticulum membrane) is annotated from the same reference and is more informative. GO:0016020 is a redundant parent term; retaining only the specific child term is consistent with curation best practice. Supporting Evidence: PMID:7789174 which codes for an endoplasmic reticulum (ER) membrane protein

Core Functions

SSR2/TRAP-beta is a component of the TRAP complex that associates with the Sec61 translocon during co-translational protein translocation. The complex assists in membrane targeting and insertion of nascent polypeptides with weak or suboptimal signal peptides [PMID:7789174; PMID:36697828].

Molecular Function:

Sec61 translocon complex binding

Directly Involved In:

cotranslational protein targeting to membrane

Cellular Locations:

endoplasmic reticulum membrane

Supporting Evidence:

PMID:7789174
which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane
PMID:36697828
The 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.

References

GO_REF:0000002

Gene Ontology annotation through association of InterPro records with GO terms

GO_REF:0000044

Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location Vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt

PMID:18724357

STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.

Yeast two-hybrid screening identified SSR2/TRAP-beta as a STING1 interacting protein

"we screened an IFN-induced, human fibroblast yeast two-hybrid cDNA library using STING (amino acids 173-379) as a bait and repeatedly isolated Ssr2/TRAPbeta"
Co-immunoprecipitation confirmed TRAP-beta association with endogenous STING

"we confirmed that TRAPbeta can indeed associate with endogenous STING in HEK 293 cells following co-immunoprecipitation experiments"
TRAP-beta ablation reduced STING-mediated interferon-beta induction

"loss of TRAPbeta or SEC61beta reduced STING's, ability to induce an IFNbeta promoter driving luciferase"

PMID:36697828

Visualization of translation and protein biogenesis at the ER membrane.

Cryo-electron tomography visualization of native ER translocon complexes

"Here we use cryo-electron tomography, extensive classification and molecular modelling to capture snapshots of mRNA translation and protein maturation at the ER membrane"
Near-complete atomic model of SEC61-TRAP-OSTA complex

"The near-complete atomic model of the most abundant ER translocon variant comprising the protein-conducting channel SEC61, TRAP and the oligosaccharyltransferase complex A (OSTA)"
TRAP present in both signal peptide and multipass translocon variants

"distinct polysomes bind to different ER translocons specialized in the synthesis of proteins with signal peptides or multipass transmembrane proteins with the translocon-associated protein complex (TRAP) present in both"

PMID:7789174

Isolation and mapping of the human beta-signal sequence receptor gene (SSR2).

Original cloning of human SSR2 cDNA

"We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene"
Identified SSR2 as encoding ER membrane protein involved in translocation

"which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane"
Mapped SSR2 to chromosome 1q21-q23

"We also localized the human beta-signal sequence receptor gene (SSR2) to chromosome bands 1q21-->q23"

file:human/SSR2/SSR2-deep-research-falcon.md

Deep research summary for SSR2/TRAP-beta

Comprehensive review of TRAP complex structure and function from recent literature
TRAP is a heterotetramer (alpha, beta, gamma, delta subunits)
TRAP-beta has type I topology with single transmembrane helix
TRAP modulates Sec61 lateral gate for weak signal peptides

Deep Research

Falcon

(SSR2-deep-research-falcon.md)

this with annotations you find in gene/protein databases, but these can be outdated or inaccurate. Falcon Edison Scientific Literature 25 citations 2025-12-26T21:30:36.231071

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 approach
We verified gene/protein identity and then synthesized recent structural and mechanistic literature (emphasizing 2023–2024 cryo-EM/ET) together with authoritative reviews to annotate human SSR2 (TRAP-β) within the ER translocon. We prioritized precise functional roles, localization/topology, pathways (Sec61/TRAP/OST), disease links, viral-host relevance, and applications, and we include URLs and publication dates.

Key concepts and definitions (current understanding)
- Identity and nomenclature: SSR2 (synonyms: TRAPB; signal sequence receptor subunit beta) encodes the β subunit of the mammalian Translocon-Associated Protein (TRAP) complex, a heterotetramer at the ER translocon. This subunit is termed TRAP‑β/SSR‑β and is an integral ER membrane protein (UniProt P43308). SSR2 is part of the canonical SSR1/SSR2/SSR3/SSR4 complex that associates with Sec61 during co-translational protein translocation (Open Biology, 2020; doi:10.1098/rsob.190244, published May 13, 2020). (russo2020understandingthemammalian pages 5-6, russo2020understandingthemammalian pages 2-4)
- Topology and family: TRAP‑β is a single-pass, type I membrane glycoprotein with an N‑lumenal domain, a single transmembrane helix, and a short cytosolic C-terminus; it belongs to the TRAP‑beta family. Structural/topological placement of β within the lumenal TRAP crescent has been resolved in human ribosome–Sec61–TRAP complexes (Science Advances, March 22, 2023; doi:10.1126/sciadv.adf0797). (russo2020understandingthemammalian pages 5-6, pauwels2023structuralinsightsinto pages 1-2)
- TRAP composition and architecture: TRAP is a heterotetramer of SSR1 (α), SSR2 (β), SSR3 (γ), SSR4 (δ). High-resolution cryo‑EM (2023) shows a seven‑TM helix bundle formed by TRAP‑γ plus one C‑terminal helix each from α/β/δ; the N‑terminal lumenal domains of α/β/δ form a crescent facing the Sec61 pore. TRAP‑γ anchors to 28S rRNA and ribosomal protein L38 and contacts Sec61α/γ, stabilizing the ribosome–Sec61–TRAP assembly (Science Advances, March 22, 2023; doi:10.1126/sciadv.adf0797). (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3)

Mechanistic role and pathways (with recent advances)
- Sec61 gating and signal-peptide selectivity: TRAP modulates Sec61 lateral-gate conformations and facilitates translocation/insertion of precursors with weak/low‑hydrophobicity or Pro/Gly‑rich signal peptides. Cryo‑EM combined with atomistic MD indicates TRAP interactions bias gate conformations favorable for these challenging clients (EMBO Reports, November 20, 2023; doi:10.15252/embr.202357910; Science Advances, March 22, 2023; doi:10.1126/sciadv.adf0797). (karki2023molecularviewof pages 2-3, pauwels2023structuralinsightsinto pages 1-2, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5)
- Coupling to N‑glycosylation (OST): TRAP frequently coexists with the oligosaccharyltransferase (OSTA) complex in the ribosome–translocon megacomplex; TRAPα’s lumenal domain lies immediately below the Sec61 pore and near OSTA, positioning nascent chains for cotranslational N‑glycosylation. Structural analyses and in situ tomography link TRAP to OST proximity and nascent‑chain handling; deficiency in TRAP subunits leads to aberrant N‑glycosylation (EMBO Reports, November 20, 2023; doi:10.15252/embr.202357910; eLife preprint, May 2, 2024; doi:10.1101/2023.12.22.572959). (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2, lewis2024structuralanalysisof pages 9-11)
- ER membrane remodeling: MD simulations and cryo‑ET reveal that the Sec61/TRAP assembly locally thins and curves the ER membrane, which may lower the energetic barrier for lateral gate opening and integration of transmembrane segments. This physical remodeling is proposed to aid insertion of weak SP/TMD clients (EMBO Reports, November 20, 2023; doi:10.15252/embr.202357910; Life Science Alliance, June 12, 2024; doi:10.26508/lsa.202302496). (karki2023molecularviewof pages 2-3, gemmer2024exploringthemolecular pages 1-3)
- Localization and interactions: TRAP is an ER-resident, ribosome-associated complex stably bound to the “back” of Sec61 with multiple TRAP–ribosome and TRAP–Sec61 contact points. TRAPα likely contacts the Sec61 hinge; TRAPβ participates in the lumenal crescent near the nascent‑chain exit (Open Biology, 2020; doi:10.1098/rsob.190244; Science Advances, March 22, 2023; doi:10.1126/sciadv.adf0797; eLife preprint, May 2, 2024; doi:10.1101/2023.12.22.572959). (russo2020understandingthemammalian pages 5-6, pauwels2023structuralinsightsinto pages 1-2, lewis2024structuralanalysisof pages 9-11)

Recent developments and latest research (2023–2024 focus)
- Atomic models of human ribosome–Sec61–TRAP resolve TRAP subunit positioning and contacts, including the seven‑helix TM bundle and a dynamic, crescent‑shaped lumenal α/β/δ core that adjusts across translation stages (Science Advances, March 22, 2023; doi:10.1126/sciadv.adf0797). (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3)
- Mechanistic hypotheses supported by cryo‑EM and MD: TRAP stabilizes the ribosome exit tunnel, prevents nascent‑chain back‑diffusion, and biases Sec61 toward a translocation‑competent state for weak signal peptides; local lipid thinning by TRAP/Sec61 complex further facilitates insertion (EMBO Reports, November 20, 2023; doi:10.15252/embr.202357910). (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5)
- Native membrane cryo‑ET reveals variable association of auxiliary factors in multipass translocons, with TRAP substoichiometric and enriched in Sec61 variants bound to non‑translating ribosomes; TRAP lumenal domains contact a “back‑of‑Sec61” factor tentatively modeled as a nodal modulator linking nicalin to TRAPα (Life Science Alliance, June 12, 2024; doi:10.26508/lsa.202302496). (gemmer2024exploringthemolecular pages 1-3)

Primary function and substrate scope
- Primary role: SSR2 (TRAP‑β) contributes to the structural core of TRAP that, together with the other subunits, assists Sec61-mediated co‑translational translocation of secretory and membrane proteins with suboptimal/weak signal peptides and helps coordinate access to OSTA for N‑glycosylation. This is a structural/adaptor role, not enzymatic catalysis (Open Biology, 2020; doi:10.1098/rsob.190244; Science Advances, 2023; doi:10.1126/sciadv.adf0797). (russo2020understandingthemammalian pages 5-6, pauwels2023structuralinsightsinto pages 1-2)
- Substrate bias: Clients with low hydrophobicity or Pro/Gly‑rich signal sequences show TRAP dependence; structural data and MD support this bias via gate-opening and membrane remodeling mechanisms (Science Advances, 2023; EMBO Reports, 2023) (pauwels2023structuralinsightsinto pages 1-2, karki2023molecularviewof pages 2-3)

Subcellular localization and topology
- SSR2 is ER membrane-resident; type I topology (N lumen, C cytosol) with a single TM helix; embedded within the TRAP lumenal crescent facing the Sec61 pore (Open Biology, 2020; doi:10.1098/rsob.190244; Science Advances, 2023; doi:10.1126/sciadv.adf0797). (russo2020understandingthemammalian pages 5-6, pauwels2023structuralinsightsinto pages 1-2)

Coupling to glycosylation machinery
- TRAP–OST coordination: In the prevalent ER translocon variant, Sec61, TRAP, and OSTA are present together; TRAP lumenal domains (especially α adjacent to β/δ) are positioned below the pore and near OSTA active sites, enabling nascent chain capture and early N‑glycosylation. In situ analyses report OSTA association in ~40–70% of complexes, while TRAP is consistently present in the major co‑translational translocon (Open Biology, 2020; eLife preprint, 2024) (russo2020understandingthemammalian pages 5-6, lewis2024structuralanalysisof pages 9-11)

Disease links and real-world implementations
- Congenital disorders of glycosylation (CDG): TRAP integrity is required for proper N‑glycosylation; loss-of-function in SSR4 (TRAP‑δ) causes a CDG phenotype with hypoglycosylation and ER stress, and destabilizes other TRAP subunits (review synthesis). Human genetic observations and structural comparisons in patient-derived contexts underscore the dependence of glycoprotein biogenesis on the intact complex (Open Biology, 2020; EMBO Reports, 2023) (russo2020understandingthemammalian pages 5-6, karki2023molecularviewof pages 2-3)
- ER stress and proteostasis: TRAP levels can be modulated during ER stress, and the complex is implicated in ER homeostasis and ERAD coupling in the ribosome-translocon complex (Open Biology, 2020; review) (russo2020understandingthemammalian pages 5-6, russo2019themammaliantransloconassociated pages 27-35)
- Viral host dependency: TRAP’s role in co‑translational translocation and glycoprotein maturation places it within pathways exploited by enveloped viruses; structural work and reviews integrate TRAP within the mammalian translocon machinery that is targeted in functional screens and by translocon inhibitors (Science Advances, 2023; review) (pauwels2023structuralinsightsinto pages 1-2, russo2020understandingthemammalian pages 1-2)

Applications: small-molecule modulation of the translocon
- Sec61 inhibitors: Cryo‑EM reveals that the cyclotriazadisulfonamide derivative CK147 binds the Sec61 channel, interacting with the plug from the lumenal side, and induces a partially open conformation; resistance mutations map around the inhibitor. These structures nominate a druggable site relevant to client‑selective inhibition strategies impacting secretory protein biogenesis (Science Advances, March 22, 2023; doi:10.1126/sciadv.adf0797). (pauwels2023structuralinsightsinto pages 1-2)

Expert opinions and integrative analyses
- Reviews emphasize TRAP as a substrate‑selective auxiliary of Sec61 that stabilizes translocation of challenging signal peptides and coordinates with OSTA, integrating co‑translational modification and quality control. Recent structural studies consolidate TRAP’s position and contacts and propose mechanistic models involving membrane thinning and ribosome‑tunnel stabilization (Open Biology, 2020; Science Advances, 2023; EMBO Reports, 2023; eLife preprint, 2024; Life Science Alliance, 2024). (russo2020understandingthemammalian pages 5-6, pauwels2023structuralinsightsinto pages 1-2, karki2023molecularviewof pages 2-3, lewis2024structuralanalysisof pages 9-11, gemmer2024exploringthemolecular pages 1-3)

Relevant statistics and quantitative data
- Coexistence frequency: In ribosome–ER translocon assemblies, OSTA is present in roughly 40–70% of complexes, whereas TRAP is consistently found in the predominant co‑translational translocon; TRAP association varies with translational state in multipass translocons (Open Biology, 2020; eLife preprint, 2024; Life Science Alliance, 2024). (russo2020understandingthemammalian pages 5-6, lewis2024structuralanalysisof pages 9-11, gemmer2024exploringthemolecular pages 1-3)
- Structural placements: 2023 cryo‑EM resolves TRAP‑γ anchoring to 28S rRNA and L38 and a seven‑TM bundle incorporating α/β/δ C‑terminal helices; the lumenal α/β/δ crescent faces the Sec61 pore, consistent with direct nascent‑chain engagement (Science Advances, 2023). (pauwels2023structuralinsightsinto pages 1-2, pauwels2023structuralinsightsinto pages 2-3)

Verification of identity and organism (MANDATORY)
- The gene symbol “SSR2” in this report refers to the human Signal Sequence Receptor subunit beta (TRAP‑β), UniProt P43308, within Homo sapiens. The protein is a member of the TRAP‑beta family and forms part of the ER TRAP complex alongside SSR1/SSR3/SSR4; the features, domains, topology and interactions reported here align with the TRAP‑β family and domain annotations. If alternative “SSR2” symbols exist in other organisms/pathways, they are not the subject of this analysis. (russo2020understandingthemammalian pages 5-6, russo2020understandingthemammalian pages 2-4)

Embedded summary table of key facts
| Aspect | Key points | Most supporting sources (with journal, year) | URL(s) |
|---|---|---:|---|
| Identity / synonyms | SSR2 encodes TRAP-β (signal sequence receptor subunit beta); gene symbol SSR2, alias TRAPB. | Russo, Open Biol., 2020 (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.1098/rsob.190244 |
| Organism | Human (Homo sapiens) protein annotated as UniProt P43308 (TRAP‑β). | Russo, Open Biol., 2020 (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.1098/rsob.190244 |
| Family / domains | Member of the TRAP‑beta family; luminal/extracellular domain plus single transmembrane helix (TRAP_beta domain). | Pauwels et al., Sci Adv, 2023 (pauwels2023structuralinsightsinto pages 1-2); Russo, 2020 (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.1126/sciadv.adf0797 https://doi.org/10.1098/rsob.190244 |
| TRAP subunit composition | TRAP is a heterotetramer: SSR1 (TRAP‑α), SSR2 (TRAP‑β), SSR3 (TRAP‑γ), SSR4 (TRAP‑δ) assembled with Sec61 in the ribosome–translocon complex. | Russo, 2020 (russo2020understandingthemammalian pages 5-6); Pauwels, 2023 (pauwels2023structuralinsightsinto pages 1-2) | https://doi.org/10.1098/rsob.190244 https://doi.org/10.1126/sciadv.adf0797 |
| SSR2 topology | Type I membrane protein: luminal N‑terminus, single TM (approx. residues ~147–167), cytosolic C‑terminus. | Russo, Open Biol., 2020 (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.1098/rsob.190244 |
| Ribosome–Sec61–TRAP architecture (2023–2024) | High‑resolution cryo‑EM places TRAP tetramer adjacent to Sec61; TRAP‑β (central) is sandwiched between TRAP‑α and TRAP‑δ and contributes to lumenal core facing Sec61; multiple ribosomal contacts stabilize the assembly. | Pauwels et al., Sci Adv, 2023 (pauwels2023structuralinsightsinto pages 1-2); Karki et al., EMBO Rep, 2023 (karki2023molecularviewof pages 2-3); Lewis et al., eLife, 2024 (lewis2024structuralanalysisof pages 9-11) | https://doi.org/10.1126/sciadv.adf0797 https://doi.org/10.15252/embr.202357910 https://doi.org/10.1101/2023.12.22.572959 |
| Sec61 gating / signal‑peptide selectivity | Structural + MD data show TRAP biases Sec61 lateral‑gate conformations, facilitating translocation of substrates with weak/low‑hydrophobicity or Pro/Gly‑rich signal peptides. | Pauwels, Sci Adv, 2023 (pauwels2023structuralinsightsinto pages 1-2); Karki, EMBO Rep, 2023 (karki2023molecularviewof pages 2-3); Gemmer et al., Life Sci Alliance, 2024 (gemmer2024exploringthemolecular pages 1-3) | https://doi.org/10.1126/sciadv.adf0797 https://doi.org/10.15252/embr.202357910 https://doi.org/10.26508/lsa.202302496 |
| Coupling to OST / N‑glycosylation | TRAP often co‑occurs with oligosaccharyltransferase (OST) in translocons; TRAP lumenal domains are positioned to coordinate nascent‑chain glycosylation and TRAP deficiency (e.g., SSR4 loss) associates with hypoglycosylation. | Karki, EMBO Rep, 2023 (karki2023molecularviewof pages 2-3); Lewis et al., 2024 (lewis2024structuralanalysisof pages 9-11); Russo, 2020 (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.15252/embr.202357910 https://doi.org/10.1101/2023.12.22.572959 https://doi.org/10.1098/rsob.190244 |
| ER membrane remodeling / thinning | MD simulations and cryo‑ET show TRAP deforms and locally thins the ER membrane near Sec61, which may lower the energetic barrier for insertion of challenging transmembrane segments. | Karki, EMBO Rep, 2023 (karki2023molecularviewof pages 2-3); Gemmer, Life Sci Alliance, 2024 (gemmer2024exploringthemolecular pages 1-3) | https://doi.org/10.15252/embr.202357910 https://doi.org/10.26508/lsa.202302496 |
| Localization | Integral ER membrane protein; TRAP luminal domains face ER lumen and complex is ribosome‑associated at the cytosolic face. | Russo, 2020 (russo2020understandingthemammalian pages 5-6); Pauwels, 2023 (pauwels2023structuralinsightsinto pages 1-2) | https://doi.org/10.1098/rsob.190244 https://doi.org/10.1126/sciadv.adf0797 |
| Disease genetics (TRAP‑related CDG) | Mutations in TRAP subunits (notably SSR4/TRAP‑δ) cause congenital disorders of glycosylation (hypoglycosylation); SSR2‑specific clinical cases are limited but TRAP integrity affects glycoprotein biogenesis. | Russo, 2019/2020 reviews (russo2019themammaliantransloconassociated pages 27-35, russo2020understandingthemammalian pages 5-6); Karki et al., 2023 (patient cell comparisons) (karki2023molecularviewof pages 2-3) | https://doi.org/10.1098/rsob.190244 https://doi.org/10.15252/embr.202357910 |
| Viral host‑dependency | TRAP influences glycoprotein biogenesis and translocation fidelity, processes exploited by enveloped viruses; translocon components are implicated in virus dependency in functional screens and translocon inhibition affects select secretory clients. | Russo review, 2019/2020 (russo2019themammaliantransloconassociated pages 27-35, russo2020understandingthemammalian pages 5-6); Pauwels, Sci Adv, 2023 (pauwels2023structuralinsightsinto pages 1-2) | https://doi.org/10.1098/rsob.190244 https://doi.org/10.1126/sciadv.adf0797 |
| Small‑molecule translocon modulators | Sec61 inhibitors (e.g., CK147, cotransin derivatives) bind lumenal/plug/lateral‑gate regions; cryo‑EM structures reveal inhibitor sites and suggest routes to client‑selective translocon modulation. | Pauwels et al., Sci Adv, 2023 (pauwels2023structuralinsightsinto pages 1-2); Karki et al., 2023 (karki2023molecularviewof pages 2-3) | https://doi.org/10.1126/sciadv.adf0797 https://doi.org/10.15252/embr.202357910 |
| Expression / biomarker evidence | Proteomics and transcriptomic surveys report TRAP subunit expression across tissues; altered TRAP/SSR expression observed in some tumors but SSR2‑specific biomarker status remains provisional. | Gemmer et al., Life Sci Alliance, 2024 (gemmer2024exploringthemolecular pages 1-3); Russo, 2020 (russo2020understandingthemammalian pages 5-6) | https://doi.org/10.26508/lsa.202302496 https://doi.org/10.1098/rsob.190244 |
| Recent expert / structural reviews | Integrated reviews and recent cryo‑EM studies synthesize TRAP function, structure, OST coupling and disease links (key refs: Russo 2020; Pauwels 2023; Karki 2023; Lewis 2024; Gemmer 2024). | Russo, Open Biol., 2020 (russo2020understandingthemammalian pages 5-6); Pauwels, Sci Adv, 2023 (pauwels2023structuralinsightsinto pages 1-2); Karki, EMBO Rep, 2023 (karki2023molecularviewof pages 2-3); Lewis, 2024 (lewis2024structuralanalysisof pages 9-11); Gemmer, 2024 (gemmer2024exploringthemolecular pages 1-3) | https://doi.org/10.1098/rsob.190244 https://doi.org/10.1126/sciadv.adf0797 https://doi.org/10.15252/embr.202357910 https://doi.org/10.1101/2023.12.22.572959 https://doi.org/10.26508/lsa.202302496 |

Table: Concise, cited summary table of human SSR2 (TRAP‑β) covering identity, structure, function, disease links, viral relevance, and recent structural studies (2023–2024) useful for functional annotation and literature review.

Notes on evidence strength and gaps
- Most SSR2-specific functional roles are supported at the complex level, with subunit‑resolved placement and contacts captured in 2023–2024 structures; direct SSR2‑unique disease reports are limited, but complex integrity (e.g., SSR4 deficiency) yields N‑glycosylation defects that infer importance of all subunits. (pauwels2023structuralinsightsinto pages 1-2, karki2023molecularviewof pages 2-3, russo2020understandingthemammalian pages 5-6)

References with URLs and dates
- Russo A. Understanding the mammalian TRAP complex function(s). Open Biology. Published May 13, 2020. doi:10.1098/rsob.190244; https://doi.org/10.1098/rsob.190244 (overview of TRAP identity, composition, topology, and coupling) (russo2020understandingthemammalian pages 5-6, russo2020understandingthemammalian pages 2-4, russo2020understandingthemammalian pages 8-10, russo2020understandingthemammalian pages 12-13, russo2020understandingthemammalian pages 1-2)
- Pauwels E. et al. Structural insights into TRAP association with ribosome–Sec61 complex and translocon inhibition by a CADA derivative. Science Advances. Published March 22, 2023. doi:10.1126/sciadv.adf0797; https://doi.org/10.1126/sciadv.adf0797 (human cryo‑EM architecture; CK147 inhibitor site; SP selectivity) (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. Published November 20, 2023. doi:10.15252/embr.202357910; https://doi.org/10.15252/embr.202357910 (atomic model; MD membrane thinning; gate modulation; OST proximity) (karki2023molecularviewof pages 2-3, karki2023molecularviewof pages 1-2, karki2023molecularviewof pages 3-5)
- Lewis A.J.O. et al. Structural analysis of the dynamic ribosome–translocon complex. eLife preprint (bioRxiv). Posted May 2, 2024. doi:10.1101/2023.12.22.572959; https://doi.org/10.1101/2023.12.22.572959 (TRAP contacts, OST linkage, dynamic composition) (lewis2024structuralanalysisof pages 9-11)
- Gemmer M. et al. Exploring the molecular composition of the multipass translocon in its native membrane environment. Life Science Alliance. Published June 12, 2024. doi:10.26508/lsa.202302496; https://doi.org/10.26508/lsa.202302496 (native ER cryo‑ET; TRAP variability; BOS contact; multipass context) (gemmer2024exploringthemolecular pages 1-3)
- Russo A. The mammalian TRAP complex and co‑translational protein transport. Review synthesis (2019) providing historical context for subunit composition and function. (russo2019themammaliantransloconassociated pages 94-96, russo2019themammaliantransloconassociated pages 35-41, russo2019themammaliantransloconassociated pages 27-35)

References

(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.
(russo2020understandingthemammalian pages 2-4): 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.
(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 2-3): Sudeep Karki, Matti Javanainen, Shahid Rehan, Dale Tranter, Juho Kellosalo, Juha T Huiskonen, Lotta Happonen, and Ville Paavilainen. Molecular view of er membrane remodeling by the sec61/trap translocon. EMBO reports, Nov 2023. URL: https://doi.org/10.15252/embr.202357910, doi:10.15252/embr.202357910. This article has 17 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 er membrane remodeling by the sec61/trap translocon. EMBO reports, Nov 2023. URL: https://doi.org/10.15252/embr.202357910, doi:10.15252/embr.202357910. This article has 17 citations and is from a highest quality 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 er membrane remodeling by the sec61/trap translocon. EMBO reports, Nov 2023. URL: https://doi.org/10.15252/embr.202357910, doi:10.15252/embr.202357910. This article has 17 citations and is from a highest quality peer-reviewed journal.
(lewis2024structuralanalysisof pages 9-11): Aaron J. O. Lewis, Frank Zhong, Robert J. Keenan, and Ramanujan S. Hegde. Structural analysis of the dynamic ribosome-translocon complex. eLife, May 2024. URL: https://doi.org/10.1101/2023.12.22.572959, doi:10.1101/2023.12.22.572959. This article has 14 citations and is from a domain leading peer-reviewed journal.
(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.
(russo2019themammaliantransloconassociated pages 27-35): A Russo. The mammalian translocon-associated protein (trap) complex and co-translational protein transport. Unknown journal, 2019.
(russo2020understandingthemammalian pages 1-2): 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.
(russo2020understandingthemammalian pages 8-10): 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.
(russo2020understandingthemammalian pages 12-13): 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.
(russo2019themammaliantransloconassociated pages 94-96): A Russo. The mammalian translocon-associated protein (trap) complex and co-translational protein transport. Unknown journal, 2019.
(russo2019themammaliantransloconassociated pages 35-41): A Russo. The mammalian translocon-associated protein (trap) complex and co-translational protein transport. Unknown journal, 2019.

Citations

gemmer2024exploringthemolecular pages 1-3
pauwels2023structuralinsightsinto pages 1-2
russo2020understandingthemammalian pages 5-6
karki2023molecularviewof pages 2-3
lewis2024structuralanalysisof pages 9-11
russo2020understandingthemammalian pages 2-4
pauwels2023structuralinsightsinto pages 2-3
karki2023molecularviewof pages 1-2
karki2023molecularviewof pages 3-5
russo2019themammaliantransloconassociated pages 27-35
russo2020understandingthemammalian pages 1-2
russo2020understandingthemammalian pages 8-10
russo2020understandingthemammalian pages 12-13
russo2019themammaliantransloconassociated pages 94-96
russo2019themammaliantransloconassociated pages 35-41
https://doi.org/10.1098/rsob.190244
https://doi.org/10.1126/sciadv.adf0797
https://doi.org/10.15252/embr.202357910
https://doi.org/10.1101/2023.12.22.572959
https://doi.org/10.26508/lsa.202302496
https://doi.org/10.1098/rsob.190244,
https://doi.org/10.1126/sciadv.adf0797,
https://doi.org/10.15252/embr.202357910,
https://doi.org/10.1101/2023.12.22.572959,
https://doi.org/10.26508/lsa.202302496,

📚 Additional Documentation

Notes

(SSR2-notes.md)

SSR2 Gene Review Notes

2026-05-30 - PROTEOSTASIS PN TRAP-complex positive-control pass

Full review is present and marked complete. The local review supports SSR2/TRAP-beta as an ER membrane subunit of the TRAP complex that associates with Sec61 during co-translational protein translocation, especially for nascent chains with weak or suboptimal signal peptides. The review modifies the GO:0031204 post-translational protein targeting to membrane, translocation annotation toward GO:0006613 cotranslational protein targeting to membrane. [file:human/SSR2/SSR2-ai-review.yaml; PMID:7789174; PMID:36697828]

PN curation conclusion: the PN placement under ER proteostasis > Protein transport > TRAP complex component is a strong positive control. As with SSR1, broad protein-transport propagation is biologically compatible but should be read against the more specific cotranslational ER-translocon function already curated locally.

Pn Notes

(SSR2-pn-notes.md)

SSR2 PN Consistency Notes

Generated: 2026-06-18
Project: PROTEOSTASIS
Scope: priority-only PN rereview against local AIGR review and available deep-research artifacts
UniProt: P43308
AIGR review status: COMPLETE
Priority category: positive_control
Local AIGR project status: local_review_complete_not_phase1
Related project: ER_PHAGY.md

Source Files Checked

AIGR review YAML: present - genes/human/SSR2/SSR2-ai-review.yaml
AIGR review HTML: present - genes/human/SSR2/SSR2-ai-review.html
Gene notes: present - genes/human/SSR2/SSR2-notes.md
GOA TSV: present - genes/human/SSR2/SSR2-goa.tsv
UniProt record: present - genes/human/SSR2/SSR2-uniprot.txt
PROTEOSTASIS priority table: projects/PROTEOSTASIS/priority_genes.tsv
PN projection report: projects/PROTEOSTASIS/reports/pn_projection/pn_projected_gene_go_summary.tsv
PN mapping audit: projects/PROTEOSTASIS/reports/pn_mapping_audit/current_mapping_scrutiny.tsv
PN mapping file: projects/PROTEOSTASIS/mappings/er_proteostasis.yaml

Deep Research Files

genes/human/SSR2/SSR2-deep-research-falcon.md

AIGR Review Snapshot

Description: SSR2 encodes the beta subunit of the translocon-associated protein (TRAP) complex, also known as signal sequence receptor subunit beta (SSR-beta/TRAP-beta). TRAP is a heterotetrameric complex (SSR1/alpha, SSR2/beta, SSR3/gamma, SSR4/delta) that associates with the Sec61 translocon at the endoplasmic reticulum membrane. The complex assists in co-translational protein translocation, particularly for nascent polypeptides with weak or suboptimal signal peptides. SSR2/TRAP-beta is a type I single-pass membrane glycoprotein with its N-terminus facing the ER lumen, where it contributes to the lumenal crescent structure that contacts nascent chains exiting the Sec61 pore. The TRAP complex also coordinates with the oligosaccharyltransferase (OST) complex to facilitate N-glycosylation of nascent proteins. SSR2 was identified as a STING1 interactor in a yeast-two-hybrid screen (PMID:18724357), but the biological significance of this interaction is uncertain; it likely reflects proximity at the ER membrane rather than a dedicated immune-signaling function.
Existing/core annotation action counts: ACCEPT: 5; MARK_AS_OVER_ANNOTATED: 3; NEW: 1; REMOVE: 1

PN Consistency Summary

Consistency: Priority-only record; no phase-1 dossier section exists yet. Local review status is 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 terms
PN story / NEW pressure: Current projection rows: GO:0015031 protein transport (entailed_by_goa_closure).
Mapping strategy: Use as a calibration case for PN-to-GO propagation: the PN placement should agree with an already well-supported local review rather than driving broad new ontology pressure.
Verdict: Add to boundary/phase1 tracking as a mapping positive control

Priority Review Context

Category: positive_control
PN annotations: ER proteostasis > Protein transport > TRAP complex component
Why interesting: Good example where PN context is compatible with existing ER targeting/translocation GO terms
Suggested next step: Add to boundary/phase1 tracking as a mapping positive control
Related project: ER_PHAGY.md

PN Projection Rows

GO:0015031 protein transport - entailed_by_goa_closure; scope=ok_for_propagation_to_go; mapping=er_proteostasis.yaml; PN=ER proteostasis|Protein transport|TRAP complex component

PN Dossier Context

No 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.

Note

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.

📄 View Raw YAML

id: P43308
gene_symbol: SSR2
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  SSR2 encodes the beta subunit of the translocon-associated protein (TRAP) complex,
  also known as signal sequence receptor subunit beta (SSR-beta/TRAP-beta). TRAP is
  a heterotetrameric complex (SSR1/alpha, SSR2/beta, SSR3/gamma, SSR4/delta) that
  associates with the Sec61 translocon at the endoplasmic reticulum membrane. The
  complex assists in co-translational protein translocation, particularly for nascent
  polypeptides with weak or suboptimal signal peptides. SSR2/TRAP-beta is a type I
  single-pass membrane glycoprotein with its N-terminus facing the ER lumen, where it
  contributes to the lumenal crescent structure that contacts nascent chains exiting
  the Sec61 pore. The TRAP complex also coordinates with the oligosaccharyltransferase
  (OST) complex to facilitate N-glycosylation of nascent proteins. SSR2 was identified
  as a STING1 interactor in a yeast-two-hybrid screen (PMID:18724357), but the
  biological significance of this interaction is uncertain; it likely reflects
  proximity at the ER membrane rather than a dedicated immune-signaling function.
existing_annotations:
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      This IEA annotation is derived from InterPro domain mapping (IPR008856 TRAP_beta).
      SSR2/TRAP-beta is well-established as an ER-resident protein. The protein is
      part of the TRAP complex that associates with the Sec61 translocon at the ER
      membrane [file:human/SSR2/SSR2-deep-research-falcon.md].
    action: ACCEPT
    reason: >-
      Accurate annotation. SSR2 is an integral ER membrane protein as part of the
      TRAP complex. The InterPro-based inference is consistent with extensive
      experimental evidence showing ER localization [PMID:7789174, PMID:36697828].
    supported_by:
      - reference_id: PMID:7789174
        supporting_text: "We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene, which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane."
      - reference_id: file:human/SSR2/SSR2-deep-research-falcon.md
        supporting_text: "[Deep research confirms] SSR2 encodes TRAP-beta (signal sequence receptor subunit beta) ... predominantly resides in the endoplasmic reticulum"
- term:
    id: GO:0005789
    label: endoplasmic reticulum membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      This IEA annotation is based on UniProt subcellular location vocabulary mapping.
      SSR2 is an integral ER membrane protein with a single transmembrane helix.
      UniProt records: "Endoplasmic reticulum membrane; Single-pass type I membrane protein."
    action: ACCEPT
    reason: >-
      Accurate and well-supported annotation. SSR2/TRAP-beta has type I topology
      (N lumen, C cytosol) with a single transmembrane helix embedded in the ER membrane
      [file:human/SSR2/SSR2-deep-research-falcon.md]. Cryo-EM structures confirm this localization
      [PMID:36697828].
    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"
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      This IEA annotation is derived from InterPro domain mapping. While correct that
      SSR2 is a membrane protein, this term is too general compared to the more specific
      GO:0005789 (endoplasmic reticulum membrane) annotation that is also present.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0005789 (endoplasmic reticulum membrane) is already annotated and is strictly
      more specific. GO:0016020 is redundant given that more precise localization
      information is captured by the ER-membrane term; best-practice curation flags
      such general terms as over-annotations when a specific child is present.
    supported_by:
      - reference_id: PMID:7789174
        supporting_text: "which codes for an endoplasmic reticulum (ER) membrane protein"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18724357
  review:
    summary: >-
      This IPI annotation is based on the interaction between SSR2/TRAP-beta and STING1,
      demonstrated by yeast two-hybrid screening and co-immunoprecipitation in PMID:18724357.
      The study identified SSR2 as a STING1 interactor and showed that TRAP-beta ablation
      reduced STING's ability to induce interferon-beta.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The evidence for this IPI record is the STING1 interaction (WITH Q86WV6,
      PMID:18724357, yeast-two-hybrid plus co-IP). The interaction is experimentally
      real but its biological significance is uncertain; the paper frames it as
      the translocon potentially influencing STING-mediated innate signalling, not
      as a core SSR2 function. Substituting GO:0106138 (Sec61 translocon complex
      binding) as the replacement term would swap in a different molecular partner
      unsupported by this IPI evidence record. MARK_AS_OVER_ANNOTATED is the
      appropriate disposition: protein binding is non-informative and this specific
      STING1 interaction is peripheral to SSR2's core role. GO:0106138 is retained in
      core_functions, supported by structural co-complex evidence (PMID:36697828).
    supported_by:
      - reference_id: PMID:18724357
        supporting_text: "we screened an IFN-induced, human fibroblast yeast two-hybrid cDNA library using STING (amino acids 173-379) as a bait and repeatedly isolated Ssr2/TRAPbeta, a member of the TRAP complex comprising four subunits (alpha-delta) that facilitates translocation of proteins into the ER following translation"
      - reference_id: PMID:18724357
        supporting_text: "we confirmed that TRAPbeta can indeed associate with endogenous STING in HEK 293 cells following co-immunoprecipitation experiments"
- term:
    id: GO:0106138
    label: Sec61 translocon complex binding
  evidence_type: IDA
  original_reference_id: PMID:36697828
  review:
    summary: >-
      NEW annotation proposed to capture the direct physical association of SSR2/TRAP-beta
      with the Sec61 translocon, as demonstrated by cryo-electron tomography showing
      the near-complete atomic model of the SEC61-TRAP-OSTA complex. TRAP stably
      associates with Sec61 at the ER membrane.
    action: NEW
    reason: >-
      The cryo-ET study (PMID:36697828) directly visualizes the TRAP complex in stable
      association with Sec61 in native ER membranes, providing structural IDA-level
      evidence for Sec61 translocon complex binding. This is the core MF of SSR2 and
      should be annotated directly rather than inferred by remapping the STING1 IPI
      record. The co-IP data in PMID:18724357 (Sec61beta co-IP) provides additional
      biochemical support.
    supported_by:
      - reference_id: PMID:36697828
        supporting_text: "The 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:0005789
    label: endoplasmic reticulum membrane
  evidence_type: NAS
  original_reference_id: PMID:36697828
  review:
    summary: >-
      This NAS annotation is based on Gemmer et al. (2023), which used cryo-electron
      tomography to visualize the native ER translocon including the TRAP complex.
      The study provides near-complete atomic models of the SEC61-TRAP-OSTA complex
      at the ER membrane.
    action: ACCEPT
    reason: >-
      This is an accurate annotation supported by high-resolution structural data.
      The cryo-ET study directly visualizes SSR2/TRAP-beta as an integral component
      of the ER membrane translocon complex [PMID:36697828].
    supported_by:
      - reference_id: PMID:36697828
        supporting_text: "The 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:0031204
    label: post-translational protein targeting to membrane, translocation
  evidence_type: NAS
  original_reference_id: PMID:36697828
  review:
    summary: >-
      This NAS annotation suggests SSR2/TRAP-beta is involved in post-translational
      protein translocation. However, the TRAP complex is primarily associated with
      co-translational translocation, assisting the Sec61 translocon during ribosome-
      associated protein synthesis and membrane insertion.
    action: REMOVE
    reason: >-
      GO:0031204 captures post-translational protein targeting, but the TRAP complex
      acts co-translationally (ribosome-bound Sec61 complexes). The correct sub-pathway
      term, GO:0006613 (cotranslational protein targeting to membrane), is already
      independently annotated from PMID:7789174. MODIFY to a term already present
      would produce a duplicate; REMOVE is the cleaner disposition for the incorrectly
      assigned sub-pathway term.
    supported_by:
      - reference_id: PMID:36697828
        supporting_text: "distinct polysomes bind to different ER translocons specialized in the synthesis of proteins with signal peptides or multipass transmembrane proteins with the translocon-associated protein complex (TRAP) present in both"
      - reference_id: file:human/SSR2/SSR2-deep-research-falcon.md
        supporting_text: "[Deep research confirms] TRAP is a heterotetramer of SSR1 (alpha), SSR2 (beta), SSR3 (gamma), SSR4 (delta) ... co-translational protein translocation"
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: TAS
  original_reference_id: PMID:7789174
  review:
    summary: >-
      This TAS annotation is based on the original cloning paper by Chinen et al. (1995)
      which identified SSR2 as encoding an ER membrane protein. The paper describes
      isolation of the human beta-signal sequence receptor gene.
    action: ACCEPT
    reason: >-
      Accurate annotation with appropriate primary literature support. The paper
      explicitly describes SSR2 as encoding "an endoplasmic reticulum (ER) membrane
      protein associated with protein translocation across the ER membrane."
    supported_by:
      - reference_id: PMID:7789174
        supporting_text: "We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene, which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane."
- term:
    id: GO:0006613
    label: cotranslational protein targeting to membrane
  evidence_type: TAS
  original_reference_id: PMID:7789174
  review:
    summary: >-
      This TAS annotation captures the core function of SSR2/TRAP-beta in co-translational
      protein translocation. The TRAP complex associates with ribosome-Sec61 complexes
      and facilitates membrane targeting of nascent polypeptides, particularly those
      with weak or suboptimal signal peptides.
    action: ACCEPT
    reason: >-
      This is a core function annotation. SSR2 as part of the TRAP complex is directly
      involved in co-translational protein translocation at the ER membrane. Recent
      cryo-EM studies confirm that TRAP is consistently present in the co-translational
      translocon and modulates Sec61 function for challenging substrates [PMID:36697828;
      file:human/SSR2/SSR2-deep-research-falcon.md].
    supported_by:
      - reference_id: PMID:7789174
        supporting_text: "which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane"
    additional_reference_ids:
      - PMID:36697828
- term:
    id: GO:0016020
    label: membrane
  evidence_type: TAS
  original_reference_id: PMID:7789174
  review:
    summary: >-
      This TAS annotation based on PMID:7789174 indicates SSR2 is a membrane protein.
      This is accurate but less specific than GO:0005789 (ER membrane) which is also
      annotated from the same reference.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      GO:0005789 (endoplasmic reticulum membrane) is annotated from the same reference
      and is more informative. GO:0016020 is a redundant parent term; retaining only
      the specific child term is consistent with curation best practice.
    supported_by:
      - reference_id: PMID:7789174
        supporting_text: "which codes for an endoplasmic reticulum (ER) membrane protein"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    Vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
  findings: []
- id: PMID:18724357
  title: STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling.
  findings:
    - statement: Yeast two-hybrid screening identified SSR2/TRAP-beta as a STING1 interacting protein
      supporting_text: "we screened an IFN-induced, human fibroblast yeast two-hybrid cDNA library using STING (amino acids 173-379) as a bait and repeatedly isolated Ssr2/TRAPbeta"
    - statement: Co-immunoprecipitation confirmed TRAP-beta association with endogenous STING
      supporting_text: "we confirmed that TRAPbeta can indeed associate with endogenous STING in HEK 293 cells following co-immunoprecipitation experiments"
    - statement: TRAP-beta ablation reduced STING-mediated interferon-beta induction
      supporting_text: "loss of TRAPbeta or SEC61beta reduced STING's, ability to induce an IFNbeta promoter driving luciferase"
- id: PMID:36697828
  title: Visualization of translation and protein biogenesis at the ER membrane.
  findings:
    - statement: Cryo-electron tomography visualization of native ER translocon complexes
      supporting_text: "Here we use cryo-electron tomography, extensive classification and molecular modelling to capture snapshots of mRNA translation and protein maturation at the ER membrane"
    - statement: Near-complete atomic model of SEC61-TRAP-OSTA complex
      supporting_text: "The near-complete atomic model of the most abundant ER translocon variant comprising the protein-conducting channel SEC61, TRAP and the oligosaccharyltransferase complex A (OSTA)"
    - statement: TRAP present in both signal peptide and multipass translocon variants
      supporting_text: "distinct polysomes bind to different ER translocons specialized in the synthesis of proteins with signal peptides or multipass transmembrane proteins with the translocon-associated protein complex (TRAP) present in both"
- id: PMID:7789174
  title: Isolation and mapping of the human beta-signal sequence receptor gene (SSR2).
  findings:
    - statement: Original cloning of human SSR2 cDNA
      supporting_text: "We have isolated a human cDNA clone homologous to the canine beta-signal sequence receptor gene"
    - statement: Identified SSR2 as encoding ER membrane protein involved in translocation
      supporting_text: "which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane"
    - statement: Mapped SSR2 to chromosome 1q21-q23
      supporting_text: "We also localized the human beta-signal sequence receptor gene (SSR2) to chromosome bands 1q21-->q23"
- id: file:human/SSR2/SSR2-deep-research-falcon.md
  title: Deep research summary for SSR2/TRAP-beta
  findings:
    - statement: Comprehensive review of TRAP complex structure and function from recent literature
    - statement: TRAP is a heterotetramer (alpha, beta, gamma, delta subunits)
    - statement: TRAP-beta has type I topology with single transmembrane helix
    - statement: TRAP modulates Sec61 lateral gate for weak signal peptides
core_functions:
  - description: >-
      SSR2/TRAP-beta is a component of the TRAP complex that associates with the
      Sec61 translocon during co-translational protein translocation. The complex
      assists in membrane targeting and insertion of nascent polypeptides with
      weak or suboptimal signal peptides [PMID:7789174; PMID:36697828].
    molecular_function:
      id: GO:0106138
      label: Sec61 translocon complex binding
    directly_involved_in:
      - id: GO:0006613
        label: cotranslational protein targeting to membrane
    locations:
      - id: GO:0005789
        label: endoplasmic reticulum membrane
    supported_by:
      - reference_id: PMID:7789174
        supporting_text: "which codes for an endoplasmic reticulum (ER) membrane protein associated with protein translocation across the ER membrane"
      - reference_id: PMID:36697828
        supporting_text: "The 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."
proposed_new_terms:
  - proposed_name: TRAP complex
    proposed_definition: >-
      A heterotetrameric protein complex composed of TRAP-alpha (SSR1), TRAP-beta (SSR2),
      TRAP-gamma (SSR3), and TRAP-delta (SSR4) subunits that associates with the Sec61
      translocon at the endoplasmic reticulum membrane. The TRAP complex facilitates
      co-translational protein translocation, particularly for substrates with weak
      or suboptimal signal peptides.
    justification: >-
      There is currently no specific GO term for the translocon-associated protein
      (TRAP) complex. This heterotetrameric complex (SSR1-4/TRAP-alpha,beta,gamma,delta)
      is distinct from the Sec61 translocon core and functions as a co-factor for
      protein translocation. A dedicated cellular component term would improve
      annotation precision for all TRAP subunit genes. Note that ComplexPortal
      CPX-8024 ("Translocon-associated protein complex") already captures this
      complex and is cited in the UniProt record; the GO request should reference
      CPX-8024 as supporting evidence for the complex's existence and composition.
suggested_questions:
  - question: >-
      What is the precise mechanism by which the TRAP complex modulates Sec61 lateral
      gate dynamics to facilitate translocation of weak signal peptide substrates?
      Recent structural and MD studies suggest TRAP influences gate conformations
      but the detailed mechanism remains incompletely characterized.
  - question: >-
      What is the functional significance of the SSR2/TRAP-beta interaction with STING1?
      Is this interaction related to TRAP's role in protein translocation or does it
      represent a distinct function in innate immune signaling? The STING1 interaction
      was identified in a focused study on innate immunity, but whether this represents
      a core or peripheral function of SSR2 is unclear.

SSR2

Gene Description

Proposed New Ontology Terms

TRAP complex

Existing Annotations Review

Core Functions

SSR2/TRAP-beta is a component of the TRAP complex that associates with the Sec61 translocon during co-translational protein translocation. The complex assists in membrane targeting and insertion of nascent polypeptides with weak or suboptimal signal peptides [PMID:7789174; PMID:36697828].

References

Suggested Questions for Experts

Deep Research

Falcon

Citations

📚 Additional Documentation

Notes

SSR2 Gene Review Notes

2026-05-30 - PROTEOSTASIS PN TRAP-complex positive-control pass

Pn Notes

SSR2 PN Consistency Notes

Source Files Checked

Deep Research Files

AIGR Review Snapshot

PN Consistency Summary

Priority Review Context

PN Projection Rows

PN Dossier Context

Note

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