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.
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.
| 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 |
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Download this section (compressed HTML)Q: 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.
Q: 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.
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